LISTED EURONEXT Paris NASDAQ Copenhagen

EPA ONXEO

TODAYrsquoS SCIENCE TARGETING TUMOR

DNA FUNCTIONS

TOMORROWrsquoS NEW HOPE AGAINST RESISTANT CANCER

February 2020

IMPORTANT You must read the following before continuing In accessing this document you agree to be bound by the following terms and conditions

This document has been prepared by Onxeo SA (together with its subsidiaries the Group) and is for information purposes only The content of this document is provisional and for information purposes only and is notto be construed as providing investment advice The information statements and opinions contained in this document (the ldquoInformationrdquo) are provided as of the date of this document only and may be subject tosignificant changes at any time without notice Neither the Group nor its advisors nor any other person is under any obligation to update the Information Subject to applicable law none of the Company or its advisorsaccepts any responsibility whatsoever and makes no representation or warranty express or implied as to the fairness accuracy completeness or correctness of the Information The Information has not been subject toindependent verification and is qualified in its entirety by the business financial and other information that the Group is required to publish in accordance with the rules regulations and practices applicable to companieslisted on Euronext Paris including in particular the risk factors in the Companyrsquos Registration Document filed with the French Financial Markets Authority (Autoriteacute des marcheacutes financiers) under number D17-0423 onApril 24 2017 in any other periodic report and in any other press release which are available free of charge on the websites of the Group (wwwonxeocom) andor the AMF (wwwamf-franceorg)

This document contains information on the use of the Groups products and its competitive position Some of the Information is from third parties While this third party information has been obtained from sourcesbelieved to be reliable there is no guarantee of the accuracy or completeness of such data In addition certain of the industry and market data comes from the Groups own internal research and estimates based on theknowledge and experience of the Groups management While the Group believes that such research and estimates are reasonable and reliable they and their underlying methodology and assumptions have not beenverified by any independent source for accuracy or completeness and are subject to change without notice Accordingly undue reliance should not be placed on any of the industry market or competitive position datacontained in the Information

The Information is not directed to or intended for distribution to or use by any person or entity that is a citizen or resident of or located in any locality state country or other jurisdiction where such distribution or usewould be contrary to law or regulation or which would require any registration or licensing within such jurisdiction The Information does not constitute or form part of and should not be construed as an offer or thesolicitation of an offer to subscribe for or purchase of any securities No public offering of securities may be conducted in France prior to the delivery by the French Financial Markets Authority of a visa on a prospectusthat complies with the provisions of Directive 200371CE as amended This document is for information purposes only and does not constitute an offering document or an offer of securities to the public in the UnitedKingdom to which section 85 of the Financial Services and Markets Act 2000 of the United Kingdom applies Securities may not be offered or sold in the United States absent registration under the US Securities Act of1933 as amended or an exemption from registration thereunder

This document contains certain forward-looking statements All statements in this document other than statements of historical fact are or may be deemed to be forward looking statements These statements are notguarantees of the Groups future performance These forward-looking statements relate without limitation to the Groups future prospects developments marketing strategy regulatory calendar clinical milestonesassumptions and hypothesis clinical development approach and financial requirements and are based on analyses of earnings forecasts and estimates of amounts not yet determinable and other financial and non-financial information Forward-looking statements are subject to a variety of risks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materialize in the futureForward-looking statements cannot under any circumstance be construed as a guarantee of the Groups future performance as to strategic regulatory financial or other matters and the Grouprsquos actual performanceincluding its financial position results and cash flow as well as the trends in the sector in which the Group operates may differ materially from those proposed or reflected in the forward-looking statements contained inthis document Even if the Grouprsquos performance including its financial position results cash-flows and developments in the sector in which the Group operates were to conform to the forward-looking statementscontained in this document such results or developments cannot be construed as a reliable indication of the Groups future results or developments The Group expressly declines any obligation to update or to confirmprojections or estimates made by analysts or to make public any correction to any prospective information in order to reflect an event or circumstance that may occur after the date of this document

Important Information

February 2020

Developing disruptive therapies in the field of DNA Damage Response (DDR) to address unmet needs in oncology

4

NEXT KEY MILESTONES FUNDEDFinancial visibility to Q3 2020 supports strategic plan to deliver key near-term clinical milestones

STRONG MANAGEMENT amp OPERATIONAL TEAMA highly skilled team of 30 with capabilities to lead compounds from preclinical to proof-of-concept in man led by experienced management with demonstrated track record in product amp business development

DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSEPlatONtrade proprietary chemistry platform of decoy oligonucleotides generatingnew compounds

AsiDNAtrade lead candidate at clinical stage a first-in-class decoy agonist showing unique anti-tumoral propertiesOX401 a newly optimized next-gen PARPi

A WELL-DEFINED BUSINESS MODELCreate value by bringing drug candidates to best inflection points and monetizing these assets to generate revenues

LISTED EURONEXT Paris NASDAQ Copenhagen

EPA ONXEO

February 2020

FRANCOISE BONO (PHD)

CSO(Sanofi Evotec)

Formerly Executive Vice-President Oncology of Evotec

Experienced management team with demonstrated track record in product amp business development

5

JUDITH GRECIET (PHARMD)

CEO

OLIVIER DE BEAUMONT (MD)

CMO(Aventis Quintiles Stallergenes Greer)

Formerly Senior Vice President Head of Global Clinical Development Pharmacovigilance and Medical Affairs

PHILIPPE MAITREEVP of Onxeo US CBDO

(Aventis PPD Oscient mAbRx)

Formerly Chief Executive Officer and Co-Founder of mAbRx

NICOLAS FELLMANN

CFO(Ernst amp Young Pfizer)

Formerly Director of Treasury Tax amp Audit of Pfizer France

(Pharmacia Wyeth (Pfizer) Eisai)Formerly President of Eisai France

February 2020

Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II PHASE III MARKET

platONtrade Proprietary Platform of Decoy Oligonucleotides

OX401Next-gen PARPi + STING pathway activation

AsiDNAtrade IT + radiotherapy

AsiDNAtrade IV

AsiDNAtrade IV + chemotherapy

AsiDNAtrade IV + PARPi

Beleodaqreg2

belinostat + platONtrade

Cutting-edge RampD pipeline with unique mechanisms of action in DDR

DRIIV -1b

DRIIV study in solid tumors

GENERATION OF DISRUPTIVE COMPOUNDS TARGETING DNA-BINDING FUNCTIONS

Epig

enet

ics

DN

A D

amag

e

Re

spo

nse

1 IT intratumoral ndash IV intravenous 2 Beleodaqreg commercial brand name of belinostat (IV form) in the US in rr PTCL3 4 PTCL Peripheral T-cell lymphoma ndash a rare form of blood cancer

4 Commercialized in the US by Onxeorsquos partner under a conditional market authorization from the FDA for the use of Beleodaqreg in the treatment of 2nd line PTCL

DRIIM study in metastatic melanoma

2nd line PTCL3 US4

Completed or ongoing Planned short-term Legend

DD

R

+ IO

Solid tumors

REVocan

6

AsiDNAtrade

Unique Decoy Agonist Mechanism of Action in DNA Damage Response

February 2020

AsiDNAtrade a first-in-class product in DNA Damage Response (DDR)

8

A purpose-designed cholesterol-oligonucleotide conjugate

5rsquo

3rsquo

3rsquo

5rsquo

Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1

Active 32 bp DNA duplex Cholesterol

Loop

1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113

Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule2Binding and activating DNA-PK and PARP signaling

enzymes

Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1

Sequence non-homologous and not immunogenic (CpG-free)

AsiDNA is not an RNAi therapy thus avoiding toxicity issues of this class

February 2020

Patent Protection (Composition of

Matter on AsiDNAtrade amp related compounds)

until 2031

Extendable to 2036 with SPC amp PTE

Combinationpatents up to 2038

and more

IP

February 2020

AsiDNAtrade a differentiated product in the clinically-validated field of DDR

9Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193

DDR inhibition is clinically-validated in oncology (PARPi)

DecoyAgonist mechanism of action avoids compensatory mechanisms blocking the induction of resistance

AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of genetic context

Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile

AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip

hellip diverts them away from the true damage hellip hellip leading to cellular death

February 2020

An extensive preclinical program paves the way to ambitious clinical translation

10

Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)

Autosensitization and noresistance observed In multiple cell lines Confirmed

Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines

No restriction to specific genetic context

AsiDNAtrade increases survival amp responders to

PARPi

Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival

Abrogation of resistance to PARPi In multiple cell lines Ongoing AsiDNAtrade stops resistance to PARPi

Abrogation of resistance to TKi Validated with EGFRi in multiple cell linesPrelim data confirming prolongation of EGFRiefficacy

In vitro data In vivo data

February 2020

Small Cell Lung Cancer PARPi sensitive

AsiDNAtrade leads to cancer cell death and does not induce resistance

11

NCI-H446

1st cycle 2nd cycle 3rd cycle 4th cycle0

20

40

60

80

100

120AsiDNA Talazoparib

Surv

ival (

NT)

Source Onxeo data on file

No surviving cells

Repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance

Emergence of Resistant cells

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

IMPORTANT You must read the following before continuing In accessing this document you agree to be bound by the following terms and conditions

This document has been prepared by Onxeo SA (together with its subsidiaries the Group) and is for information purposes only The content of this document is provisional and for information purposes only and is notto be construed as providing investment advice The information statements and opinions contained in this document (the ldquoInformationrdquo) are provided as of the date of this document only and may be subject tosignificant changes at any time without notice Neither the Group nor its advisors nor any other person is under any obligation to update the Information Subject to applicable law none of the Company or its advisorsaccepts any responsibility whatsoever and makes no representation or warranty express or implied as to the fairness accuracy completeness or correctness of the Information The Information has not been subject toindependent verification and is qualified in its entirety by the business financial and other information that the Group is required to publish in accordance with the rules regulations and practices applicable to companieslisted on Euronext Paris including in particular the risk factors in the Companyrsquos Registration Document filed with the French Financial Markets Authority (Autoriteacute des marcheacutes financiers) under number D17-0423 onApril 24 2017 in any other periodic report and in any other press release which are available free of charge on the websites of the Group (wwwonxeocom) andor the AMF (wwwamf-franceorg)

This document contains information on the use of the Groups products and its competitive position Some of the Information is from third parties While this third party information has been obtained from sourcesbelieved to be reliable there is no guarantee of the accuracy or completeness of such data In addition certain of the industry and market data comes from the Groups own internal research and estimates based on theknowledge and experience of the Groups management While the Group believes that such research and estimates are reasonable and reliable they and their underlying methodology and assumptions have not beenverified by any independent source for accuracy or completeness and are subject to change without notice Accordingly undue reliance should not be placed on any of the industry market or competitive position datacontained in the Information

The Information is not directed to or intended for distribution to or use by any person or entity that is a citizen or resident of or located in any locality state country or other jurisdiction where such distribution or usewould be contrary to law or regulation or which would require any registration or licensing within such jurisdiction The Information does not constitute or form part of and should not be construed as an offer or thesolicitation of an offer to subscribe for or purchase of any securities No public offering of securities may be conducted in France prior to the delivery by the French Financial Markets Authority of a visa on a prospectusthat complies with the provisions of Directive 200371CE as amended This document is for information purposes only and does not constitute an offering document or an offer of securities to the public in the UnitedKingdom to which section 85 of the Financial Services and Markets Act 2000 of the United Kingdom applies Securities may not be offered or sold in the United States absent registration under the US Securities Act of1933 as amended or an exemption from registration thereunder

This document contains certain forward-looking statements All statements in this document other than statements of historical fact are or may be deemed to be forward looking statements These statements are notguarantees of the Groups future performance These forward-looking statements relate without limitation to the Groups future prospects developments marketing strategy regulatory calendar clinical milestonesassumptions and hypothesis clinical development approach and financial requirements and are based on analyses of earnings forecasts and estimates of amounts not yet determinable and other financial and non-financial information Forward-looking statements are subject to a variety of risks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materialize in the futureForward-looking statements cannot under any circumstance be construed as a guarantee of the Groups future performance as to strategic regulatory financial or other matters and the Grouprsquos actual performanceincluding its financial position results and cash flow as well as the trends in the sector in which the Group operates may differ materially from those proposed or reflected in the forward-looking statements contained inthis document Even if the Grouprsquos performance including its financial position results cash-flows and developments in the sector in which the Group operates were to conform to the forward-looking statementscontained in this document such results or developments cannot be construed as a reliable indication of the Groups future results or developments The Group expressly declines any obligation to update or to confirmprojections or estimates made by analysts or to make public any correction to any prospective information in order to reflect an event or circumstance that may occur after the date of this document

Important Information

February 2020

Developing disruptive therapies in the field of DNA Damage Response (DDR) to address unmet needs in oncology

4

NEXT KEY MILESTONES FUNDEDFinancial visibility to Q3 2020 supports strategic plan to deliver key near-term clinical milestones

STRONG MANAGEMENT amp OPERATIONAL TEAMA highly skilled team of 30 with capabilities to lead compounds from preclinical to proof-of-concept in man led by experienced management with demonstrated track record in product amp business development

DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSEPlatONtrade proprietary chemistry platform of decoy oligonucleotides generatingnew compounds

AsiDNAtrade lead candidate at clinical stage a first-in-class decoy agonist showing unique anti-tumoral propertiesOX401 a newly optimized next-gen PARPi

A WELL-DEFINED BUSINESS MODELCreate value by bringing drug candidates to best inflection points and monetizing these assets to generate revenues

LISTED EURONEXT Paris NASDAQ Copenhagen

EPA ONXEO

February 2020

FRANCOISE BONO (PHD)

CSO(Sanofi Evotec)

Formerly Executive Vice-President Oncology of Evotec

Experienced management team with demonstrated track record in product amp business development

5

JUDITH GRECIET (PHARMD)

CEO

OLIVIER DE BEAUMONT (MD)

CMO(Aventis Quintiles Stallergenes Greer)

Formerly Senior Vice President Head of Global Clinical Development Pharmacovigilance and Medical Affairs

PHILIPPE MAITREEVP of Onxeo US CBDO

(Aventis PPD Oscient mAbRx)

Formerly Chief Executive Officer and Co-Founder of mAbRx

NICOLAS FELLMANN

CFO(Ernst amp Young Pfizer)

Formerly Director of Treasury Tax amp Audit of Pfizer France

(Pharmacia Wyeth (Pfizer) Eisai)Formerly President of Eisai France

February 2020

Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II PHASE III MARKET

platONtrade Proprietary Platform of Decoy Oligonucleotides

OX401Next-gen PARPi + STING pathway activation

AsiDNAtrade IT + radiotherapy

AsiDNAtrade IV

AsiDNAtrade IV + chemotherapy

AsiDNAtrade IV + PARPi

Beleodaqreg2

belinostat + platONtrade

Cutting-edge RampD pipeline with unique mechanisms of action in DDR

DRIIV -1b

DRIIV study in solid tumors

GENERATION OF DISRUPTIVE COMPOUNDS TARGETING DNA-BINDING FUNCTIONS

Epig

enet

ics

DN

A D

amag

e

Re

spo

nse

1 IT intratumoral ndash IV intravenous 2 Beleodaqreg commercial brand name of belinostat (IV form) in the US in rr PTCL3 4 PTCL Peripheral T-cell lymphoma ndash a rare form of blood cancer

4 Commercialized in the US by Onxeorsquos partner under a conditional market authorization from the FDA for the use of Beleodaqreg in the treatment of 2nd line PTCL

DRIIM study in metastatic melanoma

2nd line PTCL3 US4

Completed or ongoing Planned short-term Legend

DD

R

+ IO

Solid tumors

REVocan

6

AsiDNAtrade

Unique Decoy Agonist Mechanism of Action in DNA Damage Response

February 2020

AsiDNAtrade a first-in-class product in DNA Damage Response (DDR)

8

A purpose-designed cholesterol-oligonucleotide conjugate

5rsquo

3rsquo

3rsquo

5rsquo

Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1

Active 32 bp DNA duplex Cholesterol

Loop

1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113

Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule2Binding and activating DNA-PK and PARP signaling

enzymes

Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1

Sequence non-homologous and not immunogenic (CpG-free)

AsiDNA is not an RNAi therapy thus avoiding toxicity issues of this class

February 2020

Patent Protection (Composition of

Matter on AsiDNAtrade amp related compounds)

until 2031

Extendable to 2036 with SPC amp PTE

Combinationpatents up to 2038

and more

IP

February 2020

AsiDNAtrade a differentiated product in the clinically-validated field of DDR

9Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193

DDR inhibition is clinically-validated in oncology (PARPi)

DecoyAgonist mechanism of action avoids compensatory mechanisms blocking the induction of resistance

AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of genetic context

Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile

AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip

hellip diverts them away from the true damage hellip hellip leading to cellular death

February 2020

An extensive preclinical program paves the way to ambitious clinical translation

10

Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)

Autosensitization and noresistance observed In multiple cell lines Confirmed

Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines

No restriction to specific genetic context

AsiDNAtrade increases survival amp responders to

PARPi

Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival

Abrogation of resistance to PARPi In multiple cell lines Ongoing AsiDNAtrade stops resistance to PARPi

Abrogation of resistance to TKi Validated with EGFRi in multiple cell linesPrelim data confirming prolongation of EGFRiefficacy

In vitro data In vivo data

February 2020

Small Cell Lung Cancer PARPi sensitive

AsiDNAtrade leads to cancer cell death and does not induce resistance

11

NCI-H446

1st cycle 2nd cycle 3rd cycle 4th cycle0

20

40

60

80

100

120AsiDNA Talazoparib

Surv

ival (

NT)

Source Onxeo data on file

No surviving cells

Repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance

Emergence of Resistant cells

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

Developing disruptive therapies in the field of DNA Damage Response (DDR) to address unmet needs in oncology

4

NEXT KEY MILESTONES FUNDEDFinancial visibility to Q3 2020 supports strategic plan to deliver key near-term clinical milestones

STRONG MANAGEMENT amp OPERATIONAL TEAMA highly skilled team of 30 with capabilities to lead compounds from preclinical to proof-of-concept in man led by experienced management with demonstrated track record in product amp business development

DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSEPlatONtrade proprietary chemistry platform of decoy oligonucleotides generatingnew compounds

AsiDNAtrade lead candidate at clinical stage a first-in-class decoy agonist showing unique anti-tumoral propertiesOX401 a newly optimized next-gen PARPi

A WELL-DEFINED BUSINESS MODELCreate value by bringing drug candidates to best inflection points and monetizing these assets to generate revenues

LISTED EURONEXT Paris NASDAQ Copenhagen

EPA ONXEO

February 2020

FRANCOISE BONO (PHD)

CSO(Sanofi Evotec)

Formerly Executive Vice-President Oncology of Evotec

Experienced management team with demonstrated track record in product amp business development

5

JUDITH GRECIET (PHARMD)

CEO

OLIVIER DE BEAUMONT (MD)

CMO(Aventis Quintiles Stallergenes Greer)

Formerly Senior Vice President Head of Global Clinical Development Pharmacovigilance and Medical Affairs

PHILIPPE MAITREEVP of Onxeo US CBDO

(Aventis PPD Oscient mAbRx)

Formerly Chief Executive Officer and Co-Founder of mAbRx

NICOLAS FELLMANN

CFO(Ernst amp Young Pfizer)

Formerly Director of Treasury Tax amp Audit of Pfizer France

(Pharmacia Wyeth (Pfizer) Eisai)Formerly President of Eisai France

February 2020

Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II PHASE III MARKET

platONtrade Proprietary Platform of Decoy Oligonucleotides

OX401Next-gen PARPi + STING pathway activation

AsiDNAtrade IT + radiotherapy

AsiDNAtrade IV

AsiDNAtrade IV + chemotherapy

AsiDNAtrade IV + PARPi

Beleodaqreg2

belinostat + platONtrade

Cutting-edge RampD pipeline with unique mechanisms of action in DDR

DRIIV -1b

DRIIV study in solid tumors

GENERATION OF DISRUPTIVE COMPOUNDS TARGETING DNA-BINDING FUNCTIONS

Epig

enet

ics

DN

A D

amag

e

Re

spo

nse

1 IT intratumoral ndash IV intravenous 2 Beleodaqreg commercial brand name of belinostat (IV form) in the US in rr PTCL3 4 PTCL Peripheral T-cell lymphoma ndash a rare form of blood cancer

4 Commercialized in the US by Onxeorsquos partner under a conditional market authorization from the FDA for the use of Beleodaqreg in the treatment of 2nd line PTCL

DRIIM study in metastatic melanoma

2nd line PTCL3 US4

Completed or ongoing Planned short-term Legend

DD

R

+ IO

Solid tumors

REVocan

6

AsiDNAtrade

Unique Decoy Agonist Mechanism of Action in DNA Damage Response

February 2020

AsiDNAtrade a first-in-class product in DNA Damage Response (DDR)

8

A purpose-designed cholesterol-oligonucleotide conjugate

5rsquo

3rsquo

3rsquo

5rsquo

Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1

Active 32 bp DNA duplex Cholesterol

Loop

1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113

Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule2Binding and activating DNA-PK and PARP signaling

enzymes

Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1

Sequence non-homologous and not immunogenic (CpG-free)

AsiDNA is not an RNAi therapy thus avoiding toxicity issues of this class

February 2020

Patent Protection (Composition of

Matter on AsiDNAtrade amp related compounds)

until 2031

Extendable to 2036 with SPC amp PTE

Combinationpatents up to 2038

and more

IP

February 2020

AsiDNAtrade a differentiated product in the clinically-validated field of DDR

9Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193

DDR inhibition is clinically-validated in oncology (PARPi)

DecoyAgonist mechanism of action avoids compensatory mechanisms blocking the induction of resistance

AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of genetic context

Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile

AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip

hellip diverts them away from the true damage hellip hellip leading to cellular death

February 2020

An extensive preclinical program paves the way to ambitious clinical translation

10

Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)

Autosensitization and noresistance observed In multiple cell lines Confirmed

Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines

No restriction to specific genetic context

AsiDNAtrade increases survival amp responders to

PARPi

Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival

Abrogation of resistance to PARPi In multiple cell lines Ongoing AsiDNAtrade stops resistance to PARPi

Abrogation of resistance to TKi Validated with EGFRi in multiple cell linesPrelim data confirming prolongation of EGFRiefficacy

In vitro data In vivo data

February 2020

Small Cell Lung Cancer PARPi sensitive

AsiDNAtrade leads to cancer cell death and does not induce resistance

11

NCI-H446

1st cycle 2nd cycle 3rd cycle 4th cycle0

20

40

60

80

100

120AsiDNA Talazoparib

Surv

ival (

NT)

Source Onxeo data on file

No surviving cells

Repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance

Emergence of Resistant cells

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

FRANCOISE BONO (PHD)

CSO(Sanofi Evotec)

Formerly Executive Vice-President Oncology of Evotec

Experienced management team with demonstrated track record in product amp business development

5

JUDITH GRECIET (PHARMD)

CEO

OLIVIER DE BEAUMONT (MD)

CMO(Aventis Quintiles Stallergenes Greer)

Formerly Senior Vice President Head of Global Clinical Development Pharmacovigilance and Medical Affairs

PHILIPPE MAITREEVP of Onxeo US CBDO

(Aventis PPD Oscient mAbRx)

Formerly Chief Executive Officer and Co-Founder of mAbRx

NICOLAS FELLMANN

CFO(Ernst amp Young Pfizer)

Formerly Director of Treasury Tax amp Audit of Pfizer France

(Pharmacia Wyeth (Pfizer) Eisai)Formerly President of Eisai France

February 2020

Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II PHASE III MARKET

platONtrade Proprietary Platform of Decoy Oligonucleotides

OX401Next-gen PARPi + STING pathway activation

AsiDNAtrade IT + radiotherapy

AsiDNAtrade IV

AsiDNAtrade IV + chemotherapy

AsiDNAtrade IV + PARPi

Beleodaqreg2

belinostat + platONtrade

Cutting-edge RampD pipeline with unique mechanisms of action in DDR

DRIIV -1b

DRIIV study in solid tumors

GENERATION OF DISRUPTIVE COMPOUNDS TARGETING DNA-BINDING FUNCTIONS

Epig

enet

ics

DN

A D

amag

e

Re

spo

nse

1 IT intratumoral ndash IV intravenous 2 Beleodaqreg commercial brand name of belinostat (IV form) in the US in rr PTCL3 4 PTCL Peripheral T-cell lymphoma ndash a rare form of blood cancer

4 Commercialized in the US by Onxeorsquos partner under a conditional market authorization from the FDA for the use of Beleodaqreg in the treatment of 2nd line PTCL

DRIIM study in metastatic melanoma

2nd line PTCL3 US4

Completed or ongoing Planned short-term Legend

DD

R

+ IO

Solid tumors

REVocan

6

AsiDNAtrade

Unique Decoy Agonist Mechanism of Action in DNA Damage Response

February 2020

AsiDNAtrade a first-in-class product in DNA Damage Response (DDR)

8

A purpose-designed cholesterol-oligonucleotide conjugate

5rsquo

3rsquo

3rsquo

5rsquo

Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1

Active 32 bp DNA duplex Cholesterol

Loop

1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113

Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule2Binding and activating DNA-PK and PARP signaling

enzymes

Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1

Sequence non-homologous and not immunogenic (CpG-free)

AsiDNA is not an RNAi therapy thus avoiding toxicity issues of this class

February 2020

Patent Protection (Composition of

Matter on AsiDNAtrade amp related compounds)

until 2031

Extendable to 2036 with SPC amp PTE

Combinationpatents up to 2038

and more

IP

February 2020

AsiDNAtrade a differentiated product in the clinically-validated field of DDR

9Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193

DDR inhibition is clinically-validated in oncology (PARPi)

DecoyAgonist mechanism of action avoids compensatory mechanisms blocking the induction of resistance

AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of genetic context

Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile

AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip

hellip diverts them away from the true damage hellip hellip leading to cellular death

February 2020

An extensive preclinical program paves the way to ambitious clinical translation

10

Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)

Autosensitization and noresistance observed In multiple cell lines Confirmed

Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines

No restriction to specific genetic context

AsiDNAtrade increases survival amp responders to

PARPi

Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival

Abrogation of resistance to PARPi In multiple cell lines Ongoing AsiDNAtrade stops resistance to PARPi

Abrogation of resistance to TKi Validated with EGFRi in multiple cell linesPrelim data confirming prolongation of EGFRiefficacy

In vitro data In vivo data

February 2020

Small Cell Lung Cancer PARPi sensitive

AsiDNAtrade leads to cancer cell death and does not induce resistance

11

NCI-H446

1st cycle 2nd cycle 3rd cycle 4th cycle0

20

40

60

80

100

120AsiDNA Talazoparib

Surv

ival (

NT)

Source Onxeo data on file

No surviving cells

Repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance

Emergence of Resistant cells

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II PHASE III MARKET

platONtrade Proprietary Platform of Decoy Oligonucleotides

OX401Next-gen PARPi + STING pathway activation

AsiDNAtrade IT + radiotherapy

AsiDNAtrade IV

AsiDNAtrade IV + chemotherapy

AsiDNAtrade IV + PARPi

Beleodaqreg2

belinostat + platONtrade

Cutting-edge RampD pipeline with unique mechanisms of action in DDR

DRIIV -1b

DRIIV study in solid tumors

GENERATION OF DISRUPTIVE COMPOUNDS TARGETING DNA-BINDING FUNCTIONS

Epig

enet

ics

DN

A D

amag

e

Re

spo

nse

1 IT intratumoral ndash IV intravenous 2 Beleodaqreg commercial brand name of belinostat (IV form) in the US in rr PTCL3 4 PTCL Peripheral T-cell lymphoma ndash a rare form of blood cancer

4 Commercialized in the US by Onxeorsquos partner under a conditional market authorization from the FDA for the use of Beleodaqreg in the treatment of 2nd line PTCL

DRIIM study in metastatic melanoma

2nd line PTCL3 US4

Completed or ongoing Planned short-term Legend

DD

R

+ IO

Solid tumors

REVocan

6

AsiDNAtrade

Unique Decoy Agonist Mechanism of Action in DNA Damage Response

February 2020

AsiDNAtrade a first-in-class product in DNA Damage Response (DDR)

8

A purpose-designed cholesterol-oligonucleotide conjugate

5rsquo

3rsquo

3rsquo

5rsquo

Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1

Active 32 bp DNA duplex Cholesterol

Loop

1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113

Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule2Binding and activating DNA-PK and PARP signaling

enzymes

Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1

Sequence non-homologous and not immunogenic (CpG-free)

AsiDNA is not an RNAi therapy thus avoiding toxicity issues of this class

February 2020

Patent Protection (Composition of

Matter on AsiDNAtrade amp related compounds)

until 2031

Extendable to 2036 with SPC amp PTE

Combinationpatents up to 2038

and more

IP

February 2020

AsiDNAtrade a differentiated product in the clinically-validated field of DDR

9Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193

DDR inhibition is clinically-validated in oncology (PARPi)

DecoyAgonist mechanism of action avoids compensatory mechanisms blocking the induction of resistance

AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of genetic context

Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile

AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip

hellip diverts them away from the true damage hellip hellip leading to cellular death

February 2020

An extensive preclinical program paves the way to ambitious clinical translation

10

Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)

Autosensitization and noresistance observed In multiple cell lines Confirmed

Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines

No restriction to specific genetic context

AsiDNAtrade increases survival amp responders to

PARPi

Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival

Abrogation of resistance to PARPi In multiple cell lines Ongoing AsiDNAtrade stops resistance to PARPi

Abrogation of resistance to TKi Validated with EGFRi in multiple cell linesPrelim data confirming prolongation of EGFRiefficacy

In vitro data In vivo data

February 2020

Small Cell Lung Cancer PARPi sensitive

AsiDNAtrade leads to cancer cell death and does not induce resistance

11

NCI-H446

1st cycle 2nd cycle 3rd cycle 4th cycle0

20

40

60

80

100

120AsiDNA Talazoparib

Surv

ival (

NT)

Source Onxeo data on file

No surviving cells

Repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance

Emergence of Resistant cells

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

AsiDNAtrade

Unique Decoy Agonist Mechanism of Action in DNA Damage Response

February 2020

AsiDNAtrade a first-in-class product in DNA Damage Response (DDR)

8

A purpose-designed cholesterol-oligonucleotide conjugate

5rsquo

3rsquo

3rsquo

5rsquo

Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1

Active 32 bp DNA duplex Cholesterol

Loop

1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113

Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule2Binding and activating DNA-PK and PARP signaling

enzymes

Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1

Sequence non-homologous and not immunogenic (CpG-free)

AsiDNA is not an RNAi therapy thus avoiding toxicity issues of this class

February 2020

Patent Protection (Composition of

Matter on AsiDNAtrade amp related compounds)

until 2031

Extendable to 2036 with SPC amp PTE

Combinationpatents up to 2038

and more

IP

February 2020

AsiDNAtrade a differentiated product in the clinically-validated field of DDR

9Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193

DDR inhibition is clinically-validated in oncology (PARPi)

DecoyAgonist mechanism of action avoids compensatory mechanisms blocking the induction of resistance

AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of genetic context

Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile

AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip

hellip diverts them away from the true damage hellip hellip leading to cellular death

February 2020

An extensive preclinical program paves the way to ambitious clinical translation

10

Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)

Autosensitization and noresistance observed In multiple cell lines Confirmed

Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines

No restriction to specific genetic context

AsiDNAtrade increases survival amp responders to

PARPi

Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival

Abrogation of resistance to PARPi In multiple cell lines Ongoing AsiDNAtrade stops resistance to PARPi

Abrogation of resistance to TKi Validated with EGFRi in multiple cell linesPrelim data confirming prolongation of EGFRiefficacy

In vitro data In vivo data

February 2020

Small Cell Lung Cancer PARPi sensitive

AsiDNAtrade leads to cancer cell death and does not induce resistance

11

NCI-H446

1st cycle 2nd cycle 3rd cycle 4th cycle0

20

40

60

80

100

120AsiDNA Talazoparib

Surv

ival (

NT)

Source Onxeo data on file

No surviving cells

Repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance

Emergence of Resistant cells

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

AsiDNAtrade a first-in-class product in DNA Damage Response (DDR)

8

A purpose-designed cholesterol-oligonucleotide conjugate

5rsquo

3rsquo

3rsquo

5rsquo

Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation1

Active 32 bp DNA duplex Cholesterol

Loop

1 Quanz M et al PLoS ONE 2009 4(7) doi 101371journalpone00062982 Berthault N et al Cancer Gene Therapy (2011) 1-12 doi 101038cgt20113

Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule2Binding and activating DNA-PK and PARP signaling

enzymes

Phosphorothioate substitutions at the 5rsquo and 3rsquo ends to prevent degradation1

Sequence non-homologous and not immunogenic (CpG-free)

AsiDNA is not an RNAi therapy thus avoiding toxicity issues of this class

February 2020

Patent Protection (Composition of

Matter on AsiDNAtrade amp related compounds)

until 2031

Extendable to 2036 with SPC amp PTE

Combinationpatents up to 2038

and more

IP

February 2020

AsiDNAtrade a differentiated product in the clinically-validated field of DDR

9Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193

DDR inhibition is clinically-validated in oncology (PARPi)

DecoyAgonist mechanism of action avoids compensatory mechanisms blocking the induction of resistance

AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of genetic context

Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile

AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip

hellip diverts them away from the true damage hellip hellip leading to cellular death

February 2020

An extensive preclinical program paves the way to ambitious clinical translation

10

Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)

Autosensitization and noresistance observed In multiple cell lines Confirmed

Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines

No restriction to specific genetic context

AsiDNAtrade increases survival amp responders to

PARPi

Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival

Abrogation of resistance to PARPi In multiple cell lines Ongoing AsiDNAtrade stops resistance to PARPi

Abrogation of resistance to TKi Validated with EGFRi in multiple cell linesPrelim data confirming prolongation of EGFRiefficacy

In vitro data In vivo data

February 2020

Small Cell Lung Cancer PARPi sensitive

AsiDNAtrade leads to cancer cell death and does not induce resistance

11

NCI-H446

1st cycle 2nd cycle 3rd cycle 4th cycle0

20

40

60

80

100

120AsiDNA Talazoparib

Surv

ival (

NT)

Source Onxeo data on file

No surviving cells

Repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance

Emergence of Resistant cells

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

AsiDNAtrade a differentiated product in the clinically-validated field of DDR

9Quanz M et al Clin Cancer Res 2009 151308-1316 2 Quanz M et al PLoS ONE 2009 4(7) doi 101371 journalpone0006298 3 Jdey W et al Oin Can Res 201622DOI 101158 1078-0432CCR-16-1193

DDR inhibition is clinically-validated in oncology (PARPi)

DecoyAgonist mechanism of action avoids compensatory mechanisms blocking the induction of resistance

AsiDNAtrade acts upstream of the DDR enabling cytotoxic activity regardless of genetic context

Cytotoxic activity is restricted to cancer cells translating into an outstanding safety profile

AsiDNAtrade mimics DNA breaks in the tumor cell (decoy) binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing signaling and repairing) hellip

hellip diverts them away from the true damage hellip hellip leading to cellular death

February 2020

An extensive preclinical program paves the way to ambitious clinical translation

10

Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)

Autosensitization and noresistance observed In multiple cell lines Confirmed

Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines

No restriction to specific genetic context

AsiDNAtrade increases survival amp responders to

PARPi

Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival

Abrogation of resistance to PARPi In multiple cell lines Ongoing AsiDNAtrade stops resistance to PARPi

Abrogation of resistance to TKi Validated with EGFRi in multiple cell linesPrelim data confirming prolongation of EGFRiefficacy

In vitro data In vivo data

February 2020

Small Cell Lung Cancer PARPi sensitive

AsiDNAtrade leads to cancer cell death and does not induce resistance

11

NCI-H446

1st cycle 2nd cycle 3rd cycle 4th cycle0

20

40

60

80

100

120AsiDNA Talazoparib

Surv

ival (

NT)

Source Onxeo data on file

No surviving cells

Repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance

Emergence of Resistant cells

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

An extensive preclinical program paves the way to ambitious clinical translation

10

Safety profile No cytotoxic activity in healthy cells Very favorable data in tox study (monkey)

Autosensitization and noresistance observed In multiple cell lines Confirmed

Efficacy synergy with PARPi In multiple PARPi sensitive amp resistant cell lines

No restriction to specific genetic context

AsiDNAtrade increases survival amp responders to

PARPi

Efficacy synergy with chemo In multiple cell lines AsiDNAtrade increases efficacy amp survival

Abrogation of resistance to PARPi In multiple cell lines Ongoing AsiDNAtrade stops resistance to PARPi

Abrogation of resistance to TKi Validated with EGFRi in multiple cell linesPrelim data confirming prolongation of EGFRiefficacy

In vitro data In vivo data

February 2020

Small Cell Lung Cancer PARPi sensitive

AsiDNAtrade leads to cancer cell death and does not induce resistance

11

NCI-H446

1st cycle 2nd cycle 3rd cycle 4th cycle0

20

40

60

80

100

120AsiDNA Talazoparib

Surv

ival (

NT)

Source Onxeo data on file

No surviving cells

Repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance

Emergence of Resistant cells

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

Small Cell Lung Cancer PARPi sensitive

AsiDNAtrade leads to cancer cell death and does not induce resistance

11

NCI-H446

1st cycle 2nd cycle 3rd cycle 4th cycle0

20

40

60

80

100

120AsiDNA Talazoparib

Surv

ival (

NT)

Source Onxeo data on file

No surviving cells

Repeated treatment with AsiDNAtrade leads to sensitization to AsiDNAtrade and does not generate resistance

Emergence of Resistant cells

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

AsiDNAtrade synergizes with PARPi in PARPi-resistant tumors

NT olaparib AsiDNAtrade AsiDNAtrade + olaparib

High responders 06 - 0 High responders 28 - 25 High responders 48 - 50 High responders 57 - 71

MDA-MB-231 (TNBC HR proficient tumor cells) xenograft in mice

Treatment Median Survival (days)

NT 39Olaparib 54AsiDNAtrade 61

AsiDNAtrade + olaparib 75

Vo

lum

e (

mm

3)

Time after treatment (days)

Source Onxeo data on file 12

AsiDNAtrade increases number of responders to PARPi and median survival

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020 13

UWB1289 (Ovarian cancer model ndash BRCA1--)

0 10 20 30 40 500

4times104

8times104

12times105

16times105

2times105

Nira

Nira+Asi at D34

Days post treatment

Cell

num

ber

Niraparib

AsiDNAtrade admin

Emergence of resistant cells

Cell death

AsiDNAtrade abrogates acquired resistance to PARP inhibitors (class effect)

AsiDNAtrade leads to niraparib-resistant cells eradication in ovarian cancer model even if introduced only once resistance emerges (CA 125 increase)

Source Onxeo data on file

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pgm

l)

AsiDNAtrade admin

Introduction at CA125 increase (REVocan study protocol ndash slide 22)

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

AsiDNAtrade stops resistance to olaparib even if introduced only once resistance emerges (in vivo interim results)

AsiDNAtrade abrogates acquired resistance to PARP inhibitors

0 10 20 30 40 50 60

0

500

1000

1500NT

OLAPARIB 100mgKgPO

AsiDNA_10mg + OLAPARIB_100mg

Mean OLAPARIB 100mgKgPO

Mean AsiDNA + Olaparib

Days post-treatment

Tu

mo

r vo

lum

e (

mm

3)

AsiDNAtrade admin

MDAMB-436 TNBC HR deficient

14

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

Non Small Cell Lung Cancer model ndash anti-EGFR sensitive

AsiDNAtrade eradicates EGFRi and ALKi resistant cells

AsiDNAtrade prevents resistance to TKi

15

0 3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

-20

0

20

40

60

80

100

120

ErlotinibErlotinib+AsiDNA

Time (days)

Su

rviv

ing

ce

lls (

)

No surviving cells

Emergence of resistant cells

No surviving cells

Emergence of resistant cells

PC9-3 (NSCLC EGFRmut) - EGFR T790 mutation is preexisting in PC9 parental cell line PC9-3 cell line is a sub-clone of PC9 without preexisting T790M

Non Small Cell Lung Cancer model ndash anti-ALK sensitive

H3122 (NSCLC EML4-ALK)

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

AsiDNAtrade

Clinical Development Plan

Positioning AsiDNAtrade to Address 1 Challenge in Oncology

Resistance

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

Delivering the promises of AsiDNAtrade to patients

DRIIM Phase 1 in adv melanomaIT combo with radiotherapy

Excellent safety via IT

Signals of efficacy

DRIIV-1 Phase 1First IV administration in Solid tumors

Excellent safety via IV

Proof of mechanism in tumors

DRIIV-1b Phase 1b (IV)Combo with carboplatin +- paclitaxel (ongoing)

Excellent safety in combination with chemotherapy

Preliminary signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b2 (IV)Ovarian Cancer in combination w PARPi niraparib

Proof of Concept Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b2 (IV)Non Small Cell Lung Cancer in combination w EGFRi

Proof of Concept Prevention of resistance to TKi

SHO

RT

MID

-TE

RM

ON

GO

ING

17

CO

MP

LETE

D

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

DRIIV-1 Phase 1 Favorable safety profile

Phase I study in IV

Open-label 3+3 dose escalation from 200mg to 1800mg

22 patients 5 doses

Study coordinator Pr C Le Tourneau (Institut Curie)

Objectives Determine safety and PKPD profile

Primary objective reached very favorable safety outcome

90 of adverse events were grade 1 2 mostly ( 77) non related and no specific type of toxicity

AsiDNAtrade 200mg 400mg 600mg No drug-related SAEs and No dose-limiting toxicity

AsiDNAtrade 900mg amp 1300mg 3 related SAEs including 2 DLTs per dose

Orthostatic hypotension (grade 3 unlikely related)

2 increase of hepatic enzymes ( grade 3 unlikely related and grade 4possibly related)

MTD has not been reached

DRIIV-1 results were presented at EORTC-NCI-AACR on 102719

18

181 (89)

22(11)

1

Grade 12 Grade 3

Non-related95

Non- related77

Adverse Events

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

DRIIV-1 Phase 1 Beyond safety proof-of-mechanism demonstrated

19

Activity pharmacodynamic biomarkers (on tumor biopsies)

AsiDNAtrade 600mg

Pre-treatment Post-treatment

γH2AX Readout of DNA-PK target engagement

Patient 003-001

Strong activation of γH2AX at cell level reflecting DNA-PK pathway engagement

γγ

DRIIV-1 study presented at EORTC-NCI-AACR 27th Oct 2019

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

PHASE 1b

Open-label 3+3 patient cohort

patients with advanced solid tumors eligible to the CT regimen

Institut Jules Bordet Bruxelles Grand Hocircpital de Charleroi

OBJECTIVES To confirm AsiDNAtrade IV at 600 mg safety and tolerance in combination

To detect signal of efficacy (RECIST criteria)

To explore predictive biomarker (gene signature retrospective analysis on initial biopsy)

MAY 2019FIRST PATIENT DOSED

TREATMENT SCHEDULE ASIDNATM 1-hour IV infusion

H1 2020 END OF STUDY

AsiDNAtrade

DAY 1 22 2 3 8 15

CYCLE 1 28 days CYCLE 2 and beyond 21 days

Q3 2019 Q42019

29

AsiDNAtrade AsiDNAtrade AsiDNAtrade AsiDNAtrade

PRELIMINARY EFFICACY OUTCOMES

DRIIV-1b Phase 1b Confirm AsiDNAtrade safety and efficacy in combination with carboplatin +- paclitaxel

AsiDNATM

600 mgCohort 13 pts

carboplatin

AsiDNATM

600 mgcarboplatin +

paclitaxel

Cohort 26 pts

+

+

completed

ongoing

Carbo CarboCohort 1

Pacli PacliPacli PacliCohort 2 Carbo Carbo

20

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

DRIIV-1b Phase 1b Preliminary data confirm safety and efficacy signals

21

AsiDNAtrade 600 mg

Cohort 1

carboplatin

AsiDNAtrade 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ge 3 prior lines of treatment progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 23 patients for 55 mo (TNBC 6th L) and 10 mo (NSCLC 3rd L)

Disease controlled with AsiDNAtrade for significantly longer than with any of the prior treatment lines

3 pts

Preliminary efficacy results expected H1 2020

Full data set by mid-2020

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

Phase IbII study Proof-of-concept of the abrogation of resistance to PARP inhibitors

22

Patients selection patients under 2nd line of maintenance with niraparib gt 6 months

Inclusion at CA 125 increase (CA 125 well established predictive biomarker of resistance)

n= up to 26 patients Platinum-Sensitive Relapsed Ovarian Cancer

Primary objective Safety run amp CA125 decrease (GCIG criteria)

Secondary objective Efficacy PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNAtrade and Niraparib

FPI expected from H1 2020 =gt Preliminary data by end 2020

PI Dr Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

AsiDNAtrade

Objectives Financial Outlook

amp Upcoming Milestones

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

Our strategic priority raise AsiDNAtrade as the new treatment paradigm to abrogate resistance

24

Preventing resistance to targeted therapies would lead to prolonged efficacy the major hurdle of PARP inhibitors and TKIs

❶

❷

ldquoResistance is the biggest challenge in cancer biologyrdquo (Paul Workman ndash ICR)

Strategic objectives Targeted Indications OpportunityApproval

Optimal market access (fast favorable PampR)

2L with niraparib(PARPi) in OC

Short endpoint PFSExpansion of maintenance treatment and delay new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo marketsrdquo (TKI)

1L with osimertinib (TKI) in EGFRm non-small cell lung cancer

Target specific population with high-risk of progressionAddress 1st line of treatment

2025

REVocanCombo w PARPi

Combo w EGFRi(TKi)

Pamp R pricing amp reimbursement

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

Resistance and beyond realizing the full potential of AsiDNAtrade

25

Strategic objectives and steps

Targeted Indications (for approval)

Unmet needs Therapeutic goals Opportunity Approval

Optimal market access - fast favorable PampR

2L maintenance with niraparib (PARPi) in platinum sensitive ovarian cancer after CA125 increase

Introduce AsiDNA at first signs of resistance to abrogate it and prolong PFS

Short endpoint PFSExpansion of maintenance treatment and delaying new course of platinum

2024

Establish presence in oncology ldquohigh-endrdquo markets (TKI)

1L treatment of EGFRm NSCLC with osimertinib (TKI EGFRi)

Prevent resistance to osimertinib and prolong PFS

Specific population with high-risk of progression to maintain favorable PampR conditions

2025

+ Expand combos with PARPi and TKI

1L maintenance ovarian cancer with PARPi

2L treatment of HER2 negative metastatic breast cancer

1L treatment of ALKm NSCLC with anti-ALK TKI

2028

Address growth opportunities in combos with DNA breakers

Neoadjuvant TNBC with carboplatin + paclitaxel

2L treatment ovarian cancer with carboplatin + paclitaxel

1L treatment ovarian cancer with carboplatin + paclitaxel2029

PampR pricing amp reimbursement

+

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

Financial resources are in line with development milestones objectives

26

Financiegravere de la Montagne14

Other institutions19

Retail62

Misc 5

Cash position of euro63m at 06302019 (FY19 results on 033120)

Cash runway through Q3 2020

Shares outstanding 613m

Average Daily Volume (18 months)

125927shares

Dual listing Euronext Paris amp Nasdaq Copenhagen

ISIN FR0010095596

at 123119 at 123119

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

AsiDNAtrade clinical development designed to validate synergy and effect on resistance with key readouts in 2020

27

REVOCANwith niraparib

DRIIV-1b cohort 2

final data

First data by year-end

FPIQ2 20

Synergistic effect

Reversion of resistance

DRIIVndash1bwith CTx

DRIIV-1b cohort 2

prelim data

H1 2019 H2 2019 H1 2020 H2 2020

DRIIV-1b study AsiDNAtrade combo with CTx Mid-2020

REVOCAN study AsiDNAtrade added to niraparib H2 2020

+ OX401 preclinical proof-of concept H2 2020

2020

DRIIV-1b cohort 1

prelim data

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

AsiDNAtrade a promising opportunity with a unique MoA overcoming resistance

A promising opportunity available for licensing

Significantly de-risked pipeline assetPotential to play a cornerstone role in an oncology portfolio through multiple combinationsSizeable market potential in indications with large unmet needs

A broad development and commercial potential in multiple indications

Confirmed activity in man and favorable safety profile in IV including in combinationEntering now in Phase 1b2

Demonstrated potential to abrogate resistance to multiple targeted therapiesSolid preclinical package supporting a broad range of potential indications

28

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

Publications

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

AsiDNAtrade Publications (12)

30

Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response Quanz M et al PLoS One 2009 4e6298

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers Redon CE et al Clin Cancer Res 2010 16(18)

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems Berthault N et al Cancer Gene Ther 2011 18695-706

Heat shock protein 90 (Hsp90) is phosphorylated in response to DNA damage and accumulates in repair foci Quanz M et al J Biol Chem 2012 2878803-15

Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer Devun F et al J Gastroenterol 2012 47266-75

Pharmacokinetics and toxicity in rats and monkeys of coDbait a therapeutic double-stranded DNA oligonucleotide conjugated to cholesterol Schlegel A et al Mol Ther Nucleic Acids 2012 1e33

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of 5 glioblastoma Coquery N et al PLoS One 20127(7)e40567

Resistance to PARP-Inhibitors in Cancer Therapy Montoni A et al Front Pharmacol 2013 4 18

Kinesin KIFC1 actively transports bare double-stranded DNA Farina F et al Nucleic Acids Res 2013 414926-37

Inhibition of DNA damage repair by artificial activation of PARP with siDNA Croset A et al Nucleic Acids Res 2013 417344-55

DNA-PK target identification reveals novel links between DNA repair signaling and cytoskeletal regulation Kotula E et al PLoS One 2013 8(11)e80313

Colorectal cancer metastasis the DNA repair inhibitor Dbait increases sensitivity to hyperthermia and improves efficacy of radiofrequency ablation Devun F et al Radiology 2014 270736-46

A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma Biau J et al Neoplasia 2014 16835-44

An update on PARP inhibitors for the treatment of cancer Benefif S et al

Dbait An innovative concept to inhibit DNA repair and treat cancer Biau J et al Bull Cancer 2016 103 227ndash235

The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis Herath NI et al Mol Cancer Ther 2016 Jan15(1)15-22

Targeting DNA Repair in Cancer Beyond PARP Inhibitors Brown JS et al Cancer Discov December 21 2016 DOI 1011582159-8290CD-16-0860

Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy Viallard C et al Oncotarget 2016 Mar 157(11) 12927-36

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients in with skin metastases from melanoma Le Tourneau C et al Br J Cancer 2016 May 24114(11)1199-205

Potentiation of Doxurubicin efficacy in hepatocellular carcinoma by the DNA repair inhibitor DT01 in preclinical models Herath NI et al Eur Radiol 2017 Oct 27(10)4435-4444

Drug Driven Synthetic Lethality bypassing tumor cell genetics with a combination of AsiDNA and PARP inhibitors Jdey W et al Clin Cancer Res 2017 Feb 1523(4)1001-1011

Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA Jdey W et al Cancer Res 2017 Aug 1577(16)4207-4216

February 2020

AsiDNAtrade Publications (22)

31

The DNA Repair Inhibitor Dbait Is Specific for Malignant Hematologic Cells in Blood Thierry S et al Mol Cancer Ther 2017 Dec16(12)2817ndash27

Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma Efficacy and Protein Biomarkers of Resistance in Preclinical Models Biau J et al Front Oncol 2019 Jun 199549

Moving From Poly (ADP-Ribose) Polymerase Inhibition to Targeting DNA Repair and DNA Damage Response in Cancer Therapy Gourley C et al J Clin Oncol 2019 May 3

AsiDNAtrade treatment induces cumulative antitumor efficacy with a low probability of acquired resistance Jdey W et al Neoplasia (2019)21 863ndash871

Preclinical studies comparing efficacy and toxicity of DNA repair inhibitors olaparib and AsiDNA in treatment of carboplatin resistant tumors Jdey W et al Front Oncol 12 November 2019 | httpsdoiorg103389fonc201901097

Posters AACR 2013

Preclinical study of Dbait an inhibitor of three DNA repair pathways in breast cancer treatment

ASCO 2015

First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma

AACR 2017

AsiDNAtrade induces tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer

AACR 2018

AsiDNAtrade and HDAC inhibitors A cross-potentiation team work to kill tumor cellsEvolution of tumor cells under Dbait (AsiDNA) treatment results in ldquoautosensitizationrdquo

AACR 2019

AsiDNAtrade abrogates acquired resistance to PARP inhibitorsDevelopment of a Biomarker-driven patient selection strategy for AsiDNAtrade treatment

Molecular analysis of the mechanism of action of AsiDNAtrade brings new clues on DNA damage response regulationAsiDNAtrade a novel DNA repair inhibitor to radio-sensitize aggressive medulloblastomasubtypes

EORTC-NCI-AACR 2019

Phase I dose escalation study evaluating the safety pharmacokinetics (PK) and pharmacodynamics (PD) of AsiDNAtrade a first-in-class DNA Repair Inhibitor administered intravenously (IV) in patients with advanced solid tumors

CONTACTSJudith Greciet ndash CEO

Nicolas Fellmann ndash CFOFranccediloise Bono ndash CSO

Olivier de Beaumont - CMO

Tel +33 1 45 58 76 00COMPANY INFORMATION

wwwonxeocom