LISTED EURONEXT │ Paris NASDAQ │ Copenhagen

EPA: ONXEO

ANNUAL GENERAL MEETINGMAY 29, 2020

MANAGEMENT PRESENTATION

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Important Information

May 2020

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

3

NEXT KEY MILESTONES FUNDEDFinancial visibility into Q2 2021 supports strategic plan to deliver key near-term clinical milestones

STRONG MANAGEMENT & OPERATIONAL TEAMA highly skilled team of 30, with strong translational & clinical expertise, led by experienced management and board of directors with demonstrated track record in product & business development

DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSEPlatON™, proprietary chemistry platform of decoy oligonucleotides, generating new compounds

AsiDNA™, 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 from preclinical stage to proof-of concept in man, the best inflection points to monetize these assets and generate revenues.

LISTED EURONEXT │ Paris NASDAQ │ Copenhagen

EPA: ONXEO

* PARP inhibitors (PARPi) are a leading class of targeted therapies, the first approved and marketed in the field of DDR

May 2020

Cutting-edge R&D pipeline with unique mechanisms of action in DDR

4

Programs OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II

platON™ Proprietary Platform of Decoy Oligonucleotides

OX401Next-gen PARPi + STING pathway activation

AsiDNA™ IT + radiotherapy

AsiDNA™ IV

AsiDNA™ IV + chemotherapy

AsiDNA™ IV + PARPi

DRIIV -1b

DRIIV study in solid tumors

GENERATION OF NEW COMPOUNDS TARGETING DNA FUNCTIONS

DN

A D

amag

e

Re

spo

nse

1 IT: intratumoral – IV: intravenous

DRIIM study in metastatic melanoma

Ongoing proof-of concept

DD

R

+ IO

REVocan

Completed or ongoing Legend Planned short-term

May 2020

Intense development efforts focused on AsiDNA™ and OX401

5

2019

OX401 presented at European ESMO-TAT

Congress 2020

Jan Mar

5 abstracts presented at AACR on AsiDNA™

Apr 2020

AsiDNA™ OX401

Sep

Pipeline expansion w/OX401, a next-gen PARPi: no resistance and immune

response activation

Positive interim results from DRIIV-1b study

FPI in DRIIV-1b study of AsiDNA™ in

combination w/chemotherapy

May

Agreement with Gustave Roussy to conduct

REVOCAN, a phase 1b/2 study of AsiDNA™ &

niraparib for treatment of relapsed ovarian cancer

Apr

$6.6m exclusive agreement with Acrotech on

belinostat

Oct

€495,000 grant as part of the Innov'up

Leader program PIA

Feb

Agreement to settle the remaining actions in the

litigation with SpePharm and SpeBio

Corporate

Jun

Final results of DRIIV-1 : strong activity via IV route,

optimal dose at 600mg

May

New equity line started with Nice & Green – Total

of 12 million warrants

Kepler Cheuvreux initiates coverage w/

“Buy” recommendation

Bryan Granier & Co initiates coverage w/

“Buy” recommendation

May May

REVOCAN receivesapproval from regulatory

authorities

May 2020

April 6, 2020: a successful transaction to complete Onxeo’s strategic transition to a DDR focus company

6

Transaction grants full and worldwide rights to all territories ( ex. North America and India, already licensed to Acrotech), IP and know-how on all belinostat forms

License with Pint Pharma for Latin America and contracts with Clinigen and iQone for the Named Patient Program in Europe assigned to Acrotech

All future potential revenues from the belinostat franchise to revert to Acrotech

Reflects Onxeo ability in terms of BD, alliance management and NPP around the world

$6.6m paid by US partner Acrotech Biopharma LLC for exclusive WW rights to belinostat

Financial visibility extended into Q2 2021, beyond key clinical milestones* for AsiDNA™

* Timelines may be affected by Covid-19 pandemic

May 2020

Consolidated P&L account

7

In € thousands 12/31/2019 12/31/2018

Recurring revenue from licensing agreements 3,455 2,310

Non-recurring revenue from licensing agreements 833 3,817

TOTAL REVENUES 4,289 6,127

Purchases (350) (215)

Personnel expenses (4,808) (5,438)

External expenses (7,857) (8,731)

Taxes and duties (127) (346)

Net depreciation, amortization and provisions (671) (92)

Other current operating expenses (365) 622

OPERATING EXPENSES (14,178) (14,200)

Other current operating income 95 4,546

CURRENT OPERATING INCOME (LOSS) (9,794) (3,527)

Other operating income and expenses (24,543) (12,117)

Share of profit from equity affiliates (39) 5,176

OPERATING LOSS AFTER SHARE OF PROFIT FROM EQUITY AFFILIATES (34,376) (10,468)

Income from cash and cash equivalents 19 15

Gross cost of financial debt (1,037) (601)

Other financial income and expenses (659) (104)

FINANCIAL INCOME (LOSS) (1,677) (691)

Income tax expense 2,324 1,760

- of which deferred taxes 2,330 1,764

CONSOLIDATED NET INCOME (LOSS) (33,728) (9,399)

Good performance of commercialization activities (notably by US partner Acrotech)

Impairment of R&D assets + goodwill €14.9m / depreciation of SpeBio shares €3.7m / provision SpePharm €6m

Cost of bond financing (proportional to royalties received from Acrotech)

Decrease of deferred tax liability due to impairment of R&D assets

May 2020

Consolidated balance sheet - Assets

8

Assets in € thousands 12/31/2019 12/31/2018

Non-current assets

Intangible assets 23,358 38,573

Tangible assets 109 296

Right-of-use assets 2,718 -

Investments in equity-accounted companies 20 3,701

Other financial fixed assets 141 304

TOTAL NON-CURRENT ASSETS 26,345 42,874

Current assets

Stocks and work in progress 64 47

Accounts receivable and related accounts 991 1,479

Other receivables 4,520 7,597

Cash and Cash equivalent 5,708 11,253

TOTAL CURRENT ASSETS 11,284 20,376

TOTAL ASSETS 37,629 63,250

Impairment of goodwill -€2m and belinostat-related R&D assets -€12.9m

Rights of use relating to leases in the scope of IFRS 16

Depreciation of JV SpeBio shares sold at nominal value in Feb. 2020 within settlement with SpePharm

Reduction of receivables in line with R&D activity

May 2020

Consolidated balance sheet - Liabilities

9

Liabilities and Shareholders’ Equity in € thousands 12/31/2019 12/31/2018

Shareholders’ equity

Share capital 15,329 13,344

Minus: treasury shares (189) (97)

Share premium 44,924 48,824

Reserves (9,139) (270)

Earnings (33,728) (9,399)

TOTAL EQUITY 17,197 45,402

Non-current liabilities

Deferred tax liabilities 2,330

Provisions 6,821 531

Other financial liabilities 7,412 6,593

TOTAL NON-CURRENT LIABILITIES 14,233 9,455

Current liabilities

Short-term borrowings and financial debts 1,170 450

Trade payables and related accounts 3,672 4,145

Other liabilities 1,358 3,798

TOTAL CURRENT LIABILITIES 6,199 8,393

TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY 37,629 63,250

Capital increase from the equity line €4.8m

Variation of deferred tax resulting from the €12.9m impairment of assets

Provision of €6m payable to SpePharm before 01/31/24

Loan relating to leases (IFRS 16) +€2m / Repayment of bond financing -€1.1m

Impact of SpeBio/SpePharm €2.8m penalty paid early 2019(netted with the €1.5m current account)

May 2020

Consolidated cash outlook

10

5 708

(10 111)(2 729)

2 412

4 743 14011 253

0

2 000

4 000

6 000

8 000

10 000

12 000

Cash January 1,2019

Net operatingincome

& expenses

R&D tax credit Capital increase -equity line

Repayment ofloans

Other Cash December31, 2019

€7.3m in cash at May 31, 2020

$6.6m from Acrotech Biopharma

Financial visibility extendedinto Q2 2021

Post Q1 2020 information

May 2020

AsiDNA™: a first-in-class product in DNA Damage Response (DDR)

11

A purpose-designed cholesterol-oligonucleotide conjugate

5’

3’

3’

5’

Double-stranded 32 bp DNA is tethered with a loop to prevent disassociation2

Active 32 bp DNA duplex

Cholesterol

Loop

1 Berthault N, et al. Cancer Gene Therapy (2011), 1-12, doi: 10.1038/cgt.2011.3 2 Quanz M, et al. PLoS ONE. 2009 4(7), doi: 10.1371/journal.pone.0006298

Tumoral and nuclear uptake of the DNA mediated via a covalently linked cholesterol molecule1

Binding and activating DNA-PK and PARP signaling enzymes

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

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

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

Patent Protection (Composition of

Matter on AsiDNA™ & related compounds)

until 2031.

Extendable to 2036 with SPC & PTE.

Combinationpatents up to 2040

IP

May 2020

AsiDNA™ is a first-in-class therapy for combination designed to address the #1 challenge in oncology: resistance to treatment

12

Decoy Agonist mechanism of action does not induce resistance

Differentiated Decoy Agonist mechanism of action in the clinically-validated field of DNA Damage Response

Long IP (up to 2040)

Clinical-stage assetFavorable safety profile incl. in combination Proof of mechanism / signals of efficacy

Strategic focus on the abrogation of resistance to targeted therapies

Collaborations with top-academic centers(Institut Curie - Gustave Roussy – Oncopole Toulouse…)

REVocan Phase 1b/2 to evaluate the addition of AsiDNA™ on the abrogation resistance to niraparib (to start H1 2020)

Depletes the cells from which resistance to targeted therapy emerges

May 2020

AsiDNA™: a differentiated product in the clinically-validated field of DDR

13

Source : Quanz M, et al. Clin Cancer Res 2009 15:1308-1316; Quanz M, et al. PLoS ONE. 2009 4(7), doi: 10.1371/ journal.pone.0006298; Jdey W, et al. Clin Can Res. 2016;22:DOI: 10.1158/ 1078-0432.CCR-16-1193

* PARP inhibitors (PARPi) are a leading class of targeted therapies, the first approved and marketed in the field of DDR

DDR inhibition is clinically-validated in oncology (PARPi*)

Decoy Agonist mechanism of action avoids compensatory mechanisms, blocking the induction of resistance

AsiDNA™ 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

AsiDNA™ mimics DNA breaks in the tumor cell (decoy), binds and hyperactivates the proteins (agonist) involved in the DDR cascade (sensing, signaling and repairing) …

… diverts them away from the true damage …., … leading to cellular death.

May 2020

Delivering the promises of AsiDNA™ to patients

DRIIV-1 Phase 1First IV administration in solid tumors

Favorable safety via I.V.

Proof of mechanism in tumors

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

Excellent safety in combination with chemotherapy

Prelim. signals of efficacyCohort 2 (Carboplatin + Paclitaxel) ongoing

REVOCAN Phase 1b/2 (IV)Ovarian cancer in combination w/ PARPi niraparib

Proof of Concept: Abrogation of resistance to PARPiFPI expected Q2 2020

Phase 1b/2 (IV)Combination w/ other targeted therapy (i.e. NonSmall Cell Lung Cancer with TKI…)

Proof of Concept: Abrogation of resistance to Targeted therapies

SHO

RT/

MID

-TE

RM

ON

GO

ING

14

CO

MP

LETE

D

May 2020

Our strategic priority: raise AsiDNA™ as the new treatment paradigm to abrogate resistance

15

Preventing resistance – a major challenge for targeted therapies such as PARPis & Targeted therapy - would lead to prolonged efficacy

❶

❷

“Resistance is the biggest challenge in cancer biology” (Paul Workman – ICR)

Strategic objectives Targeted Indications OpportunityApproval /

Full Market Size

Optimal market access (fast, favorable P&R*)

2L with niraparib (PARPi) in ovarian cancer

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

2025/26$6,7B (1)

A large WW market

Possibly 1L with TKI/targeted therapy in non-smallcell lung cancer

Target specific population with high risk of progression

TBD

(NSCLC:$15B(1))

REVocanCombo w/ PARPi

Combo w/ Targeted therapy

* P&R : pricing & reimbursement - (1) GlobalData (8MM)

May 2020 16

UWB1.289 (Ovarian cancer model – BRCA1-/-)

AsiDNA™ abrogates acquired resistance to PARP inhibitors

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

REVocan study (REVersion of resistance in ovarian cancer with AsiDNA™ and niraparib) ) was designed on the basis of these results

D17

D24

D31

D40

D17

D24

D31

D40

0

5

10

15

20

30

60

90

120

150

CA

12

5

(pg/m

l)

Introduction at CA125 increase (REVocan study protocol)

Start of AsiDNA™ administration

Source: Onxeo, data on file

Niraparib

AsiDNA adminEmergence of Resistant cells

Cell death

0 20 40 600

2×104

4×104

6×104

8×104

1×105

1×1062×1063×1064×1065×1066×106

Nira

Nira+Asi continuous

Nira+Asi at D34

Days post treatment

Cell

num

ber

May 2020

Results confirmed in in vivo experiments in a triple negative breast cancer model

AsiDNA™ abrogates acquired resistance to PARP inhibitors

17

MDAMB-436 (TNBC HR deficient - PARPi sensitive)

Source: Onxeo, data on file

May 2020

Relapsed ovarian cancer: a high unmet medical need

18

2nd line treatment : platinum-based chemotherapy (for patients sensitive to platinum)

2nd line maintenance : PARP inhibitors

Median PFS 9,3 mo in non-BRCA mutated patients (86% of pts)(1) treated with niraparib in 2nd line maintenance ( vs. 21 mo in patients with BRCA mutation)(2)

Development of resistance to PARPi limits duration of response(3)

3rd line with platinum-based CT in sensitive patients, but loss of sensitivity after subsequent relapses leads to lack of therapeutic options

> 128,000 new incident cases in 2018(1)

Potential to extend maintenance / PFS, especially in non-BRCA mutated patients

Potential to maintain sensitivity to platinum for subsequentlines of treatment

Current options

Challenges

Population

US

23,000

Japan

10,000

5 EU

31,000

China

64,000

(1) GlobalData (8MM = 5EU + US + JPN + Urban China) (2) NOVA study (3) Mweempwa A, Wilson MK. Mechanisms of resistance to PARP inhibitors - an evolving challenge in oncology. Cancer Drug Resist2019;2:608-17.

AsiDNA™ opportunity

May 2020

Ready to start REVocan Phase Ib/II study: obtain proof-of-concept of the abrogation of resistance to PARP inhibitors by late 2020/early 2021

19

Patients selection: patients under 2nd line of maintenance with niraparib > 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 & CA125 decrease (GCIG criteria)

Secondary objective: Efficacy: PFS (RECIST criteria) - OS

REVocanREVersion of resistance in Ovarian Cancer with AsiDNA™ and Niraparib

Preliminary data expected by end 2020/early 2021 *

PI: Dr. Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts and 6 centers

* Timelines may be reviewed based on Covid-19 pandemic evolution

May 2020

Ongoing DRIIV-1b Phase 1b study : Confirm safety and efficacy signals in reference combo by year end

20

AsiDNA™ 600 mg

Cohort 1

carboplatin

AsiDNA™ 600 mg

carboplatin + paclitaxel

Cohort 26 pts

ongoing

+

+

Patients with ≥ 3 prior lines of treatment, progressing at inclusion

Very good tolerance of the combination (no DLT)

Disease stabilized (SD) in 2/3 patients for 5.5 mo. (TNBC 6th L) and 10 mo. (NSCLC 3rd L)

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

3 pts

Preliminary data by end 2020 *

* Timelines may be reviewed based on Covid-19 pandemic evolution

May 2020

Short term key catalysts in 2020/early 2021 with moderate impact of Covid-19 on milestones to date

21

FPI

DRIIV-1b cohort 2

topline data

H2 2019 H1 2020 * H2 2020 *

DRIIV-1bcohort 1

prelim. data

* Timelines include first estimates of Covid-19 impact, and may be reviewed depending on the pandemic evolution

REVOCAN First data set

DRIIV-1b cohort 2

preliminary data

AsiDNA™ + TKI …data to support

clinical plan

AsiDNA™ + TKI… data to support

clinical plan

Preclinical validation of OX401 profile

Tolerance in combination + first signals of efficacyDRIIV–1bAsiDNA™ +

carboplatin +/-paclitaxel

REVOCANphase 1b/2

AsiDNA™ + niraparib

Clinical Research agreement

Reversion of resistance

Prevention of resistanceAsiDNA™ + TKI/Kras/BRAF...

Preclinical proof-of-concept

Next-gen PARPi + activation of immune responseOX401Preclinical

proof-of-mechanism

*

*

*

May 2020

Onxeo: A fruitful year 2019 and ready for the 2020 challenges

22

AsiDNA™: positioned to address resistance, the biggest challenge in oncology

The only decoy agonist in clinical development in the field of DDR

Confirmed activity in man and very favorable safety profile in IV, including in combo

Key readouts from Phase 1b/2 REVOCAN study to validate the ability to abrogate resistance to targeted therapies expected in late 2020/early 21

OX 401: Compelling next candidate designed by capitalizing on company expertise

Cash visibility extended to Q2 2021, bridging our key catalysts

Operations maintained with minimal impact to date from Covid-19 on planned operations and key milestones

Thank you for your attention!