MET-233i / Pfizer - LARVOL DELTA

Association Study of OATP1B3 Polymorphisms on Hepatic Uptake and Drug-Drug Interaction In Vitro. (PubMed, ACS Omega) - "The SNPs rs4149117 and rs7311358, corresponding to Ser112Ala and Met233Ile substitutions, were confirmed as the most frequent alleles...However, because effects are substrate-specific and other hepatic transporters may compensate, final clinical interpretation should be substrate- and evidence-based. Targeted pharmacokinetics and pharmacogenetic studies remain necessary for drugs where OATP1B3 is a major disposition determinant."

Journal • Preclinical

Pfizer wins $10 billion bidding war for Metsera as Novo Nordisk exits (Reuters) - "Metsera accepted a sweetened offer from Pfizer late on Friday, citing U.S. antitrust risks in Novo's bid that it had previously called superior...Pfizer has agreed to pay $86.25 per share in cash, a premium of 3.69% to Metsera's Friday close, Metsera said in a statement. The offer includes $65.60 per share in cash and a contingent value right entitling holders to additional payments of up to $20.65 per share in cash...In a statement, Pfizer said it was pleased to have reached a revised agreement with Metsera, and expects to close the merger soon after Metsera's November 13 shareholder meeting....Metsera's experimental obesity drugs, MET-097i, a GLP-1 injectable, and MET-233i, which mimics the pancreatic hormone amylin, are projected to reach $5 billion in combined peak sales, according to Leerink Partners analyst David Risinger."

Commercial • Sales projection • Obesity

Pfizer Completes Acquisition of Metsera (Businesswire) - "Through this acquisition Pfizer has added a portfolio of promising therapeutic candidates that are complementary to Pfizer’s Internal Medicine pipeline, including MET-097i, a weekly and monthly injectable GLP-1 receptor agonist (RA) about to begin Phase 3 development; MET-233i, a monthly amylin analog candidate being evaluated as monotherapy and in combination with MET-097i in Phase 1 development..."

M&A • Obesity

fizer Inc…and Metsera, Inc…announced the companies have entered into a definitive agreement under which Pfizer will acquire Metsera, a clinical-stage biopharmaceutical company accelerating the next generation of medicines for obesity and cardiometabolic diseases. (Pfizer Press Release) - "Under the terms of the agreement, Pfizer will acquire all outstanding shares of Metsera common stock for $47.50 per share in cash at closing, representing an enterprise value of approximately $4.9 billion. Additionally, the agreement includes a non-transferable contingent value right (CVR) entitling holders to potential additional payments of up to $22.50 per share in cash tied to three specific clinical and regulatory milestones: $5 per share following the Phase 3 clinical trial start of Metsera’s MET-097i+MET-233i combination, $7 per share following U.S. Food and Drug Administration (FDA) approval of Metsera’s monthly MET-097i monotherapy, and $10.50 per share following FDA approval of Metsera’s monthly MET-097i+MET-233i combination, if achieved."

Commercial • Obesity

MET-233 is a differentiated efficacious amylin analogue in preclinical studies, combinable with MET-097, an ultra-long acting GLP-1 receptor agonist (EASD 2025) - "Here, we profile MET-233, comparing it to other clinical-stage amylin analogues, cagrilintide, GUB014295, and petrelintide, and present data supporting the development of MET-233 and MET-097 as a combination therapeutic.Materials and Compounds were characterised in vitro via cAMP accumulation assays at human and rat calcitonin receptors (hCTR/rCTR) and human amylin receptor 3 (hAMYR3). In preclinical models, MET-233 is differentiated by its potency (efficacy at very low doses), PK durability, and combinability with MET-097, a fully-biased ULA GLP-1RA. Taken together, these properties suggest the potential for MET-233 to be combined with MET-097 as a differentiated, ULA treatment option for obesity and related diseases."

Preclinical • Metabolic Disorders • Obesity

Metsera to Present Research Highlighting its Next-Generation Obesity Portfolio at the 61st EASD Annual Meeting (GlobeNewswire) - "'Our late-breaker highlights the initial clinical results for our ultra-long acting amylin analog MET-233i, showcasing a potential best-in-class profile. We also have two preclinical presentations, including one highlighting how MET-233i can be combined with MET-097i, our ultra-long acting GLP-1 receptor agonist, in a first-in-category multi-NuSH combination.'"

Late-breaking abstract • P1 data • Preclinical • Obesity

Pharmacokinetics, weight loss, and tolerability of the ultra-long acting amylin analogue MET-233 (EASD 2025) - P1/2 | "In this clinical trial, MET-233 demonstrated a pharmacokinetic profile consistent with monthly dosing, robust body weight loss, and placebo-like tolerability at anticipated starting doses."

Late-breaking abstract • PK/PD data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

[EASD] Metsera monthly amylin analogue 'MET-233' phase 1 study showed up to 8.4% weight loss. [Google translation] (BioNews) - "In a single-dose (SAD) study, subjects were assigned to five dose groups, ranging from 0.15 mg to 2.4 mg, or a placebo. Analysis on day 8 revealed that a single dose of MET-233 alone resulted in up to 5.3% weight loss compared to the placebo, demonstrating a significant weight loss effect even in the short term....In the multiple-dose regimen (MAD), patients received weekly doses of 0.15–1.2 mg for 5 weeks. At day 36, the MET-233 group demonstrated up to 8.4% weight loss compared to placebo, with the effect being more pronounced in doses of 0.6 mg or higher....There were no safety concerns."

P1 data • Obesity

Pipeline Highlights and Upcoming Milestones (Metsera Press Release) - "We expect to release topline data from VESPER-1 together with interim data from the titration phase of VESPER-3 in September 2025. Combined, these data will inform the weekly dosing regimens we plan to investigate in Phase 3 trials; We expect to release topline 28-week results from the monthly dosing portion of VESPER-3 by year-end 2025 or in early 2026; We are on track to initiate the Phase 3 program of MET-097i in late 2025...We expect to announce topline 12-week data from the MET-233i monotherapy trial in late 2025...We expect to announce topline 12-week data from the MET-233/097 co-administration trial by year-end 2025 or in early 2026....MET-097o program and alternate candidate MET-224o on track; four-week topline data for selected lead expected in late 2025."

Clinical data • Preclinical • Obesity

Therapeutic NuSH Cocktails—Coadministration of Ultra-Long-Acting GLP-1, GIP, Glucagon, and Amylin Peptide Analogs Induce Profound Weight Loss in DIO Mice (ADA 2025) - "We sought preclinical proof of concept of their mixability and concerted efficacy. ULA analogs of human GLP-1, GIP, glucagon, and amylin afforded MET-097, MET-034, MET-067, and MET-233, respectively—a peptide combo we call M4...The M4 (25 nmol/kg total peptide) effects on body weight and food intake were compared to retatrutide (26 nmol/kg). In minipigs, M4 peptides had similar half-lives (range: 87-114 h)... M4 peptides may allow for infrequent coadministration in humans. Results from chronic M4 administration to rats confirm that engaging multiple mechanisms can achieve more weight loss. Further, a polymolecular approach allows adjusting of individual agent dose levels to enhance M4's efficacy to tolerability window, even in a semipersonalized way."

Preclinical • Metabolic Disorders

MET-233 Is an Ultra-Long-Acting Amylin Receptor Agonist (ADA 2025) - "The pharmacokinetics of MET-233 and cagrilintide were compared after single administration in pigs... The long half-life of MET-233 observed in pigs suggests that infrequent administration in humans may be achievable. Results from chronic administration to rats indicate that MET-233 is highly effective, and additive impact on body weight was observed when coadministered with MET-097. The potency, durability, and combinability of MET-233 and MET-097 highlight the potential of MET-233 as a differentiated treatment option."

Metabolic Disorders • Obesity

Based on positive topline data, Metsera is rapidly advancing MET-233i as a monotherapy and in combination with MET-097i: - "An ongoing monotherapy trial evaluates 12 weekly doses of MET-233i with dose titration, followed by an exposure-matched monthly dose at week 13. Topline data from this trial are expected in late 2025; Metsera has extended an ongoing co-administration trial of MET-233i and MET-097i to twelve weeks, with topline data expected by year-end 2025 or early 2026; The Company also expects to report topline clinical data from its ultra-long acting GIP receptor agonist, MET-034i, in combination with MET-097i, in late 2025. We anticipate that MET-034i will be the third peptide engineered with Metsera’s HALO™ platform to enter clinical testing."

New trial • P1 data • P2b data • Pipeline update • Obesity

A Study of MET233 in Individuals With Obesity or Overweight (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: Metsera

New P1/2 trial • Genetic Disorders • Obesity

Metsera Announces Positive Phase 1 Data of First-in-Class Once-Monthly Amylin Candidate MET-233i (Metsera Press Release) - P1 | N=132 | NCT06924320 | Sponsor: Metsera | "Metsera, Inc...announced positive topline data from the Phase 1 clinical trial of MET-233i, an ultra-long acting amylin analog engineered for class-leading durability, potency, and combinability with Metsera’s fully-biased monthly GLP-1 receptor agonist candidate, MET-097i. In the study, MET-233i demonstrated up to 8.4% mean placebo-subtracted weight loss at Day 36, a 19-day observed half-life supporting once-monthly dosing, and a favorable tolerability profile with no safety signals...MET-233i’s exposure profile after multiple doses matched that of MET-097i, supporting combinability as a potential first-in-category once-monthly multi-NuSH combination...There were no severe or serious adverse events observed in the SAD or MAD portion of the trial to date."

P1 data • Obesity

Metsera to Present New Research Highlighting the Breadth and Momentum of its Next-Generation Obesity Portfolio at the 85th Scientific Sessions of the American Diabetes Association (GlobeNewswire) - "Four presentations on MET-097i, a fully biased, monthly, ultra-long acting GLP-1 receptor agonist, including two clinical data presentations; Additional preclinical presentations on other differentiated portfolio assets, including MET-233i, a monthly, ultra-long acting amylin analog."

Clinical data • Preclinical • Obesity

MET-233i: Five-week monotherapy data readout expected in Q2 2025, with additional monotherapy and co-administration readouts planned in late 2025 (GlobeNewswire) - "Preliminary five-week weight loss, tolerability, and pharmacokinetic data from the monotherapy Phase 1 trial are expected in Q2 2025, and 12-week data from this trial are expected in late 2025; Preliminary five-week weight loss, tolerability, and pharmacokinetic data from the Phase 1 co-administration trial are expected in late 2025."

P1 data • Obesity