Ryvu Therapeutics SA · GPW:RVU
Ryvu Therapeutics SA — Investor Presentation (August 2022)
43 slides from Ryvu Therapeutics SA's investor presentation, August 2022
Slide 1: Targeted therapeutics at the forefront of oncology
Targeted therapeutics at the forefront of oncology CORPORATE PRESENTATION August 2022
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 Clinical Pipeline Small Molecule Discovery Platform Fully Integrated Across Heme and Solid Tumors Novel Synthetic Lethality Targets Research Organization RVU120 Developing small molecule therapies which address high value emerging targets Team ~150 scientists (with ~80 PhDs) Wholly
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 PETER LITTLEWOOD, MSc MARTIN SWARBRICK, Ph.D. MATEUSZ
Slide 5: Broad pipeline addressing emerging targets in oncology
Broad pipeline addressing emerging targets in oncology 5
Slide 6: Ryvu evolution
Ryvu evolution 2007 - 2014 2019 2019 - 2022 SEL24 RVU120 2007: Selvita, a hybrid Corporate spin-out of • Successfully completed • Preliminary positive Phase I model biotech company, Selvita (CRO) from Ryvu Phase I in AML clinical & preclinical data with joint CRO and Therapeutics completed • Positiv
Slide 7: 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 8: RVU120: First-in-class CDK8/CDK19 inhibitor
RVU120: First-in-class CDK8/CDK19 inhibitor Mechanism of action applicable to hematologic and solid tumors CDK8/19 inhibition by RVU120 triggers CDK8/19 pathway promotes tumor growth differentiation and apoptosis Viability of tumor cells Apoptosis of tumor cells Maintenance of malignant stem cells A
Slide 9: RVU120: Potential across a broad range of tumors
RVU120: Potential across a broad range of tumors Blood Cancers & Disorders Solid tumors Neuroendocrine AML Breast MDS JAK2 mut MPN Sarcoma NHL HCC Diamond-Blackfan Anemia Colorectal Prostate • Early signs of efficacy in AML/HR-MDS, • Preclinical evidence in TNBC including CR; Phase I update at EHA 2
Slide 10: RVU120: Highly selective and potent inhibitor of CDK8/19
RVU120: Highly selective and potent inhibitor of CDK8/19 Small molecule, orally bioavailable RVU120: Potent/Selective → Targeted/Safer * • Low nM activity on CDK8/19: Predictions indicate near complete target engagement at clinically feasible drug exposure. • Excellent kinase selectivity: lack of bi
Slide 11: 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 12: 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 13: 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 14: RVU120: Phase I AML/MDS Study
RVU120: Phase I AML/MDS Study Recruitment in Part 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 patient stra
Slide 15: RVU120 shows favorable safety and predictable PK characteristics
RVU120 shows favorable safety and predictable PK characteristics Favorable safety profile of RVU120 in the first 16 treated patients Phase I Study in R/R AML and HR-MDS Data cutoff 26 May 2022 • 16 patients: 14 AML and 2 HR-MDS • Median age 72 years • Median of 3 prior lines of therapy • No DLTs wer
Slide 16: RVU120 Phase I data show early signs of efficacy in AML and HR-MDS
RVU120 Phase I data show early signs of efficacy in AML and HR-MDS EHA 2022: Data cutoff 26 May 2022 CLINICAL BENEFIT IN FIVE PATIENTS: • Hematologic Improvement – Erythroid Response: DNMT3A- mutated HR-MDS patient on treatment for more than 18 months with stable disease • Complete Remission: DNMT3A
Slide 17: More than 50% target inhibition has already been achieved at the dose of 75mg
More than 50% target inhibition has already been achieved at the dose of 75mg – dose escalation continues RVU120 exposure and pSTAT5 inhibition in leukemic blasts Higher level of target inhibition is expected with higher exposure, predicted to result in even stronger clinical activity of RVU120. 17
Slide 18: Case Focus: AML patient achieved Complete Remission
Case Focus: AML patient achieved Complete Remission despite poor prognostics, including DNMT3A/NPM1 mutations Resolution of skin lesions: Patient • AML with mutations in FLT3, DNMT3A, NPM1 Characteristics • Failed 3 prior lines of therapy, including 2 FLT3 inhibitors and venetoclax + decitabine – kn
Slide 19: Case Focus: HR-MDS patient achieved Erythroid Response
Case Focus: HR-MDS patient achieved Erythroid Response, duration of therapy greater than 18 months Hematological improvement-erythroid (HI-E) • High risk MDS with DNMT3A mutation; failed 3 number of RBC transfusions Patient 10 Characteristics prior lines of therapy, including HMA, associated with 8
Slide 20: RVU120 in Solid Tumors
RVU120 in Solid Tumors Broad potential in solid tumors with strong preclinical evidence in TNBC Evidence in TNBC Solid • Preclinical evidence of activity RVU120 tested in subcutaneous xenograft of a TNBC cell line. Tumors across various solid tumors Tumor volume kinetics Body weight kinetics • Poten
Slide 21: RVU120: Phase I Solid Tumor Study
RVU120: Phase I Solid Tumor Study Recruitment in Part 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 one week off l
Slide 22: RVU120: Market Opportunity in AML
RVU120: Market Opportunity in AML Significant revenue growth in AML therapeutics Acute Myeloid Leukemia ~$1,300m Samples with mutation data (531 patients / 622 samples) AML Market1 ~$600m DNMT3A 2020 2025 $8.0 billion ~$500m DNMT3A $1.2 billion 46% + NPM1 ~30% ~$400m CAGR ~$300m NPM1 ~$300m RYVU CLI
Slide 23: RVU120 Clinical Development and Commercialization strategy
RVU120 Clinical Development and Commercialization strategy HEMATOLOGY CANCERS US Patient 2022 2023 2024 2025 2026 2027 2028 Opportunity1 Fast-to-market strategy: Ph I RVU120 monotherapy 3,400+ in R/R AML/HR-MDS Pivotal Ph II Combo expansion: Ph I Dose Finding RVU120 + preclinically Ph II Combo Expan
Slide 24: RVU120: Acceleration of value creation in 2022 and beyond
RVU120: Acceleration of value creation in 2022 and beyond Leading with Science Clinical Trials Execution strategy Financial strength • Wholly owned, • Demonstrating proof-of- • Defined pathway to the • Cost-efficient first-in-class, selective oral concept, single-agent activity registration of RVU12
Slide 25: SEL24 (MEN1703): First-in-Class PIM/FLT3 Inhibitor in AML
SEL24 (MEN1703): First-in-Class PIM/FLT3 Inhibitor in AML
Slide 26: 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 Value through PIM and FLT3 are oncogenes global deal with MENARINI 1 involved in AML • Partnered globally with Menarini, TOP 40 global pharma company, based in Italy, in 2017 2 Dual targeting creates potential for • M
Slide 27: SEL24 (MEN1703) Phase II data confirm manageable safety profile
SEL24 (MEN1703) Phase II data confirm manageable safety profile Results from DIAMOND-01 (CLI24-001) Trial: First-in-Human Study of SEL24/MEN1703, a Dual PIM/FLT3 kinase inhibitor, in patients with Acute Myeloid Leukemia Results & Safety Demographics and Baseline Patient Characteristics • 48 patients
Slide 28: SEL24 (MEN1703) showed single-agent efficacy in R/R AML patients
SEL24 (MEN1703) showed single-agent efficacy in R/R AML patients, in particular in the IDH+ population, in the Dose Escalation/Cohort Expansion study Efficacy • Objective responses have been reported in 4 out of 48 patients (8%) across DE and CE phases, with 3 out of 4 responders harboring IDH mutat
Slide 29: Initial results from the ongoing, fully-enrolled IDHm AML expansion cohort
Initial results from the ongoing, fully-enrolled IDHm AML expansion cohort confirm promising single agent efficacy Efficacy EHA 2022: As of 21 April 2022, 25 patients were enrolled in the IDHm AML In total, 15 patients completed ≥1 treatment expansion cohort cycle and were efficacy evaluable • Promi
Slide 30: Small Molecule Platform with Focus on Synthetic Lethality
Small Molecule Platform with Focus on Synthetic Lethality
Slide 31: 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 32: 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 Target #1 • Single-most synthetic lethal target
Slide 33: Experimental target discovery platform – three approaches
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 Cellular stress in CRISPR screens tumor micr
Slide 34: 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 KEY RATIONALE exert synthetic lethal phenotype in MTAP deleted cells MECHANISM MTA-cooperative inhibitors OF ACTION MRTX RVU4 RVU5 RVU6 1
Slide 35: 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 36: Small molecule STING agonists (RVU-27065)
Small molecule STING agonists RYVU APPROACH STATUS PRECLINICAL CANDIDATE APPROACH ▪ Small molecule, systemic, direct STING agonists ▪ Superior in vitro activity and anti-tumor efficacy DIFFERENTIATION ▪ Suitable either for systemic or targeted delivery IP RIGHTS STATUS ▪ Several patent applications
Slide 37: 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 • In July 2022, Exelixis and Ryvu entered into an exclusive license agreement to expand Exelixis’ portfolio of biotherapeutics: Exelixis will combine Ryvu’s proprietary small molecule STING
Slide 38: HPK1 inhibitors
HPK1 inhibitors HPK1 KINASE IN TCR SIGNALLING RYVU APPROACH STATUS LEAD OPTIMIZATION ▪ Small molecule, selective, orally bioavailable APPROACH inhibitors of HPK1 kinase activity ▪ High selectivity against kinases from TCR pathway DIFFERENTIATION ▪ Immunostimulatory activity in immunosuppressed, resi
Slide 39: Corporate Progress
Corporate Progress
Slide 40: 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 41: Full-Year Financial Results: Q1 2022
Full-Year Financial Results: Q1 2022 $ million 2021* Q1 2021* Q1 2022* Cash position Revenues, incl.: 9.6 1.7 1.7 June 30, 2022 # of employees Partnering 2.7 0.1 0.0 $9.6M Grants 6.5 1.6 1.6 Total Costs**, incl.: 23.8 5.8 6.2 Available grant funding Clinical Pipeline 5.0 0.9 1.6 Preclinical Pipeline
Slide 42: Near term milestones
Ryvu: developing small molecule therapies to address high value emerging targets in oncology • First-in-class selective CDK8 inhibitor (RVU120) NEAR/MID TERM MILESTONES with potential across multiple indications CLINICAL RVU120 VALIDATION • Differentiated, first-in-class dual PIM/FLT3 inhibitor lice
Slide 43: Contact data
CONTACT DATA: Ryvu Therapeutics S.A. www.ryvu.com [email protected] 43
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