Biomea Fusion, Inc. · NASDAQ:BMEA
Biomea Fusion — Investor Presentation (November 2021)
34 slides from Biomea Fusion's investor presentation, Nov 15, 2021
Slide 1: Corporate Presentation November 2021
Biomea fusion tm Corporate Presentation November 2021
Slide 2: Disclaimer and Forward-Looking Statement
Disclaimer and Forward-Looking Statement Certain statements in this presentation and the accompanying oral commentary are forward-looking statements. These statements relate to future events or the future financial performance of Biomea Fusion, Inc. (the “Company”) and involve known and unknown risk
Slide 3: Company overview: FUSION platform and BMF-219
Experienced and Successful Management Team Novel FUSION™ Platform BMF-219—Clinical Stage Oncology Asset Multiple Oncology Programs built from FUSIONTM Platform revolutionize current medicine by creating and developing novel single agent and combination therapies that maximizes patient benefit Biomea
Slide 4: Our Team
Our Team Experienced and successful team designed, discovered, and developed breakthrough therapies Thomas Butler Ramses Erdtmann Franco Valle Naomi Cretcher Heow Tan Steve Morris MD Thorsten Kirschberg Jim Palmer Chairman & CEO President & COO Chief Financial Chief of People Chief Technical & Chief
Slide 5: Our Scientific Advisory Board
Our Scientific Advisory Board Bruce Lipshutz PhD Urte Gayko, PhD Dave Ball PhD Rohit N. Kulkarni, M.D., Ph.D. Xianxin Hua, M.D., Ph.D. David Smith, Ph.D. Jeffery Rubnitz, M.D., Ph.D. Professor of Chemistry SVP, Drug Dev. & Reg. Professor of Chemistry Professor of Medicine Professor of Cancer Biostat
Slide 6: Our Vision – We Aim to Cure
Our Vision – We Aim to Cure Biomea leverages the FUSIONTM Platform to create a suite of novel agents to maximize the depth and durability of response Validated Targets For Covalent Inhibition Biology Breakthrough Covalent Chemistry Chemistry Proprietary Combinations Medicine Drugs pursuing validated
Slide 7: Our Technology Platform
Our Technology Platform Traditional Small Molecule Design (Library Screening and Synthesis) FUSION™ Platform (AI/VR Matching + Custom Synthesis) Year 1 Year 2 Year 3 Year 4 Year 5 Year Target To Hit Hit To Lead Lead Optimization Preclinical Library Screening Small Molecule Target Exploration 2 3 4 L
Slide 8: Biomea Pipeline
Biomea Pipeline A suite of novel agents in multiple cancer indications and metabolic disease IND Target Population Program Discovery Phase 1 Phase 2 Phase 3 Next Milestone Enabling (US) MLL-R & NPM1 Liquid Tumors 2.5K 7.5K Patient enrollment (AML/ALL) MLL-r NPM1 BMF-219 Additional Liquid Tumors ~6K
Slide 9: Biomea's Value Proposition
Biomea’s Value Proposition Team Vision Platform Pipeline Execution Strategy Process Value Creation Experience designing and Combining validated Leveraging our platform Developing best-in-class developing leading small biology and proven with non-traditional drug covalent inhibitors for molecule drug
Slide 10: Irreversible Inhibitors Have a History of Medical Success
Irreversible Inhibitors Have a History of Medical Success Notable Irreversible Inhibitors Aspirin Penicillin Osimertinib (TAGRISSO) Tenofovir (VIREAD) Sofosbuvir (SOVALDI) Ibrutinib (IMBRUVICA) • Aspirin was the first commercialized irreversible drug—Discovered in 1899, Aspirin is the most utilized
Slide 11: Advantages of irreversible inhibitors
Greater Deep Target High Selectivity Therapeutic Inactivation Window • Irreversible drugs have non- • Irreversible permanent inactivation inhibitors can of cause • Irreversible to maintain drugs their effect are designed in the covalent and covalent interactions, which increase bound protein drug ab
Slide 12: Irreversible Inhibition Enables Large Therapeutic Window
Irreversible Inhibition Enables Large Therapeutic Window Irreversible small molecule inhibitors have uncoupled drug effect from drug exposure, resulting in more optimal PD/PK profile that maximizes target engagement Drug Exposure over 24 hrs Irreversible drugs: • Can quickly achieve nearly complete
Slide 13: Menin-MLL: A Complex Interaction
Menin-MLL: A Complex Interaction Role of Menin-MLL Complex Modified after Uckelmann (Scott Armstrong Lab) , ASH 2018, Abstract # 546 BMF-219 an irreversible covalent inhibitor at the Menin-MLL interface Menin-MLL Fusions Different fusions result in different binding affinities between MLL fusion pro
Slide 14: BMF-219 Impacts More than MLL Driven Tumors
BMF-219 Impacts More than MLL Driven Tumors Mechanism of Action NPM1 BMF-219 covalent binding to menin disrupts menin-MLL protein-protein interaction, resulting in global change of function Menin MLL Other Resulting change of function of menin impacts important binding partners involved in oncogenes
Slide 15: BMF-219 Shows Strong Cell-Growth Inhibition Across Menin Dependent Cell Lines
BMF-219 Shows Strong Cell-Growth Inhibition Across Menin Dependent Cell Lines MLLr BAL Cell Line MLLr AML Cell Line FLT3-ITD/NPM1 AML Cell Line (MV4;11) (MOLM-13) (OCI-AML3) 1200 5000 4000 (K) 1000 3500 4000 Units 3000 800 2500 600 3000 2000 Fluorescent 2000 1500 400 1000 200 1000 Relative 500 0 0 0
Slide 16: BMF-219 Produces Near Complete Inhibition of Growth in AML ex-vivo Samples
BMF-219 Produces Near Complete Inhibition of Growth in AML ex-vivo Samples Growth Inhibition of Ex-Vivo AML Cells from Patients (1μM 100% Patient 320: NPM1 AML, Treatment Patient 340: NPM1 AML, Treatment 90% Patient 400: MLL-r AML, Treatment 80% 70% tion 60% Inhibi 50% Growth 40% 30% 20% 10% 0% BMF
Slide 17: BMF-219 Shuts Down Target Gene – MEN1
BMF-219 Shuts Down Target Gene – MEN1 MEN1 Gene Expression Decreases w/ BMF-219 Treatment @6 hours @6 hours No significant change in MEN1 expression was observed after Wu Y et al. Disruption of the menin-MLL treatment of a reversible menin interaction triggers menin protein degradation inhibitor, MI
Slide 18: BMF-219 Shuts Down Gene Expression of Oncogenes
BMF-219 Shuts Down Gene Expression of Oncogenes w/ BMF-219 @6 hours @24 hours (Transcripts per Million is a measure of gene expression) • Irreversible inhibitor, BMF-219, downregulates expression of Menin (via the target MEN1 gene) and critical leukemogenic genes (e.g. MEIS1 and HOXA9)—MEIS1 is a ge
Slide 19: Survival Benefit in Disseminated Leukemia Xenograft Model
BMF-219 Showed Significant Survival Benefit in a Disseminated Leukemia Xenograft Model vs. Standard of Care • Mice were inoculated with xenograft cancer cells at high levels (1x107 MV4;11-luc) with greater than 90% viability • BMF-219 treatment showed notable reduction in tumor burden and survival b
Slide 20: Menin Can Play a Key Role in the Regulation of Oncogenesis
Menin Can Play a Key Role in the Regulation of Oncogenesis Transcription Histone Histone Regulators Factors Regulators • MLL1/MLL2 Menin • HDAC/SIRT • PRMT5 • SUV39H1 • DOT1L Menin Target Transcription Factors Genes • MYC / NPM1 • Beta Catenin Menin Target Genes • PTEFb • LEDGF • HOXA9 • TERT • AP-1
Slide 21: DLBCL, MM, & Other Tumors Have High Menin Dependency
DLBCL, MM, & Other Tumors Have High Menin Dependency Double knock-out of MEN1 via Broad Institute’s DEPMAP dataset shows that menin is essential for a wide variety of tumor types, including DLBCL, MM, leukemias and lymphomas BROAD Institute Cancer Dependency Map (DEPMAP) for Menin (MEN1) Note: CERES
Slide 22: Menin is Critical for MYC-dependent Aggressive DLBCL
Menin is Critical for MYC-dependent Aggressive DLBCL MYC is a transcription factor implicated in oncogenesis. MYC regulates genes associated with cellular proliferation, differentiation, and apoptosis MYC Overexpression Is a Critical Factor For Menin is Critical for Expression of MYC Target Genes Hi
Slide 23: BMF-219 Elicits Broad Impact on Complexes Surrounding Menin
BMF-219 Elicits Broad Impact on the Complexes Surrounding Menin. Resulting in Strong Modulation of MYC Driven Expression Figure: Transcription factor (TF) activity inference using ChIP-seq of differentially expressed genes in MOLM-13 cells incubated with 500 nM BMF-219 at 24 hours. Each bar represen
Slide 24: BMF-219 Inhibits Growth in Double Hit DLBCL Cell Lines
BMF-219 Inhibits Growth in Double Hit DLBCL Cell Lines. Providing Initial Validation of Anti-Cancer Activity Beyond AML DB TOLEDO 120 IC50 IC50 Top %Max 120 IC50 %Max BMF-219 0.316 98.64 IC50 Top 100 60 BMF-219 0.2877 99.47 Clinical Reversible ) 100 BMF-219 0.2877 99.47 (%) Clinical Reversible Inhib
Slide 25: BMF-219 Impairs Growth in Multiple Myeloma and KRAS Solid Tumor Cell Lines
BMF-219 Impairs Growth in Multiple Myeloma and KRAS Solid Tumor Cell Lines Multiple Myeloma Cell Viability (KMS-20 cells, 0.560µM dose) 80000 70000 60000 (relativeunits) 50000 Cellst 40000 30000 Survivingfluorescen 20000 10000 0 Day 4 Day 7 Day 11 Day 14 DMSO BMF-219 Impairment of survival in multip
Slide 26: BMF-219 is Highly Selective In Key Screening and Safety Panels
BMF-219 is Highly Selective In Key Screening and Safety Panels Kinase screening • 169 kinases screened; only two wild type kinases showed greater than 50% inhibition upon treatment with BMF-219 • In-house analysis of menin revealed no relevant structural similarity between targeted binding pocket an
Slide 27: Biomea Pipeline
Biomea Pipeline A suite of novel agents in multiple cancer indications and metabolic disease IND Target Population Program Discovery Phase 1 Phase 2 Phase 3 Next Milestone Enabling (US) MLL-R & NPM1 Liquid Tumors 2.5K 7.5K Patient enrollment (AML/ALL) MLL-r NPM1 Menin Programs BMF-219 Additional Liq
Slide 28: BMF-219: Biomea's Covalent Menin Inhibitor
BMF-219: Biomea’s Covalent Menin Inhibitor BMF-219: A Molecule That Really Grabs You and Won’t Let Go BMF-219 Properties Molecular Weight Approximately 500 kD Nanomolar Potency in Key Targeted Cell Lines: MLL-r NPM1 FLT3-ITD DLBCL MYC Driven Tumors MM KRAS Mutants (pan mutation) hERG inhibition ~5%
Slide 29: BMF-219 Phase I Study in r/r Acute Leukemia Patients
BMF-219 Phase I Study in r/r Acute Leukemia Patients Phase I first-in-human dose-escalation and dose-expansion study of BMF-219 will enroll adult patients with acute leukemia, including those with an MLL/KMT2A gene rearrangement or NPM1 mutation Phase I Study Design Dose Escalation Dose Expansion R/
Slide 30: Role of Menin in Diabetes: Beta Cell Regeneration
Role of Menin in Diabetes: Beta Cell Regeneration Menin is implicated in the proliferation of beta islet cells, providing rationale for a menin inhibitor as an agent for beta cell regeneration and turnover Pancreatic beta cells proliferation regulated via the menin/JunD/Pbk axis • Pbk is crucial for
Slide 31: Role of Menin in Diabetes: Glucose Tolerance
Role of Menin in Diabetes: Glucose Tolerance Potential for menin inhibition demonstrated by beta cell ablation diabetes model in MEN1 excised mice MEN1 Excision Prevents Development of STZ-induced Hyperglycemia Multiple low-dose streptozotocin (MLD-STZ) administered to the control and Men1-excised m
Slide 32: Near Term Milestones
Near Term Milestones BMF-219 – Liquid Tumors Completed IND Clearance DLBCL Preclinical Completed ASH 2021 Abstract BMF-219 Ph. I In Progress AML Trial Initiation Additional Preclinical Q1 2022 Data in DLBCL/MM BMF-219 – Solid Tumors Additional Preclinical Q1 2022 Data in KRAS Tumors BMF-219 – Diabet
Slide 33: Company Financials
Company Financials Detailed Financials (unaudited) Three Months Ended Nine Months Ended September 30, September 30, 2021 2020 2021 2020 Operating expenses: R&D $ 7,886 $ 789 $ 16,908 $ 1,339 G&A $ 4,752 $ 346 $ 10,022 $ 489 Total Operating Expenses $ 12,638 $ 1,135 $ 26,930 $ 1,828 Loss from operati
Slide 34: Thank You
Thank You
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