Full Press Release Details
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 M nster, 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 M nster, Purdue University Corporate Finance MBA - Finance & Mgmt and medical oncologist Ph.D., Chemistry Ph.D. Organic Chemistry (Yale University School of Medicine)
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: Jovanovi , 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- lvarez, M., Aguilera, ., & Garc a-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
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 (0.500 M 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 M, 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