Targeted therapeutics · 7 Milestones achieved in 2020 and anticipated in the next 12 months CLINICAL SEL24 –SUCCESSFULLY COMPLETED PHASE I IN AML PATIENTS IN MARCH Study results

Targeted therapeuticsat the forefront of oncology

June 2020

CORPORATE PRESENTATION

2

These slides and the accompanying oral presentation contain forward-looking statements

and information. Forward-looking statements are subject to known and unknown risks, uncertainties,

and other factors that may cause our or our industry’s actual results, levels or activity, performance

or achievements to be materially different from those anticipated by such statements. The use

of words such as “may”, “might”, “should”, “could”, “will”, “expect”, “plan”, “anticipate”, “believe”,

“estimate”, “project”, “intend”, “future”, “potential” or “continue”, and other similar expressions are

intended to identify forward looking statements. For example, all statements we make regarding

(i) the initiation, timing, cost, progress and results of our preclinical and clinical studies

and our research and development programs, (ii) our ability to advance compounds into,

and successfully complete, clinical studies, (iii) the timing or likelihood of regulatory filings

and approvals, (iv) our expectations regarding our ability to obtain and maintain intellectual property

protection for our product candidates, (v) our expectations regarding our ability to grow, are forward

looking.

All forward-looking statements contained in this presentation are based on management's good-faith

belief and reasonable judgment based on current information, and these statements are qualified

by important risks and uncertainties, many of which are beyond our control, that could cause

our actual results to differ materially from those forecasted or indicated by such forward-looking

statements.

We undertake no obligation to publicly update or revise any forward-looking statement, whether

as a result of new information, future events or otherwise, except as required by law.

This presentation is not, and nothing in it should be construed as, an offer, invitation

or recommendation in respect of Ryvu Therapeutics securities, or an offer, invitation

or recommendation to sell, or a solicitation of an offer to buy, any of the securities in any jurisdiction.

Neither this presentation nor anything in it shall form the basis of any contract or commitment.

The presentation describes the business of Ryvu Therapeutics, biotechnology company publicly listed

on the Warsaw Stock Exchange (“Company”) and a focused oncology drug discovery and development

company.

Some financial data in this presentation are preliminary and used for demonstration purpose only.

They are approximate and current as of the date hereof and may be adjusted on or prior

to the completion of the process.

Accordingly, no representation or warranty, express or implied, is made or given by or on behalf

of the Company, or any of its directors and affiliates or any other person, as to, and no reliance should

be placed for any purposes whatsoever on, the fairness, accuracy, completeness or correctness of,

or any errors or omissions in, the information contained herein or any other information, whether

written or oral, transmitted or made available to you herewith. Neither the Company, its management,

officers or employees nor any other person accept any legal responsibility whatsoever for any loss

howsoever arising from investment activities based on the indicative financial data or any use

of the materials contained in this presentation. This presentation is not intended to be relied upon

as advice to investors or potential investors and does not take into account the investment objectives,

financial situation or needs of any investor. Investors should base their investment decisions

on the basis of full audited statements of Ryvu Therapeutics S.A.. The information contained in these

materials has not been independently verified and is subject to verification, completion and change

without notice.

Note on the presentation and forward looking statements

3

Clinical stage company developing novel small molecule therapies addressing high value targets in oncology

* As of April 9, 2020.** Maximum non-dilutive research funding if all projects succeed according to the current research plans and grant contracts

• Fully-owned lead asset, first-in-class CDK8/CDK19 inhibitor for blood cancers and solid tumors SEL120, first patient dosed in AML/MDS in September 2019.

• First-in-class dual PIM/FLT3 inhibitor SEL24/MEN1703 for blood cancers partnered globally with Menarini entered single agent Phase 2 studies in March 2020

• All clinical trials of SEL24/MEN1703 and SEL120 are conducted in the U.S.

• Development of SEL120 in multiple hemato-oncology and solid tumor indications

• All Ryvu programs have been discovered internally - robust discovery engine addressing targeted cancer therapies and immuno-oncology

• Expected one new pre-clinical candidate per year for self development or partnering

TWO PROJECTS IN CLINICAL TRIALS HIGH VALUE UPSIDE

ASSETS STRATEGY

• Listed on the Warsaw Stock Exchange (WSE:RVU)

• ~ $260M market capitalization

• ~ $14M* in cash and short-term investments

• ~$ 5M quarterly cash burn

• > $25M** in grant funding secured until 2023

• >150 employees

MATURE CORPORATE GOVERNANCE

CORPORATE

4

Broad pipeline addressing emerging targets in oncology

5

Differentiated internally discovered small-molecule drug candidates and new programs

SMALL MOLECULE

SYSTEMIC

STING AGONIST

SELECTIVE

HPK1 INHIBITOR

SMARCA4-SELECTIVE

SMARCA2

DEGRADER

SEL24/MEN1703

DUAL PIM/FLT3

INHIBITOR

SEL120

SELECTIVE

CDK8/CDK19

INHIBITOR

NON-GLP TOXICOLOGY LATE LEAD OPTIMIZATION HIT-TO-LEADLEAD OPTIMIZATIONCLINICAL CLINICAL

DUAL ADENOSINE

A2A/A2B ANTAGONIST

A2A/A2B

STING

HPK1

o As efficacious in vivo in mice as the most potent disclosed STING agonists (GSK) while suitable for systemic as well as local delivery

o Induces long-term immunological memory

o Strong, direct binder to heterogenous STING alleles

o The only dual A2A/A2B receptor antagonist known to efficiently overcome immunosuppression in the adenosine-rich tumor microenvironment

o Orders of magnitude more potent than known adenosine receptor antagonists in development, including AstraZeneca, Corvus, Arcus

o Novel, emerging kinase target with unique dual potential in oncology: boosting immune response and making T cells more resistant to immunosuppressive tumor microenvironment

o First-in-class potential

IMMUNO-ONCOLOGY SYNTHETIC LETHALITYTARGETED THERAPIES

SMARCA2o Targets SWI/SNF chromatin

remodeling complex implicated in multiple cancers, including NSCLC

o First-in-class potential

o Most selective disclosed SMARCA2 with confirmed synthetically lethal phenotype

o Unique allosteric ATPase inhibitors with PROTAC approach

SEL24o Partnered globally with

o Dual targeting for broader efficacy and durable responses in AML

o Potential for patients who relapse or are unresponsive to FLT3-selective inhibitors

o Single agent efficacy in R/R AML

SEL120 o First-in-class unique mechanism: direct cytotoxicity and eradication of leukemic stem cells as a single-agent

o Administered independently of mutational status

o Safe and effective combo with SoC and recent emerging agents

OTHER S/L TARGETS

o MTAP, WRN and multiple other undisclosed targets

o Unmet indications in solid tumors

6

Key milestones in 2019

FIRST PATIENT DOSED WITH SEL120

CORPORATE SPLIT BETWEEN RYVU THERAPEUTICS AND SELVITA (CRO) COMPLETED

UPDATES AND PROGRESS IN CLINICAL AND DRUG DISCOVERY PROJECTS

PRESENTED AT MULTIPLE CONFERENCES

• SEL24/MEN 1703 – ASCO, EHA, ASH

• SEL120 – ASH, AACR

• STING, A2A/A2B - AACR, SITC

2 PROGRAMS RECEIVE NON-DILUTIVE GRANT FUNDING FROM THE POLISH NCBiR

WITH A TOTAL VALUE OF $17.5 M*

STRENGTHENED SUPERVISORY BOARD AND MANAGEMENT BOARD

ACCOMPLISHED BIOTECH INDUSTRY VETERANS

„Discovery and Phase I development of a targeted therapy for tumors with MTAP deletion” ($9.5 M)

„Discovery and Phase I development of a synthetic

lethality program” ($7.9 M)

SETAREH SHAMSILI MD, PHD

Chief Medical Officer, Management Board Member

COLIN GODDARD Ph.D.AXEL GLASMACHER Ph.D.

JARL ULF JUNGNELIUS M.D.THOMAS TURALSKI

New members of the Supervisory Board:

SELECTION OF A2A/B ANTAGONIST PRECLINICAL CANDIDATE FOR NON-GLP TOX STUDIES

U.S. FDA APPROVES INITIATION OF CLINICAL DEVELOPMENT FOR SEL120

SEPTEMBER

MARCH

AUGUST

DECEMBER

OCTOBER

SEPTEMBER

DECEMBER

MARCH

* 1 $ = 4.14 PLN as of 14.04.2020

THROUGHOUT THE YEAR

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Milestones achieved in 2020 and anticipated in the next 12 months

SEL24 – SUCCESSFULLY COMPLETED PHASE I IN AML PATIENTS IN MARCHCLINICAL

Study results will be presented by Menarini at EHA 2020 in June

SEL120 – ORPHAN DRUG DESIGNATION by FDA IN MARCH

PUBLICATION OF PRELIMINARY DATA FROM PHASE I – H1 2021

VALUABLE DATA FROM PRECLINICAL STUDIESDISCOVERY

• Four posters with data from STING, SMARCA, HPK1 and A2A/B programs will be published during AACR virtual meeting in June 2020

ONE NEW CANDIDATE IN PRECLINICAL STUDIES

• Currently non-GLP toxicological studies ongoing for A2A/B antagonists• Currently ongoing studies for STING agonists leading to selection of a preclinical candidate

CORPORATE AND BUSINESS DEVELOPMENT

DEAL WITH GALAPAGOS IN INFLAMMATORY DISORDERS ANNOUNCED IN APRIL

RYVU SPIN-OUT COMPANY NODTHERA RAISES $55M IN JUNE

ADDITIONAL DEALS EXPECTED BY END OF THE YEAR

INITIATION OF PHASE II IN APRIL

NON-DILUTIVE FUNDING - $6M GRANT FOR HPK1 INHIBITORS IN JUNE

MOVE TO THE NEW RESEARCH CENTER IN JUNE

ADDITIONAL DOSE EXPANSION DATA IN 2021

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New research collaboration between Ryvu and Galapagosannounced on April 16, 2020

• Discovery and development of first-in-class small molecules and drug candidates targeting inflammatory disorders

• Based on a novel drug target, technology platform and related intellectual property contributed by Ryvu

• Ryvu and Galapagos will provide resources to support the collaboration, as well as bring their expertise in target validation, high-throughput screening, medicinal chemistry,in vitro and in vivo biology, and toxicology

• Upon the option exercise Galapagos will have an exclusive license to intellectual property developed so far at Ryvu and jointly during the research collaboration

• The collaboration consists of a joint research phase after which Galapagos will further research and develop the molecules on its own

DEAL STRUCTURE

RYVU HAS RECEIVED AN UP-FRONT PAYMENT

POSSIBILITY OF ADDITIONAL OPTION AND MILESTONE PAYMENTS

RYVU WILL ALSO RECEIVE SINGLE-DIGIT ROYALTIES ON SALES OF PRODUCTS DEVELOPED AS A RESULT OF THE COLLABORATION

DEAL TERMS: https://ryvu.com/wp-content/uploads/2020/04/Raport-ESPI-2020-07.pdf

FINANCIAL TERMS

Clinical-stage biotechnology company specialized in the discovery and development of small molecule medicines with novel modes of action

Founded in 1999725 employees

Pipeline comprises Phase 3, 2, 1 studies, pre-clinical studies and discovery programs in inflammation, fibrosis and other indications.

Lead program filgotinib JAK1 inhibitor in Phase IIIstudies

Listed on Euronext & NASDAQ: Market cap € 12.2 billion

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First therapeutic area of Ryvu focus: acute myeloid leukemia

0% 20% 40% 60% 80% 100%

5 – Year Relative Survival Rate

Media

nAge

at

Dia

gnosi

s

2,800

83,000

Incidence scale

AML

MDS

MM

CML NHLCLL

MPNs

HL

ALL (Age 20+)

ALL (Age<20)

Source: Leukemia & Lymphoma Society, 2018

2 Most common leukemia type in adults

67

AML patients with a ITD mutation

in the FMS-like tyrosine kinase 3 (FLT3)

gene linked to a less favorable prognosis

Median age at diagnosis (in years) Highest incidence in the older adults

3-4 people/100 000 individuals

30%

AML: Lowest survival among all blood cancers

26% of patients surviving 5 years after the diagnosis

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Clinical landscape: targeted small molecule therapies for acute myeloid leukemia

CDK8/CDK19

FLT3

Dual PIM/FLT3

PIM

IDH1 or IDH2

Others

Phase 1/2 Phase 3 Approved

RYVU CLINICAL PROGRAMS

FULLFIL UNMET NEEDS IN AML

• SEL120 is the only CDK8/CDK19 inhibitor actively developed in the clinic

• MEN1703/SEL24 is an unique, clinical dual PIM/FLT3 inhibitor

overcoming resistance to single-target mutation-specific inhibitors

efficacy in broader patient populations

reducing chemotherapy-based treatment regimens

all oral regimen

11

SEL120: Highly selective first-in-class CDK8/CDK19 inhibitor

with broad potential in multiple indications

BREAST CANCER

COLORECTAL CANCER

SOLID TUMORS

HR-MDS

AML

BLOOD CANCERS

LYMPHOMA

ALL

DIAMOND-BLACKFAN ANEMIA

ORPHAN INDICATIONS

SEL120Biology of CDK8/CDK19 different from other CDKs

• Different tumors responding to inhibitors

• Different toxicity profile

• Different stratification of responders and biomarkers of response

Therapeutic potential via two mechanisms of action

• Direct cytotoxicity (induction of apoptosis)

• Eradication of Leukemic Stem Cells (LSC) known to be responsible for tumor relapse in AML

Different features compared to current treatments

• Can be given to patients independently of mutational status

• Can be safely and effectively combined with standard-of-care chemo (e.g. Ara-C), as well as with recent emerging compounds (e.g. venetoclax)

SEL120 has received $3.25 M from

Leukemia & Lymphoma Society

Therapy Acceleration Program (TAP)

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o Selectively targets leukemic cells, sparing normal blood cells

(unaffected normal hematopoiesis)

o Promotes cell death (differential cytotoxicity on STAT5+ AML)

o Represses increased levels of anti-apoptotic proteins

and induces lineage commitment genes in undifferentiated AML cells

o Transcriptional deregulation is a hallmark of AML

o CDK8 is a kinase subunit of the Mediator complex serving as a bridge between

basal transcription and regulatory elements involved in:

⁻ Deregulation of super enhancers (SE)

⁻ Affected differentiation and pro/anti-apoptotic genes

RATIONALE FOR CDK8/CDK19 INHIBITORS IN AML

EFFICACY OF SEL120 - CDK8/CDK19 INHIBITOR - IN AML

SEL120: potential role of CDK8/CDK19 in AML treatment

13

Excellent on-target activity of SEL120 in pSTAT positive AML cell models

p-STAT5 Ser726

p-STAT1 Ser727

• U.S. patent granted in 2017

• Spares CDK2, CDK4, CDK6, CDK7, CDK9, etc.

SEL120 is a potent and selective CDK8/CDK19 inhibitor

Low nM activity on CDK8/CDK19

and excellent kinase selectivity (broad kinome)

pSTAT1/pSTAT5 levels discriminate responder/ non-responder

RE

LA

TIV

E I

NT

EN

SIT

Y

(WE

ST

ER

N B

LO

T, P

RO

TE

IN Q

UA

NT

IFIC

AT

ION

)

RESPONDERS NON-RESPONDERS

RESPONDERS NON-RESPONDERS

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SEL120 induces complete regression and bone marrow recoveryin CD34+ AML patient-derived xenografts

COMPLETE REGRESSION(PERIPHERAL BLOOD)

HEMATOLOGIC RECOVERY(BONE MARROW)

REDUCED SPLENOMEGALY

Research performed at:

PDX cells NSG mice

17 days latency Daily treatment 29/30 days

Vehicle / SEL120Dose: 46mg/kg

Leukemia burden analysis

P20: CD34+ NPM1wt

0 5 10 15 20 25 30

-20

-15

-10

-5

0

5

Body Weight Change

Day of administration

Me

an

bo

dy

we

igh

t c

ha

ng

e [

%]

SE

M

Vehicle, QD, po

SEL120, 45 mg/kg QD, po

BONE MARROW SPLEENBODY WEIGHT CHANGETUMOR GROWTH KINETICS

PERIPHERAL BLOOD

DAYS DAYS CONTROL SEL120 CONTROL SEL120

SP

LE

EN

WE

IGH

T [

mg

]

%m

CD

45

+

%h

CD

45

+

ŚR

ED

NIA

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IAN

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AS

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IAŁ

A [

%]

±S

EM

15

SEL120: Broad potential in oncology beyond AML and orphan blood disease

* Small Molecule Screens Identify CDK8-Inhibitors as Candidate Diamond-Blackfan Anemia Drugs – Lund University, Jun Chen, MD, PhD – Presentation at ASH 2018

MANTLE CELL LYMPHOMA

WILMS’ TUMOR

DIAMOND BLACKFAN ANEMIA*

QUICK FACTS

• SEL120 treatment results in on-target efficacy

in preclinical models of AML

• Emerging therapeutic opportunities in solid cancers

(breast and prostate cancer) and orphan hematological disorders

BREAST CANCER

COLORECTAL CANCER

SOLID TUMORS

HR-MDS

AML

BLOOD CANCER

LYMPHOMA

ALL

DIAMOND-BLACKFAN ANEMIA

ORPHAN INDICATIONS

SEL120

0 5 10 15 20

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500

1000

1500

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2500

3000

Efficacy of SEL120 in SK-NEP1 model


Me

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Disc. SEL120Disc. SEL120

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Efficacy of SEL120 in MDA-MB-468 model


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Disc. SEL120Disc. SEL120

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DAYS

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EFFICACY OF SEL120 IN Z-138 MODEL

EFFICACY OF SEL120 IN SK-NEP1 MODEL EFFICACY OF SEL120 IN MDA-MB-468

MODEL

BREAST CANCER

16

Potential medical need for SEL120 in AML patients

FIRST LINE

RELAPSED/REFRACTORY

UNFIT PATIENTS

LOW INTENSITYTHERAPY



TARGETED THERAPY

TARGETED THERAPY

OR

SEL120

NO RELEVANT MUTATIONS

MUTATION -DRIVEN

FIT PATIENTS

INTENSIVE INDUCTIONCHEMOTHERAPY

AGGRESSIVE SALVAGECHEMOTHERAPY

SEL120 MONOTHERAPY

INTENSIVE INDUCTION CHEMOTHERAPY

TARGETED THERAPY

TARGETED THERAPY

TARGETED THERAPY

+

+SEL120

TARGETED THERAPY

+

SEL120


+SEL120

NO

RELEVANT

MUTATIONS

MUTATION -

DRIVEN

17

SEL120: Phase 1b study – first patient dosed in September 2019

Study title: A Phase 1b Study of SEL120 in Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

H1 2021

27.03.2020

PROJECT MILESTONES

ORPHAN DRUG DESIGNATION RECEIVED FROM THE FDA

H2 2021

INITIAL RESULTS FROM PHASE 1b

FINAL RESULTS FROM PHASE 1b

2019 2020 2021

Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4

PHASE 1 DOSE ESCALATION

SITE ACTIVATION

EXPANSION: SEQUENTIAL OR COMBINED TREATMENT

STUDY POPULATION:• Patients with relapsed/refractory AML or high risk MDS• No upfront patient stratification

PRIMARY OBJECTIVES:• To assess safety and tolerability of SEL120 • To determine the recommended dose of SEL120

SECONDARY OBJECTIVES:• To evaluate the pharmacokinetics of SEL120• To evaluate the preliminary anti-leukemic activity of SEL120

EXPLORATORY OBJECTIVE:• To evaluate the pharmacodynamics of SEL120

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VALUE THROUGH GLOBAL DEAL WITH

$5.6M

DEVELOPED BY RYVU UP TO INITIATION OF CLINICAL STUDIES AND OUT-LICENSING

• Partnered globally with Menarini in 2017 TOP 40 global pharma company, based in Italy

• Menarini is fully responsible for clinical development and funds translational research at Ryvu

UPFRONT PAYMENT

$104MTOTAL POTENTIAL VALUE OF MILESTONES& REFUND OF R&D COSTS

xx% UP TO DOUBLE-DIGIT ROYALTIES FOR RYVU FROM MENARINI

SEL24/MEN1703 is a differentiated, first-in-class PIM/FLT3 dual kinase inhibitor

2020

APRIL 2020

5.03.2020

2020 MILESTONES

SUCCESSFUL COMPLETION OF PHASE 1 DOSE ESCALATION STUDY FOR SEL24/MEN1703BY MENARINI and establishing of the recommended dose for phase 2 studies of the drug

Q2 2020

PLANNED STUDY EXPANSION IN EUROPE

RYVU RECEIVED MILESTONE PAYMENT OF $1.9 M

PHASE 2 DOSE EXPANSION STARTS IN USA

PIM and FLT3 are oncogenes involved in AML

Dual targeting creates potential for broader activity, more durable responses than selective FLT3 inhibitors such as gilteritinib

Potential for treating patients that have relapsed on selective FLT3 inhibitors - PIM kinases are largely responsible for the development of resistance to FLT3 inhibitors

1 2 3

19

SEL24/MEN1703 Phase I data summary (EHA abstract from May 14 2020)

Results:

• As of February 11th, 2020 (cut-off date), n=25 patients were treated across 6 dose levels (25, 50, 75, 100, 125, 150 mg). Median age

was 68 (range: 25-84) years. Overall, 14 (56%) and 11 (44%) patients had non de novo AML and primary refractory AML, respectively.

Patients with relapsed or untreated AML were 11 (44%) and 2 (8%), respectively. Adverse karyotype was reported in 10 (40%)

patients; FLT3-ITD was found in 5 (20%) patients. Median number of cycles was 2 (range 1-8).

• DLTs were reported in 1 patient at 25 mg (G3 hypophosphatemia), 1 patient at 125 mg (G5 fungal pneumonia) and 3 patients at 150

mg (G5 venous stroke, G3 increased transaminases and G3 increased alkaline phosphatase, respectively). Since 3 out of 4 patients at

150 mg experienced a DLT, RD was defined at 125 mg. Most frequent serious treatment-emergent AEs (serious TEAEs) were febrile

neutropenia (28%), sepsis (16%) and pneumonia (12%). Most frequent G≥3 TEAEs were neutrophil count decrease (40%), febrile

neutropenia and thrombocytopenia (32%) and anemia (24%).

• Objective responses were observed in 2 patients: one complete remission (CR) at 75 mg dose by Cycle 5

in an 81-y.o. patient with DNMT3A/IDH2 mutated AML progressed on enasidenib; one CR with incomplete

hematologic recovery (CRi) at 125 mg dose by Cycle 5 in a 75-y.o. patient with prior myelodysplastic syndrome

and ASXL1/EZH2 mutated AML relapsed after standard chemotherapy.

• PK data indicated that SEL24/MEN1703 exposure tends to increase with increasing doses in a slightly more than dose proportional

manner. Tmax was reached after 4-6 hours following drug administration and the terminal half-life was ~40 hours

• Summary/Conclusion: SEL24/MEN1703 showed an acceptable safety profile up to the RD established at

125 mg. Throughout the DE, initial evidence of efficacy was observed with 1 CR and 1 CRi in elderly patients who

had exhausted standard therapeutic options. CE in relapsed/refractory AML patients will further investigate the

single agent activity and the safety profile of SEL24/MEN1703

Unique profile: Demonstrated single agent efficacy in relapsed/refractory FLT3 negative Patients

Dose expansion planned at multiple clinical sites in the US. and in several European countries

20

Broad early discovery pipeline addressing major cancer-related molecular pathways

Synthetic lethality: potential pre-clinical candidates in 2021

Immunoncology & immunometabolism: two potential initiationsof IND-enabling studies in 2020

Novel targets

• Novel targets and attractive fast follower programs

• Deep expertise focused on novel immunokinases, helicases, ATPases

• Challenging scaffold proteins

• Excellent know how from hit ID to clinical candidate

• Strong medicinal chemistry division

• Discovery engine geared to generate one new clinical candidate per year

FOCUS ON NOVEL TARGETS THAT LEVERAGE IN-HOUSE EXPERTISE

21

Ryvu develops dual A2A/A2B adenosine receptor antagonists

KEY SUCCESS FACTORS, COMPETITIVE ADVANTAGE

STATUS

IN 2019 RVU330 WAS SELECTED AS A PRECLINICAL CANDIDATE

NON-GLP TOX STUDIES ARE ONGOING

Strong potential of best-in-class drug: The only disclosed dual A2A / A2B antagonist exhibiting immunostimulatory activity in vitro at high concentrations of adenosine

2021

Q2 2020

2020 MILESTONES FOR RVU330

COMPLETION OF NON-GLP TOX STUDIES

2020

INITIATION OF IND ENABLING STUDIES

INITIATION OF PHASE I CLINICAL TRIALS

PRELIMINARY TRANSLATIONAL STUDIES ALLOWING TO IDENTIFY PATIENTS WITH POTENTIAL BEST TREATMENT BENEFITS

2H 2020

RYVU APPROACH OF TARGETING BOTH A2A AND A2B RECEPTORS PROVIDES STRONG PRECLINICAL

COMPETITIVE ADVANTAGE

22

KEY SUCCESS FACTORS, COMPETITIVE ADVANTAGESTATUS

STAGE: SELECTION OF PRELINICAL CANDIDATESTRONG ANTITUMOR EFFICACY AFTER SYSTEMIC ADMINISTRATION

OPTIMIZATION AND PROFILING OF COMPOUNDS -POTENTIAL CANDIDATES FOR NON-GLP TOX STUDIES

2020

Q1-Q3 2020

2020 MILESTONES

PROFILING AND ASSESSMENT OF THE POTENTIAL FOR BEST COMPOUNDS – DRUG CANDIDATES

2H 2020 INITIATION OF NON-GLP TOX STUDIES

Small molecule, direct STING agonists with systemic route of administration and activity on all STING haplotypes (broad patient population may benefit); Potential for antibody drug conjugatation (ADC)

W T R 2 3 2 H A Q R 2 9 3 Q G 2 3 0 A

0

5

1 0

1 5

2 0

T h e r m a l s h i f t r e s u l t s f o r h S T I N G m u t a n t s

T

m [

C]

A D U - S 1 0 0

WT R232H AQ R293Q G230A0

10

20

30

40

T

m [C

]

SLV-25466

STING HAPLOTYPES STING HAPLOTYPES

RYVU STING AGONISTADURO COMPOUND

STRONG COMPETITIVE ADVANTAGEA broad patient population carrying multiple STING haplotypes may benefit

(TH

ER

MA

L S

HIF

T A

SS

AY

)

Small molecule, direct, systemic STING agonists with confirmed efficacy in intravenous and intratumoral mouse tumor models

PRELIMINARY TRANSLATIONAL STUDIES ALLOWING TO IDENTIFY PATIENTS WITH POTENTIAL BEST TREATMENT BENEFITS

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1750

2000

2250

2500



Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40

0

250

500

750

1000

1250

1500

1750

2000

2250

2500



Tu

mo

r vo

lum

e [

mm

3]

Ryvu STING agonists eliminate established tumors after systemic and intratumoral administration

0 10 20 30 40

0

500

1000

1500

2000

2500

Vehicle 5 ml/kg iv Days 1,3,5


Tu

mo

r vo

lum

e [

mm

3]

CR 4/10

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000

Control, EODx3, IT


Tu

mo

r vo

lum

e[m

m3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000

ADURO, 5.0 mg/kg EODx3, IT


Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000

SLV-24024, 0.5 mg/kg, EODx5, IT


Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000



Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000



Tu

mo

r vo

lum

e [

mm

3]

0 10 20 30 40

0

500

1000

1500

2000

2500

RVU-24024, 3 mg/kg iv Days 1,6,11

Days post randomization

Tu

mo

r vo

lum

e [

mm

3]

CR 6/10

3 mg/kg E5Dx3, IV

RYVU STING AGONIST

0 10 20 30 40

0

500

1000

1500

2000

2500



Tu

mo

r vo

lum

e [

mm

3]

0 10 20 30 40

0

500

1000

1500

2000

2500

RVU-24836, 1.5 mg/kg iv Days 1,4,7


Tu

mo

r vo

lum

e [

mm

3]

0 10 20 30 40

0

500

1000

1500

2000

2500

RVU-24024, 2 mg/kg iv Days 1,6,11


Tu

mo

r vo

lum

e [

mm

3]

0 10 20 30 40

0

500

1000

1500

2000

2500

RVU-24024, 3 mg/kg iv Days 1,6,11


Tu

mo

r vo

lum

e [

mm

3]

0 10 20 30 40

0

500

1000

1500

2000

2500

RVU-24024, 2 mg/kg iv Days 1,8,15


Tu

mo

r vo

lum

e [

mm

3]

0 10 20 30 40

0

500

1000

1500

2000

2500

RVU-24024, 3 mg/kg iv Days 1,8,15


Tu

mo

r vo

lum

e [

mm

3]

GSK REFERENCE

CR 4/10

1.5 mg/kg E3Dx3, IV

5 mg/kg EODx2, SC

SY

ST

EM

IC A

DM

INIS

TR

AT

ION

: IN

TR

AV

EN

OU

S

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000

Control, EODx3, IT


Tu

mo

r vo

lum

e[m

m3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000



Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000



Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000



Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000



Tu

mo

r vo

lum

e [

mm

3]

CR 7/10

5 mg/kg EODx3, IT

RYVU STING AGONIST

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000

Control, EODx3, IT


Tu

mo

r vo

lum

e[m

m3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000



Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000



Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000



Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000



Tu

mo

r vo

lum

e [

mm

3]

5 mg/kg EODx3, IT

CR 3/10

ADU-S100 REFERENCE

LO

CA

L A

PP

LIC

AT

IO

N:

IN

TR

AT

UM

OR

AL

SY

ST

EM

IC

AD

MIN

IS

TR

AT

IO

N:

SU

BC

UT

AN

EO

US

DAYS

DAYS

DAYS

DAYS DAYS

DAYS

DAYS DAYS

TU

MO

R V

OLU

ME [

mm

3]

TU

MO

R V

OLU

ME [

mm

3]

TU

MO

R V

OLU

ME [

mm

3]

CONTROL

TU

MO

R V

OLU

ME [

mm

3]

TU

MO

R V

OLU

ME [

mm

3]

TU

MO

R V

OLU

ME [

mm

3]

CONTROL

TU

MO

R V

OLU

ME [

mm

3]

TU

MO

R V

OLU

ME [

mm

3]

CONTROL

RYVU STING AGONIST

• Efficacy data in a CT26 mouse colon cancer model

• CR = COMPLETE REGRESSION • 4/10 = 4 OUT OF 10 MICE IN THE

STUDY GROUP

LEGEND

CR 0/10 CR 0/10 CR 0/10

24

Ryvu develops selective SMARCA2 inhibitors and degraders targeting tumors with SMARCA4 loss of function based on synthetic lethality mechanism

RYVU APPROACH

RYVU STRATEGYSUCCESS FACTORS

WELL DEFINED PATIENTS POPULATION WITH

SMARCA4 LOF MUTATIONS

#1 LEAD STRUCTURE OPTIMIZATION#2 HIT TO LEAD FOR CHEMOTYPESTATUS

RVU311-5363

REFERENCE

PHYS-CHEM MW/ clogP/ PSA <1400/5.1/292 <1000/3.7/209

BINDING TO SMARCA2(RECOMBINANT

PROTEIN)

MST - DNA Kd [µM] 0.7no binding

(BRD domain)

DEGRADATION

Remaining SMARCA2 after 24h 10% 2%

Remaining SMARCA4 after 24h 46% 9%

SMARCA4

SMARCA2

GAPDH

RVU311-5363 BOEHRINGER REFERENCE

• 5-10% NSCLC with inactivating (LOF) and truncating mutations SMARCA4 (BRG1)

• Other SMARCA4 mut cancers (GI, Skin, Cervical, Bladder, Colorectal)

• Unique, allosteric inhibitors of ATPase activity selectively degrading SMARCA2 with a confirmed in vitro phenotype of synthetic lethality in cancer cells

• A potentially better safety window for the PROTAC series compared to competitors

SMARCA2/SMARCA4 selectivity is criticalto avoid toxicity and provide safety window

RYVU SMARCA2 PROTACs SELECTIVELY DEGRADE SMARCA2

OVER SMARCA4 IN CONTRAST TO REFERENCE COMPOUND

2H 2020

2020

CONFIRMATION OF ANTITUMOR ACTIVITY IN MOUSE XENOGRAFT MODELS (SMARCA4-MUT CANCERS)

MULTIPARAMETER OPTIMIZATION

2020 PLANS AND MILESTONES

25

2019 FINANCIAL RESULTS

26

Benefits of the corporate split: oncology therapeutics (Ryvu) and CRO (Selvita)

March 2019 April 2019 September 2019 September 2019 October 2019 October 16, 2019

Ph1 Dose Escalation First day of SLV and RVU separate listingon WSE

Split registered by the court (KRS)

Shareholder approval of the split (72% of value Ryvu, 28% Selvita)

Selvita CRO prospectus approved by the Polish Financial Supervision Authority (KNF)

Selvita CRO prospectus filed with the Polish Financial Supervision Authority (KNF)

Corporate split plan announced

Swift execution of the split process

Generating additional

value for Ryvu

shareholders

SLV market capitalization

on June 4, 2020

First day of SLV

listing on WSE

SLV on the day of the split

Reference value

Average exchange rate in 2019 (NBP): 1 $ = 3.8395 PLN

$191M

$87M

$75M

In October 2019 Ryvu shareholders

received one SLV share in addition to each 1 Ryvu share held

Ryvu share price was adjusted down

by the reference value of SLV share (PLN17.3)

27

Achievement of the goals related to the corporate split

84%

▪ Achievement of the objectives related to the corporate split:

• Unlocking potential for shareholders: greater value and liquidity compared to the previous structure

• Full corporate focus and transparency for patients, business partners

• Greater opportunities to recruit as well as motivate an existing team

* Comparison of the exchange rate from October 8, 2019 (last trading day before division) and June 4, 2020** Average session turnover in the 3 months preceding divisions (7-10.2019) and the last months 2020 (1-6 2020)Exchange rate used – average NBP value for 2019 – 1 USD = 3,8395 PLN

SLVRVU

4.5

12.3

11.5

17.1

Cumulated share price SLV and RVU ($)*

16.0

29.4

Jun 20Oct 19

119

73

83

Average daily trading value (thousands of $)**

202

177%

2019 2020

28

Ryvu Therapeutics annual financial results

2019 vs 2018 in compliance IFRS

$ million 2018 2019 4Q 2018 4Q 2019

Revenues 10.2 8.9 3.3 2.1

Partnering 2.8 1.0 0.6 0.2

Grants 7.3 7.8 2.7 1.9

Others 0.1 0.1 0.1 0.0

Operational costs 16.1 20.7 5.7 5.0

EBIT -6.0 -11.8 -2.4 -2.9

EBITDA

(excl IFRS 16) -5.0 -10.2 -2.0 -2.4

Net result from continued activities -2.1 -9.4 -3.3 -2.6

> $19MCash positionDecember 2019

Cash positionApril 2020 ~$14M

*Exchange rate used: average exchange rate for a given period

29

Increase in capital and R&D expenditures

• Intensification of R&D activities - implementation of the strategy for 2017-2021

• Increase in employment - mainly experienced scientists from Poland and abroad

• Significantly increased expenditure allocation for project development in the clinical phase; stable level of expenditure on early stage projects

• Expenditures associated with the construction of R&D Center for Innovative Drugs

14%

398%

R&D expenditures ($ million) CAPEX ($ million)

0.73.9

13.5

14.7

1.0

2.2

2018 2019

Faza kliniczna (SEL120, SEL24) Projekty wczesnej fazy Inne

429%

Early pipeline Other

1.6

7.93.2

1.7

2018 2019

Centrum BR Innowacyjnych Leków Inwestycje odtworzeniowe

398%

R&D Center for Innovative Drugs Replacement investmentsClinical (SEL120, SEL24)

* Exchange rate used – average NBP for 2019 – 1 USD = 3,8395 PLN

30

Investment in the new Ryvu R&D Center for Innovative Drugs

2017 April 2018 August 2018 April 2020 June 2020

Ph1 Dose EscalationObtaining permits, launching the first

laboratories

Completion of major construction works; in progres

of the permits’ granting procedures

Initiation of construction works

Obtaining a construction permit

Preparations for the investment; obtaining a

grant from the Ministry of Development

Planned move in June 2020

> 86,000 sq. ftUsable areaof the Center

Value of the grant from the Polish Ministry

of Development

~$9M~ 300 associates# workplaces

> $20MInvestment budget

* Exchange rate used – average NBP for 2019 – 1 USD = 3.8395 PLN

• Investment initiated in 2017 before the corporate split

• Provides Ryvu with adequate and consolidated research infrastructure

• Has enabled the spin-out of Selvita (CRO) and value creation of $170 M for Ryvu shareholders

• Ryvu has secured funds for investment from joint pre-split cash balance

31

Ryvu R&D Center for Innovative Drugs – planned move in Q2 2020

32

Covid-19 impact on Ryvu Therapeutics

Clinical trials:

• Industry risk: Clinical trials in locations impacted by Covid-19 such as the US has been by Covid-19 pandemic in multiple ways

(slow or suspended enrollment, difficulties in patient monitoring, delayed DRCs, etc.)

• Clinical studies provide patients suffering from life threatening disorders such as AML and hrMDS with potential new therapeutic options – risk/benefit

management policies are mainly dependent on individual site decisions

• Several SEL120 clinical sites suspended enrollment in March/April – slowly coming back on-line

• Expected impact on enrollment - ~3 months delay vs. the original plans – data availability in H1 2021 vs. Q4 2020 originally planned

Laboratory operations:

• Thanks to the early government intervention (March 12) Poland is so far one of the countries least impacted by Covid-19 in Europe

(as of June 4 total of 24 826 cases and 1117 deaths for 38 milion people, peak of infections and deaths passed in April/early May)

• Ryvu introduced the first risk Covid-19 management steps already in February and reduced laboratory operations to critical experiments

from March 30 to April 11

• Full restart of laboratory activities on April 12 with appropriate risk management

• 50% of non-lab associates work from home until the move to the new building

• Outsourcing – limited capacity at some European CROs. Key providers less impacted. Risk-management with Asian CROs.

Other industry specific risks

• Slowed-down business development (pharma demand)

• Market volatility and more difficult access to capital

33

Ryvu investment highlights and near term milestones

• Developing novel small molecule therapies that address

emerging targets in oncology

• Targeting kinases, synthetic lethality, immune response

and immuno-metabolism pathways

• Validation from strategic collaborations

• Partnership options for early stage candidates

• Limited cash burn thanks to non-dilutive grants and cost-efficient

discovery platform, significant resources located in Poland

• Potential milestone payments and royalties

from partnered programs

• Steady generation of differentiated candidates

IND enabling studies

for new pre-clinical candidates

SEL24/MEN1703

Phase 1 data (2020)

NEA

R T

ER

M M

ILESTO

NES:

SEL120

Phase 1 interim data (H1 2021)

Partnering deals

in the early pipeline

Data from

early programs

✓

✓

34

Pawel PrzewiezlikowskiChief Executive Officer

[email protected]

Ryvu Therapeutics S.A.www.ryvu.com

[email protected]

Contact data

35

Back-up slides

36

Management team with strong clinical and shareholder value creation track record

PAWEL PRZEWIEZLIKOWSKI, MSc, MBA

CEO and Founder

KRZYSZTOF BRZOZKA Ph.D., MBA

CSO

SETAREH SHAMSILI M.D., Ph.D.

CMO

LUIGI STASI Ph.D.

Director of Chemistry

PETER LITTLEWOOD Ph.D.

Director of DMPK

TOMASZ NOCUN, MSc, MBATOMASZ RZYMSKI Ph.D., MBAMATEUSZ NOWAK Ph.D., MBA KAMIL SITARZ Ph.D.

Director of R&D Operations

MONIKA DOBRZANSKA Ph.D.

Portfolio Management Director Director of Biology Director of Research FinancingDirector of Early Discovery & Innovation

37

Supervisory Board assembling industry veterans and financing experts

RAFAL CHWAST

MSc

COLIN GODDARD

Ph.D.

AXEL GLASMACHER

M.D.

TADEUSZ WESOLOWSKI

Ph.D.

PIOTR ROMANOWSKI

M.D. Ph.D., CHAIRMAN

JARL ULF JUNGNELIUS

M.D.

THOMAS TURALSKI

Board Member and CFOat the New Style group.

Past: VP and CFO at Comarch, responsible for financial supervision of group’s subsidiaries, raising capital throughthe stock exchange. CEO of the Association of Stock Exchange Issuers, and member of the Capital Market Council.

CMO at NOXXON Pharma. Past: VP of Clinical Research and Development, Solid Tumors at Celgene. Contributed to Abraxane®, Alimta®, Gemzar®and Revlimid®.

BOD: Isofol Medical, Biovica, Oncopeptides, Monocl.M.D. from Karolinska Institutet.

Independent consultant.Past: Senior VPand Head of the Clinical R&D Hematology Oncology at Celgene.Worked on: Revlimid®, Idhifa® and Vidaza®.

Research and teaching at University Hospital in Bonn.

BOD: 4D Pharma.Medical advisory: Oncopeptides.

Chairman and CEO of BlinkBio. Past: CEO of OSI Pharmaceuticals for 12 years: Tarceva ® development & launch, through to $4 billion acquisition by Astellas.

BOD: Mission Therapeutics and Endocyte.

PhD in cancer chemotherapy and post-doc at the NCI, Bethesda, MD.

Senior advisor & investor in biotech, deep tech and financial services

Past: Partner at PwC, Partner at McKinsey & Company, Board Member at Bank Millennium

MD, PhD (cancer genetics) from Medical Academyof Gdansk, Poland; PhD (cell cycle regulation) from University of Cambridge, UK

Portfolio Manager leading investment team at Revidea Ventures.

Past: 11yrs at Perceptive Advisors responsible e.g. for investment in Myogen, Morphosys and Pharmacyclics and Acerta Pharma, where he was a member of the founding team as well as BOD.

Graduate of Columbia University.

Highly experienced investor and manager.

Past: Founder and CEO of PROSPER, for more than 17 years one of the leading pharmaceutical distributors in Poland.

BOD: Neuca, wholesale distributor of pharmaceuticals.

38

Scientific advisory board assembles expertise across hematology, oncology and precision medicine

GREG NOWAKOWSKI M.D.

Mayo Clinic

RALF-DIETER HOFHEINZ M.D.

Mannheim University Hospital

HEINZ-JOSEF LENZ M.D.

University of Southern California

PRZEMYSLAWJUSZCZYNSKI M.D., Ph.D.

CEZARY SZCZYLIK M.D., Ph.D.

ECZ Otwock, Poland

MICHAEL SAVONA M.D.

Vanderbilt University

ALWIN KRAEMER M.D.

University of Heidelberg Warsaw Institute of Hematology & Transfusion

CLINICAL COLLABORATIONS OR ASSOCIATIONS CLINICAL COLLABORATIONS OR ASSOCIATIONS CLINICAL COLLABORATIONS OR ASSOCIATIONS

39

SEL120 specifically targets STAT5+/CD34+ AML cellsand induces differentiation in leukemic stem cells

STAT5 AND LSC GENE SIGNATURES DISCRIMINATE RESPONDER/NON-RESPONDERS EFFICACY AND LINEAGE COMMITMENT IN CD34+ AML LSC

AML LSC model (CD34+, CD96+, CD123+, CD38-)

SEL120

c o n t r o l

S E L 1 2 0 - 3 4 A 5 u M

S E L 1 2 0 - 3 4 A 1 , 6 7 u M

S E L 1 2 0 - 3 4 A 0 , 5 6 u M

S E L 1 2 0 - 3 4 A 0 , 1 8 u M

S E L 1 2 0 - 3 4 A 0 , 0 6 u M

S E L 1 2 0 - 3 4 A 0 , 0 2 u M

S E L 1 2 0 - 3 4 A 0 , 0 0 7 u M

0 5 1 0 1 5

0

1 1 06

2 1 06

3 1 06

4 1 06

T E X , S E L 1 2 0 - 3 4 A

d a y s

th

eo

re

tic

al

ce

ll n

um

be

r

40

Single agent efficacy of SEL120 in vivo

• Favorable PK enables once daily oral administration or less frequently

• Efficacy in vivo correlates with inhibition of specific CDK8 biomarkers pSTAT1/STAT5

Radiometric ATP activity CDK8 assaySINGLE AGENT EFFICACYIN CD34+ AND PSTAT5+ AML MODELS IN VIVO

SINGLE AGENT EFFICACYIN CD34- AND P STAT5+ AML MODELS IN VIVO

41

In vitro synergy of SEL120 in combination with Venetoclax (ABT-199)

VENETOCLAX SENSITIVE

MCL-1NOT ENOUGH MCL-1 TO SEQUESTER

ALL THE RELEASED BIM

BIM

BAX/BAK

CELL DEATH

BIM

BIM

SEL120 INCREASED BIM

VENETOCLAX RESISTANT

MCL-1MCL-1 SEQUESTERS

ALL THE RELEASED BIM

BIM

BAX/BAK

NO CELL DEATH

MCL-1

BIM

SEL120 BIM

3

MCL-1

BIM

Bax cleaved

Caspase-3 cleaved

Actin

SEL120 potentially addressestreatment resistant disease through indirect MCL-1

downregulation in cancer cells

Compelling potential for SEL120in combination with Venetoclax

at low concentrations

0.004

10.0

3.3

1.1

0.4

0.1

0.04

0.01

0.004 0.01 0.04 0.1 0.4 1.1 3.3 10.0

SEL120 (µM)

Ven

eto

cla

x(µ

M)

42

In vivo synergy of SEL120 in combination with Venetoclax (ABT-199)

AML regression and bone marrow recovery in vivo

COMPLETE REGRESSIONHEMATOLOGIC RECOVERY

(BONE MARROW)

MV-411 cellsLatency Daily, PO, 21 days

SEL120+VenetoclaxLeukemia burden analysis

veh

icle

AB

T-1

99 1

00m

g/k

g

SE

L120 2

0m

g/k

g

SE

L120 4

0m

g/k

g

AB

T+S

EL

120 2

0m

g/k

g

AB

T+S

EL

120 4

0m

g/k

g

0

2 0

4 0

6 0

8 0

1 0 0

%h

CD

45

ce

lls

*

*

* * * *

B o n e M a rro w

veh

icle

AB

T-1

99 1

00m

g/k

g

SE

L120 2

0m

g/k

g

SE

L120 4

0m

g/k

g

AB

T+S

EL

120 2

0m

g/k

g

AB

T+S

EL

120 4

0m

g/k

g

0

1 .01 0 9

2 .01 0 9

3 .01 0 9

4 .01 0 9

Nu

mb

er o

f m

urin

e B

M c

ell

s

*

* *

* *

* * *

* * * ** * *

NSG miceIV

TUMOR GROWTH INHIBITION AND COMPLETE REGRESSIONS

MV-411 cellsLatency Daily, PO, 21 days

SEL120+VenetoclaxLeukemia burden analysis

SC

43

Targeting FLT3 and PIM simultaneously may provide improved efficacyand durability over narrowly targeted agents

SEL24/MEN1703 VS PIM INHIBITOR AZD1208 AND FLT3 INHIBITOR QUIZARTINIB IN AML CELL LINES

SEL24/MEN1703 AZD1208 Quizartinib Cytarabine SEL24/MEN1703 AZD1208 Quizartinib Cytarabine

MV-4-11 (FLT3-ITD positive)

GI50(µM)

GI50(µM)

Dual PIM/FLT3 inhibitor

SEL24/MEN1703

Selective PIM inhibitor

Selective FLT3 inhibitor

Quizartinib

AZD1208(*)

0,

0,4

0,8

1,2

1,61.6

1.2

0.8

0.4

0,

0,175

0,35

0,525

0,7

0,875

0.7

0.525

0.35

0.175

MOLM-16 (FLT3-ITD negative)

44

Potent efficacy of oral SEL24/MEN1703

in models of multiple AML subtypes

FLT3-ITD POSITIVE FLT3-ITD NEGATIVE

MV-4-11 MOLM-16MOLM-13 KG-1

BID – twice a day, QD –once a day

0 5 10 15

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

Efficacy of SEL24/MEN1703 in MOLM-13 model


Me

an

tu

mo

r v

olu

me (

mm

3)

SE

M

Vehicle, QD, po

SEL24/MEN1703, 50 mg/kg QD, po

AZD1208, 30 mg/kg QD, po

Quizartinib, 10 mg/kg QD, po

SEL24/MEN1703, 100 mg/kg QD

100% TGI

45% TGI

24% TGI

0 5 10 15 20 25

0

500

1000

1500

2000

Efficacy of SEL24/MEN1703 in KG-1 model


Me

an

tu

mo

r v

olu

me (

mm

3)

SE

M

Vehicle, QD, po

SEL24/MEN1703, 50 mg/kg QD, po

AZD1208, 30 mg/kg QD, po

Quizartinib, 10 mg/kg QD, po

SEL24/MEN1703, 100 mg/kg QD

4% TGI

56% TGI

55% TGI

0 5 10 15

0

500

1000

1500

2000

2500

3000

3500

4000

Efficacy of SEL24/MEN1703 in MOLM-16 model


Me

an

tu

mo

r v

olu

me (

mm

3)

SE

M

Vehicle, QD, po

SEL24/MEN1703, 75 mg/kg BID, po


SEL24/MEN1703, 75 mg/kg BID, disc.

81% TGI

98% TGI0 5 10 15

0

500

1000

1500

2000

2500

3000

3500

4000

Efficacy of SEL24/MEN1703 in MV4-11 model


Me

an

tu

mo

r v

olu

me (

mm

3)

SE

M

Vehicle, QD, po



SEL24/MEN1703

Disc. 50 mg/kg BID

51% TGI

81% TGI

45

RVU330 - best-in-class dual A2A/A2B antagonist

KEY SUCCESS FACTORSCOMPETITIVE ADVANTAGE

PLANNED INFLECTION POINTS AND MILESTONES

Dual mode of action manifesting in activity in all immune cell types, unlike competitors compounds, providing potentially more pronounced anti-tumor effect

Best-in-class potentialThe only dual A2A/A2B antagonist efficient in high adenosine tumor environment

May be efficacious in patients in which „1st wave” A2A (repositioned PD drugs) do not work

Nomination of preclinical candidate and initiation of IND enabling studies: H1 2020

Initiation of phase I clinical trials: 2021

Ryvu developed most potent, known A2A/A2B antagonist with nanomolar activity in vitro in functional immune

assays outperforming competitors

1

2

Confirmed immunostimulatory mode of action

▪ Induction of antitumor cytokine production by T cells and dendritic cells – stimulation of both innate and adaptive immunity

▪ Macrophages repolarization▪ NK cells mobilization▪ Exceptionally potent, superior to clinical competitors,

blockade of CREB phosphorylation in human whole blood assay – clinical biomarker used by most of competitors (Arcus, Corvus)

46

RVU330 efficiently modulates pCREB(main PD clinical biomarker used by competitors) in in vitro human whole blood assay

46

RVU330 modulates PD biomarkerin CD8+ T-cells

RVU330 modulates PD biomarkerin CD4+ T-cells

Concentration [nM]

0

5 0

1 0 0

% o

f r

ec

ov

er

y

U

T

N E C A

R V U 3 3 0

L A S 1 0 1 0 5 7

C P I - 4 4 4

A B 9 2 8

iT e o s E x . 7

1 0 0 0 01 0 0 01 0 01 01

A Z D 4 6 3 5

Concentration [nM]

0

5 0

1 0 0

% o

f r

ec

ov

er

y

U

T

N E C A

R V U 3 3 0

L A S 1 0 1 0 5 7

C P I - 4 4 4

A B 9 2 8

iT e o s E x . 7

1 0 0 0 01 0 0 01 0 01 01

A Z D 4 6 3 5

0

5 0

1 0 0

% o

f in

hib

it

io

n

U T

N E C A

1 0 0 0 01 0 01 010 . 1 1 0 0 0

0

5 0

1 0 0

% o

f in

hib

it

io

n

U T

N E C A

1 0 0 0 01 0 01 010 . 1 1 0 0 0

AZD4635 CPI-444 AB928 Example 7 RVU330

pCREB WBA CD4+ T cells EC50 [nM] 1186 ±860 7798 ± 1734 182 ± 140 1.1 ± 0.6 1.6 ± 0.9

pCREB WBA CD8+ T cells EC50 [nM] > 10 000 > 10 000 83.7 ± 0.1 2.4 ± 2.3 2.2 ± 1.4

47

RVU330 A2A/B antagonists outperform competitors in in vitro activation of immune cells at high adenosine concentrations

AZD4635 CPI-444 AB928 Example 7 RVU330

TNFa moDCS - EC50 [nM] >10 000 >10 000 699 ± 144 > 3 000 13 ± 5IL-2 CD4+ CELLS - EC50 [nM] >10 000 >10 000 203 ± 97 4 ± 0.1 0.4 ± 0.2

0

5 0

1 0 0

% o

f r

ec

ov

er

y

U T

A D O

1 0 0 0 01 0 010 . 10 . 0 0 1 1 0

RVU330 restores functional activity CD4+ T cells that is suppressed by high adenosine concentration (IL-2 production)

0

5 0

1 0 0

% o

f r

ec

ov

er

y

U

T

N E C A

R V U 3 3 0

L A S 1 0 1 0 5 7

C P I - 4 4 4

A B 9 2 8

iT e o s E x . 7

1 0 0 0 01 0 0 01 0 01 01

A Z D 4 6 3 5

IL-2

Concentration [nM]

0

5 0

1 0 0

% o

f r

ec

ov

er

y

U T

N E C A

1 0 0 0 01 0 0 01 0 01 01

Concentration [nM]

RVU330 reactivates dendritic cells (moDC) suppressed by high adenosine concentration (TNFa production)

TNFa0

5 0

1 0 0

% o

f r

ec

ov

er

y

U

T

N E C A

R V U 3 3 0

L A S 1 0 1 0 5 7

C P I - 4 4 4

A B 9 2 8

iT e o s E x . 7

1 0 0 0 01 0 0 01 0 01 01

A Z D 4 6 3 5

48

Ryvu STING agonist outperforms antitumor efficacy of Aduro agonist and provides immunological memory in mouse CT26 colorectal carcinoma model

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000

ADU-S100, 5.0 mg/kg EODx3, IT

Day of administrationT

um

or

vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000

RVU-24024, 5.0 mg/kg, EODx3, IT


Tu

mo

r vo

lum

e [

mm

3]

0 5 10 15 20 25 30 35 40 45 50 55 60

0

500

1000

1500

2000

2500

3000

Control, EODx3, IT


Tu

mo

r vo

lum

e[m

m3]

CR 7/10CR 3/10

5 mg/kg (100 µg), EODx3, IT 5 mg/kg (100 µg), EODx3, IT

3MICE WITH

TUMOR

REGRESSION

0 10 20 30

0

1000

2000

3000

4000

CTRL, ADU-S100 5 mg/kg

Days post inoculation

Mean

tu

mo

r vo

lum

e (

mm

3)

SE

M Control (naive mice)

ADU-S100, 5 mg/kg, EODx3 IT

0 10 20 30

0

1000

2000

3000

4000

CTRL, RVU 5mg/kg

Days post inoculation

Mean

tu

mo

r vo

lum

e (

mm

3)

SE

M Control (naive mice)

RVU-24024, 5 mg/kg, EODx3 IT

Subcutaneous inoculation

with CT26 mouse colorectal

carcinoma cells

INTRATUMORAL

ADMINISTRATION

OF STING AGONIST

2

1

RE-CHALLENGE

Subcutaneous inoculation

with CT26 mouse colorectal

carcinoma cells

LONG-TERM

IMMUNOLOGICAL

MEMORY

No tumor growth

5

4

CONTROL GROUP REFRENCE ADURO ADU-S100 RYVU STING AGONIST

49

Ryvu is developing next-generation direct STING agonists for immunotherapy of resistant tumors

RYVU STRATEGY

RYVU STRATEGY

SYNERGISTIC POTENTIAL

STATUS LEAD TO CANDIDATE STAGE

Best-in-class small molecule direct, systemic STING agonists active across STING haplotypes

Malignant tumors resistant to checkpoint inhibitor monotherapy;Synergistic potential in combination with immunotherapy (anti-PD1/PDL1, CTLA4), chemotherapy and radiotherapy

AIM: OVERCOMEIMMUNOSUPPRESSION

COLD, RESISTANTTUMORS

HOT, INFLAMED TUMORS

AIM: ACTIVATION OF IMMUNE RESPONSE

STING

AGONISTS

STING agonists mobilize immune system sensitizing resistant tumors to therapy

STING agonists are immune boosters inducing long-term immunological memory

STING agonists stimulate immune system facilitating tumor neoantigen presentation by dendritic cells, activation of CD8+ T cells

and release of proinflammatory cytokines

50

REFERENCE GSK diABZI

0 10 20 30 40

0

500

1000

1500

2000

2500



Tu

mo

r vo

lum

e [

mm

3]

0 10 20 30 40

0

500

1000

1500

2000

2500

RVU-24836, 1.5 mg/kg iv Days 1,4,7


Tu

mo

r vo

lum

e [

mm

3]

1.5 mg/kg, E3Dx3, IV

CR 4/10

CONTROL GROUP

Ryvu STING agonists lead to elimination of established tumors after systemic administration

RYVU STING AGONIST, INTRAVENOUS ADMINISTRATION

0 10 20 30 40

0

500

1000

1500

2000

2500

RVU-24024, 1 mg/kg iv Days 1,4,7


Tu

mo

r vo

lum

e [

mm

3]

0 10 20 30 40

0

500

1000

1500

2000

2500



Tu

mo

r vo

lum

e [

mm

3]

0 10 20 30 40

0

500

1000

1500

2000

2500



Tu

mo

r vo

lum

e [

mm

3]

CR 0/10 CR 4/10

1 mg/kg, E3Dx3, IV 2 mg/kg, E3Dx3, IV 3 mg/kg, E3Dx3, IV

CR 5/10

Ryvu STING agonist leads to dose-dependent tumor regression anc complete remissions (CRs)

in CT26 mouse model after intravenous administration

on par with the most potent disclosed reference STING agonist (GSK) currently in Phase 1 clinical trials

51

Ryvu is developing SMARCA2 inhibitors with first-in-class potential

TOP SUCCESS FACTORS, COMPETITIVE ADVANTAGE

UPCOMING VALUE INFLECTION POINTS

In vivo PoC in relevant mouse models carring mutation in SMARCA4: 2020

First in class potential:Most selective SMARCA2 over SMARCA4 inhibitors known with confirmed synthetic lethal phenotype in vitro

Unique mechanism of action:Allosteric small molecule inhibitors of SMARCA2 ATPase activitySelective PROTACs based on proprietary Ryvu series

Ryvu has the only disclosed program of small molecule allosteric inhibitors of ATPase activity and PROTAC series selectively degradating SMARCA2 showing synthetic lethal phenotype in vitro; competitor series based on bromodomain ligands

1

3

4▪ Powerful Synthetic Lethality Platform consisting of unique

bioinformatic tools and cellular models allowing identyfication and validation of novel synthetic lethal targets in oncology

▪ Confirmed targeted cell death in SMARCA4 mutated cancer cell lines (synthetic lethal phenotype) and strong differentiation factors from known competitors

Strong responder hypothesis – validated panel of cancer cell lines carrying SMARCA4 LOF mutations; - clearly defined patient population

2

Well defined patient population

52

Successful Ryvu spin-out company, NodThera

~6.2%OWNED BY RYVU

Discovery and development of next generation

NLRP3 inflammasome inhibitors

PIONEERING DEVELOPMENT IN THE FIELD OF INFLAMMASOME/NLRP3 BIOLOGY

First Ryvu deal

in the immunology area

NodThera Ltd. was launched

in 2016 by Epidarex Capital,

based on research conducted

at Ryvu since 2012

Ryvu had originally 45% shares

in NodThera

Focused on the treatment

of diseases driven by chronic

inflammation

Productive medicinal chemistry

platform

Addressing inflammation

and fibrosis that drive NASH

$48 M Series A in 2018

$55 M Series B in 2020

On completion of B Series

- 2nd tranche Ryvu will own 4.8%

in NodThera

No

dT

he

ra i

nve

sto

rs

53

What sets Ryvu apart

• Mix of wholly-owned and partnered programs

• Potential first-in-class, clinical stage candidates

• Diverse kinase, synthetic lethality, immuno-oncologyand immunometabolism programs

• Strong early data relative to competitors

• 80 Ph.D.- level scientists

• History of identifying molecules

with differentiated properties

• Plan to generate one new clinical

candidate per year

• Platforms, by design, address key

challenges of current treatments

• Focus on internal development

and partnering

BROAD, DIVERSIFIED PIPELINE IN SMALL MOLECULE ONCOLOGY

• Driven by breakthrough science

• Global partnerships with Menarini,

Galapagos and Merck KGaA

• Research validated

by Leukemia & Lymphoma Society

• Efficient R&D organization

• Secured non-dilutive financing with

follow-on opportunities

HIGH THROUGHPUTDISCOVERY ENGINE

SCIENTIFIC AND ORGANIZATIONAL EXPERTISE

Documents

Targeted therapeutics · 7 Milestones achieved in 2020 and anticipated in the next 12 months CLINICAL SEL24 –SUCCESSFULLY COMPLETED PHASE I IN AML PATIENTS IN MARCH Study results