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MET-233i A potential first-in-class, best-in-class monthly amylin candidate Phase 1 clinical trial | Topline data June 9, 2025
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FORWARD-LOOKING ST A TEMENTS 2 ©Metsera 2025 | Confidential This presentation includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. The Company intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. All statements contained in this presentation other than statements of historical fact should be considered forward-looking statements, including, without limitation, statements related to the timelines and design of the Company’s clinical trials and data releases; the Company’s product candidate pipeline and milestone events; potential benefits of treatment with the Company’s product candidates; and anticipated market opportunity and strategy. When used herein, words including “anticipate,” “believe,” “can,” “continue,” “could,” “designed,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements use these words or expressions. All forward-looking statements are based upon the Company’s current expectations and various assumptions. The Company believes there is a reasonable basis for our expectations and beliefs, but they are inherently uncertain. The Company may not realize our expectations, and our beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, our limited operating history; our ability to generate revenue or become profitable; failure to obtain additional capital when needed on acceptable terms or at all; raising additional capital may cause dilution to our stockholders or require us to relinquish rights to our technologies or product candidates; our dependence on the success of our product candidates; risks associated with preclinical and clinical development; difficulties or delays in the commencement or completion, or the termination or suspension, of clinical trials; our ability to timely enroll patients in our clinical trials; if our current or future product candidates are associated with side effects, adverse events or other properties or safety risks; risks associated with the regulatory approval processes of the FDA and comparable foreign authorities; risks associated with conducting clinical trials and preclinical studies outside of the United States; our reliance on third parties to conduct clinical trials and preclinical studies; our reliance on third parties for the manufacture and shipping of our product candidates; risks associated with our license and collaboration agreements and future strategic alliances; significant competition in our industry; product candidates for which we intend to seek approval as biologic products may face competition sooner than anticipated; our success is dependent on our ability to attract and retain highly qualified management and other clinical and scientific personal; if we or our licensors are unable to obtain, maintain, defend and enforce patent or other intellectual property protection for our current or future product candidates or technology; risks associated with our common stock and the other important factors discussed under the caption “Risk Factors” in our filings with the Securities and Exchange Commission, including in our Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2025, which is accessible on the SEC’s website at www.sec.gov and the Investors section of the Company’s website at investors.metsera.com. Any such forward-looking statements represent management’s estimates as of the date of this presentation. While the Company may elect to update such forward- looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause the Company’s views to change. These forward- looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this presentation. INDUSTRY AND OTHER DATA Unless otherwise indicated, information contained in this presentation concerning our industry and the markets in which Metsera operates, including our general expectations, market position and market opportunity, is based on management’s estimates and research, as well as industry and general publications and research, surveys and studies conducted by third parties. While Metsera believes the information from these third-party publications, research, surveys and studies is reliable, it does not guarantee the accuracy or completeness of such information, and Metsera has not independently verified this information. Management’s estimates are derived from publicly available information, their knowledge of the Company's industry and their assumptions based on such information and knowledge, which they believe to be reasonable. This data involves a number of assumptions and limitations which are necessarily subject to a high degree of uncertainty and risk due to a variety of factors, including those described in Metsera’s periodic reports filed with the SEC under the captions “Forward Looking Statements,” "Risk Factor Summary" and “Risk Factors.” These and other factors could cause Metsera’s future performance and market expectations to differ materially from our assumptions and estimates.
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MET-233i Phase 1 clinical trial results 3 AGENDA ©Metsera 2025 | Confidential 1 Opening remarks Whit Bernard, CEO 2 Phase 1 trial results Steve Marso, M.D., CMO 3 Concluding remarks Whit Bernard, CEO 4 Q&A Whit Bernard, CEO Steve Marso, M.D., CMO Brian Hubbard Ph.D., CSO Chris Visioli, CFO
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4 ©Metsera 2025 | Confidential MET-233i Opening remarks Whit Bernard Chief Executive Officer
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A non-incretin mechanism with important potential advantages 5 AMYLIN IS A HIGHL Y VALUABLE NuSH T ARGET ©Metsera 2025 | Confidential Potentiated cardiovascular benefits Tolerability potentially better than GLP-1 RAs Additive to GLP-1 enabling category- leading weight loss Compelling single agent weight loss effect Combination therapy with GLP-1 RAs & other NuSH analogs Monotherapy alternative to GLP-1 RAs TWO ANTICIPATED VALUE DRIVERS GLP-1 RA: GLP-1 receptor agonist NuSH: nutrient-stimulated hormone(s)
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Potential for clear-cut differentiation within a massive therapeutic category 6 CHARACTERISTICS OF THE IDEAL AMYLIN ANALOG ©Metsera 2025 | Confidential POTENT Best-in-class weight loss at low, scalable dose levels COMBINABLE With best-in-class GLP-1 RAs in a simple, scalable device DURABLE Monthly dosing, optimized tolerability and scalability
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Pre-clinical profile demonstrated durability, potency, and combinability with MET-097i 7 MET-233i WAS ENGINEERED TO BE AN IDEAL AMYLIN ANALOG ©Metsera 2025 | Confidential 0 48 96 144 192 1000 100 10 5 6.2 7 7.6 0.4 0.3 0.2 0.1 0 Concentration (ng/mL) Time (hours) pH Absorbance Supports monthly dosing Miscible with MET-097i (GLP-1RA) MET-097i (2 mg/mL) MET-233i (2 mg/mL) MET-097i + MET-233i (0.5 mg/mL) Data presented as means ± standard error of the mean. PK data reflect multiple doses in pigs. Body weight loss data reflect Day 3 body weight change after a single dose, adjusting for vehicle in rats. Exposure over time after a single dose of Metsera NuSH peptides in pigs ~3x more potent than cagrilintide Body weight effects at Day 3 after a single dose in rats Solubility of Metsera NuSH peptides and combination at different pH DURABLE POTENT COMBINABLE Empirically determined solubility threshold 0 2 4 6 8 10 12 14 16 18 1 3 10 10 Dose (nmol/kg) MET-233i Cagrilintide MET-233i 50 μg/kg MET-097i 50 μg/kg Weight loss (%) 5.7 10.4 15.9 5.7
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8 ©Metsera 2025 | Confidential MET-233i Phase 1 trial results Steve Marso, M.D. Chief Medical Officer
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Three primary study objectives 9 MET-233i SINGLE AND MUL TIPLE ASCENDING DOSE STUDY ©Metsera 2025 | Confidential 1 Characterize pharmacokinetics Measure one- and five-week weight loss Identify well-tolerated starting doses 2 3
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A randomized, placebo-controlled trial in people with overweight / obesity 10 MET-233i PHASE 1 CLINICAL TRIAL ©Metsera 2025 | Confidential SINGLE ASCENDING DOSE (SAD) 5-WK MULTIPLE ASCENDING DOSE (MAD) Objectives Pharmacokinetics, body weight loss, tolerability/safety Participants People with overweight / obesity without T2DM Design N=40 N=40 5 cohorts x 4 cohorts x MET-233i active drug Placebo 0.15 mg 0.30 mg 0.60 mg 1.2 mg 2.4 mg 0.15 mg 0.30 mg 0.60 mg 1.2 mg
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Generalizable, with mean BMI in obese range 11 BASELINE CHARACTERISTICS ©Metsera 2025 | Confidential SAD MAD MET-233i N=30 Placebo N=10 MET-233i N=32 Placebo N=8 Age (yrs) Mean ± SD 42.6 ± 12.8 42.9 ± 11.4 41.2 ± 13.3 45.8 ± 16.1 Female n (%) 15 (50%) 5 (50%) 12 (37.5%)1 4 (50%) Weight at baseline (kg) Mean ± SD 89.5 ± 12.4 90.1 ± 13.8 93.0 ± 14.5 86.7 ± 9.3 BMI at baseline (kg/m2) Mean ± SD 31.5 ± 3.1 32.1 ± 2.8 31.7 ± 3.0 30.9 ± 2.7 1. 7 out of 8 participants in the 0.3 mg cohort were male; other cohorts relatively balanced Placebo: Pooled Placebo; MET-233i: Pooled MET-233i doses
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Dose-linear pharmacokinetics with low variability 12 19-DAY OBSERVED HALF-LIFE SUPPORTS ONCE-MONTHL Y DOSING ©Metsera 2025 | Confidential MET-233i SINGLE-DOSE PHARMACOKINETICS 0 7 14 21 28 1000 100 10 1 19 0.15 mg 0.6 mg 2.4 mg 1.2 mg 0.3 mg Time (days) Mean plasma concentration (ng/mL) * Observed half-life Time to 50% Cmax MET-233i dose Note: Estimates reflect mean of available preliminary estimates across single-dose cohorts, and is calculated as the time to 50% of Cmax. *Below lower limit of quantification.
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Pharmacokinetics support a potential first-in-class monthly multi-NuSH combination 13 MUL TI-DOSE PK ENABLES COMBINABILITY WITH MET-097i ©Metsera 2025 | Confidential Time (weeks) Dose- normalized plasma concentration (nM) MULTI-DOSE PHARMACOKINETICS OF MET-233i AND MET-097i: 88% OVERLAP 75 50 25 0 0 1 2 3 4 5 MET-233 Median Predicted PK MET-097 Median Predicted PK Dose-normalized, model-predicted median and 90% prediction interval following multiple dosing of MET-097i and MET-233i MET-097 [90%] Prediction Intervals MET-233 [90%] Prediction Intervals
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Up to 8.4% placebo-subtracted mean weight loss after five doses 14 MET-233i SINGLE AND MUL TIPLE-DOSE WEIGHT LOSS ©Metsera 2025 | Confidential SAD: BODY WEIGHT CHANGE AT DAY 8 0 -1 -2 -3 -6 -7 -8 -9 -10 -4 -5 -2.6 -2.6 -5.7 -8.4 MAD: BODY WEIGHT CHANGE AT DAY 36 -9 -10 -1 -2 -3 -4 -5 -6 0 -7 -8 0.15 mg 1.2 mg0.60 mg0.30 mg0.15 mg 1.2 mg0.60 mg0.30 mg 2.4 mg Placebo- subtracted mean change from baseline in body weight1 (%) -3.0 -1.0 -0.2 -3.8 -5.3 1. Placebo change from baseline in body weight at Day 8 was -0.9% (SAD) and at Day 36 was 0.6% (MAD) SAD: Single ascending dose; MAD: Multiple ascending dose; Placebo: Pooled Placebo The error bars represent +/- standard error (SE); SAD: 6 per active dose; 10 pooled placebo ; MAD: 8 per active dose; 8 pooled p lacebo
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MAD: All gastrointestinal adverse events mild; starting doses with placebo-like tolerability 15 MET-233i WELL-TOLERA TED ©Metsera 2025 | Confidential NAUSEA VOMITING EXPOSURE Placebo MET-233i Placebo MET-233i MET-233i drug exposure level relative to Week 10.15 mg 0.3 mg 0.6 mg 1.2 mg 0.15 mg 0.3 mg 0.6 mg 1.2 mg Week N size 8 8 8 8 8 8 8 8 8 8 1 1 (12.5%) 1 (12.5%) 1 (12.5%) 6 (75.0%) 8 (100%) 0 1 (12.5%) 0 3 (37.5%) 3 (37.5%) 1.0x 2 0 0 0 0 0 0 0 0 0 0 1.8x 3 0 0 0 0 0 0 0 0 0 0 2.3x 4 0 0 0 0 1 (14.3%) 0 0 0 0 0 2.4x 5 1 (12.5%) 0 2 (25.0%) 0 1 (16.7%) 0 0 0 0 0 2.8x T otal 1 (12.5%) 1 (12.5%) 2 (25.0%) 6 (75.0%) 8 (100%) 0 1 (12.5%) 0 3 (37.5%) 3 (37.5%) ONSET OF GASTROINTESTINAL ADVERSE EVENTS BY WEEK IN MAD Candidate starting doses Candidate starting doses N is the number of treated participants. The denominator for each period includes the number of participants at risk for at least the first day of the given onset period. In the total row, the denominator is the number of participants randomized in each group. Placebo depicts pooled placebo. All gastrointestinal adverse were mild. No safety signals.
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All study objectives accomplished 16 A POTENTIAL BEST-IN-CLASS AND MONTHL Y AMYLIN ©Metsera 2025 | Confidential Characterize pharmacokinetics Measure one- and five-week weight loss Identify well- tolerated starting doses 1 2 3 ✓ Monthly dosing supported by 19-day observed half-life ✓ Matched to MET-097i ✓ Class-leading 8.4% weight loss observed after five doses ✓ Placebo-like tolerability at anticipated starting doses ✓ All GI AEs in MAD were mild
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Advancing MET-233i as a monotherapy and in combination with MET-097i 17 PA TH FORWARD ©Metsera 2025 | Confidential MET-233i dose arm 1 MET-233i dose arm 2 MET-233i dose arm 3 MET-233i dose arm 4* 12 weeks Twelve weekly doses with titration followed by a 4x monthly dose Planned N=40 | BMI 27 – 38 | No T2DM Weekly dose Potential monthly dose PROGRAM DATA TIMING MET-233/097 12-week co- administration Year-end 2025 / early 2026 MET-233i 12-week monotherapy Late 2025 *Trial will include at least 4 dose arms 12-WEEK MONOTHERAPY DESIGN
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18 ©Metsera 2025 | Confidential MET-233i Concluding remarks Whit Bernard Chief Executive Officer
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A potential first-in-class, best-in-class amylin analog & first-in-category monthly multi-NuSH combination 19 MET-233i: AHEAD OF THE CURVE ©Metsera 2025 | Confidential FIRST-IN-CLASS To date no other amylin analog has been reported with potential monthly dosing BEST-IN-CLASS Class-leading five-week body weight loss Placebo-like tolerability in anticipated starting doses Rapid onset of tolerance FIRST-IN-CA TEGORY Anticipated combination of MET-233i + MET-097i: • Potential first-in-category monthly multi-NuSH candidate • Combinable in a simple, scalable, single-chamber device HALOTM Further evidence of a foundational advance in peptide engineering • Metsera now possesses the two known longest-acting therapeutic peptides in clinical development – with more to come
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20 ©Metsera 2025 | Confidential MET-233i Q&A Whit Bernard Chief Executive Officer | Steve Marso, M.D. Chief Medical Officer Brian Hubbard, Ph.D. Chief Scientific Officer | Chris Visioli Chief Financial Officer
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Execution on track towards seven further inflective events 21 KEY CA T AL YSTS IN 2025 ©Metsera 2025 | Confidential STRA TEGY MID 2025 LA TE 2025 MONTHLY GLP-1 RA MET-097i VESPER-1 28-week weight loss VESPER-3 (end 2025 / early 2026) 28-week weight loss; monthly dosing Ph. 3 initiation1 MONTHLY AMYLIN + GLP-1 RA MET-233i/MET-097i Amylin monotherapy 5-week weight loss & tolerability GLP-1 + amylin (end 2025 / early 2026) 12-week weight loss & tolerability Amylin monotherapy 12-week weight loss ORAL PEPTIDE PLATFORM MET-097o/MET-224o Lead oral GLP-1 weight loss & tolerability2 NEXT- GENERATION COMBINATIONS MET-034i GIP + GLP-1 tolerability2 1 2 3 4 1. Phase 3 initiation expected shortly after VESPER-1 completion, if successful 2. After completion of IND-enabling studies and if successful in initiating study
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22 ©Metsera 2025 | Confidential MET-233i APPENDIX
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Placebo-like tolerability in 0.15 mg and 0.30 mg doses 23 SAD TOLERABILITY ©Metsera 2025 | Confidential Pooled Placebo MET-233i 0.15 mg 0.30 mg 0.60 mg 1.2 mg 2.4 mg N 10 6 6 6 6 6 At Least One GI AE 0 0 1 (16.7%) 2 (33.3%) 5 (83.3%) 6 (100.0%) Nausea 0 0 1 (16.7%) 2 (33.3%) 5 (83.3%) 6 (100.0%) Mild 0 0 1 (16.7%) 2 (33.3%) 3 (50.0%) 6 (100.0%) Moderate 0 0 0 0 2 (33.3%) 0 Severe 0 0 0 0 0 0 Vomiting 0 0 0 1 (16.7%) 4 (66.7%) 5 (83.3%) Mild 0 0 0 1 (16.7%) 3 (50.0%) 5 (83.3%) Moderate 0 0 0 0 1 (16.7%) 0 Severe 0 0 0 0 0 0 Diarrhea 0 0 0 0 1 (16.7%) 0 N represents the number of treated participants. Number of unique participants for each Preferred Term and severity is presented. Candidate starting doses GASTROINTESTINAL ADVERSE EVENTS BY TYPE AND SEVERITY IN SAD Two discontinuations in the SAD; none attributed to AEs
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Placebo-like tolerability in 0.15 mg and 0.30 mg doses 24 MAD TOLERABILITY ©Metsera 2025 | Confidential Pooled Placebo MET-233i 0.15 mg 0.30 mg 0.60 mg 1.2 mg N 8 8 8 8 8 At Least One GI AE 2 (25%) 1 (12.5%) 2 (25%) 6 (75%) 8 (100%) Nausea 1 (12.5%) 1 (12.5%) 2 (25%) 6 (75%) 8 (100%) Mild 1 (12.5%) 1 (12.5%) 2 (25%) 6 (75%) 8 (100%) Moderate 0 0 0 0 0 Severe 0 0 0 0 0 Vomiting 0 1 (12.5%) 0 3 (37.5%) 3 (37.5%) Mild 0 1 (12.5%) 0 3 (37.5%) 3 (37.5%) Moderate 0 0 0 0 0 Severe 0 0 0 0 0 Diarrhea 1 (12.5%) 0 0 1 (12.5%) 0 N represents the number of treated participants. Number of unique participants for each Preferred Term and severity is presented. Candidate starting doses GASTROINTESTINAL ADVERSE EVENTS BY TYPE AND SEVERITY IN MAD Three discontinuations in the MAD; none attributed to AEs
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25 ©Metsera 2025 | Confidential