Ryvu Therapeutics Sa · GPW:RVU
Ryvu Therapeutics Sa — Investor Presentation (July 2020)
54 slides from Ryvu Therapeutics Sa's investor presentation, July 2020
Slide 1: Targeted therapeutics at the forefront of oncology
Targeted therapeutics at the forefront of oncology DEVELOPMENT STRATEGY PRESENTATION July 2020
Slide 2: Note on the presentation and forward looking statements
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 the Council, or any other offer or invitation to acquire any Company's securities, nor the incentive to submit
Slide 3: Ryvu at a glance
Ryvu at a glance 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,
Slide 4: Broad pipeline addressing emerging targets in oncology
Broad pipeline addressing emerging targets in oncology 4
Slide 5: Team with strong track record of clinical development and shareholder value creation
Team with strong track record of clinical development and shareholder value creation PAWEL PRZEWIEZLIKOWSKI, MSc, MBA SETAREH SHAMSILI M.D., Ph.D. KRZYSZTOF BRZOZKA Ph.D., MBA PETER LITTLEWOOD Ph.D. LUIGI STASI Ph.D. CEO and Founder CMO CSO Director of DMPK Director of Chemistry MONIKA DOBRZANSKA Ph
Slide 6: Differentiated internally discovered small-molecule drug candidates and new programs
Differentiated internally discovered small-molecule drug candidates and new programs Targeted therapies Immuno-oncology Synthetic lethality CLINICAL CLINICAL NON-GLP TOXICOLOGY LATE LEAD OPTIMIZATION LEAD OPTIMIZATION HIT-TO-LEAD SEL120 SEL24/ DUAL ADENOSINE SMALL MOLECULE SELECTIVE SMARCA2 SELECTIV
Slide 7: Strong momentum from 2019 and 2020 YTD
Strong momentum from 2019 and 2020'YTD AUGUST Strengthened supervisory board and management board with accomplished biotech industry veterans SEPTEMBER First patient dosed with SEL120 2019 OCTOBER Corporate split between Ryvu Therapeutics and Selvita (CRO) completed, >$100M incremental value created
Slide 8: Executing on our mission
Executing on our mission Complete Phase I clinical development of our lead fully-owned asset, SEL120 in AML/MDS 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 Ryvu has one Support Phase II dev
Slide 9: SEL120: Highly selective first-in-class CDK8/CDK19 inhibitor
SEL120: Highly selective first-in-class CDK8/CDK19 inhibitor with broad potential in hematological malignancies and solid tumors Orphan drug designation in AML Therapy Acceleration Program (TAP) grant support in 2020 Total funding - $3.25 M SEL120 New treatment options Emerging therapeutic in hemato
Slide 10: First therapeutic area of Ryvu focus: acute myeloid leukemia
First therapeutic area of Ryvu focus: acute myeloid leukemia Most common, highly aggressive type of acute leukemia in adults with poor outcomes in most patients1 ~20,000 new cases diagnosed Only and >11,000 deaths in the US in 20182 AML 34%3 20% Patients aged >80 receive intensive AML makes up 1% of
Slide 11: Clinical landscape: targeted small molecule therapies for AML
Clinical landscape: targeted small molecule therapies for AML • SEL120 IS THE ONLY CDK8/CDK19 INHIBITOR CDK8/CDK19 IN CLINICAL DEVELOPMENT FLT3 • MEN1703/SEL24 IS AN UNIQUE, Dual PIM/FLT3 CLINICAL-STAGE DUAL PIM/FLT3 INHIBITOR PIM RYVU CLINICAL PROGRAMS DESIGNED TO FULFILL UNMET NEEDS IN AML IDH1 or
Slide 12: SEL120: potential role of CDK8/CDK19 in AML treatment
SEL120: potential role of CDK8/CDK19 in AML treatment RATIONALE FOR CDK8/CDK19 INHIBITORS IN AML 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
Slide 13: Excellent on-target activity of SEL120 in pSTAT positive AML cell models
Excellent on-target activity of SEL120 in pSTAT positive AML cell models SEL120 is a potent and selective CDK8/CDK19 inhibitor pSTAT1/pSTAT5 levels discriminate responder/ non-responder p-STAT5 Ser726 Low nM activity on CDK8/CDK19 and excellent kinase selectivity (broad kinome) RESPONDERS NON-RESPON
Slide 14: SEL120 induces complete regression and bone marrow recovery in AML
SEL120 induces complete regression and bone marrow recovery in AML In CD34+ AML patient-derived xenografts PDX cells NSG mice Vehicle / SEL120 Dose: 45mg/kg Leukemia burden analysis 17 days latency Daily treatment 29/30 days P20: CD34+ NPM1wt COMPLETE REGRESSION HEMATOLOGIC RECOVERY REDUCED (PERIPHE
Slide 15: SEL120 strongly synergizes with Venetoclax
SEL120 strongly synergizes with Venetoclax SEL120 potentially addresses treatment resistant disease through safe, indirect MCL-1 downregulation in cancer cells MV-4-11 cells IV NSG mice SEL120+Venetoclax Daily, PO, 21 days Leukemia burden analysis COMPLETE REGRESSION HEMATOLOGIC RECOVERY 3 (BONE MAR
Slide 16: SEL120: Phase Ib study – first patient dosed in September 2019
SEL120: Phase Ib study – first patient dosed in September 2019 Phase 1b Study of SEL120 in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome STUDY POPULATION: PRIMARY OBJECTIVE: SECONDARY OBJECTIVE: EXPLORATORY OBJECTIVE: • Patients with relapsed • To assess safety and tolerability •
Slide 17: SEL120 study design in AML/MDS and further plans
SEL120 study design in AML/MDS and further plans H2 2019-2020 Q1-Q3 2021 2022 START PART 1: ESTABLISHING RECOMMENDED PHASE 2 DOSE (RP2D) EVALUATION PART 2: SAFETY EXPANSION PHASE II EXPANSION FROM THE SINGLE PATIENT SAFETY, 6-20 COHORT TO A 3+3 DESIGN EFFICACY, DLTs evaluated at completion of cycle
Slide 18: Positioning of SEL120 in AML treatment regimen and strategic expansion
Positioning of SEL120 in AML treatment regimen and strategic expansion AML TREATMENT PROTOCOL RYVU STRATEGY FOR DEVELOPMENT UNFIT PATIENTS OF SEL120 IN AML/MDS RYVU STRATEGY NO POSITIONING IN THIRD+ LINE TREATMENT RELEVANT MUTATION - DRIVEN • Monotherapy MUTATIONS STAGE 1 • Patients unfit for intens
Slide 19: SEL120 beyond blood cancers: potential role of CDK8/CDK19 in solid tumors
SEL120 beyond blood cancers: potential role of CDK8/CDK19 in solid tumors AML CDK8/CDK19 inhibitors have therapeutic potential AML/MPN in multiple blood and solid tumors Mediator • Ryvu confirmed in vitro or in vivo potential in breast, colorectal and prostate cancer complex JAK2 Gene mutation NK ce
Slide 20: SEL120: confirmed anti-tumor efficacy in solid tumor models
SEL120: confirmed anti-tumor efficacy in solid tumor models of breast and colorectal cancers TNBC BREAST CANCER MODEL COLORECTAL CANCER MODEL 500 V e h ic le , Q D , p o 2000 C is p la tin , 8 m g /k g E 2 W , ip V e h ic le , B ID , p o 450 M e a n tu m o r v o lu m e (m m ) S E M 1800 S E L 1 2
Slide 21: SEL120: expansion plan in multiple solid tumors and other heme malignancies
SEL120: expansion plan in multiple solid tumors and other heme malignancies – preliminary plan Phase I start: 2021, preliminary results: 2022 H2 2020 2021 2022 SCREENING PART 1: ESTABLISHING RECOMMENDED DOSE PART 2: SIMON 2-STAGE DESIGN EVALUATION A 3+3 STUDY DESIGN STAGE 1 STAGE 2 18 PATIENTS 10 PA
Slide 22: SEL24/MEN1703 is a differentiated, first-in-class PIM/FLT3 dual kinase inhibitor
SEL24/MEN1703 is a differentiated, first-in-class PIM/FLT3 dual kinase inhibitor PIM and FLT3 are Dual targeting creates potential for broader activity, Potential for treating patients that have relapsed on selective 1 oncogenes involved in AML 2 more durable responses than selective FLT3 inhibitors
Slide 23: Initial Phase I data for SEL24/MEN1703 demonstrates single agent efficacy
Initial Phase I data for SEL24/MEN1703 demonstrates compelling single agent efficacy Acceptable safety data with complete responses observed ESTABLISHING RECOMMENDED PHASE II DOSE RESULTS EXPANSION FROM THE SINGLE PATIENT COHORT TO A 3+3 DESIGN Establishment of recommended dose and DLTs evaluated at
Slide 24: Differentiated internally discovered small-molecule drug candidates and new programs
Differentiated internally discovered small-molecule drug candidates and new programs BEST IN CLASS FIRST IN CLASS A2A/A2B ANTAGONIST STING HPK1 SMARCA2 OTHER S-L TARGETS Based on internal data generated First generation intratumoral STING o Unique dual potential to o Targets SWI/SNF o Synthetic
Slide 25: Ryvu develops dual A2A/A2B adenosine receptor antagonists
Ryvu develops dual A2A/A2B adenosine receptor antagonists RYVU APPROACH OF TARGETING BOTH A2A AND A2B IN 2019 RVU330 WAS SELECTED RECEPTORS PROVIDES STRONG PRECLINICAL AS A PRECLINICAL CANDIDATE COMPETITIVE ADVANTAGE STATUS NON-GLP TOX STUDIES ARE ONGOING Strong potential of best-in-class drug: KEY
Slide 26: RVU330 is efficacious as monotherapy in MCA205 syngeneic model
RVU330 IS EFFICACIOUS AS MONOTHERAPHY IN MCA205 SYNGENEIC MODEL RVU330 administration Nodule injection of MCA205 cells Euthanasia Staining (14 days) counting LUNG LOBES AFTER STAINING TOTAL I m AREA a g e a OF n a l NODULES NODULE COUNTS IN LUNGS y s is LUNG WEIGHTS WITH VISIBLE WHITE MCA205 NODULES
Slide 27: Small molecule, direct, systemic STING agonists
Small molecule, direct, systemic STING agonists with confirmed efficacy in intravenous and intratumoral mouse tumor models STAGE: SELECTION OF PRELINICAL CANDIDATE Small molecule, direct STING agonists with systemic route STRONG ANTITUMOR EFFICACY AFTER SYSTEMIC KEY DIFFERENTIATION of administration
Slide 28: RVU312-4787 clears tumors in EMT6 mouse tumor model
RVU312-4787 CLEARS TUMORS IN EMT6 MOUSE TUMOR MODEL RVU312-4787 provides dose-dependent antitumor efficacy in vivo in EMT6 tumor model (interim results – day 26) EMT6 MOUSE BREAST CANCER MODEL – INTRAVENOUS ADMINISTRATION – day 26 of ongoing study RVU312-4787 EFFICACY IN EMT6 MOUSE 1 mg/kg E5Dx3 2 m
Slide 29: Ryvu has selective, potent HPK1 inhibitors with anti-tumor efficacy in mice
Ryvu has selective, potent HPK1 inhibitors with anti-tumor efficacy in mice RYVU APPROACH RYVU SMALL MOLECULE HPK1 INHIBITORS SHOW EFFICACY IN MOUSE STATUS LEAD OPTIMIZATION SYNGENEIC MODEL COMPARABLE TO CLINICAL REFERENCE COMPOUND ▪ Small molecule, selective, orally bioavailable APPROACH inhibitors
Slide 30: Ryvu established proprietary synthetic lethality platform
Ryvu established proprietary SYNTHETIC LETHALITY PLATFORM Ryvu has a powerful engine to identify and validate novel synthetic lethal targets in oncology FIND CONTEX-SPECIFIC NOVEL IDENTIFY NOVEL SYNTHETIC 1 DRUG TARGETS 2 LETHAL TARGETS 3 NEW SYNTHETIC LETHAL TARGETS IDENFIED DATA MINING NETWORK ANA
Slide 31: Ryvu develops selective SMARCA2 inhibitors and degraders
Ryvu develops selective SMARCA2 inhibitors and degraders targeting tumors with SMARCA4 loss of function based on synthetic lethality mechanism RYVU APPROACH RYVU SMARCA2 PROTACs SELECTIVELY DEGRADE SMARCA2 OVER SMARCA4 IN CONTRAST TO REFERENCE COMPOUND STATUS HIT TO LEAD RVU311- REFERENCE 5363 • Uni
Slide 32: Broad pipeline addressing emerging targets in oncology
Broad pipeline addressing emerging targets in oncology Ryvu drives value creation from its multiple data readouts Anticipated Milestones Program/ Partners / 2020 2021 2022+ target name Indication Discovery and preclinical Phase I Phase II Collaborators SEL24 / ✓ Ph. I data • Ph. II • Ph. II complete
Slide 33: Ryvu compares favorably to other early stage small molecule oncology companies
Ryvu compares favorably to other early stage small molecule oncology companies 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 SMALL MOLECULE ONCOLOGY SMALL MOLECULE AML Lead asset o Phase
Slide 34: Benefits of the corporate split: oncology therapeutics (Ryvu) and CRO (Selvita)
Benefits of the corporate split: oncology therapeutics (Ryvu) and CRO (Selvita) Swift execution of the split process March 2019 April 2019 September 2019 September 2019 October 2019 October 16, 2019 Selvita Ph1CRODoseprospectus Escalation Selvita CRO prospectus Shareholder approval of First day of S
Slide 35: Achievement of the goals related to the corporate split
Achievement of the goals related to the corporate split Cumulated share price SLV and RVU ($)* Average daily trading value (thousands of $)** 29.4 202 84% 17.1 83 16.0 177% 11.5 119 12.3 73 4.5 Oct 19 Jun 20 2019 2020 RVU SLV ▪ Achievement of the objectives related to the corporate split: • Unlockin
Slide 36: Ryvu Therapeutics – summary of financial results under IFRS
Ryvu Therapeutics – summary of financial results under IFRS $ 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
Slide 37: Investment in the new Ryvu R&D Center for Innovative Drugs
Investment in the new Ryvu R&D Center for Innovative Drugs Planned move in June 2020 2017 April 2018 August 2018 April 2020 June 2020 Preparations for the Ph1 Dose Escalation Completion of major investment; obtaining a Obtaining a construction Initiation of construction construction works, permits’
Slide 38: Covid-19 impact on Ryvu Therapeutics
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 pat
Slide 39: Ryvu investment highlights and near term milestones
Ryvu investment highlights and near term milestones Developing small molecule therapies which address high value emerging targets and pathways in oncology SEL24/MEN1703 Phase 1 PoC data (2020) ✓ Diverse pipeline targeting kinases, synthetic lethality and immuno-oncology SEL120 First-in-class selecti
Slide 40: Executing on our mission
Executing on our mission Complete Phase I clinical development of our lead fully-owned asset, SEL120 in AML/MDS 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 Ryvu has one Support Phase II dev
Slide 41: Back-up slides
— Back-up slides RYYU THERAPEUTICS
Slide 42: Clear progression from inception
Clear progression from inception Oncology-focused Biotech Services provider Hybrid research & development organization Deep pipeline built on wholly- Fee-for-service discovery engine and CRO Clinical research services and pipeline for partnership owned discovery engine Founded in 2007 First service
Slide 43: New research collaboration between Ryvu and Galapagos announced on April 16, 2020
New research collaboration between Ryvu and Galapagos announced on April 16, 2020 DEAL STRUCTURE FINANCIAL TERMS RYVU HAS RECEIVED AN UP-FRONT PAYMENT • Discovery and development of first-in-class small molecules and drug candidates targeting inflammatory disorders POSSIBILITY OF ADDITIONAL OPTION A
Slide 44: Successful Ryvu spin-out company, NodThera
Successful Ryvu spin-out company, NodThera Discovery and development of next generation NLRP3 inflammasome inhibitors ~6.2% OWNED BY RYVU PIONEERING DEVELOPMENT IN THE FIELD OF INFLAMMASOME/NLRP3 BIOLOGY First Ryvu deal Focused on the treatment $48 M Series A in 2018 of diseases driven by chronic in
Slide 45: SEL120 specifically targets STAT5+/CD34+ AML cells and induces differentiation
SEL120 specifically targets STAT5+/CD34+ AML cells and 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-) T E X , S E L 1 2 0 -3 4 A 4 1 0 6 c
Slide 46: Single agent efficacy of SEL120 in vivo
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 SINGLE AGENT CDK8 assay EFFICACY SINGLE AGENT EFFICACY IN CD34+ AND PSTAT5+
Slide 47: Targeting FLT3 and PIM simultaneously may provide improved efficacy
Targeting FLT3 and PIM simultaneously may provide improved efficacy and durability over narrowly targeted agents SEL24/MEN1703 VS PIM INHIBITOR AZD1208 AND FLT3 INHIBITOR QUIZARTINIB IN AML CELL LINES SEL24/MEN1703 MV-4-11 (FLT3-ITD positive) 0,875 MOLM-16 (FLT3-ITD negative) Dual PIM/FLT3 inhibitor
Slide 48: Ryvu STING agonist outperforms antitumor efficacy of Aduro agonist
Ryvu STING agonist outperforms antitumor efficacy of Aduro agonist and provides immunological memory in mouse CT26 colorectal carcinoma model CONTROL GROUP REFRENCE ADURO ADU-S100 RYVU STING AGONIST 1 Subcutaneous inoculation Control, EODx3, IT 5 mg/kg ADU-S100,(100 µg), 5.0 mg/kg EODx3, EODx3, IT I
Slide 49: Ryvu STING agonists promote long-term immunological memory
Ryvu STING agonists promote long-term immunological memory RE-CHALLENGE AFTER EFFICACY WITH INTRAVENOUS ADMINISTRATION RVU312-04787, 3 mg/kgEFFICACY iv, E5Dx3 – RVU312-4787 RVU312-04787, 3 mg/kg iv, E7Dx3 Re-challenge -–day Re-challenge day2121 IMMUNOLOGICAL MEMORY – 2500 2500 2000 RESISTANCE TO RE-
Slide 50: Majority of competitive A2A inhibitors lose activity in high adenosine concentration
Majority of competitive A2A inhibitors lose activity in high adenosine concentration Ryvu advantage: activity in high, TME-like relevant adenosine concentrations COMPETITIVE A2A INHIBITORS EFFECTIVE ONLY RYVU AND iTEOS PRESERVE ACTIVITY 1 IN LOW ADENOSINE CONCENTRATION 2 IN HIGH ADENOSINE CONCENTRAT
Slide 51: Selective A2A inhibitors activate only a fraction of immune cells
Selective A2A inhibitors activate only a fraction of immune cells Ryvu advantage: dual A2A/A2B antagonists activate both innate and adaptive immunity ONLY RYVU PRESERVES ACTIVITY 1 SELECTIVE A2A ANTAGONISTS DO NOT ACTIVATE ANTIGEN-PRESENTING CELLS 2 IN HIGH ADENOSINE CONCENTRATION A2A/A2B ANTAGONIST
Slide 52: RVU330 A2A/A2B efficiently modulates pCREB
RVU330 A2A/A2B efficiently modulates pCREB (main PD clinical biomarker used by competitors) in in vitro human whole blood assay RVU330 modulates PD biomarker RVU330 modulates PD biomarker in CD4+ T-cells in CD8+ T-cells UT UT 100 in h ib it io n 100 o f re co v e ry in h ib it io n o f re co v e ry
Slide 53: RVU330 A2A/A2B antagonists outperform competitors in in vitro activation of immune cells
RVU330 A2A/A2B antagonists outperform competitors in in vitro activation of immune cells at high adenosine concentrations RVU330 restores functional activity CD4+ T cells that RVU330 reactivates dendritic cells (moDC) suppressed is suppressed by high adenosine concentration (IL-2 production) by high
Slide 54: Contact data
Contact data Pawel Przewiezlikowski Chief Executive Officer ir@ryvu.com Ryvu Therapeutics S.A. www.ryvu.com ryvu@ryvu.com 54
Ryvu Therapeutics — Investor Presentation (July 2020) on 6ix