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| Item 7.01. | Regulation FD Disclosure. |
Biomea Fusion, Inc. (the “Company”) from time to time presents and/or distributes to the investment community at various industry and other conferences slide presentations to provide updates and summaries of its business. On January 12, 2022, the Company will present an updated corporate presentation virtually at the 40th Annual J.P. Morgan Healthcare Conference and post the presentation in the “Investors & Media” portion of its website at www.biomeafusion.com. A copy of the Company’s current corporate slide presentation is attached to this Current Report on Form 8-K as Exhibit 99.1. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.
The information contained in Item 7.01 of this Form 8-K (including Exhibit 99.1 attached hereto) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly provided by specific reference in such a filing.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit Number |
Description | |
| 99.1 | Corporate Slide Presentation of Biomea Fusion, Inc. dated January 2022 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
1
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
| BIOMEA FUSION, INC. | ||||||
| Date: January 12, 2022 | By: | /s/ Thomas Butler | ||||
| Thomas Butler | ||||||
| Principal Executive Officer | ||||||
2
Exhibit 99.1 Corporate Presentation January 2022 1
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 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. 2
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 believe that our approach may lead to significant improvement and extension of Oncology Asset life for patients. Our team is engaged in all phases of drug discovery and development, including target selection, small molecule Multiple Oncology Programs TM design, and preclinical and clinical studies to built from FUSION Platform develop innovative medicines. 3
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 tumors Consistent On-Target Effect Pathway control and cell killing seen at same predicted dose across indications Wide Safety Margin Strong preclinical safety profile from animal studies 4
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 Officer Consultant Discovery Officer 15+ years in Life Science 15+ years in Life Science 15+ years in Life Science 15+ years in Life Science 22+ years in Life Science 25+ years in Life Science 25+ years in Life Science 30+ years in Life Science Pharmacyclics Pharmacyclics Eidos Therapeutics Pharmacyclics Pharmacyclics HealthChart LLC Terns Pharmaceuticals Biota Ltd Gilead Sciences Oxygen Investments Iovance Biotherapeutics Genentech Collegium Pharmaceutical Insight Genetics Gilead Sciences Cytopia Ltd. UCLA – MBA Finance Commerzbank Pharmacyclics UC Irvine, BA Comm Praecis Pharmaceuticals St. Jude Children’s Cell Gate Rigel, Inc. UCSB, MS – Chemistry University of Münster, CallidusCloud SF State University, Comm Ohio State University Research Hospital Golden Gate University, Celera Genomics Master’s in Banking & PricewaterhouseCoopers Santa Clara University Board certified internist MBA Prototek Inc. Corp Finance San Jose State University, BS Leavey School of Business, (Univ. of Texas SW HSC) University of Münster, Purdue University Corporate Finance MBA – Finance & Mgmt and medical oncologist Ph.D., Chemistry Ph.D. Organic Chemistry (Yale University School of Medicine) 5
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 Validated For Covalent Covalent new mechanism of action Disease Sources: Nelson et al. (2015) Nat Genet.; Thomas et al. (2016) BIO; In a Landscape of 'Me Too' Drug Development, Inhibition Chemistry What Spurs Radical Innovation? HBS Weekly Review (Jun 2018) Targets Biology Chemistry Irreversible covalent inhibitors provide deep target inactivation and a wider therapeutic Irreversible Sm. window, allowing for longer duration on therapy Sources: Singh et al. (2011) Nature Reviews Drug Discovery; Cheng et al. (2020) Journal of Hematology & Oncology; Mol. Inhibitors Strelow (2017) SLAS Discovery; Kalgutkar & Dalvie (2012) Expert Opin. Drug Discov.; Combination therapy with non-overlapping resistance mechanisms results in more durable Proprietary responses and better outcomes Combinations Proprietary Sources: Palmer et al. (2019) eLife; Mokhtari et al. (2017) Oncotarget Combinations Medicine 6
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 Oncology: Osimertinib and Ibrutinib both target kinases and are used in subpopulations with specific genetic biomarkers - Antivirals: Sofosbuvir and Tenofovir both target reverse transcriptases and are leveraged to treat HCV and HIV Ibrutinib (IMBRUVICA) Tenofovir (VIREAD) Sofosbuvir (SOVALDI) 7
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 inactivation of bound protein effect without sustained initial reversible binding systemic exposure, unlike followed by 2) covalent conventional reversible drugs, interaction, which increases • can drive target elimination which typically need to be target selectivity through normal cellular present to provide benefit degradation processes • Greater ligand efficiency provides high selectivity and • Uncoupling of drug effects from • can trigger rapid apoptosis or potency without jeopardizing drug exposure can potentially differentiation into normal, pharmaceutical properties enable lower drug dosing or less mature cells frequent dosing regimens vs. reversible approaches 8
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 life of Long Kinetic Half Life ~4-6 hrs but prolonged receptor % Active-Site Occupancy (left axis) occupancy indicates irreversible BTK Inhibition at cancer sites • Ibrutinib rapidly achieved high receptor Short Biologic Half Life Plasma concentration (right axis) occupancy, sustained for over 24 hours, reflects systemic exposure to body without constant systemic exposure • Reversible inhibitors often require constant systemic exposure to maintain occupancy and reach IC , thereby 90 potentially limiting tolerability 0 2 4 6 8 10 12 14 16 18 20 22 24 Systemic Exposure Receptor Occupancy 9 BTK: Bruton’s Tyrosine Kinase (ng/ml)
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 approach provides Detailed crystal structures Emphasis on optimizing Traditional medicinal Synthesis) starting points for drug required to understand potency and specificity can chemistry methods may potential binding sites used design, uncovering insights force trade offs not completely improve on optimal engagement to generate “hits” key drug properties Modified after Insilico Medicine & Paul, S. M.et al. (2010). How to improve R&D productivity: the pharmaceutical industry’s grand challenge. Nature Reviews Drug Discovery, 9(3), 203–214. Year 1 Year 2 Year 3 Year 4 Custom design at lead stage Target Custom Lead Preclinical To Hit Lead Optimization accelerates timeline Biomea Library of Custom Scaffold FUSION™ Platform 1 Target Validation 2 3 4 Refinement Covalent Engagers Creation (AI/VR Matching AI/VR driven matching Crystal structures leveraged Small molecules created Custom scaffolds put + for deep structural process that is validated from scratch through through refinement process Custom Synthesis) through insights from knowledge and biologic custom synthesis based on for optimal drug like physical synthesis relevance insights from AI/VR properties 10
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 Tumors ~18K ~35K BMF-219 Patient enrollment (MM, DLBCL) DLBCL MM (Oncology) ~60K ~60K ~70K KRAS Solid Tumors IND filing Lung CRC Panc. (Lung, Pancreatic, CRC) (KRAS) (RAS) (RAS) Menin Preclinical data Diabetes Mellitus 1.6M 25.3M presentation at an Inhibition (Type 2, Type 1) Type 2 Type 1 upcoming meeting (Metabolic) Additional Lead candidate and N/A Oncology Target #2 Oncology target announcement Undisclosed Programs Update on progress in N/A Oncology Target #3 Undisclosed 2022 11
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 Cancer Cancer Acute Leukemias Additional Liquid Tumors Solid Tumors 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> 12 US Incident Patient Population
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 tumors Consistent On-Target Effect Pathway control and cell killing seen at same predicted dose across indications Wide Safety Margin Strong preclinical safety profile from animal studies 13
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% AF10 8% ELL 4% PTD 4% MEIS1 …80+ additional fusions 16% Modified after Uckelmann (Scott Armstrong Lab) , ASH 2018, Abstract # 546 Source: Meyer, C. et al. (2017). The MLL recombinome of acute leukemias in 2017. Leukemia, 32(2), 273–284. BMF BMF -219 -21 : an irreversible covalent inhibitor at the Menin-MLL interface 14
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. MEIS1 and @6 hours HOXA9) - 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 (Transcripts per Million is a measure of gene expression) 90%+ reduction at 24 hours 15
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 ~50-60% 0.2 reduction >90% reduction 0.0 DMSO BMF-219 BMF-219 500 nM, 24 1 μM, 24 hrs hrs Blood (2021) 138 (Supplement 1): 3357. • BCL2 expression was reduced ~20 to 30-fold at 24 hrs post-treatment with BMF-219 and remained largely unaltered at 6 hrs post-treatment with BMF-219 • HOXA9 expression was reduced ~15-fold at 24 hrs post treatment with BMF-219 • MYC expression was reduced ~100-200 fold at 6 hrs and 24 hrs post-treatment with BMF-219 16 Fold-Change (mRNA expression) Relative to DMSO Control
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 tumors Consistent On-Target Effect Pathway control and cell killing seen at same predicted dose across indications Wide Safety Margin Strong preclinical safety profile from animal studies 17
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, MYC • DHT / DEL DLBCL resulting in global change of function • Multiple Myeloma MYC Menin • KRAS mutant (CRC, Lung, Pancreatic) MLL Other • Liquid and Solid Tumors Other Resulting change of function of menin impacts BMF-219 has the potential to address additional important binding partners involved in oncogenesis patient populations that are dependent on menin or some of its binding partners 18
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 exploring the potential for irreversible 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 19
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 differentially expressed genes in MOLM-13 cells incubated with 500 nM Blood (2021) 138 (Supplement 1): 3340. BMF-219 at 24 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 • Significantly less impact on MYC expression (2x fold) and transcription factors regulating gene expression are genomic function by clinical reversible menin inhibitor MYC and MAX • In contrast, BMF-219 treatment led to a ~100-200x • IRF4, MYC, and MAX are known drivers for some forms of reduction in MYC expression at 24 hours DLBCL, (addicted) multiple myeloma, and multiple additional tumors 20
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 p p signaling, including MYC, MAPK/ERK, and JunD p Menin • ~30% of newly diagnosed NSCLC have a KRAS mutation MYC TEFb RNA Polymerase • ~97% of pancreatic cancer patients have a RAS mutation MYC Target Genes• ~45% of CRC patients have a RAS mutation Source: Madden et al., Molecular Cancer volume 20, Article number: 3 (2021); Martínez-Martín et al. Cancer Drug Resist 2021;4:842-65; Xia Y. et al., Acta Haematol 2020;143:520–528; Zhu L., et al. (2017).. Nat. Commun. 8, 15278.; Musti et al., Oncogene . 2002 Sep 19;21(42):6434-45. Multiple Myeloma (MM) Diffuse Large B-Cell Lymphoma (DLBCL) • MYC addiction increases with stage and line of therapy• Double and Triple Hit and Double expressors (BCL2 and MYC • ~20-50% MYC dysregulation or translocations in newly overexpression) DLBCL represents ~40% of patients diagnosed MM patients• >50% of relapsed/refractory DLBCL are double expressors • ~50-70% of advanced r/r MM patients have MYC dysregulation 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 21 the RAS-dependent chemoresistance: The Warburg connection. Seminars in cancer biology, 54, 80–90. https://doi.org/10.1016/j.semcancer.2018.01.016
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 tumors Consistent On-Target Effect Pathway control and cell killing seen at same predicted dose across indications Wide Safety Margin Strong preclinical safety profile from animal studies 22
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% effective @ 1μM in MOLM-13 cells MOLM-13 OCI-AML3 MV4;11 MOLM13 OCI-AML3 BMF-219 @ 560nM Estimated Average of Clinical Reversible Inhibitors @ 1μM Approximately half the dose of reversible inhibitors • BMF-219 killed >90% of AML cells in MLL-rearranged and NPM1 mutant cell lines at 4 days post-treatment • Reversible menin inhibitors generally report significantly less cell killing of AML cell lines as a single agent Blood (2021) 138 (Supplement 1): 3340., ASH 2021. 23 % of Cells with Calcein Staining
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 600 2000 2000 1500 400 1000 1000 200 500 0 0 0 T4 T7 T11 T14 T4 T7 T11 T14 T4 T7 T11 T14 DMSO BMF-219 MI-503 • BMF-219 demonstrated rapid shut down of metabolic activity, sustained over the 14-day study duration • BMF-219 responses were superior to a tested reversible menin inhibitor (MI-503) with respect to both onset and durability of metabolic suppression 24 Relative Fluorescent Units (K)
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 1500000 30000 1000000 20000 500000 10000 0 0 Day 4 Day 7 Day 11 Day 14 Day 4 Day 7 Day 11 DMSO BMF-219 DMSO BMF-219 MI-503 Impairment of survival in G12C KRAS mutation driven pancreatic Impairment of survival in multiple myeloma model (KMS-20 cell line, 0.56µM doses) by irreversible menin inhibitor BMF- cancer model (MIA-PaCa-2, 0.56µM doses) by irreversible menin 219 inhibitor BMF-219 versus a reversible menin inhibitor (MI-503) 25 Surviving Cells (relative fluorescent units)
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 BMF-219 70% produces robust growth 60% inhibition in both NPM1 and MLL-R ex-vivo cell lines 50% • BMF-219 responses were 40% superior to a tested 30% reversible menin inhibitor, MI- 503, with respect to cell growth 20% inhibition 10% 0% BMF-219 MI-503 26 Growth Inhibition
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 BMF-219 0.3160 98.64 100 BMF-219 BMF-219 0.2877 99.47 Clinical Reversible Clinical Reversible KKO-5 O-539 39 3.070 100.0 KKO-5 O-539 39 1.490 99.84 Inhibitor-1 1.49 99.84 Inhibitor-1 3.07 100 80 80 SSy yndnd -56-5 13613 N 0. o 04 Res20 pon7 se 9.730 SSy yndnd -56-5 13613 N Unst o Resab ponle se -8.431 Clinical Reversible No Clinical Reversible No Inhibitor-2 Response 9.7 Inhibitor-2 Response -8.4 60 60 40 40 20 Cell Lines Cell Type Translocations 20 DB and Toledo cells DB GCB-DLBCL MYC/BCL2 0 0 were incubated with TOLEDO GCB-DLBCL MYC/BCL2 compounds for 4 days -20 -20 0.001 0.01 0.1 1 10 0.001 0.01 0.1 1 10 Compound Concentration (uM) Compound Concentration (uM) Source: Blood (2021) 138 (Supplement 1): 4318. ASH, 2021. • Irreversible menin inhibition by BMF-219 led to marked growth inhibition in multiple DLBCL cell lines • We believe this is due to disruption of Menin-MYC • One of the clinical stage reversible menin inhibitors tested displayed activity, but at 5-10x higher concentration • The other clinical reversible inhibitor did not achieve IC50 in the tested cell lines at any concentration tested 27 Cell Proliferation Inhibition (%) Cell Proliferation Inhibition (%)
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 tumors Consistent On-Target Effect Pathway control and cell killing seen at same predicted dose across indications Wide Safety Margin Strong preclinical safety profile from animal studies 28
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 interactions have long Drug life greater than 50% inhibition upon treatment with BMF-219 half-lives (min) • In-house analysis of menin revealed no relevant structural Omeprazole 123.3 • BMF-219 had less reactivity than the approved similarity between targeted binding pocket and tyrosine Neratinib 197.7 irreversible drugs omeprazole and neratinib kinases with known involvement in hematological cancers Ibrutinib >360 based on the results from the study BMF-213 322.3 BMF-214 >360 BMF-219 >360 Oncopanel screening Safety screen Metabolic Activity (%) BMF-219 Vehicle 100 • BMF-219 was also profiled on the SafetyScreen44 • Minimal impact of BMF-219 treatment on cell panel (CEREP/Eurofins Discovery), an in-vitro panel of metabolism in leukemia and lymphoma cell lines that 80 44 common selected targets to identify significant have wild type MLL, but no menin-linked mechanism for 60 off-target interactions disease 40 • Findings showed no meaningful impact (greater • Findings are consistent with external studies, showing 20 than 50% activation or inhibition) of BMF-219 across that menin-MLL interaction is not generally cell- 0 these key safety assays essential and only critical to survival in those cells BC-1 BCP-1 BV-173 K562 U937 that contain aberrant biology 29
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 levels (1x10 MV4;11-luc) with greater than 90% viability • BMF-219 treatment showed notable reduction in tumor burden and survival benefit over vehicle control (72% at 20mg/kg and 94% at 40mg/kg) • Daily dosing for 14 days was well-tolerated and caused minimal body weight changes 30 Vehicle BMF-219* Relative Body Weight
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: MLL-r NPM1 FLT3-ITD MTD Not Determined in IND Enabling Tox DLBCL MYC Driven Tumors MM KRAS Mutants (pan mutation) ‘219 Targeted Efficacious AUC 2,000 hERG inhibition ~5% at 10 μM Significant Downregulation of HOXA9, MEN1, and MYC No Histopath Findings in IND Enabling Tox Studies 31 AUC (ng/hr/ml)
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 Therapeutic Window Limited impact on Key Gene Signaling (MEN1, HOXA9, Significant Impact on MEN1, HOXA9, and MYC MYC) at Clinically Achievable Dose Levels Broad Tumor Type Impact via MYC Inhibition (ALL, Focused on Menin-MLL Disruption For AML/ALL AML, DLBCL, MM, RAS activated Solid Tumors) Deep Tumor Impact Across Multiple Tumor Types Poor impact on Cell Viability in Key Leukemia Sub-Types (ALL, AML, DLBCL, MM, RAS activated Solid Tumors) Minimum Impact on hERG at 10uM Dose Limiting Cardiac Toxicity (at ≥10x the Targeted Clinical Dose Level) Single Agent CR Rate @ 6-month ~10% TBD - Currently Enrolling Patients Complete Remission (CR) is defined as: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary 9 9 32 disease; ANC ≥1.0 X 10 /L (1,000/μL); platelet count ≥100 X 10 /L (100,000/ μL)
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 ALL, AMPL, AML Eligibility: R/R ALL, AMPL, AML • All patients: – R/R ALL, AMPL, AML agnostic of mutation – > 18 years Endpoints: N = 12 N = TBD • Phase I: Safety, PK, determine the Optimal Biological Dose and the Recommended Phase II Dose R/R ALL, AMPL, AML R/R ALL, AMPL, AML Treatment: • BMF-219 will be administered orally daily N = 12 N = TBD Accelerated titration design followed by 3+3 Abbreviations: ALL Acute Lymphoblastic Leukemia AML Acute Myeloid Leukemia AMPL Acute Mixed Phenotype Leukemia CRR Complete Response Rate CYP3A4 Cytochrome 450 3A4 DLT Dose Limiting Toxicity FIH First-in- human KMT2A Lysine Methyltransferase 2A MLL Mixed Lineage Leukemia MLLr Mixed Lineage Leukemia-rearranged NPM1 Nucleophosmin 1 PO Administered by Mouth PK Pharmacokinetic R/R Relapsed/Refractory RP2D Recommended Phase 2 Dose TEAE Treatment Emergent Adverse Event 33 Arm B Arm A CYP3A4 No CYP3A4 Arm B Arm A CYP3A4 No CYP3A4
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 IND Initiation CRC Data Filing (KRAS Mut.) Menin Ph. I Trial Diabetes IND Preclinical Inhibition (T1D/T2D) Filing Initiation Data (Metabolic) 34
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 streptozotocin (MLD-STZ) STZ model, which was observed in the control group administered to the control and Men1-excised mice to induce beta cell damage and a diabetes-like environment Sources: Yang et al. (2010) Deletion of the Men1Gene Prevents Streptozotocin-Induced Hyperglycemia in Mice. Experimental Diabetes Research, 2010, 1–11. doi:10.1155/2010/876701 35
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 for diabetes Zucker Diabetic Engage with the FDA in Q1 2022 STZ-Induced Rat Fatty (ZFD) Rat and File IND by H2 2022 • Model inhibits production of • Model works to decrease beta cell counts and induce insulin insulin by beta cells in Conduct Additional Translational addition to inducing beta cell resistance in male rats - While males develop diabetes, Work death Female rats do not develop diabetes - High dose models lead to rapid ablation of beta cells and hyperglycemia while low dose Submit Data for 2022 Conference models lead to less pronounced reduction in beta cells and insulin Publication secretion Sources: King, A. J. (2012). The use of animal models in diabetes research. British Journal of Pharmacology, 166(3), 877–894; Willcox, A., Richardson, S. J., Bone, A. J., Foulis, A. K., & Morgan, N. G. (2010). Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes. Diabetologia, 53(9), 2020–2028. 36 Experiments Results Next Steps
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 addressable market and scarcity of effective treatment options for clinically targeted tumor types IND enabling work in progress for diabetic patients Capitalized into 2024 37
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 Initiation in AML/ALL Additional Preclinical H1 2022 Data in DLBCL/MM Additional Programs BMF-219 Phase I H1 2022 nd 2 Pipeline Candidate DLBCL/MM Trial Initiation H1 2022 Announced rd 3 Pipeline Candidate To Be Announced BMF-219 – Solid Tumors Announced Additional Preclinical Data in H1 2022 KRAS Mutant Tumors IND Filing H2 2022 BMF-219 Phase I KRAS Mutant Trial Initiation Q4 2022 (Pancreatic, Lung, Colorectal) 38
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 operations $ (12,638) $ (1,135) $ (26,930) $ (1,828) Interest and other income, net $ 32 — $ 73 $ 2 Net loss $ (12,606) $ (1,135) $ (26,857) $ (1,826) Other comprehensive loss: Changes in unrealized gain on short term investments, net — — $ 2 — Comprehensive loss $ (12,606) $ (1,135) $ (26,855) $ (1,826) Net loss per common share, basic and diluted $ (0.43) $ (0.10) $ (1.21) $ (0.18) Weighted-averaged number of common shares used to compute 29,001,213 11,724,100 22,105,321 10,082,667 basic and diluted net loss per common share $192M Cash, cash equivalents, and investments as of the end of Q3 2021 39
Thank You 40