Ryvu Therapeutics Sa · GPW:RVU
Ryvu Therapeutics Sa — Investor Presentation (March 2024)
46 slides from Ryvu Therapeutics Sa's investor presentation, March 2024
Slide 1: Corporate Presentation
Corporate Presentation March 2024 Developing therapeutics at the forefront of oncology
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 subm
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 RVU120 MEN1703 Developing small molecule therapies which address high-value emerging targets and pathways in oncology • First-in-class, selective, • First-in-cla
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, PhD, MBA Hendrik Nogai, MD Kamil Sitarz, PhD, MBA Vatnak Vat-Ho, MBA CEO and Founder CSO CMO COO CBO Miika Ahdesmäki, PhD, MBA Jakub Janowski, MSc Bartlomiej Ko
Slide 5: Broad pipeline addressing emerging targets in oncology
Broad pipeline addressing emerging targets in oncology EXPECTED PROGRAM INDICATION DISCOVERY PRECLINICAL PHASE I PHASE II PARTNER MILESTONES CLINICAL PROJECTS R/R AML/HR-MDS (RIVER-52) Complete Ph I data in 2Q24; (monotheraphy) Initial Ph II data in 4Q24 R/R AML (RIVER-81) Initial Ph II data in 4Q24
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 fully-owned CDK8/19 inhibitor currently in Phase II
RVU120 is a fully-owned CDK8/19 inhibitor currently in Phase II • First-in-class • High selectivity • Easy to formulate • High potency • Low risk of DDI • Orally available CDK8/19 mediator promotes CDK8/19 inhibition by RVU120 triggers RVU120 is highly selective AML growth differentiation and apopto
Slide 8: RVU120: opportunities across a broad range of cancers
RVU120: opportunities across a broad range of cancers Blood Cancers & Disorders Solid Tumors Medulloblastoma AML High-risk MDS ACC Low-risk MDS Breast Myelofibrosis (MF) MDS/MPN overlap syndrome Sarcoma NHL Diamond-Blackfan Anemia • Signs of clinical activity in AML/HR-MDS • Translational evidence i
Slide 9: RVU120 for potential treatment of Acute Myeloid Leukemia (AML)
RVU120 for potential treatment of Acute Myeloid Leukemia (AML) Preclinical Evidence: AML Acute Myeloid Leukemia CD34+ AML patient-derived xenografts: • Most common, highly aggressive type of acute leukemia in adults Complete regression Hematologic recovery • Poor outcomes in most patients1 (periphe
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 P = 0.0051 recurrent DNMT
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 Synergy is driven by regulation of MCL-1: sensitive and venetoclax resistant models: Venetoclax sensitive cell line RVU120 RVU120 Venetoclax resistant 4000 T u m o r v o lu m e ,
Slide 12: RVU120 validated preclinically as a drug candidate in myelofibrosis (MF)
RVU120 validated preclinically as a drug candidate in myelofibrosis (MF) Opportunity in myelofibrosis Mechanism of RVU120 activity in MF • 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: Clinical results demonstrating erythroid improvement support further studies in HR-MDS and LR-MDS
Clinical results demonstrating erythroid improvement support further studies in HR-MDS and LR-MDS Induction of erythroid gene expression programs confirmed by RNAseq Growing number of patients treated with RVU120 show hematological improvement Several patients with AML and HR-MDS showed signs of imp
Slide 14: RVU120: Phase I AML/MDS study – RIVER-51
RVU120: Phase I AML/MDS study – RIVER-51 5 SITES IN THE U.S. STUDY POPULATION TREATMENT • Patients with Three-week cycle: Single oral dose of RVU120 every other day for a total relapsed/refractory AML of 7 doses/cycle followed by one week off or high-risk MDS • No upfront patient stratification 5 SI
Slide 15: RVU120 has a favorable safety profile at doses tested to date
RVU120 has a favorable safety profile at doses tested to date Antiemetic prophylaxis introduced recently improves compliance and tolerability at higher doses Most common* Treatment RVU120 (10-250 mg) RVU120 was well tolerated at doses Emergent Adverse Events between 10 and 250 mg (TEAE) Any grade, n
Slide 16: RIVER-51 clinical update at ASH 2023
RIVER-51 clinical update at ASH 2023: 14 of 28 (50%) evaluable patients showed clinical benefit Data cut-off: Nov 10, 2023 A total of 38 patients have been treated (28 evaluable) • Median age 72 years • 34 patients had AML and 4 had HR-MDS • Patients relapsed or were refractory to a median of 3 prio
Slide 17: Patients with NPM1- and DNMT3A-mutated AML and HR-MDS achieved significant blast reductions
Patients with NPM1- and DNMT3A-mutated AML and HR-MDS achieved significant blast reductions Best BM blast % reduction After the disclosure of the chart at the ASH Annual Meeting & Exposition a further decrease of blasts from 24% to 3% (88% reduction) was reported in patient 111-001 consistent with a
Slide 18: Clinical activity for RVU120 was observed in multiple populations
Clinical activity for RVU120 was observed in multiple populations NPM1 and DNMT3A mutations HR-MDS An NPM1 mutation was identified in 2 pts who received RVU120 • 4 pts with HR-MDS treated were failing • pt 103-002: achieved a CR with skin leukemia resolution, this patient 1-5 prior lines of treatmen
Slide 19: RVU120 achieved target engagement levels between 50-70% at a dose of 250mg
RVU120 achieved target engagement levels between 50-70% at a dose of 250mg These levels are expected to result in robust antileukemic efficacy RVU120 dose - pSTAT5 inhibition RVU120 concentration – pSTAT5 inhibition • Pharmacodynamic (PD) activity of RVU120 was assessed by measuring • Results of RVU
Slide 20: RVU120: Phase I Solid Tumor study – AMNYS-51
RVU120: Phase I Solid Tumor study – AMNYS-51 2 SITES IN POLAND + 3 SITES IN SPAIN STUDY POPULATION TREATMENT Patients with r/r solid Three-week cycle: Single oral dose of RVU120 every other day for tumors progressing after a total of 7 doses/cycle followed by one week off at least one previous line
Slide 21: AMNYS-51 - ESMO 2023 data release
AMNYS-51 - ESMO 2023 data release 39 patients treated at doses up to 400 mg Data cut-off: Sept 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) or ot
Slide 22: 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) AML and HR-MDS LR-MDS MF Translational Studies RIVER-52 REMARK POTAMI-61 Solid tumors RIVER-81 Blast reductions Blast reductions Blast reductions Evidence in medulloblas
Slide 23: RIVER-52: Phase II study with RVU120 as a single agent
RIVER-52: RIVER-52 : Phase II study with RVU120 as a single agent Based on convincing translational rationale and clinical data, patients will be selected based on the disease features and genetic background STUDY DESIGN • Primary endpoints: ― Rate of CR, CRh, CRi, with and without MRD, and DoR • Se
Slide 24: RIVER-81: Phase II study testing RVU120 in combination with venetoclax
RIVER-81: RIVER-81 : Phase II study testing RVU120 in combination with venetoclax STUDY DESIGN • Primary endpoints: ― Rate of CR, CRh, CRi, with and without MRD, and DoR • Secondary endpoints: Transfusion independence, PFS, RFS, OS RVU120 + • For Part 2: including PRO and HRQoL change from baseline
Slide 25: REMARK: RVU120 in LR-MDS – IIT
REMARK: REMARK RVU120 in LR-MDS – IIT conducted by Prof. Uwe Platzbecker and the EMSCO network STUDY DESIGN PHASE II • Population: ― Relapsed/refractory low-risk MDS for the treatment of anemia in patients failing available options EXPLORATORY ― Opportunity for the first line (1L) setting RVU120 AS
Slide 26: Clinical development of RVU120 focuses on hematologic malignancies
Clinical development of RVU120 focuses on hematologic malignancies, while translational research explores additional opportunities 2024 2025 2026 2027 2028 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 Approval in selected regions • RIV
Slide 27: 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 Planned locations for RVU120 Ph II studies: worldwide Part 1: exploratory data Part 2: expansion Number of Ph II clinical Number of cou
Slide 28: 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 aggressive • Disease leading to bone marrow • MF is a bone marrow disease type of acute leukemia occurring in damage, classified as cancer ch
Slide 29: MEN1703 (SEL24): First-in-Class PIM/FLT3 Inhibitor
MEN1703 (SEL24): First-in-Class PIM/FLT3 Inhibitor
Slide 30: MEN1703 (SEL24)
MEN1703 (SEL24) Licensed to Menarini Group, currently in Phase II Future directions – 2023+ DLBCL PARTNERSHIP AGREEMENT PROVEN SAFETY AND WITH MENARINI GROUP CLINICAL ACTIVITY • Development to continue with the initiation of a new Phase II study in relapsed/refractory diffuse large B-cell (2017) lym
Slide 31: 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 • Non-Hodgkin’s lymphomas (NHL) are a heterogeneous • Strong unmet medical need: estimated 23k incident DLBCL cases in group of lymphoproliferative disorder
Slide 32: Initiating Phase II in DLBCL
Initiating Phase II in DLBCL MEN1703 PROFILE • First-in-class dual PIM/FLT3 inhibitor with a unique mechanism of action • Differentiated activity in cellular models compared to selective PIM inhibitors (broader activity profile) CLINICAL STUDIES TO DATE • H1 2017- H1 2021 Phase I dose escalation and
Slide 33: Small Molecule Platform with Focus on Synthetic Lethality
Small Molecule Platform with Focus on Synthetic Lethality
Slide 34: Integrated Discovery Engine at Ryvu
Integrated Discovery Engine at Ryvu TARGET IDENTIFICATION DRUG RESEARCH AND VALIDATION DISCOVERY 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 35: Ryvu's Target Discovery Platform is focused on identification of novel synthetic lethal pairs
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 Published Data Sets Novel Oncogenic Drivers 35
Slide 36: 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 37: PRMT5 MTA-cooperative inhibitors
PRMT5 MTA-cooperative inhibitors PRMT5 SL INHIBITOR PROGRAM IN RYVU RYVU HAS SL PRMT5 INHIBITORS WITH THE BEST-IN-CLASS POTENTIAL PRMT5 MTA-cooperative inhibitors Ryvu PRMT5 inhibitors demonstrate high potency and MTA-cooperativity in vitro KEY coupled with favorable ADME profile. exert synthetic le
Slide 38: Small molecule inhibitors of WRN
Small molecule inhibitors of WRN WRN inhibitors of ATPase activity selectively targeting tumors with microsatellite instability WRN INHIBITOR PROGRAM AT RYVU Helicase function validated 1 in vitro as critical requirement KEY Synthetic lethality of WRN for synthetic lethal phenotype RATIONALE with mi
Slide 39: 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 1 Multi-target discovery collaboration on small molecule programs in immune modulation 2 STING agonist license as a monotherapy and in combinations P
Slide 40: Exelixis and Ryvu: exclusive license agreement for STING agonist-based therapies
Exelixis and Ryvu: exclusive license agreement to develop novel STING agonist-based targeted cancer therapies July 2022 1 Building STING-based antibody drug conjugates (ADCs) 2 Leveraging Ryvu’s STING agonist portfolio and Exelixis’s ADC technology Partnership Key Financial Terms • Exclusive license
Slide 41: Corporate Progress
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Slide 42: Full-Year Financial Results: 2023
Full-Year Financial Results: 2023 $ million 2022* 2023* Revenues, incl.: 15.8 16.3 Partnering 8.7 11.2 Cash position Ryvu Grants 6.6 4.9 March 13, 2024 Employees Total Costs**, incl.: 26.4 37.6 Clinical Pipeline 6.4 13.0 $66.5M >270 Early Pipeline 12.8 15.8 G&A 7.2 8.8 EBIT** -10.6 -21.3 Available E
Slide 43: 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 1 Instrument structure adapted to the business model Long-term financing repaid through bullet repayment, and remuneration independent of interest rates, partially secured by the Compa
Slide 44: Business pipeline: 2024 key goals and financing
Ryvu’s Vision: from 2026, Ryvu will improve the lives of cancer patients worldwide 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 strateg
Slide 45: Ryvu equity summary
Ryvu equity summary Top Holders3 IPO on WSE Nov 2014 1 Paweł Przewięźlikowski 18% Corporate Split: Selvita and Ryvu Oct 2019 2 Allianz OFE 9.2% Ticker: WSE RVU 3 BioNTech SE 8.3% 4 Nationale-Nederlanden OFE 7.9% 52-Week Range1 PLN 53.50 – 72.40 5 Tadeusz Wesolowski (incl. Augebit) 4.9% Average Daily
Slide 46: Thank you
Thank you CONTACT DATA: Ryvu Therapeutics S.A. www.ryvu.com ryvu@ryvu.com ir@ryvu.com
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