UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact name of Registrant as Specified in Its Charter)
| (State or Other Jurisdiction of Incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
| |
||
| (Address of Principal Executive Offices) | (Zip Code) |
Registrant’s telephone number, including area code:
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading Symbol(s) |
Name of each exchange on which registered | ||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
| 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 July 19, 2021, the Company posted an updated corporate slide presentation in the “Investors & Media” portion of its website at www.biomeafusion.com. A copy of its 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
The following Exhibit 99.1 relating to Item 7.01 shall be deemed to be furnished, and not filed:
| Exhibit |
Description | |
| 99.1 | Corporate Slide Presentation of Biomea Fusion, Inc. dated July 2021 | |
| 104 | Cover Page Interactive Data File (embedded within the inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| BIOMEA FUSION, INC. | ||||||
| Date: July 19, 2021 | By: | /s/ Thomas Butler | ||||
| Thomas Butler Chief Executive Officer | ||||||
Exhibit 99.1 Corporate Presentation July 2021Exhibit 99.1 Corporate Presentation July 2021
Disclaimer and Forward-Looking Statement Certain statements in this presentation and the accompanying oral commentary are forward-looking statements. These statements relate to future events or the future financial performance of Biomea Fusion, Inc. (the “Company”) and involve known and unknown 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 clinical trials, the actions or potential action of the FDA, the status and timing of ongoing research, 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. 2Disclaimer and Forward-Looking Statement Certain statements in this presentation and the accompanying oral commentary are forward-looking statements. These statements relate to future events or the future financial performance of Biomea Fusion, Inc. (the “Company”) and involve known and unknown 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 clinical trials, the actions or potential action of the FDA, the status and timing of ongoing research, 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
Irreversible Drug Discovery & Our Mission is to revolutionize drug development Development Platform in order to create more effective therapies for patients in need. Three Innovative Programs Announced to date Biomea Fusion is a preclinical-stage biopharmaceutical company focused on the discovery and development of irreversible small-molecule drugs to treat patients with Menin Lead Product Candidate genetically defined cancers. Our discovery team is in IND-enabling Studies engaged in all phases of development, including target selection, small molecule design, and preclinical and clinical studies to develop innovative medicines. Liquid & Solid Tumor Targets 3Irreversible Drug Discovery & Our Mission is to revolutionize drug development Development Platform in order to create more effective therapies for patients in need. Three Innovative Programs Announced to date Biomea Fusion is a preclinical-stage biopharmaceutical company focused on the discovery and development of irreversible small-molecule drugs to treat patients with Menin Lead Product Candidate genetically defined cancers. Our discovery team is in IND-enabling Studies engaged in all phases of development, including target selection, small molecule design, and preclinical and clinical studies to develop innovative medicines. Liquid & Solid Tumor Targets 3
Biomea Fusion History A Discovery Platform in Development since 2017 Biomea and A2A form Lead candidates Initial Public Offering 2018 2020 Biomea Fusion to develop selected for menin (NASDAQ: BMEA) MLL-Fusion and menin Raises $158 M at $17/share reversible menin Program dependent cancers JPMorgan, Jeffries, Piper Sandler F u s io n Biomea becomes a JLABS, Biomea receives Series A South San Francisco Syndicate financing of $56M resident to support the development of Biomea's portfolio of 2021 2019 2017 irreversible inhibitors Biomea builds out its proprietary irreversible binding technology 4Biomea Fusion History A Discovery Platform in Development since 2017 Biomea and A2A form Lead candidates Initial Public Offering 2018 2020 Biomea Fusion to develop selected for menin (NASDAQ: BMEA) MLL-Fusion and menin Raises $158 M at $17/share reversible menin Program dependent cancers JPMorgan, Jeffries, Piper Sandler F u s io n Biomea becomes a JLABS, Biomea receives Series A South San Francisco Syndicate financing of $56M resident to support the development of Biomea's portfolio of 2021 2019 2017 irreversible inhibitors Biomea builds out its proprietary irreversible binding technology 4
Biomea’s Team Diverse team with significant drug development experience Taisei Kinoshita Naomi Cretcher Heow Tan Alex Cacovean MD Thorsten Kirschberg Thomas Butler Ramses Erdtmann Franco Valle Chief of People Chief Technical & Exec. Medical EVP of Chemistry VP of Biology Chairman & CEO President & COO Chief Financial Quality Officer Director Officer 22 years in Life Science 15 years in Life Science 15 years in Life Science 15 years in Life Science 13 years in Life Science 15 years in Life Science 25 years in Life Science 20 years in Life Science Pharmacyclics Iovance Inc. Pharmacyclics Pharmacyclics Pharmacyclics Eidos Therapeutics Terns Pharmaceuticals Pharmacyclics Collegium Pharmaceutical Pharmacyclics Genentech Gilead Sciences Oxygen Investments Iovance Biotherapeutics Gilead Sciences Rigel Pharmaceuticals Praecis Pharmaceuticals PPD Inc. UC Irvine, BA Comm UCLA – MBA Finance Commerzbank Pharmacyclics Cell Gate University of Tokyo, Ohio State University Henry Ford Hospital SF State University, UCSB, MS – Chemistry University of Münster, CallidusCloud Golden Gate Ph.D. Biology Santa Clara University University of Medicine Comm Master’s in Banking & PricewaterhouseCoopers University, MBA Leavey School of Business, and Pharmacy “Iuliu Corp Finance San Jose State University, University of Münster, MBA – Finance & Hatieganu” Cluj- BS Corporate Finance Ph.D., Chemistry Management Napoca, Romania, M.D. 5
Biomea FUSION™ System Discovery Platform We leverage our FUSION™ System to discover and develop novel irreversible inhibitors against targets essential for cancer Scaffold Scaffold Scaffold 2 3 1 Our FUSION™ System Discovery Platform encompasses the following: • Target selection: Expertise in structural biology and Asn Gly irreversible binding chemistry. Met Trp Scaffold • Scaffold creation: Computational approach to exploit 3 unique structural elements of target proteins and create novel scaffolds. • Molecule optimization: Proprietary suite of computational Computational Chemistry technologies, assays, analytical approaches, chemistry to maximize selectivity, potency, safety and convenience of our oral irreversible small molecule product candidates. 6Biomea FUSION™ System Discovery Platform We leverage our FUSION™ System to discover and develop novel irreversible inhibitors against targets essential for cancer Scaffold Scaffold Scaffold 2 3 1 Our FUSION™ System Discovery Platform encompasses the following: • Target selection: Expertise in structural biology and Asn Gly irreversible binding chemistry. Met Trp Scaffold • Scaffold creation: Computational approach to exploit 3 unique structural elements of target proteins and create novel scaffolds. • Molecule optimization: Proprietary suite of computational Computational Chemistry technologies, assays, analytical approaches, chemistry to maximize selectivity, potency, safety and convenience of our oral irreversible small molecule product candidates. 6
Irreversible Drugs offer several potentially significant Advantages Greater Therapeutic High Selectivity Deep Target-Inactivation Window • Irreversible inhibitors can cause • Irreversible drugs are designed to • Irreversible drugs leverage both non- permanent inactivation of bound maintain their effect in the absence covalent and covalent interactions to protein. of sustained drug exposure, unlike drive selectivity. conventional reversible drugs, which typically need to be present to • Irreversible binding may result in the • Offers greater potential selectivity provide benefit. target elimination through normal versus reversible compounds, which cellular degradation processes. rely on non-covalent bonding alone. • Uncoupling of drug effects from drug exposure can potentially enable • Target inactivation can trigger rapid • High selectivity provides potential to lower drug dosing and less frequent apoptosis or differentiation into a reduce non-specific, off-target dosing regimens versus reversible normal, mature cell. interactions that often lead to safety approaches. and tolerability challenges. 7Irreversible Drugs offer several potentially significant Advantages Greater Therapeutic High Selectivity Deep Target-Inactivation Window • Irreversible inhibitors can cause • Irreversible drugs are designed to • Irreversible drugs leverage both non- permanent inactivation of bound maintain their effect in the absence covalent and covalent interactions to protein. of sustained drug exposure, unlike drive selectivity. conventional reversible drugs, which typically need to be present to • Irreversible binding may result in the • Offers greater potential selectivity provide benefit. target elimination through normal versus reversible compounds, which cellular degradation processes. rely on non-covalent bonding alone. • Uncoupling of drug effects from drug exposure can potentially enable • Target inactivation can trigger rapid • High selectivity provides potential to lower drug dosing and less frequent apoptosis or differentiation into a reduce non-specific, off-target dosing regimens versus reversible normal, mature cell. interactions that often lead to safety approaches. and tolerability challenges. 7
Irreversible Drugs are designed to uncouple Drug-Effects from Drug-Exposure • The chart shows Ibrutinib, an approved, irreversible PK/PD – Current Commercial Drug BTK inhibitor. • Irreversible drugs can be designed to achieve nearly complete occupancy in short time, and occupancy is intended to be sustainable over 24 hours. • Irreversible drugs are also designed to be cleared rapidly to minimize off target toxicity. • Irreversible binding potentially offers: - Optimal Effect (Pharmacodynamics (PD)) / Exposure (Pharmacokinetics (PK)) - Maximum Target Engagement - Better Selectivity (Lower Molecular Weight) - Better Drug-Like Properties (Lower Molecular Weight) 8 (ng/ml)Irreversible Drugs are designed to uncouple Drug-Effects from Drug-Exposure • The chart shows Ibrutinib, an approved, irreversible PK/PD – Current Commercial Drug BTK inhibitor. • Irreversible drugs can be designed to achieve nearly complete occupancy in short time, and occupancy is intended to be sustainable over 24 hours. • Irreversible drugs are also designed to be cleared rapidly to minimize off target toxicity. • Irreversible binding potentially offers: - Optimal Effect (Pharmacodynamics (PD)) / Exposure (Pharmacokinetics (PK)) - Maximum Target Engagement - Better Selectivity (Lower Molecular Weight) - Better Drug-Like Properties (Lower Molecular Weight) 8 (ng/ml)
Biomea Irreversible Drugs have a long History in Medicine Aspirin was the first irreversible drug, discovered in 1899, and is to date the most used medicine in the world Aspirin Sofosbuvir (Sovaldi) Ibrutinib (Imbruvica) Penicillin Tenofovir (Viread) Osimertinib (Tagrisso) 9Biomea Irreversible Drugs have a long History in Medicine Aspirin was the first irreversible drug, discovered in 1899, and is to date the most used medicine in the world Aspirin Sofosbuvir (Sovaldi) Ibrutinib (Imbruvica) Penicillin Tenofovir (Viread) Osimertinib (Tagrisso) 9
High Barriers to Entry to develop Irreversible Drugs Complexity Safety and Toxicity The discovery and development of irreversible drugs has been While the irreversible binding modality can provide a high degree limited by: of selectivity, potential risks have presented barriers: • Need for specialized understanding of proteome structural • Irreversible molecules with promiscuous binding profiles can knowledge and medicinal chemistry capabilities, including the pose risk of significant off-target interactions and safety ability to construct complex novel chemical scaffolds. concerns. • Limited knowledge and availability of targets as not all • Drug developers, without the experience and specific disease causing proteins have the properties necessary for capabilities required to develop irreversible binders, have the application of irreversible binding. historically not pursued irreversible drugs. 10High Barriers to Entry to develop Irreversible Drugs Complexity Safety and Toxicity The discovery and development of irreversible drugs has been While the irreversible binding modality can provide a high degree limited by: of selectivity, potential risks have presented barriers: • Need for specialized understanding of proteome structural • Irreversible molecules with promiscuous binding profiles can knowledge and medicinal chemistry capabilities, including the pose risk of significant off-target interactions and safety ability to construct complex novel chemical scaffolds. concerns. • Limited knowledge and availability of targets as not all • Drug developers, without the experience and specific disease causing proteins have the properties necessary for capabilities required to develop irreversible binders, have the application of irreversible binding. historically not pursued irreversible drugs. 10
Biomea’s Pipeline of Irreversible Proprietary Assets We are building a platform of irreversible inhibitors in multiple tumor types KEY IND- DISCOVERY PHASE 1 PHASE 2 PHASE 3 ANTICIPATED ENABLING MILESTONES File IND in the BMF-219 menin dependent second half of Irreversible Menin cancers 2021 Inhibitor Declare Target: UNDISCLOSED candidate in the first half of Therapeutic Area: 2022 Oncology Target: UNDISCLOSED Therapeutic Area: Oncology 11 DISCOVERY DEVELOPMENT Biomea’s Pipeline of Irreversible Proprietary Assets We are building a platform of irreversible inhibitors in multiple tumor types KEY IND- DISCOVERY PHASE 1 PHASE 2 PHASE 3 ANTICIPATED ENABLING MILESTONES File IND in the BMF-219 menin dependent second half of Irreversible Menin cancers 2021 Inhibitor Declare Target: UNDISCLOSED candidate in the first half of Therapeutic Area: 2022 Oncology Target: UNDISCLOSED Therapeutic Area: Oncology 11 DISCOVERY DEVELOPMENT
Menin – a Protein important to transcriptional Regulation Menin impacts major processes such as cell cycle control, apoptosis, and DNA damage repair Liquid Tumor Role Solid Tumor Role Source: Cierpicki & Grambacka, Future Med. Chem. (2014) Modified after Uckelmann (Scott Armstrong Lab) , ASH 2018, Abstract # 546 12
Menin-MLL Interaction Schematic of key proteins and their interactions in the regulation of gene transcription • Inhibition of the menin-MLL Transcriptional interaction leads to upregulation reduction in MEN1 Biomea of leukemic drivers: transcription, resulting in HOX genes, MEIS1, down regulation of MEIS1, EZH2,… HOXA9 and DMNT3A, and differentiation of leukemic cells into myeloid cells. • BMF-219, is intended to irreversibly inhibit the Biomea interaction between menin and wild type MLL and MLL fusions. Modified after Rao & Dou (2015). Hijacked in cancer: the KMT2 (MLL) family of methyltransferases. Nat.Rev.Cancer. 15: 334-346 13Menin-MLL Interaction Schematic of key proteins and their interactions in the regulation of gene transcription • Inhibition of the menin-MLL Transcriptional interaction leads to upregulation reduction in MEN1 Biomea of leukemic drivers: transcription, resulting in HOX genes, MEIS1, down regulation of MEIS1, EZH2,… HOXA9 and DMNT3A, and differentiation of leukemic cells into myeloid cells. • BMF-219, is intended to irreversibly inhibit the Biomea interaction between menin and wild type MLL and MLL fusions. Modified after Rao & Dou (2015). Hijacked in cancer: the KMT2 (MLL) family of methyltransferases. Nat.Rev.Cancer. 15: 334-346 13
BMF-219 has demonstrated rapid Reduction in Menin dependent Gene Expression = Target Engagement • Molecular responses following MEN1 MEIS1 HOXA9 DNMT3A * TPM treatment with BMF-219 in 8 0.8 80 0.20 MOLM-13 cells (an acute myeloid leukemia cell line with a 6 0.6 60 0.15 KMT2A-MLLT3 fusion). 6h 4 0.4 40 0.10 • A reversible inhibitor (BMF-05) showed minimal impact on 2 0.2 20 0.05 signature genes at these time points as measured in Transcripts 0 0.0 0 0.00 per Million (TPM), consistent 8 0.6 50 0.3 with published findings. 40 6 0.4 0.2 24h • Our irreversible inhibitor BMF- 30 4 219 caused rapid and notable 20 effect, showing up to 80% 0.2 0.1 2 reduction in readout genes by 6 10 hours and approximately 95% 0 0.0 0 0.0 reduction at 24 hours. DMSO BMF-05 BMF-219 DMSO BMF-05 BMF-219 DMSO BMF-05 BMF-219 DMSO BMF-05 BMF-219 *TPM (Transcripts per Million, a measure of gene expression) 14BMF-219 has demonstrated rapid Reduction in Menin dependent Gene Expression = Target Engagement • Molecular responses following MEN1 MEIS1 HOXA9 DNMT3A * TPM treatment with BMF-219 in 8 0.8 80 0.20 MOLM-13 cells (an acute myeloid leukemia cell line with a 6 0.6 60 0.15 KMT2A-MLLT3 fusion). 6h 4 0.4 40 0.10 • A reversible inhibitor (BMF-05) showed minimal impact on 2 0.2 20 0.05 signature genes at these time points as measured in Transcripts 0 0.0 0 0.00 per Million (TPM), consistent 8 0.6 50 0.3 with published findings. 40 6 0.4 0.2 24h • Our irreversible inhibitor BMF- 30 4 219 caused rapid and notable 20 effect, showing up to 80% 0.2 0.1 2 reduction in readout genes by 6 10 hours and approximately 95% 0 0.0 0 0.0 reduction at 24 hours. DMSO BMF-05 BMF-219 DMSO BMF-05 BMF-219 DMSO BMF-05 BMF-219 DMSO BMF-05 BMF-219 *TPM (Transcripts per Million, a measure of gene expression) 14
BMF-219 has demonstrated Dose Dependent Cell Differentiation • Dose dependent elevation of myeloid TPM differentiation marker (ITGAM) at 24 hours irreversible reversible @10µM reversible 0.3 after administration of BMF-219 demonstrated target engagement in MOLM-13 cells. • Comparable exposures of reversible menin 0.2 inhibitors (BMF-05, BMF-13, BMF214) reflected no change from vehicle controls. • Reversible inhibitors were able to upregulate 0.1 ITGAM at 10-fold increase in exposure. This supports: - Hypothesis for the role of menin in cancer cell proliferation and 0.0 - Highlights potential need for high clinical exposures for reversible inhibitors in order to achieve sufficient menin suppression to affect the disease. *24 hours following administration 15 BMF-219 1uM BMF-219 500nM BMF-05 10uM BMF-13 10uM BMF-05 1uM BMF-214 500nM BMF-13 1uM BMF-214 1uM DMSO Transcripts per Million (TPM) BMF-219 has demonstrated Dose Dependent Cell Differentiation • Dose dependent elevation of myeloid TPM differentiation marker (ITGAM) at 24 hours irreversible reversible @10µM reversible 0.3 after administration of BMF-219 demonstrated target engagement in MOLM-13 cells. • Comparable exposures of reversible menin 0.2 inhibitors (BMF-05, BMF-13, BMF214) reflected no change from vehicle controls. • Reversible inhibitors were able to upregulate 0.1 ITGAM at 10-fold increase in exposure. This supports: - Hypothesis for the role of menin in cancer cell proliferation and 0.0 - Highlights potential need for high clinical exposures for reversible inhibitors in order to achieve sufficient menin suppression to affect the disease. *24 hours following administration 15 BMF-219 1uM BMF-219 500nM BMF-05 10uM BMF-13 10uM BMF-05 1uM BMF-214 500nM BMF-13 1uM BMF-214 1uM DMSO Transcripts per Million (TPM)
BMF-219 has demonstrated superior, rapid and durable Responses in Leukemia Cell Lines MV4;11 MOLM-13 NPM1 mutant 1200000 5000000 4000000 BMF-05 MI-503 1000000 BMF-219 DMSO 4000000 3000000 800000 3000000 600000 2000000 2000000 400000 1000000 1000000 200000 0 0 0 T4 T7 T11 T14 T4 T7 T11 T14 T4 T7 T11 T14 • BMF-219 demonstrated rapid shut down of metabolic activity, sustained over the 14-day study duration. • BMF-219 responses were superior to tested reversible menin inhibitors (BMF-05, MI-503) with respect to both onset and durability of metabolic suppression. 16 Relative Fluorescent UnitsBMF-219 has demonstrated superior, rapid and durable Responses in Leukemia Cell Lines MV4;11 MOLM-13 NPM1 mutant 1200000 5000000 4000000 BMF-05 MI-503 1000000 BMF-219 DMSO 4000000 3000000 800000 3000000 600000 2000000 2000000 400000 1000000 1000000 200000 0 0 0 T4 T7 T11 T14 T4 T7 T11 T14 T4 T7 T11 T14 • BMF-219 demonstrated rapid shut down of metabolic activity, sustained over the 14-day study duration. • BMF-219 responses were superior to tested reversible menin inhibitors (BMF-05, MI-503) with respect to both onset and durability of metabolic suppression. 16 Relative Fluorescent Units
BMF-219 Impaired Cell Survival in Multiple Myeloma and Pancreatic Cancer Models Multiple Myeloma Cell Viability KRAS Pancreatic Cancer Viability (KMS-20 cells, 0.560µM dose) (MIA-PaCa--2 cells, 0.560µM) 4000000 100000 BMF-5 BMF-219 DMSO BMF-219 MI-503 BMF-05 DMSO 80000 3000000 60000 2000000 40000 1000000 20000 0 0 Day 4 Day 7 Day 11 Day 4 Day 7 Day 11 Day 14 • Impairment of survival in multiple myeloma model • Impairment of survival in G12C KRAS mutation driven (KMS-20 cell line, 0.56µM doses) by irreversible pancreatic cancer line (MIA-PaCa-2, 0.56µM doses) menin inhibitor BMF-219 versus a reversible inhibitor shows the effects of irreversible menin inhibitor (BMF-05). BMF-219 versus a reversible inhibitor (BMF-05) at far lower dose levels. 17 Surviving Cells (relative fluorescence) Surviving Cells (relative fluorescence)BMF-219 Impaired Cell Survival in Multiple Myeloma and Pancreatic Cancer Models Multiple Myeloma Cell Viability KRAS Pancreatic Cancer Viability (KMS-20 cells, 0.560µM dose) (MIA-PaCa--2 cells, 0.560µM) 4000000 100000 BMF-5 BMF-219 DMSO BMF-219 MI-503 BMF-05 DMSO 80000 3000000 60000 2000000 40000 1000000 20000 0 0 Day 4 Day 7 Day 11 Day 4 Day 7 Day 11 Day 14 • Impairment of survival in multiple myeloma model • Impairment of survival in G12C KRAS mutation driven (KMS-20 cell line, 0.56µM doses) by irreversible pancreatic cancer line (MIA-PaCa-2, 0.56µM doses) menin inhibitor BMF-219 versus a reversible inhibitor shows the effects of irreversible menin inhibitor (BMF-05). BMF-219 versus a reversible inhibitor (BMF-05) at far lower dose levels. 17 Surviving Cells (relative fluorescence) Surviving Cells (relative fluorescence)
BMF-219 Inhibited Cell Survival in Multiple Cancer Cell Lines Cell Line/Tumor Type IC50 (µM) MOLM-13/AML 0.05 • Responses to BMF-219 were Fusion MV4;11/ALL-AML 0.07 screened across a range of NPM1 Mutation OCI-AML3/AML 0.14 cancer cell lines. MIA-PaCa-2/Pancreatic 0.23 KRAS NCI-H23/Lung 0.26 • Potent growth inhibition was KMS-20/Plasma Cell Myeloma 0.26 observed across a range of VCaP/Prostate Adenocarcinoma (met) 0.29 cancer models including liquid Menin Dependent OE-33/Barrett Esophageal Adenocarcinoma 0.30 and solid tumors. KG-1/AML 0.33 HC1187/Ductal Breast Carcinoma (TNBC) 0.46 Panc 10.05/Pancreatic 0.49 KRAS NCIH23/NSCLC 0.49 Menin Dependent BT-474/invasive ductal carcinoma NOS 0.52 KRAS SK-LU-1/Lung 0.59 18BMF-219 Inhibited Cell Survival in Multiple Cancer Cell Lines Cell Line/Tumor Type IC50 (µM) MOLM-13/AML 0.05 • Responses to BMF-219 were Fusion MV4;11/ALL-AML 0.07 screened across a range of NPM1 Mutation OCI-AML3/AML 0.14 cancer cell lines. MIA-PaCa-2/Pancreatic 0.23 KRAS NCI-H23/Lung 0.26 • Potent growth inhibition was KMS-20/Plasma Cell Myeloma 0.26 observed across a range of VCaP/Prostate Adenocarcinoma (met) 0.29 cancer models including liquid Menin Dependent OE-33/Barrett Esophageal Adenocarcinoma 0.30 and solid tumors. KG-1/AML 0.33 HC1187/Ductal Breast Carcinoma (TNBC) 0.46 Panc 10.05/Pancreatic 0.49 KRAS NCIH23/NSCLC 0.49 Menin Dependent BT-474/invasive ductal carcinoma NOS 0.52 KRAS SK-LU-1/Lung 0.59 18
BMF-219 Inhibited Patient derived AML cells at very low Exposures vs Reversible Inhibitors Patient 320: NPM1 AML, Treatment Naïve Patient 340: NPM1 AML, Treatment Naïve Patient 350: MLD AML, Relapsed Refractory Patient 400: MLL-r AML, Treatment Naïve 100% 100% Patient 320: NPM1 AML, Treatment Naïve 10 µM exposure 90% 90% Patient 340: NPM1 AML, Treatment Naïve 80% 80% Patient 350: MLD AML, Relapsed Refractory 70% 70% Patient 400: MLL-r AML, Treatment Naïve 60% 60% 1µM exposure 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0% BMF-219 BMF-T2 BMF-5 BMF-13 MI-503 BMF-05 BMF-13 MI-503 irreversible reversible reversible • Irreversible inhibition leads to dramatic growth inhibition at 1µM exposure while tested reversible inhibitors showed limited effect. • At six days, reversible menin inhibitors show similar inhibition of growth at drug exposures 10-fold greater than their respective IC90 values (10µM). • Findings support relevance of the mechanism in disease and our hypothesis that an irreversible inhibitor could potentially provide greater therapeutic benefit at lower exposure-levels versus reversible inhibitors. 19 Growth Inhibition Growth InhibitionBMF-219 Inhibited Patient derived AML cells at very low Exposures vs Reversible Inhibitors Patient 320: NPM1 AML, Treatment Naïve Patient 340: NPM1 AML, Treatment Naïve Patient 350: MLD AML, Relapsed Refractory Patient 400: MLL-r AML, Treatment Naïve 100% 100% Patient 320: NPM1 AML, Treatment Naïve 10 µM exposure 90% 90% Patient 340: NPM1 AML, Treatment Naïve 80% 80% Patient 350: MLD AML, Relapsed Refractory 70% 70% Patient 400: MLL-r AML, Treatment Naïve 60% 60% 1µM exposure 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0% BMF-219 BMF-T2 BMF-5 BMF-13 MI-503 BMF-05 BMF-13 MI-503 irreversible reversible reversible • Irreversible inhibition leads to dramatic growth inhibition at 1µM exposure while tested reversible inhibitors showed limited effect. • At six days, reversible menin inhibitors show similar inhibition of growth at drug exposures 10-fold greater than their respective IC90 values (10µM). • Findings support relevance of the mechanism in disease and our hypothesis that an irreversible inhibitor could potentially provide greater therapeutic benefit at lower exposure-levels versus reversible inhibitors. 19 Growth Inhibition Growth Inhibition
Selectivity Profiling of BMF-219 in multiple Safety Models Kinase screening Glutathione reactivity Mean half-life • In-house analysis of menin revealed limited structural • Drugs with limited non-specific interactions have long Drug (min) similarity between targeted binding pocket and tyrosine half-lives as the drug does not get consumed in a Omeprazole 123.3 kinases with known involvement in hematological reaction with wildly-used glutathione (GSH). Neratinib 197.7 • BMF-219 showed negligible interaction with the strong cancers. Ibrutinib >360 • 169 kinases screened; only two wild type kinases showed nucleophile GSH and showed less reactivity than the BMF-213 322.3 greater than 50% inhibition upon treatment with BMF- approved irreversible drugs omeprazole and neratinib. BMF-214 >360 219. BMF-219 >360 Oncopanel screening Safety screen Metabolic Activity in % BMF-219 Vehicle • BMF-219 was also profiled on the • Minimal impact of BMF-219 treatment on cell metabolism in 100 SafetyScreen44 panel (CEREP/Eurofins leukemia and lymphoma cell lines that have wild type MLL, 80 Discovery), an in vitro panel of 44 common but no menin-linked mechanism for disease. 60 selected targets to identify significant off- 40 target interactions. • Findings are consistent with external studies, showing that • Findings showed no meaningful impact 20 menin-MLL interaction is not generally cell-essential and only (greater than 50% activation or inhibition) critical to survival in those cells that contain aberrant biology. 0 of BMF-219 across these key safety assays BC-1 BCP-1 BV-173 K562 U937 20Selectivity Profiling of BMF-219 in multiple Safety Models Kinase screening Glutathione reactivity Mean half-life • In-house analysis of menin revealed limited structural • Drugs with limited non-specific interactions have long Drug (min) similarity between targeted binding pocket and tyrosine half-lives as the drug does not get consumed in a Omeprazole 123.3 kinases with known involvement in hematological reaction with wildly-used glutathione (GSH). Neratinib 197.7 • BMF-219 showed negligible interaction with the strong cancers. Ibrutinib >360 • 169 kinases screened; only two wild type kinases showed nucleophile GSH and showed less reactivity than the BMF-213 322.3 greater than 50% inhibition upon treatment with BMF- approved irreversible drugs omeprazole and neratinib. BMF-214 >360 219. BMF-219 >360 Oncopanel screening Safety screen Metabolic Activity in % BMF-219 Vehicle • BMF-219 was also profiled on the • Minimal impact of BMF-219 treatment on cell metabolism in 100 SafetyScreen44 panel (CEREP/Eurofins leukemia and lymphoma cell lines that have wild type MLL, 80 Discovery), an in vitro panel of 44 common but no menin-linked mechanism for disease. 60 selected targets to identify significant off- 40 target interactions. • Findings are consistent with external studies, showing that • Findings showed no meaningful impact 20 menin-MLL interaction is not generally cell-essential and only (greater than 50% activation or inhibition) critical to survival in those cells that contain aberrant biology. 0 of BMF-219 across these key safety assays BC-1 BCP-1 BV-173 K562 U937 20
Estimated Target Population for Irreversible Menin Inhibitor BMF-219 Leukemia Lung Cancer Liquid Tumors Solid Tumors Est. US Patient Est. US Patient NPM-1 Pancreatic Population Population Disease Disease Leukemias (Annual (Annual Cancer Incidence) Incidence) Fusion Breast AML/ALL 2,500 EWS 1,000 (MLL-R) Leukemias Cancer AML/ALL 7,000 KRAS-Lung 34,000 (NPM1) KRAS- Pediatric Fusion DLBCL* 18,000 26,000 Sarcomas Pancreatic Leukemias MM* 32,000 KRAS-CRC 17,000 * Investigation ongoing to further define menin dependent subset Patient Numbers see: AML/ALL/DLBCL/MM/Lung/Pancreatic/Colorectal: https://seer.cancer.gov SOLID TUMORSD LIQUID TUMORSD EWS: pubmed.ncbi.nlm.nih.gov/18525458/ Mutation Status see: AML/ALL MLL-R & NPM1 www.ncbi.nlm.nih.gov/pmc/articles/PMC5299633/ and www.ncbi.nlm.nih.gov/pmc/articles/PMC3069851 KRAS NSCLC G12C&D https://err.ersjournals.com/content/25/139/71# KRAS PDAC G12C&D www.cell.com/trends/biochemical-sciences/pdf/S0968-0004(13)00203-X.pdf KRAS CRC G12C&D www.ncbi.nlm.nih.gov/pmc/articles/PMC6945179/#!po=15.9091 21Estimated Target Population for Irreversible Menin Inhibitor BMF-219 Leukemia Lung Cancer Liquid Tumors Solid Tumors Est. US Patient Est. US Patient NPM-1 Pancreatic Population Population Disease Disease Leukemias (Annual (Annual Cancer Incidence) Incidence) Fusion Breast AML/ALL 2,500 EWS 1,000 (MLL-R) Leukemias Cancer AML/ALL 7,000 KRAS-Lung 34,000 (NPM1) KRAS- Pediatric Fusion DLBCL* 18,000 26,000 Sarcomas Pancreatic Leukemias MM* 32,000 KRAS-CRC 17,000 * Investigation ongoing to further define menin dependent subset Patient Numbers see: AML/ALL/DLBCL/MM/Lung/Pancreatic/Colorectal: https://seer.cancer.gov SOLID TUMORSD LIQUID TUMORSD EWS: pubmed.ncbi.nlm.nih.gov/18525458/ Mutation Status see: AML/ALL MLL-R & NPM1 www.ncbi.nlm.nih.gov/pmc/articles/PMC5299633/ and www.ncbi.nlm.nih.gov/pmc/articles/PMC3069851 KRAS NSCLC G12C&D https://err.ersjournals.com/content/25/139/71# KRAS PDAC G12C&D www.cell.com/trends/biochemical-sciences/pdf/S0968-0004(13)00203-X.pdf KRAS CRC G12C&D www.ncbi.nlm.nih.gov/pmc/articles/PMC6945179/#!po=15.9091 21
Menin Pathway Validation – Type II Diabetes • Menin (MEN1) controls differentiation of pancreatic stem cells into adult, glucose-responsive Beta Cells • Expression of MEN1 and MEN1 target genes (p27) is significantly decreased with increasing Concentrations of Glucose • Glucose induces islet Beta-cell growth while inhibiting MENIN expression both at the Transcription and Translational Level • MENIN expression also controls Beta Cell Growth and Insulin Levels in pregnant Mice and promotes Gestational Diabetes Source: Jiang et al., Diabetes (2018) 22
Biomea Fusion Intellectual Property We believe our Patent Portfolio with novel irreversible Scaffolds is strong and growing We have a strong Intellectual Property Portfolio (IP) which is growing every month. Our IP consists of several pending US and ex-US patent applications and several trademarks related to our scientific assets. Our patents cover composition of matter, pharmaceutical composition, and methods of treatment for our reversible and irreversible menin inhibitors. If issued, we expect our patents to expire between December 2039 to December 2041 (excluding possible patent term extensions which can vary in time and are not guaranteed). 23Biomea Fusion Intellectual Property We believe our Patent Portfolio with novel irreversible Scaffolds is strong and growing We have a strong Intellectual Property Portfolio (IP) which is growing every month. Our IP consists of several pending US and ex-US patent applications and several trademarks related to our scientific assets. Our patents cover composition of matter, pharmaceutical composition, and methods of treatment for our reversible and irreversible menin inhibitors. If issued, we expect our patents to expire between December 2039 to December 2041 (excluding possible patent term extensions which can vary in time and are not guaranteed). 23
Corporate Milestones Developing BMF-219 for multiple indications and building out a platform of irreversible inhibitors 2021 and beyond ü 15 April 2021, IPO. Sale of 9.823 M shares at $17 per share, raising after fees $153M with a total share count of 29.5M. Total Cash at the end of Q1 was $57.5M, together with the funds raised during the IPO, Biomea had a cash balance of about $210M. ü Completion of IND-enabling studies with irreversibly bound menin inhibitor BMF-219. nd • File IND in 2 Half of 2021. • Pre-clinical data in DLBCL with BMF 219 in Q1 2022. • Pathway validation of menin in Type II diabetes in Q1 2022. • Initiation of first in human trial with BMF-219 expected to produce clinical data for a variety of tumor types in Phase I / II Basket-Study. • Advancement of irreversible platform to generate one additional IND candidate in 1H of 2022. 24Corporate Milestones Developing BMF-219 for multiple indications and building out a platform of irreversible inhibitors 2021 and beyond ü 15 April 2021, IPO. Sale of 9.823 M shares at $17 per share, raising after fees $153M with a total share count of 29.5M. Total Cash at the end of Q1 was $57.5M, together with the funds raised during the IPO, Biomea had a cash balance of about $210M. ü Completion of IND-enabling studies with irreversibly bound menin inhibitor BMF-219. nd • File IND in 2 Half of 2021. • Pre-clinical data in DLBCL with BMF 219 in Q1 2022. • Pathway validation of menin in Type II diabetes in Q1 2022. • Initiation of first in human trial with BMF-219 expected to produce clinical data for a variety of tumor types in Phase I / II Basket-Study. • Advancement of irreversible platform to generate one additional IND candidate in 1H of 2022. 24
Thank You 25Thank You 25