Ryvu Therapeutics Sa · GPW:RVU
Ryvu Therapeutics Sa — Investor Presentation (November 2023)
44 slides from Ryvu Therapeutics Sa's investor presentation, November 2023
Slide 1: Corporate Presentation
CORPORATE PRESENTATION Targeted therapeutics at the forefront of oncology November 2023
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 Small Molecule Discovery Platform First-in-class clinical pipeline Novel Synthetic Lethality Targets & IO partnerships Developing small molecule therapies RVU120 SEL24 which address high-value emerging targets and pathways in oncology • First-in-class, selective, • First-in-class du
Slide 4: Team with a strong track record of clinical development and shareholder value creation
Team with a strong track record of clinical development and shareholder value creation PAWEL PRZEWIEZLIKOWSKI, MSc, MBA KRZYSZTOF BRZOZKA, Ph.D., MBA HENDRIK NOGAI, M.D. KAMIL SITARZ, Ph.D., MBA VATNAK VAT-HO, MBA CEO and Founder CSO CMO COO CBO JAKUB JANOWSKI, MSc BARTLOMIEJ KONICKI, MSc TOMASZ RZY
Slide 5: Broad pipeline addressing emerging targets in oncology
Broad pipeline addressing emerging targets in oncology 5
Slide 6: RVU120: First-in-Class CDK8/19 Inhibitor in Hematologic and Solid Tumor Malignancies
RVU120: First-in-Class CDK8/19 Inhibitor in Hematologic and Solid Tumor Malignancies
Slide 7: RVU120 is a CDK8/19 inhibitor currently in clinical development
RVU120 is a CDK8/19 inhibitor currently in clinical development to address unmet medical need in hematologic and solid tumors • First-in-class • High selectivity • Easy to formulate • High potency • Low risk of DDI • Orally available RVU120 is highly selective for CDK8/19 IC50 [nM] CDK8/CyclinC CDK1
Slide 8: RVU120: Potential across a broad range of cancers
RVU120: Potential across a broad range of cancers Blood Cancers & Disorders Solid tumors AML Neuroendocrine Low-risk MDS Breast High-risk MDS MDS/MPN overlap syndrome Adenoid cystic carcinoma (AdCC) Myelofibrosis (MF) Medulloblastoma NHL Sarcoma Diamond-Blackfan Anemia Prostate • Signs of clinical a
Slide 9: RVU120 for Potential Treatment of Acute Myeloid Leukemia (AML)
RVU120 for Potential Treatment of Acute Myeloid Leukemia (AML) Preclinical Evidence: AML AML • Most common, highly aggressive CD34+ AML patient-derived xenografts: type of acute leukemia in adults Complete regression Hematologic recovery • Poor outcomes in most patients1 (peripheral blood) (bone mar
Slide 10: DNMT3A and NPM1 are candidates for patient selection markers in AML
DNMT3A and NPM1 are candidates for patient selection markers in AML DNMT3A/NPM1 mutated AML is dependent on dysregulation of HOX genes Loss of viability with RVU120 treatment • Low nM activity on CDK8/19: RVU120 reduces the viability of AML PDCs, in particular those bearing recurrent DNMT3A and NPM1
Slide 11: Combination potential with venetoclax was shown in preclinical models
Combination potential with venetoclax was shown in preclinical models Synergistic activity was demonstrated in venetoclax sensitive Synergy is driven by regulation of MCL-1: and venetoclax resistant models: RVU120 RVU120 Venetoclax sensitive cell line MCL-1 BCL-2 BCL-XL 4000 T u m o r v o lu m e , d
Slide 12: RVU120 validated preclinically as a drug candidate in myelofibrosis (MF)
RVU120 validated preclinically as a drug candidate in myelofibrosis (MF) Mechanism of RVU120 activity in MF Opportunity in Myelofibrosis • Growing market with many patients undiagnosed or not treated due to lack of treatment options • Long durations of therapy and unmet medical need, for example in
Slide 13: Emerging clinical results demonstrating erythroid improvement in patients
Emerging clinical results demonstrating erythroid improvement in patients ancourage further studies in HR-MDS and LR-MDS Growing number of patients treated with RVU120 Induction of erythroid gene expression show hematological improvement programs confirmed by RNAseq Several patients with AML and HR-
Slide 14: RVU120: Phase I AML/MDS Study – RIVER-51
RVU120: Phase I AML/MDS Study – RIVER-51 Recruitment in Phase I ongoing 5 SITES IN US STUDY POPULATION: TREATMENT: Three-week cycle: Single oral dose of RVU120 every • Patients with other day for a total of 7 doses/cycle followed by relapsed/refractory AML or one week off high risk MDS • No upfront
Slide 15: RVU120 has a favorable safety profile at doses tested to date
RVU120 has a favorable safety profile at doses tested to date RVU120 (10-135 mg) Most common* Treatment Emergent RVU120 was well tolerated Adverse Events (TEAE) Any grade n of pts (%) Grade 3-5 n of pts (%) at doses between 10 and 135 mg Nausea 19 (61%) 0 Vomiting 10 (32%) 1 (3%) • No DLTs and no st
Slide 16: RIVER-51 Clinical Update at EHA 2023
RIVER-51 Clinical Update at EHA 2023: 11 of 24 evaluable patients showed clinical benefit • A total of 29 patients have been treated • Median age 71 years • Patients relapsed or were refractory to a median of 3 prior lines of therapy Signs of clinical benefit were observed in 11 patients • In total,
Slide 17: RVU120 differentiation on hematopoietic cells
RVU120 differentiation on hematopoietic cells: 6 patients with evidence of increased erythroid differentiation Pt 106-004 Erythroid and Platelet response Pt 106-004 Enhanced Erythroid differentiation 200 150 150 100 [x 1 0 / L ]H g b [g / d l] 52 50 1 1 .0 1 1 .4 22 PLTS 10 9 .6 9 10 5 1 0 1 13 1 13
Slide 18: RVU120: Phase I Solid Tumor Study – AMNYS-51
RVU120: Phase I Solid Tumor Study – AMNYS-51 Recruitment in Phase I ongoing STUDY POPULATION: TREATMENT: Three week cycle: Single oral dose of RVU120 every • Patients with r/r solid other day for a total of 7 doses/cycle followed by 2 SITES IN POLAND + 3 SITES IN SPAIN tumors progressing after at on
Slide 19: AMNYS-51 - ESMO 2023 data release
AMNYS-51 - ESMO 2023 data release - 39 patients were treated at doses up to 400 mg Data cut-off: Sep 26, 2023 ▪ A total of 39 patients have been treated in 8 cohorts ▪ Patients were unselected and heavily pretreated ▪ RVU120 demonstrates a favorable safety profile ▪ No dose limiting toxicities (DLTs
Slide 20: Comparison of the duration of RVU120 treatment against the prior line regimen
Comparison of the duration of RVU120 treatment against the prior line regimen may support single-agent clinical activity in some patients ▪ Out of 12 patients who achieved a stable disease on RVU120, treatment in 8 patients lasted longer than on previous therapy line ▪ The trend to longer treatment
Slide 21: Treatment with RVU120 results in effective inhibition of pharmacodynamic marker
Treatment with RVU120 results in effective inhibition of pharmacodynamic marker (PD) in solid and AML tumor patients in the ongoing dose-escalation trials pSTAT5 inhibition tightly correlates with RVU120 exposure pSTAT5 inhibition tightly correlates with RVU120 dose ▪ Doses of 250 mg QoD result in e
Slide 22: Conclusions from the AMNYS-51 study
Conclusions from the AMNYS-51 study ▪ RVU120 demonstrates a favorable safety profile in a heavily pretreated, unselected all-comer patient population. No dose limiting toxicities (DLTs) or other safety signals were observed confirming CDK8/19 inhibition as a viable approach for cancer therapies. ▪ L
Slide 23: Data generated in RIVER-51 study support further development of RVU120
Data generated in RIVER-51 study support further development of RVU120, primarily in AML, HR-MDS, LR-MDS and MF RIVER-51 (Phase I) Blast reductions AML and HR-MDS RIVER-52 RIVER-81 Induction of erythropoiesis LR-MDS REMARK Transfusion independence MF POTAMI-61 Improvement of bone marrow architecture
Slide 24: Clinical Development of RVU120 focuses on hematologic malignancies
Clinical Development of RVU120 focuses on hematologic malignancies, while translational research explores additional opportunities 2023 2024 2025 2026 2027 2028 III IV I II III IV I II III IV I II III IV I II III IV I II III IV Planned Ph II studies in hematologic malignancies decision point for pri
Slide 25: Phase II clinical development of RVU120 with a global footprint
Phase II clinical development of RVU120 with a global footprint Global site locations and patient population Global CROs and clinical vendors Regulatory authorities worldwide Planned locations for RVU120 Ph II studies: Part 1: exploratory data Part 2: expansion 4 10+ 170+ 270+ 30+ 50+ Number of Ph I
Slide 26: RVU120 market potential in hematological malignancies
RVU120 market potential in hematological malignancies AML (ACUTE MYELOID LEUKEMIA) MDS (MYELODYSPLASTIC SYNDROME) MF (MYELOFIBROSIS) ▪ The most common, highly ▪ Disease leading to bone marrow ▪ MF is a bone marrow disease aggressive type of acute leukemia damage, classified as cancer characterized b
Slide 27: SEL24 (MEN1703): First-in-Class PIM/FLT3 Inhibitor
SEL24 (MEN1703): First-in-Class PIM/FLT3 Inhibitor
Slide 28: MEN1703 (SEL24) – Summary
MEN1703 (SEL24) – Summary Project licensed to Menarini Group, currently in Phase II Future directions – 2023+ PARTNERSHIP AGREEMENT PROVEN SAFETY AND WITH MENARINI GROUP CLINICAL ACTIVITY DLBCL (2017) • Development to continue with the initiation of a new Phase II study in relapsed/refractory diffus
Slide 29: Unmet medical need and high commercial potential for MEN1703 in DLBCL
Unmet medical need and high commercial potential for MEN1703 in DLBCL DLBCL (Diffuse Large B-Cell Lymphoma) COMMERCIAL POTENTIAL AND UNMET NEED • Strong unmet medical need: estimated 23k incident DLBCL cases in North • Non Hodgkin’s lymphomas (NHL) are a heterogeneous group of America in 2027 and 37
Slide 30: Initiating Phase II in DLBCL
Initiating Phase II in DLBCL MEN1703 • First-in-class dual PIM/FLT3 inhibitor with a unique mechanism of action PROFILE • Differentiated activity in cellular models compared to selective PIM inhibitors (broader activity profile) • H1 2017- H1 2021 Phase I dose escalation and cohort expansion in R/R
Slide 31: Small Molecule Platform with Focus on Synthetic Lethality
Small Molecule Platform with Focus on Synthetic Lethality
Slide 32: Integrated Discovery Engine at Ryvu
Integrated Discovery Engine at Ryvu TARGET IDENTIFICATION AND VALIDATION DRUG DISCOVERY RESEARCH PIPELINE ✓ Discovery of novel synthetic lethal target ✓ Integrated, multidisciplinary processes: ✓ Broad portfolio of synthetic lethal and pairs and actionable oncogenic drivers rapid lead identification
Slide 33: Ryvu's Target Discovery Platform
Ryvu’s Target Discovery Platform is focused on identification of novel synthetic lethal pairs and oncogenic drivers INPUT DATA TARGET DISCOVERY PLATFORM PLATFORM OUTPUT CRISPR / shRNA Screens Novel Synthetic Lethalities Novel and Proprietary SL Targets Target #1 • Single-most synthetic lethal target
Slide 34: Ryvu experimental target discovery platform – three approaches
Ryvu experimental target discovery platform – three approaches Experimental CRISPR-based target discovery platforms with the use of: Isogenic cell line pair Isogenic primary cells Patient-derived material Normal conditions Stress conditions MUT1 MUT2 MUT3 MUT4 CRISPR screens Cellular stress in tumor
Slide 35: PRMT5 MTA-cooperative inhibitors
PRMT5 MTA-cooperative inhibitors RYVU HAS SL PRMT5 INHIBITORS WITH THE BEST-IN-CLASS POTENTIAL PRMT5 SL INHIBITOR PROGRAM IN RYVU Ryvu PRMT5 inhibitors demonstrate high potency and MTA-cooperativity in vitro coupled with favorable ADME profile. PRMT5 MTA-cooperative inhibitors KEY RATIONALE exert sy
Slide 36: Small molecule inhibitors of WRN
Small molecule inhibitors of WRN WRN INHIBITORS OF ATPase ACTIVITY SELECTIVELY TARGETING TUMORS WRN INHIBITOR PROGRAM AT RYVU WITH MICROSATELLITE INSTABILITY Synthetic lethality of WRN 1 KEY RATIONALE Helicase function validated with microsatellite instability (MSI-high) in vitro as critical require
Slide 37: BioNTech and Ryvu: Global Collaboration
BioNTech and Ryvu: Global Collaboration to Develop and Commercialize Immune Modulation Small Molecule Candidates Largest-ever Ryvu deal November 2022 • Multi-target discovery collaboration on small molecule programs in immune modulation • STING agonist license as a monotherapy and in combinations Pa
Slide 38: Exelixis and Ryvu: Exclusive License Agreement
Exelixis and Ryvu: Exclusive License Agreement to Develop Novel STING Agonist-Based Targeted Cancer Therapies July 2022 • Building STING-based antibody drug conjugates (ADCs) • Leveraging Ryvu’s STING agonist portfolio and Exelixis’s ADC technology Partnership Key Financial Terms • Exclusive license
Slide 39: Corporate Progress
Corporate Progress
Slide 40: Full-Year Financial Results: Q3YTD 2023
Full-Year Financial Results: Q3YTD 2023 Q3YTD Q3YTD $ million 2022* 2022* 2023* Cash position # of employees Revenues, incl.: 15.8 8.0 11.9 November 24, 2023 Partnering 8.7 3.2 8.4 Grants 6.6 4.4 3.3 $64.5M Total Costs**, incl.: 26.4 19.2 27.4 Clinical Pipeline 6.4 5.0 9.7 Available EIB Venture Debt
Slide 41: EUR 22m venture debt obtained from the European Investment Bank
EUR 22m venture debt obtained from the European Investment Bank Long-term financing for innovative growth companies: Instrument structure adapted to the business model Long-term financing repaid through bullet repayment, and remuneration independent of interest rates, partially secured by the Compan
Slide 42: Business Pipeline: 2023-2024 Key Goals and Financing
Ryvu’s Vision: From 2026, Ryvu will improve the lives of cancer patients worldwide 2023-2024 KEY GOALS AND FINANCING ▪ Research funding from existing R&D collaborations ▪ RVU120 broad development ▪ Milestones from existing R&D collaborations ▪ New grant funding (including potential fast-to-market st
Slide 43: Ryvu Equity Summary
Ryvu Equity Summary IPO on WSE Nov 2014 Top Holders3 Corporate Split: Selvita and Ryvu Oct 2019 1 Paweł Przewięźlikowski 18% 2 Allianz OFE 9.2% Ticker: WSE RVU 3 BioNTech SE 8.3% 52-Week Range1 PLN 37.05 – 72.40 4 Allianz TFI 8.3% Average Daily Volume (YTD) 1 14,297 5 Nationale-Nederlanden OFE 8.2%
Slide 44: Contact Data
CONTACT DATA: Ryvu Therapeutics S.A. www.ryvu.com [email protected] 44
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