Ryvu Therapeutics Sa · GPW:RVU
Ryvu Therapeutics Sa — Investor Presentation (July 2024)
48 slides from Ryvu Therapeutics Sa's investor presentation, July 2024
Slide 1: Corporate Presentation
Developing therapeutics at the forefront of oncology Corporate Presentation July 2024
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 to address high-value emerging targets and pathways in oncology • First-in-class, selective, • First-in-class
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) Initial Ph II data in 4Q24 (monotheraphy) R/R AML (RIVER-81) Initial Ph II data in 4Q24 (combination therapy) RVU12
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: 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 10: 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 11: 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 12: RIVER-51 clinical update – EHA 2024
RIVER-51 clinical update – EHA 2024: 15 of 30 evaluable patients showed clinical benefit Data cut-off: May 17, 2024 30 treated patients are evaluable for response (38 were treated in total) ▪ 34 patients had AML and 4 had HR-MDS ▪ Patients relapsed or were refractory to a median of 3 prior lines of
Slide 13: DNMT3A and NPM1 are potential patient selection markers in AML
DNMT3A and NPM1 are potential 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 DNMT3A an
Slide 14: Clinical activity for RVU120 was observed in multiple populations
Clinical activity for RVU120 was observed in multiple populations NPM1 and DNMT3A mutations ▪ An NPM1 mutation was identified in 2 pts who received RVU120 – one patient achieved a CR, the other suffered an unrelated SAE in C2 and progressed ▪ Three additional patients had a DNMT3A mutation without N
Slide 15: 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 16: RIVER-52 – initial Phase II results
RIVER-52 – initial Phase II results Data cut-off: May 17, 2023 ▪ A total of 10 pts received RVU120 at 250 mg ▪ 6 pts are ongoing ▪ 4 pts were withdrawn (2 for PD, 1 for SAE unrelated to RVU120, 1 for withdrawal of consent) Higher sensitivity Outcomes to RVU120 is expected in these ▪ 1 pt with AML ha
Slide 17: RIVER-51/52 – Confirmed safety at 250 mg dose
RIVER-51/52 – Confirmed safety at 250 mg dose RVU120 (250 mg) from CLI120-001 and RIVER-52 trials Treatment Emergent Total number of pts dosed at 250 mg = 13 Adverse Events (TEAE) Any grade n of pts (%) Grade 3-5 n of pts (%) Data cut-off: May 17, 2023 Nausea 3 (23) 1 (7) Abdominal pain 3 (23) 1 (7)
Slide 18: RIVER-51/52 – Conclusions
RIVER-51/52 – Conclusions Based on the data in the Phase I study, 250 mg was selected as the recommended Phase II dose. 1 No DLTs were observed at the 250 mg dose level, and sufficient target inhibition was observed RVU120 as a single agent showed clinical benefit in a heavily pretreated population
Slide 19: CDK8 inhibition by RVU120 synergizes with venetoclax in nonclinical AML models
CDK8 inhibition by RVU120 synergizes with venetoclax in nonclinical AML models Preclinical studies of RVU120 demonstrate robust anti-leukemic activity and synergy with VEN in vitro and in vivo Loewe synergy matrix for KG-1 TP53mut AML MV4-11 MLL fusion AML xenografts model cell line treated RVU120+V
Slide 20: 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 21: RIVER-81: Initial clinical safety of RVU120 with venetoclax
RIVER-81: Initial clinical safety of RVU120 with venetoclax Dose level 1 (RVU120 125 mg + VEN 200 mg) completed Initial clinical safety confirmed RVU120 125 mg + Ven 200mg Treatment Emergent Adverse Events (Cohort 1) COMPLETED (TEAEs) that occurred in more than 1 patient Any grade Grade 3-5 n (%) n
Slide 22: RIVER-81 – Conclusions
RIVER-81 – Conclusions Mechanistically, the combination of VEN and RVU120 leads to caspase-dependent degradation 1 of MCL-1 protein in AML cells Combining RVU120 and VEN represses inflammatory and AML oncogenic pathways at the 2 transcriptomic level RVU120 with VEN exerts cytotoxic and differentiati
Slide 23: 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 24: POTAMI-61
Foundations of POTAMI-61 study: RVU120 in MF • RVU120 targets JAK2 mutant cells in vitro • RVU120 stimulates erythropoiesis SCIENTIFIC • RVU120 eliminates MF symptoms in vivo VALIDATION as a single agent and shows synergy with ruxolitinib POTAMI-61 • US prevalence of ~13,000 patients STUDY UNMET NEE
Slide 25: POTAMI-61: MF Phase II study of RVU120 as mono and combo
REMARK: POTAMI-61 : MF Phase II study of RVU120 as mono and combo Study design • Population: • Ultimate opportunity in the first line in combination with a JAK inhibitor • Starting point in the second line primary or secondary MF; intermediate or high-risk MF per DIPSS; (1) previously treated with o
Slide 26: REMARK: RVU120 in LR-MDS – IIT conducted by Prof. Uwe Platzbecker
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 A
Slide 27: 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 28: 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 29: 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 30: 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 damage, classified as cancer chara
Slide 31: MEN1703 (SEL24): First-in-Class PIM/FLT3 Inhibitor
MEN1703 (SEL24): First-in-Class PIM/FLT3 Inhibitor
Slide 32: 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 33: 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 34: 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 35: Small Molecule Platform with Focus on Synthetic Lethality
Small Molecule Platform with Focus on Synthetic Lethality
Slide 36: Integrated Discovery Engine at Ryvu
Integrated Discovery Engine at Ryvu TARGET IDENTIFICATION DRUG RESEARCH AND VALIDATION DISCOVERY PIPELINE • Discovery of novel synthetic lethal • Integrated, multidisciplinary processes: • Broad portfolio of synthetic lethal and target pairs and actionable oncogenic rapid lead identification/optimiz
Slide 37: Ryvu discovers novel synthetic lethal targets through multipronged target discovery
Ryvu discovers novel synthetic lethal targets through multipronged target discovery, including the proprietary ONCO Prime platform Novel Target Discovery at Ryvu Novel Therapeutics ONCO Prime Isogenic primary cells Ryvu pipeline: • Gradual transformation of healthy primary • PRMT5 – lead optimizatio
Slide 38: ONCO Prime: Broad potential to identify novel cancer targets
ONCO Prime: Broad potential to identify novel cancer targets – first data in KRAS-driven CRC Ryvu’s KRAS-mutated CRC tumor cells are Screen of Ryvu cells yield synthetic lethal targets representative of CRC patients not seen in public data sets including DepMap Invasive cancer Adenocarcinoma SMAD4 K
Slide 39: 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 cellular potency and MTA-cooperativity in vitro KEY coupled with excellent in vivo activity exert
Slide 40: Small molecule inhibitors of WRN
Small molecule inhibitors of WRN Ryvu WRN inhibitors of ATPase activity selectively targeting tumors with microsatellite instability WRN INHIBITOR PROGRAM AT RYVU Helicase function validated X-ray of WRN helicase with Ryvu ligand KEY Synthetic lethality of WRN RATIONALE with microsatellite instabili
Slide 41: BioNTech and Ryvu: global collaboration to develop immune modulation small molecules
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 42: 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 43: Corporate Progress
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Slide 44: Financial Results: Q1 2024
Financial Results: Q1 2024 Q1YTD Q1 YTD $ million 2023* Cash position 2023* 2024* June 14, 2024 Revenues, incl.: 16.3 4.3 6.4 Partnering Grants 11.2 4.9 2.9 1.3 5.4 1.0 $64.0M pro forma including $8.6M received Total Costs**, incl.: 37.6 7.5 11.7 from the EIB for Tranche B Clinical Pipeline 13.0 1.8
Slide 45: 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 46: 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 47: 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 47.00 – 72.40 5 Tadeusz Wesolowski (incl. Augebit) 4.9% Average Daily
Slide 48: Thank you
Thank you CONTACT DATA: Ryvu Therapeutics S.A. www.ryvu.com ryvu@ryvu.com ir@ryvu.com
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