Targeted therapeuticsat the forefront of oncology

July 2020

DEVELOPMENT STRATEGY PRESENTATION

2

Note on the presentation and forward looking statements

This document does not constitute a public offering in the meaning of the Regulation (EU) 2017/1129 of the European Parliament and of theCouncil, or any other offer or invitation to acquire any Company's securities, nor the incentive to submit bids for the acquisition or subscriptionof the Company's securities.

This document does not constitute information about the Company's securities and the terms and conditions of their acquisition or offering

sufficient grounds to decide whether to purchase or acquire such securities. In particular, the document does not constitute an offer of

securities for sale in the United States, nor may the securities be offered or sold in the United States absent registration under the Securities Act

or in reliance upon an available exemption from the registration requirements of the U.S. Securities Act and in compliance with applicable state

securities laws.

The forward-looking statements contained in this document, such as those relating to the Company's income, results or development, are

based on a number of assumptions, expectations and projections, and are subject to uncertainty and may change as a result of external or

internal factors and should not be treated as binding forecasts. Neither the Company nor the persons acting on its behalf, in particular the

members of the Company's Management Board, the Company's advisers nor any other person, provide any assurance that future expectations

will be fulfilled, and in particular do not guarantee the future results or events of such statements and that the future results of the Company

will not differ materially from the forward-looking statements.

The information in this document is subject to change. Neither the Company nor any other person is obligated to update them.

3

Ryvu at a glance

Wholly owned, first-in-class, selective oral CDK8/19 inhibitor (SEL120) with therapeutic potential in multiple indications and clinical data in 2021

• Applicable across indications: acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), hematological and solid tumors

• Trial in lead indication (AML/MDS) enrolling across 6 sites in USA with first data available in early 2021

Broad early-stage pipeline delivering potential near-term clinical candidates and robust internal drug discovery engine

• Significant pipeline momentum with 2 programs expected to enter the clinic in 2021 (A2A/A2B, STING) and 2 near-term preclinical or late discovery targets (HPK1, SMARCA2)

• Deep discovery capability and track-record in generating clinical candidates; validated by partnerships including Galapagos research collaboration

Developing small molecule therapies which address high value emerging targets and pathways in oncology

• Diverse pipeline with mechanisms of action spanning kinase inhibition, RNA transcription, synthetic lethality (SMARCA2, WRN, MTAPdel cancers) and immuno-oncology (A2A/A2B, STING, HPK1)

• Initial focus of pipeline on hematological malignancies, with near term expansion planned in solid tumors

First-in-class dual PIM/FLT3 kinase inhibitor (SEL24) for Acute Myeloid Leukemia (AML) partnered with Menarini

• Dual-targeting of PIM and FLT3 designed to facilitate broader activity and potentially more durable responses

• Single agent efficacy shown in relapsed/refractory AML patients with acceptable safety profile1

Listed on Warsaw Stock Exchange, market cap of $282m2

• One of the largest drug discovery companies in the region, headquartered in Kraków, Poland

• Significant non-dilutive grant funding (>$25m secured till 2023); supportive shareholder base

1 Dose escalation study in 25 patients in relapsed / refractory FLT3 negative AML with 1 CR and 1 CRi in elderly patients who had exhausted other therapeutic options2 10 July 2020. Exchange rate (NBP): 1 $ =3.9486PLN

4

Broad pipeline addressing emerging targets in oncology

5

Team with strong track record of clinical development and shareholder value creation

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

GREG NOWAKOWSKI, M.D.

ANTHONY TOLCHER, M.D. FRCPC

JOSEPH TABERNERO, M.D. Ph.D.

MICHAEL SAVONA, M.D.

CEZARY SZCZYLIK, M.D. Ph.D.

JORGE CORTES, M.D.

PRZEMYSLAW JUSZCZYNSKI, M.D., Ph.D

PIOTR ROMANOWSKI, M.D. Ph.D., CHAIRMAN

AXEL GLASMACHER, M.D.

COLIN GODDARD, Ph.D.

JARL ULF JUNGNELIUS, M.D.

RAFAL CHWAST, MSc

THOMAS TURALSKI

TADEUSZ WESOLOWSKI, Ph.D

Supervisory Board Scientific Advisory Board and industry collaboration history

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.

Director of Strategic Planning & Portfolio Management

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

6

Differentiated internally discovered small-molecule drug candidates and new programs

SMARCA2

MTAP

WRN

HIT-TO-LEAD

SEL24/

MEN1703

DUAL PIM/FLT3

INHIBITOR

CLINICAL

SEL120

SELECTIVE

CDK8/CDK19

INHIBITOR

CLINICAL NON-GLP TOXICOLOGY

SMALL MOLECULE

SYSTEMIC

STING

AGONIST

SELECTIVE

HPK1

INHIBITOR

LATE LEAD OPTIMIZATION LEAD OPTIMIZATION

DUAL ADENOSINE

A2A/A2B

ANTAGONIST

Targeted therapies

o First-in-class unique MoA in AML: direct cytotoxicity and eradication of leukemic stem cells

o Designed to address critical unmet medical need: potential to improve responses with the expectation for eradication of minimal residual disease, extend a relapse free remission and improve the overall survival

o Expansion of indications in solid tumors: robust preclinical single agent efficacy in multiple solid tumor types

o Opportunities for combination: with SoC such as venetoclax, azacitidine, checkpoint inhibitors

SEL120

o Partnered globally with

o Dual PIM/FLT3 targeting for broader efficacy and durable responses in AML

o Potential for safe combinations with chemotherapy

o Single agent efficacy demonstrated in AML FLT3-wild-type, relapsed patients1

in Phase I study

SEL24

Immuno-oncology Synthetic lethality

o The only disclosed dual, potent A2A/A2B antagonist with the potential of restoring suppressed function in multiple immune cell types in adenosine-rich microenvironment

A2A/A2B

o Small molecule STING agonists for systemic delivery

o Shown to induce tumor regressions with long-term immunological memory in vivo on par with the most potent competitors agonists

o Direct STING binders across multiple human STING haplotypes

STING

o Selective, potent HPK1 inhibitors with single agent anti-tumor efficacy in vivo

o Designed to boost T cells activation and make them resistant to immunosuppression

HPK1

o Proprietary bioinformatic platform to discover novel synthetic lethal targets

o SMARCA2: first-in-class allosteric ATPase inhibitors and selective SMARCA2 PROTAC degraders

o Additional discovery work on MTAP, WRN and multiple other undisclosed targets

Synthetic Lethality

1. Dose escalation study in 25 patients in relapsed / refractory FLT3 negative AML with 1 CR and 1 CRi in elderly patients who had exhausted other therapeutic options

7

Strong momentum from 2019 and 2020'YTD

SEPTEMBER First patient dosed with SEL120

OCTOBER Corporate split between Ryvu Therapeutics and Selvita (CRO) completed, >$100M incremental value created for Ryvu shareholders

AUGUST Strengthened supervisory board and management board with accomplished biotech industry veterans

DECEMBER Selection of A2A/A2B antagonist pre-clinical candidate for non-GLP tox studies

MARCH SEL24 – successfully completed Phase I in acute myeloid leukemia patients

JUNE Ryvu spin-out company NodThera raises $55 M Series B funding

20

19

20

20

SEL24 – FDA approval for the initiation of Phase IIMARCH

SEL120 – orphan drug designation in AML by FDAMARCH

Collaboration with Galapagos in inflammatory disorders announcedAPRIL

JUNE

Data updates from SEL120 and multiple pre-clinical programs (STING, SMARCA, HPK1, A2A/A2B) presented at AACR Conference

Clinical posters at EHA 2020 - SEL24 Phase I data, SEL120 trial in progress

JUNE

8

Executing on our mission

Ryvu has one ultimate mission –discover and develop drugs that will improve the lives of cancer patients and their families

Complete Phase I clinical development of our lead fully-owned asset, SEL120 in AML/MDS

Support Phase II development by Menarini for lead partnered candidate, SEL24/MEN1703 in AML

Complete preclinical programs for A2A/A2B and STING candidates and advance at least one program into the clinical development

Strengthen our position in novel target discovery for synthetic lethality and immuno-oncology and developing high-specificity candidates against these targets

Partner selected early pipeline programs with biotech and pharma companies providing synergistic competences and resources, targeting at least one new deal in 2020

Expand the potential for SEL120 in solid tumors, and launch a new Phase I study in selected indications in parallel to the ongoing hemato-oncology studies

9

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

with broad potential in hematological malignancies and solid tumors

BLOOD CANCERS

DIAMOND-BLACKFAN

ANEMIA

BLOOD DISORDER

SEL120

AML

JAK2 mut

AML/MPN

MDS

ALL, NHL

SOLID TUMORS

BREAST

COLORECTAL

PROSTATE

OTHER

• Direct cytotoxicity (induction of apoptosis)

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

• Preclinical data indicate safeand synergistic combination with standard-of-care chemotherapy and approved targeted therapies

• Opportunity in another orphan indication (Diamond-Blackfan anemia)

Orphan drug designation in AML

in 2020

Therapy Acceleration Program (TAP) grant supportTotal funding - $3.25 M

• Precise, targeted mode of action by transcriptional regulation of cancer-dependent genes

• Preclinical data to support broad potential in multiple solid tumors with unmet medical needs

• Modulation of immune cell activity (NK cells) as additional component of anticancer activity

Emerging therapeutic

opportunities in solid cancers

New treatment options

in hematological disorders

10

Most common, highly aggressive type of acute leukemia in adults with poor outcomes in most patients1

1 Mayo Clinic2 Cancer.net3 Leukemia & Lymphoma society4 Walter, R; Leukemia 20155 Evaluate Pharma

2020$1.2 billion

2025$8.0 billion

AML Market5

46%CAGR

Leukemia61,000 US pts / yr3

AML34%3

Patients aged >80 receive

intensivetherapy5

Only

20%

~20,000 new cases diagnosed and >11,000 deaths in the US in 20182

Occurs in a predominantly elderly, frail patient population;75% of patients diagnosed with AML were aged >60 years4

AML makes up 1% of all cancers and 34% of all adult leukemia cases2,3

Lowest survival among all blood cancers; only 26% patients surviving 5 years after diagnosis

30% AML patients with a ITD mutation in the FLT3 gene have a less favorable prognosis, 70% of patients refractory to current inhibitors targeting FLT3 mut

First therapeutic area of Ryvu focus: acute myeloid leukemia

~$1,300m

~$600m

~$500m

~$400m

~$300m

~$300m

11

Clinical landscape: targeted small molecule therapies for AML

CDK8/CDK19

FLT3

Dual PIM/FLT3

PIM

IDH1 or IDH2

Others

Phase 1/2 Phase 3 Approved

RYVU CLINICAL PROGRAMS DESIGNEDTO FULFILL UNMET NEEDS IN AML

• SEL120 IS THE ONLY CDK8/CDK19 INHIBITOR IN CLINICAL DEVELOPMENT

• MEN1703/SEL24 IS AN UNIQUE, CLINICAL-STAGE DUAL PIM/FLT3 INHIBITOR

OVERCOMING RESISTANCE TO SINGLE-TARGET MUTATION-SPECIFIC INHIBITORS

EFFICACY IN BROADER PATIENT POPULATIONS

REDUCING CHEMOTHERAPY-BASED TREATMENT REGIMENS

FULLY ORAL REGIMEN

12

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

SEL120: potential role of CDK8/CDK19 in AML treatment

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

EFFICACY OF SEL120 - CDK8/CDK19 INHIBITOR - IN AML

13

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

p-STAT5 Ser726

p-STAT1 Ser727

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

• Type I, ATP-competitive mechanism of binding and inhibition of CDK8/19 activity

• Lack of binding to off-targets potentially associated with toxicity of pre-clinical EMD Serono CDK8/19 inhibitors(such as JNK1 or GSK3b)1

• Higher selectivity based on comparison of gene expression effects2

• Composition of matter patents granted in 2017

SEL120 is a potent and selective CDK8/CDK19 inhibitor

Low nM activity on CDK8/CDK19

and excellent kinase selectivity (broad kinome)

RE

LA

TIV

E I

NT

EN

SIT

Y

(WE

ST

ER

N B

LO

T,

PR

OT

EIN

QU

AN

TIF

ICA

TIO

N)

RESPONDERS NON-RESPONDERS

RESPONDERS NON-RESPONDERS

pSTAT1/pSTAT5 levels discriminate responder/ non-responder

1Chen et al. 2019 2Rzymski et al. 2017

14

SEL120 induces complete regression and bone marrow recovery in AML

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 / SEL120

Dose: 45mg/kgLeukemia 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

DAYSDAYS

CONTROL SEL120 CONTROL SEL120

SP

LE

EN

WE

IGH

T [

mg

]

%m

CD

45+

%h

CD

45+

ME

AN

BO

DY

WE

IGH

T C

HA

NG

E

[%]

±S

EM

In CD34+ AML patient-derived xenografts

15

SEL120 strongly synergizes with Venetoclax

3

MCL-1

BIM

Bax cleaved

Caspase-3 cleaved

Actin

COMPLETE REGRESSION HEMATOLOGIC RECOVERY(BONE MARROW)

MV-4-11 cellsDaily, PO, 21 days

SEL120+Venetoclax

Leukemia burden

analysis

NSG miceIV

Compelling potential for SEL120 in combination with Venetoclax

SEL120 potentially addresses treatment resistant disease through

safe, indirect MCL-1 downregulation in cancer cells

Veh

icle

, Q

D, p

o

Ven

eto

cla

x, 100 m

g/k

g Q

D, p

o

SE

L120, 40 m

g/k

g Q

D, p

o

Ven

eto

cla

x, 100 m

g/k

g Q

D, p

o +

SE

L120, 40 m

g/k

g Q

D, p

o

0

1 .01 0 9

2 .01 0 9

3 .01 0 9

4 .01 0 9

M u rin e c e lls in b o n e m a rro w

No

of

mu

rin

e B

M c

ell

s

* *

* * * *

*

* * *

*

Veh

icle

, Q

D, p

o

Ven

eto

cla

x, 100 m

g/k

g Q

D, p

o

SE

L120, 40 m

g/k

g Q

D, p

o

Ven

eto

cla

x, 100 m

g/k

g Q

D, p

o +

SE

L120, 40 m

g/k

g Q

D, p

o

0

2 0

4 0

6 0

8 0

1 0 0

H u m a n c e lls in b o n e m a rro w

%h

CD

45

ce

lls * *

* *

* * * *

* * * *

* * * *

16

SEL120: Phase Ib study – first patient dosed in September 2019Phase 1b Study of SEL120 in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome

H1 2021

PROJECT MILESTONES

H2 2021

INITIAL RESULTS FROM PHASE Ib

FINAL RESULTS FROM PHASE Ib

3 SITES EXPANSION IN EUROPE IN 2020/2021 • 2 SITES IN POLAND – planned in Q4 2020

• 1 SITE IN ANOTHER EU COUNTRY - planned

6 ACTIVE SITES IN USA IN 2020

STUDY POPULATION:• Patients with relapsed

/refractory AML or high risk MDS

• No upfront patient stratification

STATUS AND PLANS

H1 2022 PHASE II IN AML/MDS

2022+ INTERIM RESULTS FROM PHASE II

1

PRIMARY OBJECTIVE:• To assess safety and tolerability

• To determine the recommended dose2

SECONDARY OBJECTIVE:• To evaluate pharmacokinetics

• To evaluate the preliminary anti-

leukemic activity

3

EXPLORATORY OBJECTIVE:• To evaluate

pharmacodynamics4

17

SEL120 study design in AML/MDS and further plans

COHORT 1

COHORT 2

COHORT 3

REMAINING COHORTS

RP2DMTD

EXPANSION FROM THE SINGLE PATIENT

COHORT TO A 3+3 DESIGNDLTs evaluated at completion of cycle 1 in each cohort

SINGLE ORAL DOSE, EOD

7 DOSES/CYCLE

3 WEEKS CYCLE

SAFETY EXPANSION

19-25 PATIENTS

PART 2: SAFETY EXPANSION

6-20

PATIENTS

PART 1: ESTABLISHING RECOMMENDED PHASE 2 DOSE (RP2D)

SAFETY,

EFFICACY,

PK, PD

EVALUATION

AML SINGLE AGENT

AML COMBINATION

MDS SINGLE AGENT

MDS COMBINATION

PHASE II

H2 2019-2020 Q1-Q3 2021 2022 START

18

Positioning of SEL120 in AML treatment regimen and strategic expansion

FIRST LINE

RELAPSED/REFRACTORY

SEL120

AML TREATMENT PROTOCOL

UNFIT PATIENTS

LOW INTENSITYCHEMOTHERAPY

TARGETED THERAPY

TARGETED THERAPY

OR

TARGETEDTHERAPY(e.g. Venetoclax)

+SEL120

LOW INTENSITYCHEMOTHERAPY(e.g. Azacitidine)

+

SEL120

NO

RELEVANT

MUTATIONS

MUTATION -

DRIVEN

LOW INTENSITYCHEMOTHERAPY

LOW INTENSITY CHEMOTHERAPY

STAGE 1

RYVU STRATEGY

• Monotherapy

• Patients unfit for intensive chemotherapy

• Relapsed/refractory AML, high risk MDS

RYVU STRATEGY FOR DEVELOPMENT

OF SEL120 IN AML/MDS

STAGE 3

STAGE 2

• Monotherapy and combination with SoC

• Combo with Venetoclax or chemotherapies

• Patients unfit for intensive chemotherapy

• Relapsed/refractory to frontline or follow up

treatment AML, high risk MDS

• Combination (dublet or triplet) with SoC

• Regimen e.g. with Venetoclax+Azacitidine

• Patients unfit for intensive chemotherapy

• First line, treatment naïve, AML/MDS

POSITIONING IN FIRST LINE TREATMENT

POSITIONING IN SECOND/THIRD LINE

POSITIONING IN THIRD+ LINE TREATMENT

19

SEL120 beyond blood cancers: potential role of CDK8/CDK19 in solid tumors

CDK8/CDK19 inhibitors have therapeutic potential in multiple blood and solid tumors

• Ryvu confirmed in vitro or in vivo potential in breast, colorectal and prostate cancer

CDK8

JAK/STATSTAT1

STAT3

STAT5

TGFβ/BMP->SMAD

WNT/β-catenin

Mediator

complex

Notch

signaling

Gene

transcription

JAK2

mutation

AML/MPN

NK cells and

macrophage

response against

multiple tumors

SOX4

TNF/NFKBER-

dependent

genes Breast

cancer

Prostate,

colorectal,

breast cancer

Pancreatic

colorectal

cancer

T-ALL

AML

Unique MoA differentiates CDK8/CDK19

from other CDK family members

• Do not interfere with cell cycle progression (like CDK1, CDK2, CDK4/6)

• Unique across family mediator of transcriptional reprogramming (induction of silent genes, not physiological transcription) preventing metastasis and drug-resistance

• Different stratification of responders and biomarkers of response

• First generation of CDK8/19 inhibitors unsuccessful due to toxic off-target effects and suboptimal PK/PD profile

CDK8/19 inhibitors designed to provide targeted and safer treatment options

• Selective targeting cancer cells while sparing healthy ones

(e.g. CDK4/6, CDK9 affect both normal and cancer cells – possible cytopenias, no bone marrow recovery)

• Selective regulation of transcription in a cancer gene specific context

(e.g. CDK7/9 involved in general transcriptional programs of normal genes)

Chart inspired by Pharmaceuticals 2019, 12,92 + Ryvu data

20

SEL120: confirmed anti-tumor efficacy in solid tumor models of breast and colorectal cancers

TNBC BREAST CANCER MODEL COLORECTAL CANCER MODEL

0 5 1 0 1 5 2 0 2 5

0

5 0

1 0 0

1 5 0

2 0 0

2 5 0

3 0 0

3 5 0

4 0 0

4 5 0

5 0 0

D a y o f a d m in is tra t io n

Me

an

tu

mo

r v

olu

me

(m

m3

)

SE

M

V e h ic le , Q D , p o

C is p la tin , 8 m g /k g E 2 W , ip

S E L 1 2 0 , 6 0 m g /k g Q D , p o

D is c . S E L 1 2 0 D is c . S E L 1 2 0

0 5 1 0 1 5 2 0

0

2 0 0

4 0 0

6 0 0

8 0 0

1 0 0 0

1 2 0 0

1 4 0 0

1 6 0 0

1 8 0 0

2 0 0 0

V e h ic le , B ID , p o

S E L 1 2 0 , 3 0 m g /k g B ID , p o

D a y o f a d m in is tra t io n

Me

an

tu

mo

r v

olu

me

(m

m3

)

SE

M

D is c . S E L 1 2 0

21

SEL120: expansion plan in multiple solid tumors and other heme malignancies– preliminary planPhase I start: 2021, preliminary results: 2022

PART 1: ESTABLISHING RECOMMENDED DOSE PART 2: SIMON 2-STAGE DESIGNSCREENING

A 3+3 STUDY DESIGN

DLTs evaluated at completion of cycle 1 in each cohort

18 PATIENTS

COHORT 1

COHORT 2

COHORT 3

REMAINING COHORTS

RP2Ddetermined

SINGLE ORAL DOSE EOD

7 DOSES/CYCLE

3 WEEK CYCLE

EVALUATION

R/R TNBC

UP TO 3 OTHER ST

TYPES

+ 10 PATIENTS

+ 10 PATIENTS

PFS at 9 months

Overall survival

follow-up: 2 years

Go no go decision to enrol next 10 patients

based on RECIST ORR after cycle 3

ADULTS

R/R ALL ST COMERS

+NHL

NO MORE THAN 3

PRIOR THERAPIES

FOR ENTRY DISEASE

SAFETY,

EFFICACY,

PK, PD

STAGE 1

10 PATIENTS UP TO 20

PATIENTS

STAGE 2

H2 2020 2021 2022

22

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

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

Study title: A Phase I/II Study of SEL24 in Patients With Acute Myeloid Leukemia

SITESAIM OF THE STUDY:

• determine the recommended Phase II dose

(RP2D), the PK profile and the single agent

activity in R/R or newly diagnosed AML patients

STATUS:

• Study results published at EHA 2020 conference

• Ryvu has received 1.9 M milestone payment for

successful completion of Phase I studies

PLANS:

• Cohort expansion at the recommended Phase II

dose (RP2D) to confirm the safety profile

and assess drug efficacy starting at multiple

clinical sites in the U.S.

• Expansion in Europe in 2020

ONGOING CLINICAL TRIALS

23

Acceptable safety data with complete responses observed

Initial Phase I data for SEL24/MEN1703 demonstrates compelling single agent efficacy

ESTABLISHING RECOMMENDED PHASE II DOSE RESULTS

Establishment of recommended dose and

evaluation of safety profile

• SEL24 has acceptable safety profile up to 125mg

• RD defined at 125mg

Objective response / single agent efficacy in FLT3

wild-type patients

• Complete remission at 75mg in a 81 y.o. patient, with

DNMT3A/IDH2 mutant AML progressed on enasidenib

• Complete response with incomplete hematological

recovery at 125mg in a 75 y.o. patient with ASXL1/EZH2

mutant AML relapsed after chemotherapy and decitabine

• ABSTRACT PRESENTED AT EHA 2020

• EXPANSION OF SEL24 IN US AND EU

• PH II INTERIM DATA

• PH II COMPLETE

EXPANSION FROM THE SINGLE PATIENT COHORT TO A 3+3 DESIGN

DLTs evaluated at completion of cycle 1 in each cohort

Patients with AML

As of cut-off date (11-Feb-20), n=25 patients were treated, 22

patients were evaluable for DLTs

-Median age was 68 years (range: 25-84)

- 2 patients with newly diagnosed AML, 11 patients

with primary refractory AML, 12 patients with relapsed AML

JUNE

H2 2020

2021

2022

MILESTONES

Data disclosures subject to Menarini/Ryvu steering committee decisions

INDIVIDUAL TREATMENT DURATION

0 1 2 3 4 5 6 7 8

005–025003–008002–007001–006004–024004–023004–022003–021004–020004–019003–018004–017003–016002–015005–014004–013003–005004–012004–011002–004003–010003–009003–003003–002001–001

(Number of Cycles Completed)

CRi—CR with incomplete hematologic recovery

CR—Complete Remission

25mg

50mg

75mg

100mg

125mg

150mg

24

Based on internal data generated at Ryvu the disclosed competitors' antagonists are unable to overcome immunosuppression at high adenosine concentrations (typical to TME)

Selective A2A antagonists do not affect antigen presenting cells to prime immune system

First generation intratumoral STING agonists provided limited signs of clinical efficacy

Limited possibilities to reach multiple metastasis with IT agonists

Refractory STING alleles to first generation STING agonists do not cover whole patient population

o Unique dual potential to modulate both innate and adaptive anti-cancer immunity

o Synergistic enhancement of Tand DC cells function simultaneously making T cells resistant to immunosuppression

o Targets SWI/SNFchromatin remodellingcomplex

o Implicated in multiplecancers, including NSCLC

o Synthetic lethality arises when simultaneous mutations of gene pairs lead to cell death, whilst individual mutations does not cause a lethal effects

o Dual A2A/A2B antagonists actingon multiple subtypes of immune cells offering more pronounced anti-tumorresponse

o In vitro efficacy in immune cells superior to known A2A/B antagonists

o Direct, small molecule STING agonists

o Active in multiple human STING haplotypes

o Anti-tumor efficacy after systemic administration in preclinical mouse models on par or superior to competitors

o Hematopoietic progenitor kinase 1 (HPK1, MAP4K1)

o Important in regulation of the signalling cascade triggered by TCR activationin lymphocytes T

o Potentially multiple tumor types

o Solid tumors with SMARCA4 loss of function mutations

o MTAP deletion cancers

o WRN helicase in MSI high and other tumors

o Multiple other undisclosed targets

o Initiate IND enabling studies (2020)

o File IND (2021)

o Initiate IND enabling studies (2020)

o File IND (2021)

o Non-GLP toxicology (H1 2021) o Lead selection (2021) o Lead selection (>2021)

Differentiated internally discovered small-molecule drug candidates and new programsC

urr

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BEST IN CLASS FIRST IN CLASS

STINGA2A/A2B ANTAGONIST HPK1 OTHER S-L TARGETSSMARCA2

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25

Ryvu develops dual A2A/A2B adenosine receptor antagonists

KEY DIIFERENTIATION 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

2H 2021

Q3 2020

MILESTONES FOR RVU330

COMPLETION OF NON-GLP TOX STUDIES

2020

INITIATION OF IND ENABLING STUDIES

IND FILING

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

2022+ PHASE I CLINICAL TRIALS

26

RVU330 IS EFFICACIOUS AS MONOTHERAPHY IN MCA205 SYNGENEIC MODEL

injection of MCA205 cells RVU330 administration(14 days)

Euthanasia StainingNodulecounting

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RVU330, 15mg/kg BID

Control

LUNG LOBES AFTER STAINING WITH VISIBLE WHITE MCA205 NODULES

NODULE COUNTS IN LUNGS TOTAL AREA OF NODULES IMAGE ANALYSIS

LUNG WEIGHTS

27

KEY DIFFERENTIATIONCOMPETITIVE ADVANTAGESTATUS

STAGE: SELECTION OF PRELINICAL CANDIDATESTRONG ANTITUMOR EFFICACY AFTER SYSTEMIC ADMINISTRATION

OPTIMIZATION AND PROFILING OF COMPOUNDS -POTENTIAL CANDIDATES FOR IND STUDIES

2020

Q1-Q3 2020

MILESTONES FOR STING AGONISTS

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

2H 2020 INITIATION OF IND 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 conjugation (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

2H 2021 IND FILING

2022+ PHASE 1 CLINICAL TRIALS

28

28

RVU312-4787 CLEARS TUMORS IN EMT6 MOUSE TUMOR MODEL

RVU312-4787 clears tumors in EMT6 mouse model• Intravenous systemic administration

of Ryvu STING agonist RVU312-4787 leads to high antitumor efficacy in EMT6 mouse triple-negative breast cancer model

• Dose of 3mg/kg administered every 5th

day resulted in complete tumor regression in 10 out of 10 treated mice

EFFICACY IN EMT6 MOUSE BREAST CANCER MODEL

RVU312-4787 provides dose-dependent antitumor efficacy in vivo in EMT6 tumor model (interim results – day 26)

Dose-dependent antitumor efficacy• Administration of RVU312-4787 leads

to a dose-dependent antitumor response

CONTROL GROUP

CR 6/10 CR 10/10CR 0/10

3 mg/kg E5Dx3

3 mg/kg E7Dx3

CR 9/10

EMT6 MOUSE BREAST CANCER MODEL – INTRAVENOUS ADMINISTRATION – day 26 of ongoing study

2 mg/kg E5Dx31 mg/kg E5Dx3

RVU312-4787

RVU312-4787 Complete remissions

at d26

Mice alive at d26

EMT6CONTROL

- 0/10

EMT63 mg/kg E5D

10/10 10/10

EMT62 mg/kg E5D

6/10 6/10

EMT61 mg/kg E5D

0/10 0/10

EMT63 mg/kg E7D

9/10 10/10

29

Ryvu has selective, potent HPK1 inhibitors with anti-tumor efficacy in mice

▪ Small molecule, selective, orally bioavailable inhibitors of HPK1 kinase activityAPPROACH

CURRENT DIFFERENTIAL

FACTORS

▪ High selectivity against kinases from TCR pathway▪ Immunostimulatory activity in immunosuppresed,

resistant hPBMC and T cells across species

LEAD OPTIMIZATIONSTATUS

RYVU APPROACH

2022+

2H 2020

MILESTONES FOR HPK1 INHIBITOR

OPTIMIZED LEAD

2022

NON-GLP TOXICOLOGY

IND FILING

INITIATION OF IND-ENABLING STUDIES

1H 2021

*currently Treadwell Therapeutics, in phase I clinical trials

RVU-918 RVU-293 UHN TAKEDA/

ARIAD GENENTECH INCYTE BAYER

hHPK1IC50 [nM] 1.0 1.4 2.7 0.55 4.5 33 2.9

Ki [nM] 0.1 0.3 0.7 0.1 1.6 20.7 0.4

UHN REFERENCE* RVU-293CONTROLS

EFFICACY IN CT26 (MOUSE MODEL OF COLON CANCER)

RYVU SMALL MOLECULE HPK1 INHIBITORS SHOW EFFICACY IN MOUSE

SYNGENEIC MODEL COMPARABLE TO CLINICAL REFERENCE COMPOUND

CO

MB

INA

TIO

N W

ITH

A

NT

I-m

PD

-1

TGI = 24.4%

+anti-mPD1 5 mg/kgD1, D4, D8, D11

TGI = 60.9%

75 mg/kg BID, 21 days+anti-mPD1 5 mg/kg

TGI = 69.8%

100 mg/kg BID, 21 days+anti-mPD1 5 mg/kg

30

Ryvu established proprietary SYNTHETIC LETHALITY PLATFORM

OMICS DATA FOR CELLS AND PATIENTSHIGH CONTENT GENE INTERROGATION

DATA MINING FILTERING AND INTEGRATION

ISOGENIC PAIRSCELL LINES/PDC PANEL

EXPERIMENTAL VALIDATIONDRUG SCREENING

CORRELATION STUDIES USING

RYVU PROPRIETARY BIOINFORMATIC TOOL: MULTIDEP AND SURV-LRT

NETWORK ANALYSISCANCER DEPENDENCY MAP

FIND CONTEX-SPECIFIC NOVEL

DRUG TARGETSIDENTIFY NOVEL SYNTHETIC

LETHAL TARGETS21 NEW SYNTHETIC LETHAL

TARGETS IDENFIED 3

Ryvu has a powerful engine to identify and validate novel synthetic lethal targets in oncology

SYNTHETIC LETHAL TARGETS –

DISCOVERY STAGE

• First in class WRN inhibitors selectively targeting tumors with microsatellite instabililty (MSI)

• 10-30% of colorectal, endometrial, gastric and ovarian tumors with microsatellite instability

✓ SMARCA2 INHIBITORS: HIT-TO-LEAD

✓ WRN INHIBITORS: HIT ID

✓ TARGETING MTAP DELETED

CANCERS: HIT ID

31

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

HIT TO LEADSTATUS

RVU311-5363

REFERENCE

DEGRADATIONRemaining SMARCA2 after 24h 10% 2%

Remaining SMARCA4 after 24h 46% 9%

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

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

MILESTONES FOR SMARCA2 INHIBITORS/DEGRADERS

SMARCA4

SMARCA2

GAPDH

-2.0 -1.5 -1.0 -0.5 0.00

50

100

SLV-25767-01

log (concentration [M])

%D

MS

O

HT1080 WT

HT1080 KO

Potency

-1.0 -0.5 0.0 0.5 1.00

50

100

SLV-26447-01

log (concentration [M])

%D

MS

O

HT1080 KO

HT1080 WT

Efficacy

Potency

Ryvu SMARCA2 inhibitors are synthetically lethal

in SMARCA4 mutated cell line in contrast to reference

2021 LEAD OPTIMIZATION

2022+ PRECLINICAL DEVELOPMENT

32

Program/target name Indication Discovery and preclinical Phase I Phase II

Partners /Collaborators

SEL24 / MEN1703PIM / FLT3

AML✓ Ph. I data✓ Ph. II initiation

• Ph. II interim data

• Ph. II complete

SEL120CDK8

AML / MDS

• Ph. I dose escalation

• Initial Ph. Ib data• Final Ph. Ib data

• Ph. II initiation• Interim data

Solid tumors• Ph. I

preparations• Ph. I top line

results• Ph. II initiation• Interim data

A2A/A2B Solid tumors • IND enabling

studies• IND filing

• Ph. I dose escalation

STING Solid tumors • IND enabling

studies • IND filing• Ph. I dose

escalation

HPK1 Solid tumors • Lead optimization • Non-GLP tox• IND enabling

studies

SMARCA2 Solid tumors • In vivo PoC • Lead optimization• IND enabling

studies

WRN Solid tumors • Hit ID • Hit-to-lead• Lead optimization• IND

MTAP Solid tumors • Hit ID • Hit-to-lead• Lead optimization• IND

Ryvu drives value creation from its multiple data readouts

Broad pipeline addressing emerging targets in oncology

2020 2021

Anticipated Milestones

2 Clinical stage assets

1 Human PoC

5+ Early pipeline programs

3-4 Clinical stage assets

2 Human PoCs

7+ Early pipeline programs

2020 2021

4+ Clinical stage assets

3+ Human PoCs

10+ Early pipeline programs

2022+

2022+

33

Lead asset phase

o Phase I o Phase I o Phase I / II o Pre-clinical o Phase II o Phase Ia / Ib o Phase Ib

Portfolio focus o Prostate Cancer

o Breast Cancer

o Lung cancer

o Solid tumors o Solid tumors o Solid tumors o AML

o Solid tumors

o Hematologicalmalignancies

o AML

o MDS

o Solid tumors

Key portfolio o Protein degraders

o Synthetic lethality

o SMARCA2 degraders

o AR/ER receptors

o Kinase inhibitors

o EGFR

o HER2

o A2A/A2Bantagonist

o Anti-TIGIT Ab

o CD73 Inhibitor

o Anti-PD-1 Ab

o Synthetic lethality

o DNA damage

o ATR, POLQ, CCNE1 inhibitors

o Transcription factor activators

o CDK7, CDK12/13 Kinase inhibitors

o RARα

o Kinase inhibitors

o Transcription factor inhibitors

o Kinase inhibitors

o GPCR antagonist

o Degraders

o Immune activators

Clinical stage candidates 2 1 3 0 3 3 2

Candidates with human POC

0 – 1 0 2 - 1

SMALL MOLECULE ONCOLOGY SMALL MOLECULE AML

Combines two clinical stage, first-in-class candidates in oncology with a proven small molecule discovery engine capable of delivering at least 1 IND per year

Ryvu compares favorably to other early stage small molecule oncology companies

Source: Company website and Factset as of 06/08/20

34

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 July 10, 2020*

First day of SLV

listing on WSE

SLV on the day of the split

Reference value

$214M

$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)

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

* exchange rate (NBP): 1 $ = 3.9486 PLN

35

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

36

$ million 2019 1Q 2019 1Q 2020

Revenues 8.9 2.3 3.5

Partnering 1.0 0.3 2.0

Grants 7.8 2.0 1.5

Others 0.1 0.0 0.0

Operational costs 20.7 4.9 4.7

EBIT -11.8 -2.6 -1.3

EBITDA -9.7 -2.1 -0.6

Net result from continued activities -11.5 -2.5 -1.1

> $19MCash positionDecember 2019

Cash positionJune 2020 ~$12M

*Exchange rates: average exchange rate for a given period

Ryvu Therapeutics – summary of financial results under IFRS

37

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

2017 April 2018 August 2018 April 2020 June 2020

Ph1 Dose EscalationObtaining permits, first laboratories launched

Completion of major construction works, permits’

granting procedures in progress

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 $180M for Ryvu shareholders

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

38

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

• Expected negative impact on enrollment – 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 1 117 deaths for 38 million 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

39

Ryvu investment highlights and near term milestones

1-2 new programs expected

to enter the clinic (2021)

SEL24/MEN1703

Phase 1 PoC data (2020)

SEL120

Phase 1 interim data (H1 2021)

Partnering deals

in the early pipeline

Additional near-term PC/

late discovery targets

✓

✓

NE

AR

TE

RM

MIL

ES

TO

NE

S:

Developing small molecule therapies which address high value emerging targets and pathways in oncology

Diverse pipeline targeting kinases, synthetic lethality and immuno-oncology

First-in-class selective CDK8 inhibitor (SEL120) with potential across multiple indications

Validation from strategic collaborations including partnership with Menarini on SEL24/MEN1703

Extensive early stage pipeline delivering near term clinical candidates

Robust internal drug discovery engine and partnership options for early stage candidates

Limited cash burn thanks to non-dilutive grants and cost-efficient discovery platform, significant resources located in Poland

40

Executing on our mission

Ryvu has one ultimate mission –discover and develop drugs that will improve the lives of cancer patients and their families

Complete Phase I clinical development of our lead fully-owned asset, SEL120 in AML/MDS

Support Phase II development by Menarini for lead partnered candidate, SEL24/MEN1703 in AML

Strengthen our position in novel target discovery for synthetic lethality and immuno-oncology and developing high-specificity candidates against these targets

Partner selected early pipeline programs with biotech and pharma companies providing synergistic competences and resources, at least one new deal in 2020

Expand the potential for SEL120 in solid tumors, and launch a new Phase I study in selected indications in parallel to the ongoing hemato-oncology studies

Complete preclinical programs for A2A/A2B and STING candidates and advance at least one program into the dinical development

41

Back-up slides

42

Clear progression from inception

Founded in 2007 by entrepreneurial

management

First service contracts with pharma clients

AcquiredBioCentrumbiology CRO

First pipeline project in licensing

(SEL73 in CNS)

First partnering deal with Orion

Pharma in Alzheimer’s

Listed onNewConnect

market in Warsaw

First deals in oncology withMerck and H3 Biomedicine

IPO on the main market of

the Warsaw Stock Exchange

Bioinformatics division Ardigen

spun out with 12 FTEs

Inflammasomeassets spun-out to

NodThera

First drug in the clinic (SEL24 in AML; partnered with Menarini)

Secondary Public Offering on WSE

Services business exceeds €15 million

revenue with organic growth

Split Oncology/ CRO to form Ryvu

Oncology-focused BiotechDeep pipeline built on wholly-

owned discovery engine

Services provider Fee-for-service discovery engine and CRO

Hybrid research & development organizationClinical research services and pipeline for partnership

SEL24 toplinedata

demonstrates efficacy in humans

Discoverycollaboration

with Galapagos

SEL120 initiates Ph I

Spin-outNodthera

raises $55m

2007 2015 2016 201920182017 2020

Partnership with Leukemia &

Lymphoma Society (SEL120)

TOTAL $55M RAISED AND COMBINED SELVITA / RYVU MARKET CAP OF $436M*

* As of June 12, 2020; exchange rate (NBP): 1 $ = 3.9299 PLN

43

New research collaboration between Ryvu and Galapagos

announced 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

44

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 s

ha

reh

old

ers

45

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

46

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

47

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 SEL24/MEN1703 AZD1208 Quizartinib

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)

Dual PIM/FLT3

inhibitorPIM

inhibitor

FLT3

inhibitor

Dual PIM/FLT3

inhibitorPIM

inhibitor

FLT3

inhibitor

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

Day of administration

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

Day of administration

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

0 10 20 30 40

0

500

1000

1500

2000

2500

RVU312-04787, 3 mg/kg iv, E7Dx3

Days post randomization

Tu

mo

r vo

lum

e [

mm

3]

Contr

ol nai

ve m

ice

RVU

312-

0478

7, 0

.5 m

g/kg it

, EODx5

RVU

312-

0478

7, 5

mg/k

g it

, EODx3

0

1000

2000

3000

Re-challenge - Day 21

Tu

mo

r vo

lum

e [

mm

3]

Contr

ol nai

ve m

ice

RVU

312-

0478

7, 3

mg/k

g iv, E

5Dx3

RVU

312-

0478

7, 3

mg/k

g iv, E

7Dx3

0

500

1000

1500

2000

Re-challenge - day 21

Tu

mo

r vo

lum

e [

mm

3]

0 10 20 30 40

0

500

1000

1500

2000

2500

RVU312-04787, 3 mg/kg iv, E5Dx3

Days post randomization

Tu

mo

r vo

lum

e [

mm

3]

Ryvu STING agonists promote long-term immunological memory

3 mg/kg E5Dx3, IV

Ryvu STING agonists promote long-term immunological memory• Antitumoral action of Ryvu

compounds leads to long-term immunological memory as shown by lack or significant delay in tumor growth after repeated inoculation of CT26 cancer cells in previously cured animals.

IMMUNOLOGICAL MEMORY –RESISTANCE TO RE-CHALLENGE

Vaccine effect is observed regardless of administration route• No tumor growth or significant

tumor growth delay was observed after efficacy study with RVU312-4787 intravenously or intratumorally.

EFFICACY – RVU312-4787

RE-CHALLENGE AFTER EFFICACY WITH INTRAVENOUS ADMINISTRATION

Re-challenge – day 21

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

0

500

1000

1500

2000

2500

3000

RVU312-04787, 0.5 mg/kg it, EODx5

Day of administration

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

RVU312-04787, 5 mg/kg it, EODx3

Day of administrationT

um

or

vo

lum

e [

mm

3]

RE-CHALLENGE AFTER EFFICACY WITH INTRATUMORAL ADMINISTRATION

3 mg/kg E7Dx3, IV

Re-challenge – day 21EFFICACY – RVU312-4787

0.5 mg/kg EODx5, IT 5 mg/kg EODx3, IT

CR 6/10 CR 4/10

CR 4/10 CR 7/10

50

Majority of competitive A2A inhibitors lose activity in high adenosine concentrationRyvu advantage: activity in high, TME-like relevant adenosine concentrations

ADENOSINE

AMP

ATP

COMPETITIVE A2A INHIBITORS EFFECTIVE

IN LOW ADENOSINE CONCENTRATION

IMMUNOSUPPRESSION

Th1 and Tc ACTIVATION

Treg EXPANSION

1

2

A2A ANTAGONISTSA2A/A2B ANTAGONISTS

ADENOSINE BUILDS UP AFTER TREATMENTPRIMARY TREATMENT

A2A ANTAGONISTSA2A/A2B ANTAGONISTS

ONLY RYVU AND iTEOS PRESERVE ACTIVITY

IN HIGH ADENOSINE CONCENTRATION1 2

51

Selective A2A inhibitors activate only a fraction of immune cellsRyvu advantage: dual A2A/A2B antagonists activate both innate and adaptive immunity

ADENOSINE

AMP

ATP

SELECTIVE A2A ANTAGONISTS DO NOT ACTIVATE ANTIGEN-PRESENTING CELLS

IMMUNOSUPPRESSIO

N

ACTIVATION OF ANTIGEN-

PRESENTING CELLS:

DENDRITIC CELLS

MACROPHAGES AND CAFs

1

2

A2A ANTAGONISTSA2A/A2B ANTAGONISTS

TREATMENT

NO ACTIVITYA2B ANTAGONISTS

ADENOSINE BUILDS UP AFTER TREATMENT

ONLY RYVU PRESERVES ACTIVITY

IN HIGH ADENOSINE CONCENTRATION21

NO ACTIVITY

STATUS UNKNOWN

A2A/A2B ANTAGONISTS

A2B ANTAGONISTS

52

RVU330 A2A/A2B efficiently modulates pCREB (main PD clinical biomarker used by competitors) in in vitro human whole blood assay

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] 1 186 ±860 7 798 ± 1 734 182 ± 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

53

RVU330 A2A/A2B 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 ± 5

IL-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

54

Pawel PrzewiezlikowskiChief Executive Officer

ir@ryvu.com

Ryvu Therapeutics S.A.www.ryvu.com

ryvu@ryvu.com

Contact data