EX-99.2

EX-99.2 3 d417295dex992.htm EX-99.2 EX-99.2

Exhibit 99.2 JP Morgan 2023 Corporate Presentation 1

Disclaimer Legal Disclaimer & Forward-Looking Statements 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 unknown risks, uncertainties and other factors that may cause the actual results, levels of activity, performance or achievements of the Company or its industry to be materially different from those expressed or implied by any forward-looking statements. In some cases, forward-looking statements can be identified by terminology such as “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “potential” or other comparable terminology. All statements other than statements of historical fact could be deemed forward-looking, including any projections of financial information or profitability, the initiation, timing and results of pending or future preclinical studies and clinical trials, the actual or potential actions of the FDA, the status and timing of ongoing research, development and corporate partnering activities, any statements about historical results that may suggest trends for the Company's business; any statements of the plans, strategies, and objectives of management for future operations; any statements of expectation or belief regarding future events, potential markets or market size, or technology developments, and other factors affecting the Company's financial condition or operations. The Company has based these forward-looking statements on its current expectations, assumptions, estimates and projections. While the Company believes these expectations, assumptions, estimates and projections are reasonable, such forward- looking statements are only predictions and involve known and unknown risks and uncertainties, many of which are beyond the Company's control. These and other important factors may cause actual results, performance or achievements to differ materially from those expressed or implied by these forward-looking statements. The forward-looking statements in this presentation are made only as of the date hereof. Except as required by law, the Company assumes no obligation and does not intend to update these forward-looking statements or to conform these statements to actual results or to changes in the Company's expectations. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Page 2

Excellent Science - Combining Validated Targets with Breakthrough Chemistry We aim to cure TM Experienced Management Team Biomea Fusion is a clinical-stage biopharmaceutical company focused on the discovery and development of oral covalent small-molecule drugs to treat Novel FUSION™ System patients with genetically defined cancers and metabolic diseases. We believe that our approach may lead to significant improvement and extension of life for patients. Our team is engaged in all phases of drug discovery and development, including target selection, BMF-219 - Clinical Stage Lead Asset small molecule design, and preclinical and clinical studies to develop innovative medicines. BMF-500 and additional Programs Page 3

Developing some of the most impactful medicines of our time A long history of developing successful drugs together Heow Tan Steve Morris MD Ramses Erdtmann Naomi Cretcher Franco Valle Thomas Butler Thorsten Kirschberg Jim Palmer Chief Technical & Chief Medical President & COO Chief of People Chief Financial Chairman & CEO EVP of Chemistry VP of Drug Quality Officer Officer Officer Discovery 22+ years in Life Science 25+ years in Life Science 15+ years in Life Science 15+ years in Life Science 15+ years in Life Science 15+ years in Life Science 30+ years in Life Science 25+ years in Life Science Pharmacyclics Pharmacyclics HealthChart LLC Eidos Therapeutics Pharmacyclics Pharmacyclics Biota Ltd Terns Pharmaceuticals Gilead Sciences Oxygen Investments Genentech Collegium Pharmaceutical Insight Genetics Iovance Biotherapeutics Cytopia Ltd. Gilead Sciences UC Irvine, BA Comm Praecis Pharmaceuticals St. Jude Children’s Research UCLA – MBA Finance Commerzbank Pharmacyclics Rigel, Inc. Cell Gate UCSB, MS – Chemistry SF State University, Comm Ohio State University Hospital CallidusCloud Celera Genomics University of Münster, Golden Gate University, Santa Clara University Board certified internist Master’s in Banking & Corp PricewaterhouseCoopers Prototek Inc. MBA University of Leavey School of Business, (Univ. of Texas SW HSC) San Jose State University, Finance Purdue University Münster, Ph.D., Chemistry MBA – Finance & Mgmt and medical oncologist BS Corporate Finance Ph.D. Organic Chemistry (Yale University School of Medicine) Co-lead of Ledipasvir at Gilead Co-inventor of Remdesivir at Gilead Co-inventor of ibrutinib at Celera Page 4

TM Biomea leverages the FUSION System to Create a Suite of Novel Covalent Agents to Improve and Extend the Lives of Patients Biomea’s Development Principles Drugs pursuing Validated Disease Targets have a ~2x higher likelihood of approval than molecules pursuing Validated Validated Targets Breakthrough a new mechanism of action Targets Sources: Nelson et al. (2015) Nat Genet.; Thomas et al. (2016) BIO; In a Landscape of 'Me Too' Drug For Covalent Validated Targets Breakthrough Covalent Chemistry Development, What Spurs Radical Innovation? HBS Weekly Review (Jun 2018) Inhibition For Covalent Covalent Inhibition Chemistry Biology Covalent Small Molecule Inhibitors provide deep Chemistry target inactivation and a wider therapeutic window, allowing for longer duration on therapy Covalent Sources: Singh et al. (2011) Nature Reviews Drug Discovery; Cheng et al. (2020) Journal of Hematology & Inhibitors Oncology; Strelow (2017) SLAS Discovery; Kalgutkar & Dalvie (2012) Expert Opin. Drug Discov.; Proprietary Combinations Combination Therapy with non-overlapping resistance mechanisms results in more durable Medicine Proprietary Chemistry responses and better outcomes Sources: Palmer et al. (2019) eLife; Mokhtari et al. (2017) Oncotarget Combinations Page 5

TM Our Technology Platform – The FUSION SYSTEM TM Biomea created the Fusion System specifically to address unique targets and rapidly create highly potent and safe covalent inhibitors for them. Protein-protein interactions Shallow, limited, or dynamic binding sites Difficult to target kinases, including avoiding high homology family High affinity competitive ligands members Transcriptional factors Systemic tolerability issues at efficacious dose Low expressing targets Targeting optimal confirmation Scaffold proteins Identify small molecules for new targets Small GTPases Most proteins are considered undruggable because it’s impossible to get high enough drug exposure to effectively silence the target without significant side effects… Our Optimized Covalent Inhibitors Uniquely Solve That Problem. 6

TM Our Technology Platform – The FUSION SYSTEM – provided 3 Program leads over the past 4 years! Target identification to IND candidate in 18 months IND Target to Hit Custom Lead Lead Optimization Custom scaffold creation Target validation Library of custom engagers Refinement Proprietary AI platform with VR Custom built Synthesis to Building in drug-like Visual integration of validation matches novel DRUG create candidates with properties, optimizing PK/PD crystal structures of target and reactive LIKE PROBES to cysteines; we do desired profile, and maintaining cysteine not screen via library probes. specificity Utility: Utility: Utility: Utility: Differentiated insights from Library of covalent scaffolds AI/VR program platform yields Scaffolds are further refined X-ray crystal structures, provide for ~1,000 de novo over 300 scaffolds, which are with Mass spec, animal, and identifying target cysteines scaffolds for AI/VR scoring synthesized for in vitro testing cell-based assays to two IND candidates Page 7

Covalent Chemistry creates very powerful results Covalent Inhibitors - a History of Medical & Commercial Success Notable Covalent Inhibitors • Aspirin was the first commercialized covalent drug Aspirin Penicillin Osimertinib (TAGRISSO) • Notable precision oncology and infectious disease programs leverage covalent mechanisms - Precision Oncology: Osimertinib and Ibrutinib both target kinases and are used in subpopulations with specific genetic biomarkers - Antivirals: Remdesivir and Tenofovir both target reverse transcriptases and are Remdesivir (VEKLURY) Ibrutinib (IMBRUVICA) Sofosbuvir (SOVALDI) leveraged to treat HCV and other viruses including HIV and COVID-19 Compounds in blue were invented or developed by Biomea Fusion senior leadership Page 8

Case Study PCI-32765 IMBRUVICA - Prolonged Target Occupancy Effect Without prolonged Systemic Exposure Imbruvica – a Covalent Inhibitor with Long Kinetic but very Short Biological Half Life High Selectivity Long Kinetic Half Life Two-step inhibition: 1) Initial reversible binding followed by % Active-Site Occupancy (left axis) indicates 2) covalent interaction, increasing target selectivity irreversible BTK Inhibition at cancer sites Deep Target Inactivation Short Biologic Half Life Plasma concentration (right axis) reflects Permanent inactivation of bound protein drives target systemic exposure to body elimination through normal cellular degradation processes Greater Therapeutic Window Designed to maintain an effect without sustained systemic exposure, unlike conventional non-covalent inhibitors Page 9 9 (ng/ml)

JPM 2022 Announcement BMF-219 Goals for the year 2022 Initiation of “Clinical Trials in 7 tumor types and in Diabetes” – and WE DID IT! Completion of Healthy Volunteer Completed Portion of Study Enrollment of First Diabetes Patient Completed Plus CLL Additional Programs nd 2 Pipeline Candidate H1 2022 Announced rd To be 3 Pipeline Candidate announced Announced Page 10

In 2022 Biomea Expanded into Eight Different Solid and Liquid Tumors as well as Type 2 Diabetes Biomea’s Pipeline as of January 2023 Addressable Population IND Discovery Phase 1 Phase 2 Phase 3 Enabling (US Incidence) AML/ALL (Leukemia) ~2.5K MLL-r ~6K NPM1 DLBCL (Lymphoma) ~6.5K DLBCL (r/r MYC) COVALENT-101 (Liquid Tumors) MM (Myeloma) ~9.5K MM (r/r MYC) CLL (Leukemia) ~8K CLL (r/r) BMF-219 Menin NSCLC (Lung) ~58K NSCLC (KRAS) COVALENT-102 Program (KRAS PDAC (Pancreas) ~53K PDAC (KRAS) Solid Tumors) ~60K CRC (KRAS) CRC (Colon) COVALENT-111 Type 2 Diabetes ~37M Prevalent T2 Diabetics (Diabetes) BMF-500 COVALENT-103 AML/ALL (Leukemia) FLT3 ~6K FLT3+ AML (Liquid Tumors) Program Additional Oncology Target # 3 Undisclosed Oncology Program Page 11

BMF-219 and BMF-500 Patient Populations in the US Cancer Indications: >200K and Diabetes: >125M Addressable Annual US Patient Population for BMF-219 Diabetes Patient Population Oncology Patient Population 70,000 100 M ~90M 60K 90 M ~58K 60,000 ~53K 80 M MLL-R and 50,000 70 M NPM1 AML Initial Target 60 M 40,000 Patient 50 M Population 30,000 ~37M for menin 40 M inhibitors 30 M 20,000 20 M 9.5K 8K 10,000 6K 6K ~6.5K 10 M 2.5K 1.6M 0 M FLT3 MLL-R NPM1 DLBCL r/r with MM r/r with CLL r/r KRAS Mut. KRAS Mut. KRAS Mut. Diabetes Pre Diabetc Diabetes (BMF-500) MYC MYC Pancreatic NSCLC Colon Cancer (Type I) (Type 2) (Type II) Implication Implication Cancer Acute Leukemias Lymphoma & Myelomas Solid Tumors Metabolic Sources: Jovanović, K. K., Roche-Lestienne, C., Ghobrial, I. M., Facon, T., Quesnel, B., & Manier, S. (2018). Targeting MYC in multiple myeloma. Leukemia, 32(6), 1295–1306. https://doi.org/10.1038/s41375-018-0036-x ; Riedell, P. A., & Smith, S. M. (2018). Double hit and double expressors in lymphoma: Definition and treatment. Cancer, 124(24), 4622–4632. https://doi.org/10.1002/cncr.31646; Kempf, E., Rousseau, B., Besse, B., & Paz-Ares, L. (2016). KRAS oncogene in lung cancer: focus on molecularly driven clinical trials. European respiratory review : an official journal of the European Respiratory Society, 25(139), 71–76. https://doi.org/10.1183/16000617.0071-2015; Lanfredini, S., Thapa, A., & O'Neill, E. (2019). RAS in pancreatic cancer. Biochemical Society transactions, 47(4), 961–972. https://doi.org/10.1042/BST20170521; Serna-Blasco, R., Sanz-Álvarez, M., Aguilera, Ó., & García-Foncillas, J. (2019). Targeting the RAS-dependent chemoresistance: The Warburg connection. Seminars in cancer biology, 54, 80–90. https://doi.org/10.1016/j.semcancer.2018.01.016; Park, W., Chawla, A., & O'Reilly, E. M. (2021). Pancreatic Cancer: A Review. JAMA, 326(9), 851–862. https://doi.org/10.1001/jama.2021.13027; NCI SEER Estimated 2021 Incidence <seer.cancer.gov> Page 12 US Incident Patient Population

BMF-219 a covalent inhibitor of menin with unique properties Restoring Balance in Menin Dependents Diseases is Context Specific Pathological State Effector Genes CDK inhibition results in beta-cell quiescence Treating Cancer Treating Diabetes • Menin dependent effector genes • Menin dependent effector genes in beta-cells express proteins that in certain cancers express or repress beta-cell growth regulate proteins that drive oncogenesis BMF-219 selectively enables BMF-219 selectively enables cell cell homeostasis of menin homeostasis of menin dependent dependent cancer cells beta cells Menin suppressing Menin disrupting cell homeostasis cell homeostasis Page 13

First Development Success with BMF-219 in MLL Fusion and NPM1 Driven Tumors BMF-219 has the Potential to Impact Important Binding Partners in Multiple Tumors Mechanism of Action Target Patient Population • Acute Leukemia: MLL-r MLL HOXA9/ BMF-219 covalent binding to MEIS1 • Acute Leukemia: NPM1 mutant NPM1 menin disrupts menin-MLL NPM1 • Acute Leukemia: Ras mutant protein-protein interaction, MYC resulting in global change of • DLBCL: DHT / DEL function • Multiple Myeloma: MYC addicted Menin MYC • KRAS mutant Solid Tumors: Colorectal Lung MLL Other Pancreatic • CLL: r/r population Other • Liquid and Solid Tumors BMF-219 has the potential to address additional patient populations Resulting change of function of menin impacts important binding with tumors that are dependent on menin or some of its binding partners involved in oncogenesis partners Page 14

Novel Covalent Inhibitor of Menin BMF-219 Pipeline-in-a-Pill – Single Agent for Multiple Indications MLL Fusion & NPM1 Driven Tumors Initial clinical validation in r/r acute leukemias with MLL fusions in addition to NPM1 mutations MYC Addicted and MYC Driven Tumors Expansion into r/r diffuse large b cell lymphoma, r/r multiple myeloma and r/r chronic lymphocytic leukemia RAS/RAF Driven Solid Tumors Further expansion into KRAS and RAS mutant colorectal, lung, and pancreatic cancer Diabetes Pathway and clinical validation of covalent menin inhibition Page 15

First Development Success with BMF-219 in MLL Fusion and NPM1 Driven Tumors In Acute Leukemia Development Stage: Phase I Clinical Trial (COVALENT-101) enrolling patients with relapsed/refractory acute leukemia Key Facts MOA Relevant Pathway BMF-219 covalently blocks menin / MLL Menin / MLL interaction can modify chromatin, Estimated Addressable Population interaction activating key leukemic genes Estimated US Patient Acute Leukemia Population (Annual MLL1 (Mutation) H3K4me3 Incidence) HOXA9 MLL2 Menin MEIS1 MLL-r ~2,500 MYC NPM1 mutant ~6,000 Ras Driven ~6,000 Menin / MLL complex forms and modifies chromatin • BMF-219 directly inhibits MLL-menin interaction and at histone H3, activating HOXA9 and MEIS1 was optimized to cause cell killing, rather than cell differentiation. • In preclinical studies, BMF-219 shows robust cell killing and reduction of expression of key genes (including MYC, MEIS1, HOXA9, and BCL2) Page 16

GLP and non-GLP IND-Enabling Toxicology Studies BMF-219 Was Highly Selective in Key Screening and Safety Panels No Histopathology Findings Were Observed with BMF-219 in GLP and non-GLP IND-Enabling Toxicology Studies Kinase Screening P BMF-219 Vehicle Metabolic Activity (%) 169 kinases screened; only two showed >50% inhibition with BMF- 100 219 80 60 Oncopanel Screen P 40 20 Minimal impact of BMF-219 on cell metabolism in leukemia and lymphoma cell lines that have wild type MLL1 0 BC-1 BCP-1 BV-173 K562 U937 Safety Screen P SafetyScreen44 panel (CEREP/Eurofins Discovery)* showed no meaningful impact (>50% activation or inhibition) Mean half-life Drug *SafetyScreen44 in-vitro panel of 44 common selected targets to identify significant off-target (min) interactions Omeprazole 123.3 Neratinib 197.7 Glutathione Reactivity P Ibrutinib >360 BMF-219 had less reactivity than the approved covalent drugs omeprazole BMF-213 322.3 and neratinib BMF-214 >360 BMF-219 >360 Page 17

First Development Success with BMF-219 in MLL Fusion and NPM1 Driven Tumors BMF-219 Demonstrated Rapid and Near Complete Reduction of Expression of Oncogenes Gene Expression Changes in AML cells following treatment • Covalent inhibitor, BMF-219, w/ BMF-219 (0.500µM dose) downregulates expression of Menin (via the target MEN1 gene) and critical leukemogenic genes (e.g., MEIS1 and HOXA9 ) @6 hours - MEIS1 is a gene that can be an accelerator of leukemic transformation (along with HOXA9) - HOXA9 is a gene involved in myeloid differentiation and can be leukemogenic - DNMT3A is a gene that codes for a methyltransferase, which can be leukemogenic when mutated @24 hours • BMF-219 demonstrated up to 80% reduction in readout genes by 6 hours and approximately 90%+ reduction at 24 hours (Transcripts per Million is a measure of gene expression) Page 18

First Development Success with BMF-219 in MLL Fusion and NPM1 Driven Tumors BMF-219 Superior Cell killing of the Target AML Cell Lines at Half the Dose vs Reversible Competitive Menin Inhibitors Source Data from ASH 2021 Publications BMF-219 Non-covalent Inhibitors KO-539 is 15% effective @ 1000nM in MOLM-13 cells and 46% effective @ 1 100nM in OCI-AML3 cells 100% 15% effective 90% @ 1000nM 80% 70% 60% 50% 46% effective 40% @ 100nM 30% 20% SNDX-50469 is 12% effective @ 1000nM in MOLM-13 cells 10% And 68% effective @ 1000nM in OCI-AML3 cells 0% MOLM-13 OCI-AML3* MV4;11 MOLM13 OCI-AML3 12% effective Average of Clinical Non- BMF-219 @ 560nM @ 1000nM covalent Inhibitors @ 1000nM Approximately half the dose of non-covalent inhibitors *Only SNDX-50469 was tested at 1000 nM in this cell line • BMF-219 killed >90% of AML cells in MLL-rearranged and NPM1 mutant cell lines at 4 days 68% effective post-treatment @ 1000nM • Non-covalent menin inhibitors generally report significantly less cell killing of AML cell lines as a single agent Blood (2021) 138 (Supplement 1): 3340., ASH 2021. Page 19 % of Cells with Calcein Staining

Novel Covalent Inhibitor of Menin BMF-219 Pipeline-in-a-Pill – Single Agent for Multiple Indications MLL Fusion & NPM1 Driven Tumors Initial clinical validation in r/r acute leukemias with MLL fusions in addition to NPM1 mutations MYC Addicted and MYC Driven Tumors Expansion into r/r diffuse large b cell lymphoma, r/r multiple myeloma and r/r chronic lymphocytic leukemia RAS/RAF Driven Solid Tumors Proprietary Further expansion into KRAS and RAS mutant colorectal, lung, and pancreatic cancer Combinations Chemistry Diabetes Pathway and clinical validation of covalent menin inhibition Pathway and clinical Page 20

Menin Dependencies Observed in Multiple Tumors 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 liquid and solid tumors, beyond acute leukemias, provides rationale for further analysis in dependent tumor types • Biomea is clinically exploring the potential for covalent inhibition of menin in a variety of liquid and solid tumor types Note: CERES MENIN Dependency scores less than -1 in various tumor types imply that menin is considered essential for cell survival in those tumor types Page 21

BMF-219 Covalent Binding of Menin has Broad Impact BMF-219 Shown to Disrupt MYC Genomic Function via Broad Impact on the Complexes Surrounding Menin Covalent Menin Inhibitor – BMF-219 Non-Covalent Menin Inhibitor – SNDX-50469 TF activity inference scores greater than 10 are highly significant TF activity inference using ChIP-seq of differentially expressed genes in MOLM-13 cells incubated with 500 nM BMF-219 at 24 Blood (2021) 138 (Supplement 1): 3340. hours. Each bar represents a study in the GEO repository using the specified TF antibody. • In MOLM-13 cells treated with BMF-219, the top transcription factors • Significantly less impact on MYC expression (2x fold) and genomic function by clinical non-covalent menin inhibitor regulating gene expression are MYC and MAX • IRF4, MYC, and MAX are known drivers for some forms of DLBCL, • In contrast, BMF-219 treatment led to a ~100-200x reduction in MYC (addicted) multiple myeloma, and multiple additional tumors expression at 24 hours Page 22

First Development Success with BMF-219 in MYC Addicted and MYC Driven Tumors BMF-219 Led to near Complete Inhibition of Growth at 1μM in DLBCL in ex-vivo Samples Triple Hit Lymphoma MYC Amplified DLBCL • At ~1µM exposure, BMF-219 produces robust growth BM-101 125 BM-100 inhibition in both THL (triple hit 125 100 lymphoma) and MYC amplified 100 DLBCL ex-vivo cell lines 75 75 50 50 • BMF-219 responses were 25 25 superior to clinical reversible 0 0 (non-covalent) inhibitors with -25 -25 respect to cell growth -50 -50 inhibition at the concentrations 0.01 0.1 1 10 100 0.01 0.1 1 10 100 -75 -75 tested Compound concentration (μM) Compound concentration (μM) Clinical Reversible 1 Clinical Reversible 2 B BM MF F -2 -219 19 Clinical Reversible 1 Clinical Reversible 2 Somanath et al., AACR 2022 Abstract 2654 Growth Inhibition IC (mM) 50 Treatment BM100 BM101 BMF-219 0.250 0.151 Clinical Reversible-1 0.969 5.63 Clinical Reversible-2 6.31 Max killing <30% Page 23 % Growth Inhibition % Growth Inhibition

First Development Success with BMF-219 in MYC Addicted and MYC Driven Tumors BMF-219 Achieves >98% Cell Lethality Against Diverse CLL ex vivo models Growth inhibition of BMF-219 in CLL ex vivo models grouped by genetic background and Rai stage Growth Inhibition of Ex Vivo CLL Models Response based on Cytogenetics Response based on Rai Stage by Genetic Background 100 100 80 75 BMF-219 (1.1µM) 60 Clinical Reversible 50 40 Menin Inhibitor (1.1µM) Venetoclax (0.8µM) 25 20 0 0 -20 -2 5 Stage 1 Stage 2 Stage 2 Relapsed Stage 3 Rai Binet Stage Cytogenetic Background Somanath et al., ASCO 2022 Abstract 7541 Page 24 Normal Normal Normal Trisomy 11 13q Del Trisomy 12, KRAS NOTCH1, ATM NOTCH1 WT1 ATM TP53 TP53 % Growth Inhibition % Growth Inhibition

COVALENT-101 (ENROLLING 4 COHORTS) Phase I first-in-human dose-escalation and dose-expansion study of BMF-219 enrolling adult patients with r/r acute leukemia, r/r diffuse large B cell lymphoma, r/r multiple myeloma, and r/r chronic lymphocytic leukemia (CLL) (NCT05153330) Dose Escalation Dose Expansion Study Treatment: BMF-219 R/R ALL, AMPL, AML R/R ALL, AMPL, AML A covalent small molecule menin inhibitor, administered orally N = var Total N = 30 daily in 28-day cycles R/R ALL, AMPL, AML R/R ALL, AMPL, AML Objectives N = var Total N = 30 Primary: Determine OBD & RP2D of BMF-219 monotherapy independently for each Cohort and Arm R/R DLBCL R/R DLBCL Secondary: Evaluate safety and tolerability of BMF-219 N = var Total N < 20 Determine PK/ PD parameters of BMF-219 Explore additional evidence of efficacy and antitumor activity R/R MM R/R MM N = var Total N < 20 BMF-219 is being studied in seven different blood cancers. The design of COVALENT-101 is the following: Dose escalation of each cohort is done in parallel followed by independent dose selection and dose expansion phase. R/R CLL/SLL R/R CLL/SLL N = var Total N < 20 Accelerated titration design followed by classical 3+3 Cohort 1 for R/R AML/AMPL/AML patients Cohort 2 for R/R DLBCL with ≥ 2L of prior therapy Abbreviations: ALL Acute Lymphoblastic Leukemia AML Acute Myeloid Leukemia AMPL Acute Mixed-Phenotype Cohort 3 for R/R MM with ≥ 3L of prior therapy Leukemia CYP3A4 Cytochrome 450 OBD Optimal biologic dose DLBCL diffuse large B-cell lymphoma MM multiple Cohort 4 for R/R CLL/SLL with ≥ 2L of prior therapy myeloma R/R Relapsed/Refractory Page 25 Cohort 4 Cohort 3 Cohort 1 Cohort 2 Arm A Arm A Arm A Arm A Arm B No No No No CYP3A4 CYP3A4 CYP3A4 CYP3A4 CYP3A4

Novel Covalent Inhibitor of Menin BMF-219 Pipeline-in-a-Pill – Single Agent for Multiple Indications MLL Fusion & NPM1 Driven Tumors Initial clinical validation in r/r acute leukemias with MLL fusions in addition to NPM1 mutations MYC Addicted and MYC Driven Tumors Expansion into r/r diffuse large b cell lymphoma, r/r multiple myeloma and r/r chronic lymphocytic leukemia RAS/RAF Driven Solid Tumors Further expansion into KRAS and RAS mutant colorectal, lung, and pancreatic cancer Chemistry Diabetes Pathway and clinical validation of covalent menin inhibition Pathway and clinical Page 26

First Development Success with BMF-219 in RAS/RAF Driven Solid Tumors BMF-219 Produced Near Complete Inhibition of Growth at 1.1μM Across KRAS G12C, G12D, G13D, and G12V Mutant Cell Lines but not WT KRAS Growth inhibition of In Vitro KRAS Mutant Cell Lines Growth Inhibition of In Vitro KRAS Mutant Cell Lines 100 90 BMF-219 (1.1 μM) 80 Clinical Menin Reversible 1 (1.1 μM) Clinical Menin Reversible 2 (1.1 μM) 60 Clinical Kras G12C Irreversible 1 (1.1 μM) 50 Sotorasib KRAS G12C (1.1 μM) 40 20 0 -20 Lung Pancreas Colon Lung Pancreas Colon Stomach ALL Colon Colon Colon G12C G12D G13D G12V WT • Covalent menin inhibition by BMF-219 led to robust growth inhibition, comparable to clinical G12C inhibitors in G12C cell lines • In non-G12C cell lines, BMF-219 achieved robust growth inhibition, higher than clinical KRAS G12C inhibitors • Clinical reversible (non-covalent) inhibitors did not achieve greater than 30% growth inhibition in any cell lines at the concentrations tested Law et al., AACR 2022 Abstract 2665 Page 27 % Growth Inhibition

First Development Success with BMF-219 in RAS/RAF Driven Solid Tumors BMF-219 Produced Near Complete Inhibition of Growth at 1.1μM in KRAS G12C and G12D ex-vivo Patient Samples Growth Inhibition of ex-vivo KRAS mutant Cells from Patients (1μM Exposure) % Growth Inhibition of Ex Vivo PDX Tumors BM-208 (NSCLC) • 1.1µM exposure of BMF-219 produces robust growth inhibition in both G12C and BM-207 (Panc.) G12D ex-vivo cell lines BM-206 (Panc.) • BMF-219 responses were superior to BM-205 (CRC) clinical reversible (non-covalent) inhibitors with respect to cell growth inhibition at the BM-204 (CRC) concentrations tested BM-203 (CRC) BM-202 (NSCLC) BM-201 (NSCLC) 0 20 40 60 80 100 BMF-219 (1.1 μM) Clinical Menin Reversible 1 (1.1 μM) Law et al., AACR 2022 Abstract 2665 Clinical Menin Reversible 2 (1.1 μM) Page 28 KRAS G12C KRAS G12D

COVALENT-102 (ENROLLING 3 COHORTS) Phase I/Ib Study of BMF-219, an oral covalent menin inhibitor, in patients with KRAS Mutant, Unresectable, Locally Advanced, or Metastatic Non-Small Cell Lung Cancer (NSCLC), Pancreatic Cancer (PDAC), and Colorectal Carcinoma (CRC) (NCT05631574) Study Treatment: BMF-219 A covalent small molecule menin inhibitor, administered orally daily in 28 day cycles Objectives Primary: Determine OBD & RP2D of BMF-219 monotherapy independently for each Cohort / Indication Secondary: Classical 3+3 dose escalation design Evaluate safety and tolerability of BMF-219 Determine PK/ PD parameters of BMF-219 Explore additional evidence of efficacy and antitumor activity Abbreviations: NSCLC Non-Small Cell Lung Cancer PDAC Pancreatic Cancer CRC Colorectal Carcinoma OBD optimal biologic dose RP2D recommended phase 2 dose PK/PD pharmacokinetic/pharmacodynamic ECOG Eastern Cooperative Oncology Group var variable L prior line of systemic therapy Page 29

st Diabetes – the biggest Epidemic of the 21 century 1 in 3 Americans will develop Diabetes in their life 34.2 million US Adults have • One of the largest economic burdens on the US diabetes today a total of $380 health care system and the 7th leading cause of Billion was spent in 2021 death in the US Source: Diabetes.org • 80% of people with diabetes will die from this disease. Premature mortality caused by diabetes results in an estimated 12-14 years of life lost. Source: National library of Medicine 1(2); 2007 Jul PMC3068646 • In the United States $1 out of every $4 in US health care costs is being spent on caring for people with diabetes. In 2021 the US spent $380 Billion to treat diabetes. • According to the CDC, worldwide 463 million adults have diabetes. In the United States alone, 34.2 million adults have diabetes, 10.5% of the population. 96 million adults (more than 1 in 3) in the US have pre-diabetes. = Diabetes is an uncontrolled disease despite the availability of current medication. There is a significant need for the treatment and care of diabetes patients. Page 31

st Diabetes – the biggest Epidemic of the 21 century Types 2 Diabetes Progression: Beta Cell Loss Type 2 Diabetic Healthy Individual Pancreatic Islet • Type 1 and Type 2 Diabetes = Islet alpha-cell results in Beta Cell Loss and a Reduction in Beta = Islet beta-cell Cell Mass = Islet beta-cell containing IAPP oligomers • Standard of Care Agents = Islet delta-cell are not addressing the Loss = Enlarged islet of Beta Cells alpha-cell = Extracellular • Type 1 and Type 2 Diabetes amyloid plaque Patients remain un- controlled and continue to = Islet alpha-cell = Islet delta-cell progress = Islet beta-cell = Enlarged islet alpha-cell = Islet beta-cell = Extracellular amyloid containing IAPP plaque oligomers *Int. J. Mol. Sci. 2016, 17, 744; doi:10.3390/ijms17050744` Page 32

st Diabetes – the biggest Epidemic of the 21 century Diabetes Progression of Type 1 and Type 2 Driven by Beta Cell Loss Prior Paradigm Current Paradigm Causes Type 1 and Type 2 Diabetes results in Beta Cell Loss and Insulin Resistance leads to an increase in Beta Cell Workload which ultimately leads to Reduction in Beta Cell Mass Beta Cell Failure and Death and the Progression of Type 2 Diabetes. *Int. J. Mol. Sci. 2016, 17, 744; doi:10.3390/ijms17050744 Page 33

st Diabetes – the biggest Epidemic of the 21 century Diabetes Patient Segments Patient Population Proposed BMF-219 MOA Initial Decline in Glycemic Control Pre-Diabetes Increasing HbA1c, Increasing Insulin Resistance 90M Beta Cell Preservation Decreasing beta cell numbers and function Beta Cell Growth 6.3M Beta Cell Reactivation Beta Cell Growth 5.3M Beta Cell Reactivation Beta Cell Preservation 7.7M Beta Cell Reactivation Beta Cell Growth 13.65M Beta Cell Reactivation Beta Cell Preservation Initial Diagnosis/Disease – Stage 2/Stage 3 T1D 1.5M Beta Cell Growth Increasing HbA1c, Initial Reduction in Insulin Beta Cell Preservation Significant Decrease in beta cell numbers Page 34

st Diabetes – the biggest Epidemic of the 21 century BMF-219 Value Proposition in Diabetes First in class molecule with paradigm shifting potential for the treatment of diabetes Oral Treatment for the Regeneration, Preservation, and Reactivation of Beta Cells • Disease modification as the first treatment to potentially provide a functional cure of diabetes via restoration of beta cell homeostasis • Synergistic with GLP-1 based treatments while potentially insulin sparing. Potential utility in: • Prevention of T2D (90M prediabetic patients in the US) • 90% of T2D patients with beta cell impact • 50% of T2D patients on SOC but not at target A1C • T1D • Diabetic patients at risk for hypoglycemia • Potential reduction in insulin dependance • MOA could positively impact • NASH, CKD, CV benefit • Weight loss as monotherapy or in combination • Patients at risk for hypoglycemia under current SOC Page 35

First Development Success with BMF-219 in Type II Diabetes Potential for Menin Inhibition Demonstrated by Beta Cell Ablation Diabetes Model in MEN1 Excised Mice MEN1 Excision Prevents Development of STZ-induced Hyperglycemia Control Control Men1-excised Men1-excised Multiple low-dose streptozotocin (MLD-STZ) administered to the control Men1-excised mice did not develop hyperglycemia in STZ and Men1-excised mice to induce beta cell damage and a diabetes-like model, which was observed in the control group environment Sources: Yang et al. (2010) Deletion of theMen1Gene Prevents Streptozotocin-Induced Hyperglycemia in Mice. Experimental Diabetes Research, 2010, 1–11. doi:10.1155/2010/876701 Page 36

First Development Success with BMF-219 in Type II Diabetes STZ Rat Model Study Design The Streptozotocin (STZ)-Induced Rat Model Study Design Only direct insulin injection shows an effect in this model with high fat diet STZ treatment typically results in ~50% Beta Cell Loss Page 37

First Development Success with BMF-219 in Type II Diabetes BMF-219 Demonstrates Strong Efficacy in Beta Cell Loss Animal Model (STZ Rat) BMF-219 Achieves Glycemic Control in STZ (Beta Cell Loss) Rat Model STZ + HFD model Oral Glucose Tolerance Test (Day 17) Non-Fasting Glucose Vehicle Non-fasting Glucose Pioglitazone (30 mg/kg) 800 800 BMF-219 (175mg/kg) 600 600 400 400 200 * * 200 * * * * p<0.05 vs Vehicle 0 0 -7 -6 -5 -4 -3 -2 -1 1 8 14 0 15 30 60 90 120 Days Minutes TA dosing Vehicle Pioglitazone (30 mg/kg) BMF-219 (175mg/kg) start BMF-219 achieves lower glucose level than pioglitazone at all BMF-219 achieves lower non-fasting glucose than pioglitazone at day timepoints in OGTT (day 17) in STZ rat model 8 and day 14 in STZ rat model Butler et al., ADA 2022 (P-851) Page 38 Blood Glucose (mg/dL) Mean± SEM Mean±SE (mg/dL)

First Development Success with BMF-219 in Type II Diabetes BMF-219 Demonstrates Recovery of Beta Cell Activity • HOMA-Beta, a measurement of Beta Cell Function, was analyzed using 4-hr fasting glucose and insulin levels in animal plasma. • BMF-219 displayed a significant level of Beta Cell function compared to vehicle at Day 17 in a Beta +96% Cell Type 2 Diabetes Model. • This data supports the observed results from the Beta Cell Mass Quantitative Analysis using IHC. Importantly, Beta Cell Function is observed despite cessation of dosing. ~96% increase represents near doubling of beta cell function (Type 2 STZ Model represents ~ 50% Beta Cell Destruction) Page 39

First Development Success with BMF-219 in Type II Diabetes Zucker Diabetic Fatty Rat - a Model of Insulin Resistance The ZDF Rat Study Design Day • The ZDF rat is a model of pancreatic exhaustion, thus Treatment groups (n = 10/group): mimicking some aspects of human diabetes. 1. Vehicle 2. BMF-219 175 mg/kg • Pioglitazone and metformin provide therapeutic efficacy in this 3. Pioglitazone 30 m g/kg model. • The ZDF rat is a translatable model for studying the development of T2D. Page 40

First Development Success with BMF-219 in Type II Diabetes BMF-219 Displays Durable Glycemic Control during Drug Washout and Two Weeks after the Last Dose After 2-week Drug Washout Oral Glucose Tolerance Test (OGTT) Day 29 800 OGTT AUC on day 29 100000 600 80000 *p<0.05 vs Vehicle 400 60000 * 75% glycemic control * * maintained on day 29 40000 * * post-dosing compared to 200 * 20000 day 15 * * p<0.05 vs Vehicle 0 0 0 15 30 60 90 120 Minutes Vehicle Pioglitazone (30 mg/kg) BMF-219 (175mg/kg) ZDF rats treated with BMF-219, pioglitazone or vehicle control for 16 days were monitored for blood glucose levels by OGTT on day 29, ~2 weeks after administration of the last dose, displaying an AUC reduction of 40%, (p<0.05). Page 41 Blood Glucose (mg/dL) Mean± SEM

Fir Firs st t De Dev ve elo lop pm me en nt t S Su uc cc ce es ss s w wit ith h B BM MF F- -2 21 19 9 in in T Ty yp pe e I II I Diab Diabe et te es s BMF-219 Increases Β-islets in Pancreas Sections of ZDF Diabetic Model +2.0% • Quantitative Analysis of pancreatic islet tissue cross sections shows BMF-219 treated animals show novel effects in Beta Cell Area growth and maintenance. -28% -33% • BMF-219 was able to maintain Beta Cell function and prevent Beta Cell Area Loss in an Insulin Resistance Type 2 Diabetes Model. • Importantly, Beta Cell Area is maintained, despite cessation of dosing. Page 42

First Development Success with BMF-219 in Type II Diabetes BMF-219 Demonstrates Strong Β-cell Activity - Supporting Quantitative Analysis +351% Normal (Adequate) State • HOMA-Beta, a measurement of Beta Cell Function, was analyzed using 4-hr fasting glucose and insulin levels in animal plasma. • BMF-219 displayed a significant level of Beta Cell function compared to vehicle at Day 31 in an Insulin Resistance Type 2 Diabetes Model. • This data supports the observed results from the Beta Cell Area Quantitative Analysis using IHC. Importantly, Beta Cell Function is observed despite cessation of dosing. O.J. Fasipe et al. / Can J Diabetes 44 (2020) 663e669 Page 43

First Development Success with BMF-219 in Type II Diabetes BMF-219 Demonstrates Strong Efficacy in Insulin Resistant Animal Model (ZDF Rat) BMF-219 Reduces HbA1c After 28 days of Treatment and Maintains Effect After 14-day Washout * p<0.05 ** p<0.01 BMF-219 demonstrated significant decrease HbA1c (%) ****p<0.0001 in HbA1c (-3.5% at day 29) vs. control ✱ ✱✱ starting on day 21 of treatment ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ 15 Vehicle 0mg/kg BMF-219 treated group demonstrated ✱ ✱ ✱ ✱ ✱ ✱ ✱ ✱ BMF-219 40mg/kg (days 1-16), significant weight reduction starting at 200mg/kg (days 17-28) PO day 25 BMF-219 85mg/kg PO 10 BMF-219 170mg/kg PO Liraglutide 0.2 mg/kg BID 5 HbA1c reduction in BMF-219 highest dose groups maintained through washout period 0 Day 29 Day 43 Somanath et al., ADA 2022 (113-LB) Page 44 44 HbA1c (%), Mean± SEM

First Development Success with BMF-219 in Type II Diabetes BMF-219 Treated Groups Display Body Weight and Cholesterol Reduction BMF-219 200 mg/kg group reduces body weight during BMF-219 reduces blood lipemic levels treatment in ZDF rats measured on Day 29 Triglycerides Total Cholesterol Body weight ✱ ✱ ✱ ✱ 425 ✱ ✱ ✱ 250 400 1000 *** p<0.0005 ****p<0.0001 200 800 375 150 600 350 100 400 325 50 200 13% body weight reduction on Day 29 0 0 300 1 3 5 8 10 12 15 17 19 21 22 25 28 29 31 Days Vehicle 0mg/kg BMF-219 170mg/kg PO Liraglutide 0.2mg/kg BID BMF-219 40mg/kg (days 1-16), 200mg/kg (days 17-28) PO Page 45 Vehicle 0mg/kg BMF-219 200mg/kg PO BMF-219 170mg/kg PO Liraglutide 0.2 mg/kg BID Vehicle 0mg/kg BMF-219 200mg/kg PO BMF-219 170mg/kg PO Liraglutide 0.2 mg/kg BID Body weight (g) Mean± SEM TC (mg/dL) Mean± SEM TG (mg/dL) Mean± SEM

First Development Success with BMF-219 in Type II Diabetes COVALENT – 111 (Enrolling) A Phase 1/2 Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMF-219, an Oral Covalent Menin Inhibitor, in Healthy Adult Subjects and in Adult Subjects with Type 2 Diabetes Mellitus Study Treatment: BMF-219 SAD C1 to SAD C4 (HVs) Total N=40 A covalent small molecule menin inhibitor, administered orally daily in 28 day cycles Dose [100, 200, 400, and 600 mg] Primary Objective: MAD C1 (HVs) Evaluate safety and tolerability of BMF-219 Total N = 16 Secondary Objectives: Evaluate PK of BMF-219 MAD C2 to MAD C8 (T2D) Evaluate the effect on BMF-219 on glycemic parameters (HbA1C, PG) Total N=108 and few additional parameters using OGTT, 7-day CGM Dose [100, 200, 300, 400, 600 mg] Evaluate the changes in beta cell function Evaluate impact on lipid parameters, body weight etc. Exploratory Objectives: In the Phase 2, COVALENT-111 will enroll subjects with a HbA1C of 7-10% despite being on standard of care, up to To assess the durability of response to glycemic parameters three agents of therapy. Page 46 Phase 2 Phase 1 (MAD) (SAD)

Second Development Success with BMF-500 BMF-500 A Third Generation FLT3 Inhibitor Generation Second Generation First Generation Third Generation of FLT3 FLT3 / multi-kinase Inhibitors FLT3 Inhibitors FLT3 Inhibitors Inhibitor Quizartinib Midostaurin Lestaurtinib Sorafenib Gilteritinib Crenolanib BMF-500 (FDA Rejected (FDA Approved as (FDA Approved as (FDA Approved as (Failed in clinical due to (Phase 3 in US) (Covalent Inhibitor, Preclinical) RYDAPT) NEXAVAR) XOSPATA) trials) Products Cardiotox) • More selective • Improved PK • Improved • Drives cell death • In vitro potency against FLT3 for FLT3 properties potency D835 • Improved FLT3 potency and • Oral route of administration • Reduced KIT selectivity inhibition • Improved activity in known resistance mechanisms • Limited impact on cKIT at projected physiological dose Benefits • Adverse • Drives • TID Dosing • Limited history of covalent FLT3 • Poor kinase selectivity Events Differentiation • F619 experience in the clinic • Challenging pharmacokinetic (PK) profile • QTc impact • Myelo- Resistance • Novel scaffold with emerging • Low steady state free drug concentration • Cytopenia suppression • Drives profile • Low potency resulting from challenging PK at tolerable doses • Frequent Dose Differentiation Adj Challenges • QTc impact BMF-500 Kinome Selectivity Gilteritinib Crenolanib Sources: Levis M. (2017). Midostaurin approved for FLT3-mutated AML. Blood, 129(26), 3403–3406. https://doi.org/10.1182/blood-2017-05-782292; Drugs@FDA.gov Page 47

Second Development Success with BMF-500 BMF-500 Highly Effective FLT3 Inhibitor Against Resistance Mutations Page 48

Second Development Success with BMF-500 BMF-500 Highly Potent and Durable FLT3 Inhibitor Page 49

Second Development Success with BMF-500 BMF-500: Highly Potent and Durable FLT3 Inhibitor Individual Tumor Volume MV-4-11 Subcutaneous MV-4-11 Xenograft Model Xenograft Model

Biome Fusion WE AIM TO CURE 2023 : Exploring 8 Different Tumor Types and Type II Diabetes in the Clinic Present initial Phase II clinical data in Type 2 Diabetes: 1Q 2023 Present initial Phase I clinical data in AML: 1H 2023 Continue enrolling patients in trials exploring BMF-219 utility in KRAS driven Solid Tumors (PDAC, NSCLC, CRC) and Liquid Tumors (AML/ALL, MM, CLL, DLBCL) File IND for BMF-500: 1H 2023 Initiate Phase I trial for BMF-500: 1H 2023 Announce third pipeline asset from FUSION™ platform technology : 1H 2023 Cash as of 30 Sept 2022 $133.8M - Capitalized into 2024 Page 51

As of September 30, 2022 Company Financials (NASDAQ: BMEA) Three Months Ended Sept 30 2022 2021 Operating expenses: R&D $ 18,242 $ 7,886 G&A $ 5,242 $ 4,752 Total Operating Expenses $ 23,484 $ 12,638 $ (23,484) $ (12,638) Loss from operations $ 594 $ 32 Interest and other income, net $ (22,890) $ (12,606) Net loss Other comprehensive loss: Changes in unrealized gain on short term investments, net $ 4 - $ (22,886) $ (12,606) Comprehensive loss Net loss per common share, basic and diluted $ (0.78) $ (0.43) Weighted-average number of common shares used to compute basic and diluted net loss per 29,319,042 29,001,213 common share Cash as of 31 June 2022 $ 150.2M Net Cash Burn Q3 $ 16.4M Cash as of 30 Sept 2022 $ 133.8M Page 52

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