UNITED STATES
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FORM
CURRENT REPORT
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| Item 8.01. | Other Events. |
On August 26, 2022, Biomea Fusion, Inc. (the “Company”) issued a press release titled, “Biomea Fusion Presents Additional Preclinical Data Demonstrating Anti-Tumor Activity and Mechanistic Evidence for BMF-219 in Diffuse Large B-Cell Lymphoma and Multiple Myeloma Models at International Myeloma Society Annual Meeting.” The information described in the press release was also presented in two poster presentations at the 19th International Myeloma Society (IMS) Annual Meeting, which took place August 25-27, 2022 in Los Angeles, California.
Copies of the press release and the Company’s poster presentations are attached to this Current Report on Form 8-K as Exhibits 99.1 through 99.3 and incorporated herein by reference.
Forward-Looking Statements
Statements made or incorporated by reference in this Current Report on Form 8-K may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding the clinical and therapeutic potential of the Company’s product candidates and development programs, including BMF-219, the potential of BMF-219 as a treatment for various types of cancer and diabetes, the Company’s research, development and regulatory plans, including the progress and results of the Company’s ongoing COVALENT-101 trial of BMF-219, and the timing of such events, may be deemed to be forward-looking statements. The Company intends these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and is making this statement for purposes of complying with those safe harbor provisions.
Any forward-looking statements made or incorporated by reference in this Current Report on Form 8-K are based on the Company’s current expectations, estimates and projections only as of the date of this Current Report on Form 8-K are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that the Company may encounter delays in patient enrollment and in the initiation, conduct and completion of its planned clinical trials and other research and development activities. These risks concerning the Company’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (the “SEC”), including its most recent periodic report filed with the SEC and subsequent filings thereafter. The Company explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
2
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: August 29, 2022 | By: | /s/ Thomas Butler | ||||
| Thomas Butler | ||||||
| Principal Executive Officer | ||||||
3
Exhibit 99.1
Biomea Fusion Presents Additional Preclinical Data Demonstrating Anti- Tumor Activity and Mechanistic Evidence for BMF-219 in Diffuse Large B-Cell Lymphoma and Multiple Myeloma Models at International Myeloma Society Annual Meeting
| • | Data demonstrated robust anti-tumor activity of BMF-219 and mechanistic evidence for novel inhibition of menin protein in preclinical models of Diffuse Large B-cell Lymphoma (DLBCL) and multiple myeloma (MM). |
| • | BMF-219 displayed single agent potency, surpassing greater than 90% inhibition at clinically relevant exposures in both DLBCL and MM cell lines and patient-derived samples. |
| • | A Trial In Progress (TIP) poster was also presented, detailing the design of Biomea’s ongoing Phase I clinical trial (COVALENT-101), which is currently enrolling patients with relapsed / refractory acute leukemias, DLBCL, and MM. |
REDWOOD CITY, Calif., Aug. 26, 2022 (GLOBE NEWSWIRE) — Biomea Fusion, Inc.
(Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, announced today the presentation of two posters at the 19th International Myeloma Society (IMS) Annual Meeting, which took place August 25-27, 2022 in Los Angeles, California. Both poster presentations can be viewed on Biomea’s website at https://biomeafusion.com/publications.
“Our team has continued to accumulate novel scientific evidence demonstrating compelling preclinical activity of BMF-219 as a potential first-in-class and best-in- class menin inhibitor across a spectrum of tumor types where menin is known to play a critical role. To that end, we are pleased to present additional preclinical data at the IMS Annual Meeting that support the expansion of our ongoing COVALENT- 101 clinical trial to enroll patients with DLBCL and MM. We look forward to seeing how BMF-219’s preclinical effect translates to patient benefit in the clinical setting,” said Thomas Butler, CEO, Chairman of the Board and Co-Founder of Biomea.
Poster Presentation Details:
Poster P-107: Anti-tumor activity of covalent menin inhibitor, BMF-219, in High- Grade B-Cell Lymphoma and Multiple Myeloma Preclinical Models
Abstract Text:
Introduction
Menin is a scaffold protein that interacts with various transcriptional regulators and partner proteins to promote tumorigenesis in a context-dependent manner. Menin drives oncogenic signaling by regulating expression of genes such as HOXA9 and MEIS1 and is also known to play a key role in MYC-mediated transcriptional activities. BMF-219 is a highly selective, potent, orally bioavailable, small molecule covalent inhibitor of menin. We previously reported the ability of BMF-219 to modulate MYC expression and exhibit high potency against Double HIT Lymphoma (DHL) DLBCL (Diffuse Large B Cell Lymphoma) preclinical models.
Methods
In the current study we demonstrate the anti-tumor activity of BMF-219 in multiple myeloma (MM), and Double/Triple Hit Lymphoma (DHL/THL) and Double Expressor Lymphoma (DEL) high-grade B-cell lymphomas (HGBCL) preclinical models harboring various mutational backgrounds. Additionally, we provide mechanistic evidence for direct inhibition of menin protein, in cell line models representing MM, DHL and DEL.
Results
BMF-219 exhibited high potency in THL and DEL cell lines (IC50 = 0.27 mM and 0.37 mM, respectively), achieving >90% growth inhibition as single agent. BMF-219 was multi-fold more potent and exerted dramatically greater growth inhibition compared to clinical reversible menin inhibitors in all DLBCL cell lines tested, including an expanded panel of DHL cell lines. In ex vivo studies, an R-CHOP refractory THL patient sample and an R-EPOCH refractory MYC-amplified DLBCL patient sample were highly sensitive to BMF-219 treatment (IC50 = 0.15 mM and 0.2 mM, respectively) and demonstrated complete growth inhibition at 1 mM exposure. In contrast, two clinical reversible menin inhibitors demonstrated much lower potency (IC50 = ~1 mM to >10 mM). MM cell lines harboring mutations in TP53, KRAS and NRAS were all sensitive to BMF-219 with growth inhibition IC50 values in the range of 0.25 mM to 0.5 mM and achieved 100% inhibition at 1 mM. Notably, BMF-219 demonstrated single-agent efficacy (IC50 = 0.1 mM to 0.3 mM) against a panel of newly diagnosed and R/R ex vivo MM samples, including a p53-deleted clinical profile. Mechanistically,
BMF-219 induced a reduction in menin protein levels, the direct target of this covalent inhibitor. The dose-dependent reduction in menin protein across the collection of MM and DLBCL cell lines with varying cytogenetic and mutational backgrounds will be discussed. Analysis of additional proteins modulated by BMF- 219 in these cell line models will also be addressed.
Conclusions:
Collectively, our data demonstrate the novel and robust anti-tumor activity of BMF- 219 in HGBCL and MM preclinical models that represent categories of high unmet need. BMF-219 exhibits multi-fold higher potency and complete growth inhibition in these preclinical models compared to clinical reversible menin inhibitors, demonstrating its unique anti-tumor potential in these cancers.
Poster P-269: COVALENT-101: A Phase 1 study of BMF-219, a novel oral covalent menin inhibitor, in patients with relapsed/refractory (R/R) acute leukemia, diffuse large B-cell lymphoma, and multiple myeloma
Abstract Text:
Introduction
Trial in Progress
Background: Menin, a protein involved in transcriptional regulation, impacting cell cycle control, apoptosis, and DNA damage repair, plays a direct role in oncogenic signaling in multiple cancers. Inhibition of menin is a novel approach to cancer treatment. Preclinical data of BMF-219, a highly selective, orally bioavailable, small- molecule covalent inhibitor of menin, show sustained potent abrogation of menin- dependent oncogenic signaling in vitro and in vivo. BMF-219 exhibited a strong anti- proliferative effect on various menin-dependent acute myeloid leukemia (AML) cell lines, diffuse large B-cell lymphoma (DLBCL) lines representing Double/Triple Hit Lymphoma (DHL/THL) & Double Expressor Lymphoma (DEL), and MM cell lines with diverse mutational backgrounds. BMF-219 also showed high potency ex vivo in patient samples from MLL-rearranged and NPM1-mutant AML, THL and MYC- amplified DLBCL, and bone marrow mononuclear cells from treatment-naive and R/R MM.
Methods
COVALENT-101 (BF-MNN-101; NCT05153330) is a prospective, open-label, multi-cohort, non-randomized, multicenter Phase I study evaluating the safety, tolerability, and clinical activity of escalating doses of once daily oral BMF-219 in patients with R/R acute leukemia (AL), DLBCL, and MM who have received or are ineligible for standard therapy. Utilizing an accelerated titration design, doses of BMF-219 will be escalated in single-subject cohorts independently for each indication until 1 subject experiences either a ≥ Grade 2 related adverse event or dose limiting toxicity (DLT).
At that point, the cohort will switch to a classical “3 + 3” design. Treatment will continue in 28-day cycles until progression or intolerability. Expansion cohorts for each indication will enroll patients to obtain further safety and efficacy data.
Patients with R/R AL who have failed or are ineligible for any standard therapies, R/R DLBCL following ≥ 2 but ≤ 5 prior therapies, and R/R MM who have received ≥ 3 therapies are eligible. Patients must have ECOG PS ≤ 2, and adequate organ function. Key exclusion criteria include known CNS disease involvement, prior menin inhibitor therapy, and clinically significant cardiovascular disease.
Results
The primary objective is to determine independently for each cohort/indication the optimal biological dose (OBD)/ recommended Phase 2 dose (RP2D) of BMF-219 oral monotherapy. Key secondary objectives include further evaluation of safety and tolerability, characterization of the pharmacodynamics and pharmacokinetics of BMF-219, and assessment of its antitumor activity based on best overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and time to progression (TTP) per disease specific response criteria as assessed by the investigator. Food-effect studies will be performed in DLBCL and MM patients at certain dose levels.
Conclusions
Enrollment in COVALENT-101 commenced in January 2022.
About Biomea Fusion
Biomea Fusion is a clinical stage biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases. A covalent small molecule is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response. The company is utilizing its proprietary FUSION™ System to advance a pipeline of covalent-binding therapeutic agents against key oncogenic drivers of cancer and metabolic diseases. Biomea Fusion’s goal is to utilize its capabilities and platform to become a leader in developing covalent small molecules in order to maximize the clinical benefit when treating various cancers and metabolic diseases.
Forward-Looking Statements
Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange
Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding our cash runway, the clinical and therapeutic potential of our product candidates and development programs, including BMF-219, the potential of BMF-219 as a treatment for various types of cancer and diabetes, our research, development and regulatory plans, including the progress and results of our ongoing COVALENT-101 trial of BMF-219, and the timing of such events, may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions.
Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward- looking statements, including the risk that we may encounter delays or unforeseen results in preclinical development, IND-filing and acceptance, patient enrollment and in the initiation, conduct and completion of our ongoing and planned clinical trials and other research, development and regulatory activities. These risks concerning Biomea Fusion’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (the “SEC”), including its most recent periodic report filed with the SEC and subsequent filings thereafter. Biomea Fusion explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.
Contact Data
Contact:
Sasha Blaug
SVP Corporate Development
(650) 460-7759
Contact
Exhibit 99.2 Anti-tumor Activity of Covalent Menin Inhibitor, BMF-219, in High Grade B-Cell Lymphoma and Multiple Myeloma Preclinical Models 1 1 1 1 1 1 1 1 Daniel Lu, MS Priyanka Somanath, PhD , Brian Law, BS , Lekha Kumar, MS , James T. Palmer, PhD , Taisei Kinoshita, PhD , Mini Balakrishnan, PhD and Thomas Butler, MSc MBA , 1 Biomea Fusion, Inc. Redwood City, CA BMF-219 exerts pronounced lethality in DLBCL BMF-219 exerts >99% lethality against MM and DLBCL cell lines INTRODUCTION PDX models ex vivo BMF-219 BMF-219 MM1.R JJN3 TOLEDO DB 120 120 120 PS-341 120 PS-341 A B 100 100 100 100 80 80 MYC Amplified- Responded, then ▪ Menin is a scaffold protein that drives oncogenic function through its 80 THL- Responded, then progressed 80 60 60 60 60 on R-EPOCH progressed on R-CHOP regulation of genes such as HOXA9, with distinct effects on transcription IC = 0.42 IC = 0.37 40 50 40 50 40 IC = 0.44 IC = 0.27 40 50 50 CTG-3794 CTG-3794 20 20 20 20 that are directed by various cofactors. A recent study reported that BM-101 125 125 BM-100 0 0 0 0 120 knockdown of HOXA9 resulted in marked growth inhibition of multiple -20 -20 -20 120 100 100 -20 0.0001 0.001 0.01 0.1 1 10 0.001 0.01 0.1 1 10 0.001 0.01 0.1 1 10 0.0001 0.001 0.01 0.1 1 10 100 100 75 75 myeloma (MM) cells (Chapman et al., 2017). Compound Concentration (uM) Compound Concentration (uM) Compound Concentration (uM) Compound Concentration (uM) 80 80 50 50 BMF-219 BMF-219 SKMM1 IC = 0.25 IC = 0.15 SKMM2 VAL U2932 50 50 60 60 120 120 ▪ Double/Triple Hit Lymphoma (DHL/THL) and Double Expresser 120 120 PS-341 PS-341 25 25 40 100 100 100 40 100 Lymphoma (DEL) are high-grade B-cell lymphomas (HGBL) that exhibit 0 0 80 80 80 20 80 20 60 60 -25 -25 60 60 0 low responses to standard therapeutic regimens resulting in poor 0 IC = 0.34 IC = 0.36 50 40 40 50 40 40 IC = 0.42 IC = 0.50 -50 -50 -20 50 50 -20 prognosis. 20 20 20 20 0.01 0.1 1 10 0.01100 0.1 1 10 100 -40 -75 -75 -40 0 0 0 0 [drug], μM [drug], μM -60 -60 -20 -20 -20 ▪ DHL harbor translocations in MYC and BCL2 or BCL6, THL contain 0.01 0.1 1 10 0.01 0.1 1 10 -20 0.001 0.01 0.1 1 10 0.001 0.01 0.1 1 10 0.0001 0.001 0.01 0.1 1 10 0.0001 0.001 0.01 0.1 1 10 Compound concentration (μM) Compound concentration (μM) Compound Concentration (uM) Compound Concentration (uM) Compound Concentration (uM) translocations in MYC/BCL2/BCL6, and DEL are characterized by high Compound Concentration (uM) expression of MYC and BCL2. MM Cell Average % Max Average IC Standard DLBCL Average % Max Average IC Standard 50 ± BMF-219 Clinical RBMF B ev M eF rs --i2 b 219 1 le 9 1 CC Cl lin liiin nic cia cla al R l R eR v ee e vr e v srer is bilb e sible l e 1 2 Menin Clinical Reversible 2 50 ± Translocation Mutation Category Translocation Line Inhibition by BMF-219 Deviation ( M) Cell Line Inhibition by BMF-219 Deviation (mM) m ▪ We previously reported the ability of irreversible menin inhibitor, BMF- MM1.S t(14;16) KRAS G12A 99.5 0.47 ± 0.17 DB DHL MYC/BCL2 98.5 0.41 ± 0.07 Growth Growth % Max % Max Inhibition Inhibition MM1.R t(14;16) KRAS G12A 99.6 0.46 ± 0.17 219, to modulate MYC expression and exhibit high potency against DHL Toledo DHL MYC/BCL2 98.8 0.31 ± 0.07 Inhibition Inhibition IC ( M) IC ( M) SKMM1 t(14;20) NRAS G12A 99.2 0.47 ± 0.05mm 50 50 0.32 ± 0.03 Diffuse Large B-Cell Lymphoma (DLBCL) preclinical models (Somanath et DOHH2 DHL MYC/BCL2 99.7 SKMM2 t(11;14) TP53 80.2 0.65 ± 0.15 Treatment BM100 BM101 VAL THL MYC/BCL2/BCL6 97.1 0.27 ± 0.07 al., 2021). JJN3 t(14;16) NRAS Q61K 99.2 0.29 ± 0.02 BMF-219 0.250 100 0.151 100 MYC/BCL2 OPM2 t(4;14) TP53 98.4 0.55 U2932 DEL-ABC 92.4 0.37 ± 0.01 Overexpression Clinical Reversible 6.31 50 > 10 30 Potent killing activity of BMF-219 at clinically relevant concentrations in representative MM and DLBCL cell lines. (A). MM1.R, JJN3, SKMM1, SKMM2 and OPM2 cell lines and (B). DHL (DB, Toledo, SUDHL8 GCB - 99.6 0.60 ± 0.21 Growth inhibition of patient-derived DLBCL Triple Hit Lymphoma (THL) and MYC-amplified PDX DOHH2), THL (VAL), DEL (U2932), and GCB (SUDHL8) subtypes were cultured in the presence of Pfeiffer GCB - 99.6 0.17 ± 0.04 samples treated with BMF-219 or clinical reversible menin inhibitor after 6 days of treatment. IC 50 BMF-219 (blue) or PS-341 (red) for 4 days. Average IC values of at least two experiments, 50 OCI-LY7 GCB - 99.6 0.65 ± 0.26 values and maximal percentage cell killing are summarized in the table. maximal percentage cell killing, and cytogenetic background cell lines are summarized in the table. BMF-219 dramatically reduces growth of both newly diagnosed and R/R MM patient specimens Newly Diagnosed Relapsed/Refractory Multiple Myeloma Stage at Treatment Prior Therapy and Response Translocation 120 16-669/0219 Specimen ID Diagnosis Status 120 BMF-219 16-684/1019 120 120 BMF-219 241-9949/0619 241-10514/0720 BMF-219 BMF-219 PS-341 PS-341 PS-341 PS-341 100 Newly 100 100 100 16-669/0219 IIIA None No data Diagnosed 80 80 80 80 Newly 60 60 60 60 ▪ Here, we demonstrate the anti-tumor activity of BMF-219 in MM and 16-684/1019 IIIA None No data Diagnosed 40 40 40 40 HGBL preclinical models harboring various mutational backgrounds. IC = 0.18 IC = 0.29 IC = 0.31 IC = 0.12 50 50 50 50 241-9949/06-19 IIIA Refractory VCD N4 (resistant) p53 deletion 20 20 20 20 VCD N 4 (responded) 0 0 0 0 High dose CPH (SC-mobilization) (responded) -20 -20 -20 -20 0.0001 0.001 0.01 0.1 1 10 0.0001 0.001 0.01 0.1 1 10 0.0001 0.001 0.01 0.1 1 10 0.0001 0.001 0.01 0.1 1 10 Compound Concentration (uM) p53 deletion- Compound Concentration (uM) Consolidation (AutoSCT, double transplant) Compound Concentration (uM) Compound Concentration (uM) 241-10514/0720 IIIA Refractory negative Bortezomib- maintenance (resistant) Growth inhibition of newly diagnosed (A-B) and R/R (C-D) MM patient-derived bone marrow RVD #4 (resistant) mononuclear cells (BMMCs) after 6 days of treatment with BMF-219 (blue) or PS-341 (red). CONCLUSIONS PRD #4 (resistant) Clinical profiles of MM patient-derived BMMC specimens are summarized in the table. DHL / DEL DLBCL Multiple Myeloma BMF-219 exerts pronounced decrease in menin protein expression in MM and DLBCL cell lines ▪ BMF-219 achieved >99% cell lethality in MM cell lines with RAS mutations with IC values between 0.3mM and 0.5mM. 50 SKMM1 OPM2 TOLEDO (DLBCL-DHL) U2932 (DLBCL-DEL) ▪ BMF-219 demonstrated single-agent efficacy (IC values between 0.1mM 50 Menin Menin Menin Menin and 0.3mM) against a panel of newly diagnosed and R/R ex vivo MM Vinculin Vinculin Vinculin Vinculin samples, including a p53-deleted clinical profile. 120 120 120 120 94 98 100 100 100 100 86 ▪ BMF-219 exhibited high potency as a single agent against DHL, THL and 100 100 100 100 METHODS 81 76 75 DEL DLBCL cell lines, with IC values of 0.3mM and 0.4mM, respectively. 80 80 80 80 69 50 61 50 52 48 54 54 51 ▪ In ex vivo studies, BMF-219 was highly effective against R-CHOP and R- 60 60 60 60 43 39 ▪ MM and DLBCL cell lines were cultured in the presence of BMF-219 or EPOCH refractory patient samples with THL and MYC-amplified genetic 40 40 40 40 bortezomib (PS-341) for 4 days and cell proliferation was measured by backgrounds. 20 20 20 20 Cell Titer Glo. ▪ BMF-219 was multi-fold more potent and exerted dramatically greater 0 0 0 0 ▪ Patient-derived MM patient derived BMMCs and DLBCL PDX models growth inhibition compared to clinical reversible menin inhibitors in DLBCL were cultured ex vivo in the presence of BMF-219 or PS-341 for 6 days patient-derived ex vivo samples. and cell proliferation was measured by Cell Titer Glo. ▪ BMF-219 induces reduction of menin protein levels across MM and DLBCL ▪ MM and DLBCL cell lines were cultured in the presence of BMF-219 or cell lines. This reduction however appears to be transient. An incubation SKMM1 OPM2 TOLEDO U2932 % Cell % Cell clinical reversible menin inhibitors for 14 hours. Menin protein expression BMF-219 BMF-219 BMF-219 Clin Rev MI-503 BMF-219 BMF-219 BMF-219 Clin Rev MI-503 BMF-219 BMF-219 BMF-219 Clin Rev MI-503 BMF-219 BMF-219 BMF-219 Clin Rev MI-503 time of 14 hours may not be a good predictor of cellular growth inhibition. Death Death (0.4μM) (0.5μM) (1μM) (1μM) (3μM) (0.5μM) (0.5μM) (1μM) (1μM) (3μM) (0.4μM) (0.5μM) (1μM) (1μM) (3μM) (0.4μM) (0.5μM) (1μM) (1μM) (3μM) was measured by the Wes system and analyzed using the Compass 72 hr 72 hr 27 - 86 4 33 22 - 80 3 21 32 - 97 0 35 29 - 86 3 34 REFERENCES software (automated western blotting, Protein Simple). Signal was 14 hr - 15 25 0 13 - 8 57 0 14 14 hr - 18 12 0 11 - 19 36 0 7 ▪ Chapman, M., Lawrence, M., Keats, J. et al. Initial genome sequencing and analysis of multiple myeloma. Nature 471, 467–472 (2011). ▪ Somanath, P., Lu, D., Law, B. et al. Novel Irreversible Menin Inhibitor, BMF-219, Shows Potent Single Agent Activity in Clinically Relevant DLBCL BMF-219 reduces menin protein in MM and DLBCL cells. Quantitation of menin protein expression in SKMM1, OPM2, Toledo and U2932 cell line treated with BMF-219, clinical reversible menin inhibitor or normalized to GAPDH and referenced to DMSO control. Cells. Blood 2021; 138 (Supplement 1): 4318. preclinical reversible menin inhibitor, MI-503, for 14 hours. Average menin protein expression are of 3 independent experiments. WES blot is a representative from 1 single experiment. Cells were cultured in ▪ Wu, G., Yuan, M., Shen, S. et al. Menin enhances c-Myc-mediated transcription to promote cancer progression. Nat Commun 8, 15278 (2017). the presence of menin inhibitors for 72hr or 14hr. Average % cell killing treated at 72hr and 14hr are from 2 independent experiment.▪ Borkin, D. et al. Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell. 2015 Apr 13;27(4):589-602. DMSO BMF-219 (0.5μM) BMF-219 (1μM) Clinical Rev (1μM) MI-503 (3μM) DMSO BMF-219 (0.5μM) BMF-219 (1μM) Clinical Rev (1μM) MI-503 (3μM) DMSO BMF-219 (0.5μM) BMF-219 (1μM) Clinical Rev (1μM) MI-503 (3μM) DMSO BMF-219 (0.5μM) BMF-219 (1μM) Clinical Rev (1μM) MI-503 (3μM) %Menin Remaining Cell Proliferation Inhibition (%) Cell Proliferation Inhibition (%) %Menin Remaining Cell Proliferation Inhibition (%) Cell Proliferation Inhibition (%) %Menin Remaining Cell Proliferation Inhibition (%) Cell Proliferation Inhibition (%) Cell Proliferation Inhibition (%) Cell Proliferation Inhibition (%) %Menin Remaining Cell Proliferation Inhibition (%) Cell Proliferation Inhibition (%) Cell Proliferation Inhibition (%) Cell Proliferation Inhibition (%) % Growth Inhibition % Growth Inhibition Cell Proliferation Inhibition (%) Cell Proliferation Inhibition (%)
Exhibit 99.3 COVALENT-101 (NCT05153330) Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-219, an oral, covalent, menin inhibitor, in adult patients with acute leukemia (AL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM) 1 3 3 4 5 6 7 7 7 7 2 Farhad Ravandi, MD ; Hetty Carraway, MD ; Jack Khouri, MD ; Ashwin Kishtagari, MD ; Emily Curran, MD ; Gary Schiller, MD ; Bhagyashree Yadav, MD ; Steve Morris, MD ; Alex Cacovean, MD ; Thomas Butler, MS, MBA ; Jeffrey Lancet. MD 1 2 3 4 5 6 7 MD Anderson Cancer Center, Houston, TX; Moffitt Cancer Center, Tampa, FL; Cleveland Clinic Foundation, Cleveland, OH, Vanderbilt-Ingram Cancer Center, Nashville, TN; University of Cincinnati Medical Center, Cincinnati, OH; University of California, Los Angeles, Los Angeles, CA; Biomea Fusion, Inc., Redwood City, CA BACKGROUND STUDY DESIGN KEY ELIGIBILITY CRITERIA • Menin, a protein involved in transcriptional regulation, impacting cell cycle control, Inclusion Criteria Dose Escalation Dose Expansion apoptosis, and DNA damage repair, plays a direct role in oncogenic signaling in multiple • ≥ 18 years with ECOG performance status of 0-2 and an estimated life expectancy of Arm A R/R ALL, AMPL, AML R/R ALL, AMPL, AML 1 > 3 months cancers. Inhibition of menin is a novel approach to cancer treatment. No CYP3A4 N = var Total N = 30 • Adequate liver function: Bilirubin ≤ 1.5 ULN; ALT/AST ≤ 2.0 ULN BMF-219 • Adequate renal function: estimated creatinine clearance (eCrCl) ≥ 60 mL/min (Cohort Arm B R/R ALL, AMPL, AML R/R ALL, AMPL, AML • BMF-219, is an orally bioavailable, potent and selective covalent inhibitor of menin, an 1) or eCrCl ≥ 30 mL/min (Cohorts 2 & 3) using the Cockcroft-Gault equation CYP3A4 N = var Total N = 30 important transcriptional regulator. • Prior treatment-related toxicities resolved to ≤ Grade 2 prior to enrollment • Preclinical data of BMF-219 showed sustained potent abrogation of menin-dependent Arm A R/R DLBCL R/R DLBCL • Adequate washout from prior therapies (e.g., ≥ 60 days from RT; ≥ 60 days from stem oncogenic signaling in vitro and in vivo. No CYP3A4 N = var Total N < 20 cell infusion; ≥ 7 days from biologics or steroids; ≥ 21 days from prior immunotherapy; • BMF-219 demonstrates a strong anti-proliferative effect on various menin-dependent ≥ 14 days from completion of last chemotherapy) Arm A R/R MM R/R MM acute myeloid leukemia (AML) cell lines, DLBCL cell lines representing Double/Triple Hit No CYP3A4 N = var Total N < 20 Lymphoma (DHL/THL), Double Expressor Lymphoma (DEL), and MM cell lines harboring Indication & Prior Regimen Criteria 2 diverse mutational backgrounds. *CYP3A4 Cohort Arm Indication Prior treatment regimens inhibitors • BMF-219 also exhibits potent cell killing activity on ex vivo cultured MLL-rearranged Accelerated titration design followed by 3+3 R/R ALL, AMPL, AML and NPM1-mutant AML patient samples, THL and MYC-amplified DLBCL, bone marrow 1 A No limit, includes prior HSCT No 2 agnostic of mutation mononuclear cells from treatment-naive and R/R MM . DLT R/R ALL, AMPL, AML • For current clinical trials, BMF-219 is supplied as 25 and 100 mg strength capsules for 1 B No limit, includes prior HSCT Yes agnostic of mutation OBD/RP2D once daily oral administration. Non-DLT R/R DLBCL / DLBCL ≥ 2 with at least 1 course of COVALENT-101 (BF-MNN-101) STUDY OVERVIEW transformed from anthracycline-based chemotherapy Non-DLT w/moderate toxicity • COVALENT-101 is a prospective, open-label, multi-cohort, non-randomized, previously indolent 2 A No Time & at least 1 course of anti-CD20 lymphoma (e.g., follicular multicenter, first-in-human Phase I study evaluating the safety, tolerability, and clinical immunotherapy lymphoma) activity of escalating doses of oral BMF-219 administered either once or twice daily in • Doses of BMF-219 will be escalated in single-subject cohorts independently for patients with R/R ALL, AML, DLBCL & MM who have received standard therapy. ≥ 3 including proteosome inhibitor & each indication until 1 subject experiences either any ≥ Grade 2 related-TEAE 3 A R/R MM No immunomodulatory which does not meet DLT criteria, or a DLT in the first cycle. • Approximately 20 clinical sites in the United States. * Subjects are receiving concomitant medications considered to be strong or moderate • At that point, the dose level for the specific cohort will follow a classical “3 + 3” OBJECTIVES & ENDPOINTS inhibitors of CYP3A4 dose escalation design. Determine OBD & RP2D of BMF- •OBD/RP2D will be determined based on Exclusion Criteria 219 for each Cohort (1, 2 & 3) and Primary Æ STUDY FLOWCHART PK/PD/Safety/Efficacy Arm (A & B) • Known CNS disease involvement Post Tx Post Long Term • Prior menin inhibitor therapy Screening Treatment •TEAE / SAE incidence Further evaluate Safety and Follow-up HSCT Tx Follow-up • WBC count > 50,000/ μL (uncontrollable with cytoreductive therapy) tolerability of BMF-219 •C , T , and AUC of BMF-219 max max 0-∞ S C1 C2 Cx LTFU FU FU T1 PK/ PD evaluation of BMF-219 • Clinically significant cardiovascular disease; LVEF < 45% Secondary •Cohort 1: CRR* Æ & other efficacy f parameters per •Cohort 2: ORR Additional Evidence of Efficacy of • Mean QTcF or QTcB of > 470 millisecond (ms) Screening • Up to 28 days from consent } b investigator assessment antitumor activity •Cohort 3: ORR • Acute or chronic GVHD except disease limited to skin with adequate control using Treatment • Daily treatment with BMF-219 in 28-day cycles topical steroids •Changes in gene expression To characterize the PD effects of Post Tx Follow-Up • Regular post-tx efficacy assessment visits • Concurrent malignancy in the previous 2 years BMF-219 for each cohort Exploratory •Explore predictive and pharmacodynamic Æ independently Post HSCT Treatment • Post adequate response to BMF-219 patient may markers REFERENCES proceed with HSCT and then resume BMF-219 1. Issa, G. C., et al. (2021). Therapeutic implications of menin inhibition in acute leukemias. * Based on European LeukemiaNet (ELN) 2017 recommendation for diagnosis and management of AML or the Leukemia, 35(9), 2482–2495. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines, ALL (Version 2. 2021) Long Term Follow-Up • Survival follow-up calls f Revised criteria for response assessment of lymphoma (Cheson, 2014) 2. Anti-tumor activity of irreversible menin inhibitor, BMF-219, in High Grade B-Cell Lymphoma and b Multiple Myeloma Preclinical Models. Cancer Res (2022) 82 (12_Supplement): 2654. International Myeloma Working Group (IMWG) response criteria (Kumar, 2016) # IMS2022 Abstract ID: 1280424 Dose