Biomea Fusion, Inc. · NASDAQ:BMEA
Biomea Fusion — Investor Presentation (January 2022)
40 slides from Biomea Fusion's investor presentation, Jan 12, 2022
Slide 1: Corporate Presentation January 2022
Exhibit 99.1 Corporate Presentation January 2022 1
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 business and financial performance of Biomea Fusion, Inc. (the “Company”) and involve known and
Slide 3: We Aim To Cure
We Aim To Cure Experienced and Successful Management Team Biomea Fusion is a clinical-stage biopharmaceutical company focused on the Novel FUSION™ Platform discovery and development of irreversible small-molecule drugs to treat patients with genetically defined cancers. We BMF-219 - Clinical Stage b
Slide 4: Novel Irreversible Covalent Inhibitor of Menin: Pipeline-in-a-Pill
BMF-219 – Novel Irreversible Covalent Inhibitor of Menin Pipeline-in-a-Pill – Single Agent for Multiple Indications Strong Pathway Control Large effect on target genes and proteins leading to cell death Multiple Shots on Goal Acute leukemias, MYC addicted and driven cancers, RAS/RAF driven solid tum
Slide 5: Our Team – 10+ Years of Success Together
Our Team – 10+ Years of Success Together Heow Tan Steve Morris MD Jim Palmer Thorsten Kirschberg Franco Valle Naomi Cretcher Thomas Butler Ramses Erdtmann Chief Technical & Chief Medical Officer EVP of Chemistry VP of Drug Chairman & CEO President & COO Chief Financial Chief of People Quality Office
Slide 6: Our Vision – We Are Patient Focused and Aim to Cure
Our Vision – We Are Patient Focused and Aim to Cure TM Biomea leverages the FUSION Platform to create a suite of novel agents to improve and extend life for patients Drugs pursuing validated targets have a ~2x higher Validated Targets Breakthrough likelihood of approval than molecules pursuing a Val
Slide 7: Irreversible Inhibitors Have a History of Medical Success
Irreversible Inhibitors Have a History of Medical Success Notable Irreversible Inhibitors • Aspirin was the first commercialized irreversible drug Aspirin Osimertinib (TAGRISSO) Penicillin • Notable precision oncology and infectious disease programs leverage irreversible mechanisms - Precision Oncol
Slide 8: Important Attributes of Irreversible Small Molecule Inhibition
Important Attributes of Irreversible Small Molecule Inhibition Greater Deep Target Therapeutic High Selectivity Inactivation Window Irreversible inhibitors Irreversible inhibitors Irreversible inhibitors • can cause permanent • are designed to maintain an • two-step inhibition: 1) requires inactivat
Slide 9: Benefits of Covalent Irreversible Inhibition
Benefits of Covalent Irreversible Inhibition Irreversible inhibitors facilitate prolonged target occupancy effect, without prolonged systemic exposure Example: Ibrutinib, an Irreversible Inhibitor with Long Kinetic Half Life and Short Biologic Half Life PK/PD • Ibrutinib has a short biologic half li
Slide 10: Our Technology Platform – Irreversible Inhibitors
Our Technology Platform – Irreversible Inhibitors Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Target To Hit Hit To Lead Lead Optimization Preclinical Traditional Small Small Molecule Library Screening Molecule Design 1 2 3 4 Target Exploration Lead Optimization Synthesis (Library Screening and Library
Slide 11: Biomea Pipeline
Biomea Pipeline – Pursuing Up to 7 Tumor Types and Diabetes in the Clinic in 2022 IND Target Population Phase 1 Phase 2 Phase 3 Program Discovery Key Milestone Enabling (US Incidence) MLL-R & NPM1 Liquid Tumors 2.5K 7.5K Patient enrollment (AML, ALL) MLL-r NPM1 Menin Programs Additional Liquid Tumor
Slide 12: Target Patient Population for BMF-219
BMF-219 to Pursue Multiple Tumor Types in 2022 Target Patient Population for BMF-219 80,000 Target Population for 70,000 Reversible Menin Inhibitors 60,000 50,000 40,000 70K 30,000 60K 60K 20,000 35K 10,000 18K 2.5K 7.5K 0 MLL-R NPM1 DLBCL MM RAS Mut. Pancreatic KRAS Mut. Lung Cancer RAS Mut. Colon
Slide 13: Novel Irreversible Covalent Inhibitor of Menin: Pipeline-in-a-Pill
BMF-219 – Novel Irreversible Covalent Inhibitor of Menin Pipeline-in-a-Pill – Single Agent for Multiple Indications Strong Pathway Control Large effect on target genes and proteins leading to cell death Multiple Shots on Goal Acute leukemias, Myc addicted and driven cancers, Ras/Raf driven solid tum
Slide 14: Inhibits Complex Interaction Independent of MLL Fusion Partner
BMF-219 Shown to Inhibit A Complex Interaction Independent of the MLL Fusion Partner Role of Menin-MLL Complex Menin-MLL Fusions Different fusions result in different binding affinities between MLL fusion proteins and Menin MLL Fusions (AML/ALL) Prevalence (%) MEIS1 AF4 36% AF9 19% BMF-219 ENL 13% A
Slide 15: Rapid and Near Complete Reduction of Oncogene Expression
BMF-219 Demonstrated Rapid and Near Complete Reduction of Expression of Oncogenes Gene Expression Changes in AML cells following treatment w/ BMF-219 (0.500µM dose) • Irreversible inhibitor, BMF-219, downregulates expression of Menin (via the target MEN1 gene) and critical leukemogenic genes (e.g. M
Slide 16: Superior Impact on Key Gene Signatures in MLL-rearranged AML
BMF-219 Displayed Superior Impact on Key Gene Signatures in MLL-rearranged AML Cell Line Relative Gene Expression – BMF-219 Relative Gene Expression – Clinical Reversible Inh. (KO-539) 1.2 BCL2 MYC HOXA9 MOLM-13 MOLM-13 1.0 0.8 Significant changes to 0.6 BCL-2, MYC and HOXA9 w/ BMF-219 Treatment 0.4
Slide 17: Novel Irreversible Covalent Inhibitor of Menin: Pipeline-in-a-Pill
BMF-219 – Novel Irreversible Covalent Inhibitor of Menin Pipeline-in-a-Pill – Single Agent for Multiple Indications Strong Pathway Control Large effect on target genes and proteins leading to cell death Multiple Shots on Goal Acute leukemias, MYC addicted and driven cancers, RAS/RAF driven solid tum
Slide 18: Potential to Impact Important Binding Partners in Multiple Tumors
BMF-219 Has the Potential to Impact Important Binding Partners Involved in Multiple Tumors Mechanism of Action Target Patient Population MLL • MLL-r Acute Leukemia HOXA9/ NPM1 MEIS1 BMF-219 covalent binding to NPM1 • NPM1 mutant Acute Leukemia menin disrupts menin-MLL protein-protein interaction, MY
Slide 19: High Menin Dependency Across Tumor Types (DEPMAP)
Acute Leukemia, DLBCL, MM, & Other Tumor Types Have High Menin Dependency Based on Broad Institute DEPMAP Dataset BROAD Institute Cancer Dependency Map (DEPMAP) for Menin (MEN1) • Cell viability scores have shown that menin plays a key role in survival of multiple tumors • High menin dependency in l
Slide 20: Disrupts MYC Genomic Function
BMF-219 Shown to Disrupt MYC Genomic Function via Broad Impact on the Complexes Surrounding Menin Irreversible Covalent Menin Inhibitor – BMF-219 Reversible Menin Inhibitor – SNDX-50469 TF activity inference scores greater than 10 are highly significant TF activity inference using ChIP-seq of differ
Slide 21: Menin is a Key Node for MYC and KRAS Addicted Tumors
Menin is a Key Node for MYC and KRAS Addicted Tumors MYC is constitutively and aberrantly expressed in over 70% of human cancers MYC transcriptional complex facilitates expression of oncogenesis via MYC target genes KRAS Mutant Solid Tumors • Menin regulates downstream pathways associated with KRAS
Slide 22: Novel Irreversible Covalent Inhibitor of Menin: Pipeline-in-a-Pill
BMF-219 – Novel Irreversible Covalent Inhibitor of Menin Pipeline-in-a-Pill – Single Agent for Multiple Indications Strong Pathway Control Large effect on target genes and proteins leading to cell death Multiple Shots on Goal Acute leukemias, Myc addicted and driven cancers, Ras/Raf driven solid tum
Slide 23: Superior Cell Killing of AML Cell Lines at Half the Dose
BMF-219 Exerted Superior Cell Killing of AML Cell Lines at Half the Dose BMF-219 Reversible Inhibitors Source Data from ASH 2021 Publications 100% KO-539 is 15% effective @ 1μM in MOLM-13 cells 90% 80% 70% 60% 50% 40% 30% 20% 10% Blood (2021) 138 (Supplement 1): 3357. ASH, 2021. 0% SNDX-50469 is 12%
Slide 24: Near Complete Inhibition of Growth Across Acute Leukemia Cell Lines
BMF-219 Produced Near Complete Inhibition of Growth at 0.560μM Across Acute Leukemia Cell Lines MLLr BAL Cell Line MLLr AML Cell Line FLT3-ITD/NPM1 AML Cell Line (MV4;11cells, 0.560µM dose) (MOLM-13 cells, 0.560µM dose) (OCI-AML3 cells, 0.560µM dose) 1200 5000 4000 3500 1000 4000 3000 800 2500 3000
Slide 25: Inhibition of Growth in Multiple Myeloma and KRAS Solid Tumor Cell Lines
BMF-219 Produced Near Complete Inhibition of Growth at 0.560μM in Multiple Myeloma and KRAS Solid Tumor Cell Lines Multiple Myeloma Cell Viability KRAS Pancreatic Cancer Viability (KMS-20 cells, 0.560µM dose) (MIA-PaCa--2 cells, 0.560µM) 80000 3500000 70000 3000000 60000 2500000 50000 2000000 40000
Slide 26: Near Complete Inhibition of Growth in AML ex-vivo Samples
BMF-219 Produced Near Complete Inhibition of Growth at 1μM in AML ex-vivo Samples Growth Inhibition of ex-vivo AML Cells from Patients (1μM Exposure) 100% Patient 320: NPM1 AML, Treatment Naïve Patient 340: NPM1 AML, Treatment Naïve 90% Patient 400: MLL-r AML, Treatment Naïve 80% • 1µM exposure of B
Slide 27: Near Complete Inhibition of Growth in DLBCL Cell Lines
BMF-219 Produced Near Complete Inhibition of Growth at 1μM in DLBCL Cell Lines BMF-219 Growth Inhibition in DLBCL Cell Lines, ASH 2021 DB TOLEDO 120 120 (Double Hit / GCB Lymphoma) (Double Hit / GCB Lymphoma) IC50 %Max IC50 Top IC50 %Max IC50 Top BMF-219 0.316 98.64 BMF-219 0.2877 99.47 100 BMF-219
Slide 28: Novel Irreversible Covalent Inhibitor of Menin: Pipeline-in-a-Pill
BMF-219 – Novel Irreversible Covalent Inhibitor of Menin Pipeline-in-a-Pill – Single Agent for Multiple Indications Strong Pathway Control Large effect on target genes and proteins leading to cell death Multiple Shots on Goal Acute leukemias, Myc addicted and driven cancers, Ras/Raf driven solid tum
Slide 29: Highly Selective in Key Screening and Safety Panels
BMF-219 Was Highly Selective in Key Screening and Safety Panels No Histopathology Findings Were Observed with BMF-219 in GLP and non-GLP Toxicology Studies Kinase screening Glutathione reactivity • 169 kinases screened; only two wild type kinases showed Mean half-• Drugs with limited non-specific in
Slide 30: Significant Survival Benefit in Disseminated Leukemia Xenograft Model
BMF-219 Achieved Significant Survival Benefit in A Disseminated Leukemia Xenograft Model Anti-Tumor Effect Body Weight 110% Vehicle BMF-219, 40mg/kg 100% BMF-219, 20mg/kg 90% Dosing Period 80% Day 1 Day 8 Day 15 Day 22 *40mg/kg BMF-219 7 • Mice were inoculated with xenograft cancer cells at high lev
Slide 31: Next Generation Irreversible Covalent Menin Inhibitor BMF-219
BMF-219: Next Generation Irreversible Covalent Menin Inhibitor BMF-219: A Molecule That Really Grabs Predicted Efficacious Human AUC You and Won’t Let Go for BMF-219 BMF-219 Properties ~500,000 Molecular Weight Approximately 500 kD ’219 Expected hERG AUC Nanomolar Potency in Key Targeted Cell Lines:
Slide 32: Next Generation Menin Inhibitor
BMF-219 Next Generation Menin Inhibitor Attacks the target by forming a covalent bond (irreversible inhibitor) st Challenges of 1 Gen Menin Inhibitors Solutions Offered by BMF-219 Efficient Pharmacology (Target AUC/Daily Exposure) Poor PK/PD Properties (Inefficient Pharmacology) Leading to Wider The
Slide 33: 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 enrolling 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/R
Slide 34: Clinical Study Plan – Enrolling Multiple Tumor Types and Diabetic Patients in 2022
Clinical Study Plan – Enrolling up to 7 Tumor Types and Diabetic Patients in 2022 Program H1 2022 H2 2022 AML / ALL Trial Initiated in Q4 ’21 (MLL-r, NPM1) DLBCL Ph I. BMF-219 (DHL / DEL) Enrollment (Oncology) Menin Programs Ph I. MM (MYC driven) Enrollment Lung, Ph. I Trial Pancreatic, Preclinical
Slide 35: Potential for Menin Inhibition Demonstrated by Beta Cell Ablation Model
Potential for Menin Inhibition Demonstrated by Beta Cell Ablation Diabetes Model in MEN1 Excised Mice MEN1 Excision Prevents Development of Streptozotocin (STZ)-induced Hyperglycemia Control Control Men1-excised Men1-excised Men1-excised mice did not develop hyperglycemia in Multiple low-dose strept
Slide 36: Ameliorated Diabetes in Animal Models
BMF-219 Ameliorated Diabetes in Animal Models BMF-219 was able to normalize glucose levels in the majority of animals after just two weeks of treatment. The majority of the effect was maintained despite complete washout of BMF-219 Preclinical data support BMF-219 as an oral, long-acting treatment fo
Slide 37: Biomea Fusion – We Aim To Cure
Biomea Fusion – WE AIM TO CURE Established FUSION platform technology for discovery of irreversible covalent inhibitors Lead molecule (BMF-219) with best-in-class potential and favorable safety profile Initiate studies with BMF-219 in up to 7 tumor types (liquid and solid) in 2022 Significant addres
Slide 38: Near Term Milestones
Near Term Milestones – Biomea Fusion (NASDAQ: BMEA) BMF-219 – Liquid Tumors Menin Inh. – Diabetes Diabetes Menin IND Clearance Completed H1 2022 Pathway Validation DLBCL Preclinical Completed IND Filing H2 2022 ASH 2021 Abstract Phase I Enrolling Phase I Study H2 2022 In Progress Diabetes Trial Init
Slide 39: 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 40: Thank You
Thank You 40