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October 13, 2026 GLP-131 Phase 1 Study of BMF-650 in Otherwise Healthy Overweight or Obese Adult Participants Week 4 Topline Results
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GLP-131 Phase 1 Topline Results - October 13, 2026 Legal Disclaimer & Forward-looking Statements 2 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 nonclinical studies and clinical trials, the actual or potential actions of the U.S. Food and Drug Administration (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 and any statements of expectation or belief regarding future events, potential markets or market size, or technology developments. 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. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent annual report on Form 10-K and subsequent quarterly reports on Form 10-Q filed with the Securities and Exchange Commission (the SEC), as well as discussions of potential risks, uncertainties, and other important factors in our other subsequent filings with the SEC. 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.
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GLP-131 Phase 1 Topline Results - October 13, 2026 GLP-131 – A Phase 1 Study of BMF-650 Topline Results Agenda Ramses Erdtmann Co-Founder, Chief Operating Officer & President,Biomea Fusion Design Hypothesis for BMF-650 Juan Pablo Frías, MD Co-Chair of the Scientific Advisory Board, Biomea Fusion Mick Hitchcock, PhD Interim Chief Executive Officer & Board Member,Biomea Fusion Executive Summary GLP-131 Topline Results Thorsten Kirschberg, PhD Executive VP , Research, Biomea Fusion Opening Remarks Q & A BMF-650 3
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Opening Remarks Ramses Erdtmann Co-Founder, Chief Operating Officer & President,Biomea Fusion 4
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GLP-131 Phase 1 Topline Results – October 13, 2026 A large and growing market with a meaningful persistence challenge GLP-1 THERAPIES GLP-1 therapies have transformed obesity treatment, but broad adoption and long-term persistence remain distinct opportunities 100M+ U.S. adults living with obesity ~40% of the U.S. adult population ~1B Adults globally projected to live with obesity by 2030 A chronic disease with substantial cardiometabolic consequences ~11M Unique U.S. patients using GLP-1 based therapies across indications As of Q2 2025, highlighting rapid adoption of the class Treatment tolerability seems to prevent long-term persistence Sources: CDC/NCHS, U.S. adult obesity prevalence (Aug 2021 –Aug 2023; updated Feb 2026); World Obesity Atlas 2025; IQVIA, “Obesity Deep Dive” (Sep 2025); Rodriguez et al., JAMA Network Open (2025). ~65% Of patients without T2D discontinued use within one Large U.S. real-world cohort of >125,000 adults with overweight or obesity 5
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GLP-131 Phase 1 Topline Results – October 13, 2026 BMF-650 | Phase 1b MAD 6 Reduce adverse events that can limit treatment Easier and quicker titration Reach the targeted dose quicker and with fewer dose increases to achieve simplified administration and early adherence Persistent weight management Support continuation of treatment with convenient dosing and manageable tolerability More tolerable therapy Opportunities for a next-generation GLP-1 Receptor Agonist
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Design Hypothesis for BMF-650 Thorsten Kirschberg, PhD Executive VP , Research, Biomea Fusion 7
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GLP-131 Phase 1 Topline Results – October 13, 2026 A potential differentiated oral next-generation GLP-1 receptor agonist designed to separate GI adverse effects from weight loss Oral administration Convenience without injections One-step titration Faster path to maintenance dose and efficacy Designed for improved GI tolerability Potential for better tolerability and adherence Built for persistent use Intended for continued use BMF-650 8
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GLP-131 Phase 1 Topline Results – October 13, 2026 BMF-650 is designed as a biased small molecule GLP-1 receptor agonist, to selectively engage GLP-1 signaling Designed with reduced on-target potency to achieve less concentrated agonism No off-target activity of concern identified in the counter-screening panels Compound GLP-1 human EC50 β-arrestin EC50 BMF-650 2.6 nM > 10 µM orforglipron 0.1 nM > 10 µM Wang X, et al. ObesityWeek® 2025; Poster 085. BMF-650 | PRECLINICAL BMF-650 was designed to reduce on-target agonism to achieve long-term tolerability 9
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GLP-131 Phase 1 Topline Results – October 13, 2026 CYNOMOLGUS MONKEY PO PK DATA SPRAGUE-DAWLEY RAT PO PK DATA BMF-650 showed approx. 2-fold greater oral bioavailability in comparison to orforglipron BMF-650 | PRECLINICAL Wang X, et al. ObesityWeek® 2025; Poster 085. Compound cyno PO %F BMF-650 0.36 mg/kg 54.0 orforglipron 0.36 mg/kg 29.4 BMF-650 | PRECLINICAL Pharmacokinetics showed enhanced preclinical bioavailability signals with low variability Compound rat PO %F BMF-650 5 mg/kg 32.6 orforglipron 5 mg/kg 11.2 Favorable PK observed across species with high oral bioavailability and long exposure BMF-650 showed approx. 3-fold greater oral bioavailability in comparison to orforglipron 10
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GLP-131 Phase 1 Topline Results – October 13, 2026 BMF-650 | PRECLINICALBMF-650 | PRECLINICAL Wang, et al. Obesity 2025: 33 Sup 2 Poster #085 11 BMF-650 demonstrated robust, dose-dependent weight loss in obese monkeys with low rates of emesis BMF-650 up to ~15% body weight reduction after 28 days 0 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829 -20 -15 -10 -5 0 Day % Change from baseline Vehicle BMF-650 10mpk BMF-650 30mpk Day 8 -2.3% -4.8% -7.5% Day 15 -2.7% -7.5% -10.7% Day 22 -2.8% -10.2% -13.5% Day 29 -3.4% -12.3% -15.2% Body Weight Change from Baseline Week 1 2 3 4 Emesis (Vomiting) 18.2%* 7.0% 5.6% 1.4% *One monkey (#3) in the low-dose cohort accounted for 12 of the 23 total events. % calculated for 70 dosing events/week With 280 active dosing occurrences, there were a total of 23 emesis events (8.2%) balanced across both dosing cohorts.
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GLP-131 Phase 1 Topline Results – October 13, 2026 A next-generation oral small-molecule GLP-1 RA with a differentiated profile designed to separate GI effects from weight loss BMF-650 | Design Gradual, sustained systemic exposure Designed to limit peak-to- trough fluctuations to avoid uneven systemic GLP-1 receptor stimulation Improved oral bioavailability Intended to achieve systemic exposure with less unabsorbed drug 12 Broader intestinal absorption Intended to reduce localized concentration peaks within the GI tract, and to promote better tolerated absorption across a broader intestinal surface and time window
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GLP-131 Phase 1 Topline Results Dr. Juan Pablo Frias Chief Medical Officer of Biomea Fusion Juan Pablo Frías, MD Co-Chair of the Scientific Advisory Board, Biomea Fusion 13
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GLP-131 Phase 1 Topline Results – October 13, 2026 10 mg (fasted) 25 mg (fed)25 mg (fasted) 50 mg (fasted) 100 mg (fed)100 mg (fasted) 200 mg (fasted) Design BMF-650 | GLP-131 GLP-131: Phase 1 study design Randomized, double-blind, placebo-controlled study evaluating safety, tolerability, and weight reduction with BMF-650 in overweight or obese participants Single Ascending Dose (SAD) Phase 1a Multiple Ascending Dose (MAD) Phase 1b Primary & Secondary Objectives Safety and tolerability, PK, PD, and food effect Safety and tolerability, and efficacy (weight-loss) Eligibility Healthy overweight or obese participants (BMI 25.0–40.0 kg/m²) Healthy obese participants (BMI 30.0–45.0 kg/m²) COHORT 1 2 3 4 BMF-650 active drug placebo 50 mg → 100 mg → 200 mg → 200 mg 75 mg → 150 mg → 300 mg → 300 mg 75 mg → 200 mg → 400 mg → 400 mg Wk 1 → Wk 2 → Wk 3 → Wk 4 5 cohorts N=40 N=40 x 4 cohorts x 10 mg → 25 mg → 50 mg → 100 mg 14 BMF-650 | Phase 1
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GLP-131 Phase 1 Topline Results – October 13, 2026 Active BMF-650 Cohort 1 10/25/50/100 mg (N=8) Cohort 2 50/100/200/200 mg (N=8) Cohort 3 75/150/300/300 mg (N=8) Cohort 4 75/200/400/400 mg (N=8) MAD Cohorts 1-4 Total (N=32) Pooled Placebo (N=8) Sex, female, n (%) 6 (75) 6 (75) 3 (38) 4 (50) 19 (59) 4 (50) Age, years, mean 49.5 45.6 49.9 42.3 46.8 40.3 Weight, kg, mean 97.0 109.1 96.1 97.6 100.0 111.1 BMI, kg/m2, mean 34.8 36.2 31.9 34.4 34.3 35.9 BMF-650 | Phase 1B MAD 15 BMF-650 | Phase 1b MAD Baseline Demographics & Characteristics Doses for Weeks 1–4
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GLP-131 Phase 1 Topline Results – October 13, 2026 Mean percentage change in body weight from baseline at Day 29 Pooled Placebo (n=8) -0.1% Cohort 1 (n=8) (10/25/50/100 mg) -1.5% Cohort 2 (n=8) (50/100/200/200 mg) -2.1% Cohort 3 (n=8) (75/150/300/300 mg) -3.2% Cohort 4 (n=8) (75/200/400/400 mg) -2.1% Clinical efficacy – weight reduction 16 BMF-650 | Phase 1B MADBMF-650 | Phase 1b MAD Data are mean ± SE
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GLP-131 Phase 1 Topline Results – October 13, 2026 14 of 16 weekly dosing cohorts showed incremental weekly absolute weight reduction. The average weight loss per week when dosed at 200 mg or higher dose was 0.97 kg / week. Placebo achieved a 0.1 kg weight reduction after 4 weeks. Dose Cohort 3 showed a weight reduction of 3.0 kg after 4 weeks. PK results from Week 1 in Cohort 4 raised suspicion that patients were possibly not taking the drug, so a Cohort 5 was initiated under confinement. BMF-650 | Phase 1b MAD Analysis of weekly weight reduction 17 Pooled PLACEBO n=8 Cohort 1 10 → 25 → 50 → 100 Cohort 2 50 → 100 → 200 → 200 Cohort 3 75 → 150 → 300 → 300 Cohort 4 75 → 200 → 400 → 400 Week 1 +0.33 kg 10 mg -0.47 kg 50 mg -0.41 kg 75 mg -0.45 kg 75 mg +0.76 kg Week 2 +0.06 kg 25 mg +0.12 kg 100 mg -0.20 kg 150 mg -0.39 kg 200 mg -0.83 kg Week 3 +0.12 kg 50 mg -0.48 kg 200 mg -0.23 kg 300 mg -0.70 kg 400 mg -1.37 kg Week 4 -0.82 kg 100 mg -0.63 kg 200 mg -1.57 kg 300 mg -1.47 kg 400 mg -0.63 kg TOTAL Weight Loss -0.10 kg -1.46 kg -2.41 kg -3.01 kg -2.07 kg
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GLP-131 Phase 1 Topline Results – October 13, 2026 10 mg (fasted) 25 mg (fed)25 mg (fasted) 50 mg (fasted) 100 mg (fed)100 mg (fasted) 200 mg (fasted) Design BMF-650 | GLP-131 GLP-131: Phase 1 study design + dose cohort 5 Randomized, double-blind, placebo-controlled study, evaluating safety, tolerability, and weight reduction with BMF-650 in overweight or obese participants Single Ascending Dose (SAD) Phase 1a Multiple Ascending Dose (MAD) Phase 1b Primary & Secondary Objectives Safety and tolerability, PK, PD and food effect Safety and tolerability, and efficacy (weight-loss) Eligibility Healthy overweight or obese participants (BMI 25.0–40.0 kg/m²) Healthy obese participants (BMI 30.0–45.0 kg/m²) Cohort 5 conducted under confinement to evaluate one-step titration regimen COHORT 1 2 3 4 BMF-650 active drug placebo 50 mg → 100 mg → 200 mg → 200 mg 75 mg → 150 mg → 300 mg → 300 mg 75 mg → 200 mg → 400 mg → 400 mg Wk 1 → Wk 2 → Wk 3 → Wk 4 5 cohorts N=40 N=50 x 5 cohorts x 5 10 mg → 25 mg → 50 mg → 100 mg 18 BMF-650 | Phase 1 200 mg → 400 mg → 400 mg → 400 mg
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GLP-131 Phase 1 Topline Results – October 13, 2026 Active BMF-650 Doses for Weeks 1–4 Cohort 1 10/25/50/100 mg (N=8) Cohort 2 50/100/200/200 mg (N=8) Cohort 3 75/150/300/300 mg (N=8) Cohort 4 75/200/400/400 mg (N=8) Cohort 5 200/400/400/400 mg (N=8) MAD BMF-650 Total (N=40) Pooled Placebo (N=10) Sex, female, n (%) 6 (75) 6 (75) 3 (38) 4 (50) 5 (63) 24 (60) 5 (50) Age, years, mean 49.5 45.6 49.9 42.3 41.6 45.8 37.4 Weight, kg, mean 97.0 109.1 96.1 97.6 102.1 100.4 107.2 BMI, kg/m2, mean 34.8 36.2 31.9 34.4 34.0 34.3 35.3 BMF-650 | Phase 1B MAD 19 BMF-650 | Phase 1b MAD Baseline demographics & characteristics + dose cohort 5
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GLP-131 Phase 1 Topline Results – October 13, 2026 Cohort 5 used confinement to monitor dosing adherence, with 200 mg once daily for one week, then 400 mg once daily for three weeks. Mean weight loss with BMF-650 was 1.55 kg/week, and similar weight loss with placebo (n=2). All participants were provided 2,100 kcal/day. The 2 placebo participants consumed approximately 33% of the presented food, complicating interpretation of weight loss under confinement. BMF-650 | Phase 1b MAD Analysis of weekly weight reduction 20 Pooled PLACEBO n=8 Cohort 1 10 → 25 → 50 → 100 Cohort 2 50 → 100 → 200 → 200 Cohort 3 75 → 150 → 300 → 300 Cohort 4 75 → 200 → 400 → 400 Week 1 +0.33 kg 10 mg -0.47 kg 50 mg -0.41 kg 75 mg -0.45 kg 75 mg +0.76 kg Week 2 +0.06 kg 25 mg +0.12 kg 100 mg -0.20 kg 150 mg -0.39 kg 200 mg -0.83 kg Week 3 +0.12 kg 50 mg -0.48 kg 200 mg -0.23 kg 300 mg -0.70 kg 400 mg -1.37 kg Week 4 -0.82 kg 100 mg -0.63 kg 200 mg -1.57 kg 300 mg -1.47 kg 400 mg -0.63 kg TOTAL Weight Los -0.10 kg -1.46 kg -2.41 kg -3.01 kg -2.07 kg Cohort 5 200 → 400 → 400 → 400 200 mg -1.72 kg 400 mg -1.38 kg 400 mg -1.39 kg 400 mg -1.71 kg -6.20 kg Cohort 5 in-patient confinement
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GLP-131 Phase 1 Topline Results – October 13, 2026 Active BMF-650 Doses for Weeks 1–4 Participants, n(%) Cohort 1 10/25/50/100 mg (N=8) Cohort 2 50/100/200/200 mg (N=8) Cohort 3 75/150/300/300 mg (N=8) Cohort 4 75/200/400/400 mg (N=8) Cohort 5 200/400/400/400 mg (N=8) MAD BMF-650 Total (N=40) Pooled Placebo (N=10) Any TEAE 6 (75.0) 4 (50.0) 5 (62.5) 6 (75.0) 7 (87.5) 28 (70.0) 4 (40.0) Mild (Grade 1) 3 (37.5) 3 (37.5) 4 (50.0) 5 (62.5) 5 (62.5) 20 (50.0) 4 (40.0) Moderate (Grade 2) 3 (37.5) 1 (12.5) 1 (12.5) 1 (12.5) 2 (25.0) 8 (20.0) 0 Primary Endpoint: Overall Treatment-Emergent Adverse Events (TEAEs) All TEAEs were mild or moderate and there were no dose modifications or discontinuations related to BMF-650. TEAEs were not associated with dose escalation, dosing cohort, or time at a given dose. BMF-650 | Phase 1b MAD 21 Severe TEAE (Grade 3) Serious TEAE TEAE-leading to dose modification TEAE-leading to study discontinuation 0 0 0 0
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GLP-131 Phase 1 Topline Results – October 13, 2026 Active BMF-650 Doses for Weeks 1–4 Participants, n (%) Cohort 1 10/25/50/100 mg (N=8) Cohort 2 50/100/200/200 mg (N=8) Cohort 3 75/150/300/300 mg (N=8) Cohort 4 75/200/400/400 mg (N=8) Cohort 5 200/400/400/400 mg (N=8) MAD BMF-650 Total (N=40) Pooled Placebo (N=10) Nausea 0 3 (37.5) 1 (12.5) 2 (25.0) 1 (12.5) 7 (17.5) 0 Constipation 0 1 (12.5) 1 (12.5) 0 2 (25.0) 4 (10.0) 1 (10.0) Vomiting 1 (12.5) 0 1 (12.5) 0 1 (12.5) 3 (7.5) 0 Diarrhea 0 1 (12.5) 1 (12.5) 0 0 2 (5.0) 1 (10.0) Select Gastrointestinal TEAEs 22 BMF-650 | Phase 1B MADBMF-650 | Phase 1b MAD The select GI-related TEAEs were all Grade 1 AEs in the highest dose level cohort.
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GLP-131 Phase 1 Topline Results – October 13, 2026 70% Any TEAE* BMF-650 | Competitive Analysis 23 BMF-650 at highest dose level vs late-stage oral GLP-1 Phase 1 disclosures Select GI tolerability * Not all comparator companies reported this adverse event. 12.5% 12.5% 0% 25% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Nausea Diarrhea* Vomiting* Constipation* Lower incidence / More favorable Higher incidence / Less favorable ◆ BMF-650 ● Oral GLP-1 comparator 1 ● Oral GLP-1 comparator 2 ● Oral GLP-1 comparator 3 ● Oral GLP-1 comparator 4 ● Oral GLP-1 comparator 5 ● Oral GLP-1 comparator 6 ● Oral GLP-1 comparator 7 Cross-trial comparisons are descriptive and should be interpreted cautiously due to differences in study design, treatment duration, dose escalation, AE collection and reporting.
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GLP-131 Phase 1 Topline Results – October 13, 2026 Class-like changes in liver enzymes, fasting glucose and heart rate Active BMF-650 Doses for Weeks 1–4 Cohort 1 10/25/50/100 mg (N=8) Cohort 2 50/100/200/200 mg (N=8) Cohort 3 75/150/300/300 mg (N=8) Cohort 4 75/200/400/400 mg (N=8) Cohort 5 200/400/400/400 mg (N=8) MAD BMF-650 Total (N=40) Pooled Placebo (N=10) Alanine aminotransferase (ALT), U/L -1.6 -1.4 -7.4 -9.9 -9.4 -5.9 -6.1 Aspartate aminotransferase (AST), U/L -1.9 -1.7 -2.8 -3.7 -3.8 -2.8 -2.9 Fasting glucose, mg/dL -7.1 -5.9 -7.2 -14.7 -11.4 -9.2 -3.5 Heart rate, beats/min 0.6 8.1 10.4 3.7 9.0 6.4 0.8 Data shown represents mean change from baseline to Day 28 BMF-650 | Phase I 1b MAD 24 No adverse events involving ALT/AST elevations or heart rate were reported Reductions in fasting glucose were observed for all doses of BMF-650
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GLP-131 Phase 1 Topline Results – October 13, 2026 BMF-650 delivered target exposure with low peak to trough ratio in human PK BMF-650 | Phase 1b MAD 25 Human PK for BMF-650 aligned well with nonclinical predictions and showed low peak/trough ratio Observed human PK exposure matched favorable monkey exposure in the respective weight-loss study Cohort 5 Day 28 Cmax (peak plasma concentration) 4400 ng/mL (+ 26.4%) Cmin (trough plasma concentration) 2520 ng/mL (+ 39.4%) Peak to trough ratio 1.7 AUC0-24hrs 79000 hr*ng/mL (+ 31.8%) Selected PK parameters for Cohort 5 Day 28 * Preliminary PK analysis (mean). * Preliminary PK analysis (mean).
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GLP-131 Phase 1 Topline Results- October 13, 2026 Phase 1 findings provide support for the BMF-650 design hypothesis BMF-650 | Phase 1b MAD 26 Rapid one-step titration to 400 mg is well tolerated BMF-650 reached the target dose of 400 mg QD via a single titration step design post week 1, supporting a potentially simple and practical dosing paradigm Sustained and meaningful weight reduction observed at higher dose regimens Cohort 5 demonstrated mean weight loss at 400 mg across consecutive weeks (−1.4, −1.4 and −1.7 kg/week), reaching 6.1% at week 4, with no evidence of attenuation over the observed treatment period Encouraging GI tolerability profile No serious TEAEs, no TEAE-related dose modifications and no TEAE-related study discontinuations occurred across active MAD cohorts, supporting longer-duration evaluation
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GLP-131 Phase 1 Topline Results- October 13, 2026 Next Steps: Advancing BMF-650 development while optimizing the clinical profile BMF-650 | Phase 1b MAD 27 • Highest dose achieved with only a single titration step while maintaining favorable tolerability • Weight loss as expected in line with other GLP-1 agents • Overall, generally well tolerated with no exposure-related safety signals Clinical Findings BMF-650 Next Steps • Initiate longer-term toxicology studies to support Phase 2 dosing • Advance Phase 2 development planning incl. a “no-titration” regimen at 400 mg QD
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Executive Summary Dr. Juan Pablo Frias Chief Medical Officer of Biomea Fusion Mick Hitchcock, PhD Interim Chief Executive Officer & Board Member, Biomea Fusion 28
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Dr. Juan Pablo Frias Chief Medical Officer of Biomea Fusion Q & A 29