MET-097 / Metsera, Amneal - LARVOL DELTA

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

Cellular Characterisation of Signalling and Receptor Trafficking Induced by MET-097, a G Protein-Biased GLP-1R Agonist (ADA 2025) - "We aimed to further elucidate the signalling and trafficking profile of MET-097. In vitro BRET-based biosensors were used to compare clinically relevant GLP-1R agonists. Compared to reference agonists (GLP-1/exendin-4/semaglutide), MET-097 acted as a partial agonist for Gαs and Gαq recruitment at both the plasma membrane (36% and 22% of exendin-4) and endosomal compartments (34% and 37% of exendin-4), yet still showed full cAMP response (115% of exendin-4). We speculate the pharmacological attributes of MET-097 may contribute to a unique pharmacodynamic profile. Of particular interest will be to align these attributes with the efficacy and tolerability observed in clinical trials."

Metabolic Disorders • Obesity • ARRB1

MET-097: Preclinical Characterization of a Potent and Ultra-Long-Acting GLP-1 Receptor Agonist (ADA 2025) - "Preclinical characterization of MET-097 suggests best-in-class efficacy and an ultra-long t1/2 for MET-097. The long t1/2 of MET-097 may unlock versatile dosing options and scalability advantages due to superior weight loss per mg of peptide."

Preclinical • Metabolic Disorders • Obesity

A Twelve-Week Trial of MET097—A Potent and Ultra-Long-Acting GLP-1 Receptor Agonist (ADA 2025) - "This 12-week trial demonstrated substantial weight loss with titration-free weekly dosing. Additionally, the two-step escalation arm was exceptionally well tolerated."

Metabolic Disorders • 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

Safety, Tolerability, PK, and Efficacy of MET097—A Next-Generation Nutrient-Stimulated Hormone Peptide Analog for Chronic Weight Management (ADA 2025) - "MET097, an ultra-long acting GLP-1RA, results in significant weight loss sustained 8 wks post-treatment. Ongoing Ph2 studies will evaluate weekly and monthly dosing regimens with and without titration."

Clinical • 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

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-097i: Phase 2b program on track, with Phase 3 initiation planned in late 2025 (GlobeNewswire) - "We plan to release additional results from this trial at the American Diabetes Association’s (ADA) 85th Scientific Sessions, in addition to several other presentations focused on MET-097i...VESPER-1 is designed to assess weight loss of different weekly doses of MET-097i over 28 weeks in participants with obesity or overweight without type 2 diabetes. The trial was fully enrolled as of end-2024, and preliminary results are expected in mid-2025; VESPER-2 is designed to assess weight loss and tolerability of different weekly doses of MET-097i over 28 weeks in participants with type 2 diabetes and obesity or overweight. Preliminary results are expected in early 2026; VESPER-3 is designed to assess weight loss and tolerability of multiple monthly doses of MET-097i after 12 initial weekly doses in individuals with obesity or overweight without type 2 diabetes. Preliminary results are expected by year-end 2025 or in early 2026..."

Clinical data • New P3 trial • Obesity

VESPER-3: A Phase 2b Study to Evaluate the Efficacy and Safety of Once-Monthly MET097 in Adults With Obesity or Overweight (clinicaltrials.gov) - P2 | N=250 | Active, not recruiting | Sponsor: Metsera | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

Oral peptide platform: MET-097o oral program accelerated and alternate oral candidate MET-224o on track; four-week data for selected lead expected in late 2025 (GlobeNewswire) - "We plan to initiate Phase 1 trials of MET-097o and MET-224o in mid-2025, and to select and advance the best-performing oral candidate based on the Phase 1 clinical data. Preliminary four-week weight loss, tolerability, and pharmacokinetic data for the selected lead candidate are expected in late 2025."

P1 data • Preclinical • Obesity

VESPER-3: A Phase 2b Study to Evaluate the Efficacy and Safety of Once-Monthly MET097 in Adults With Obesity or Overweight (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: Metsera

New P2 trial • Genetic Disorders • Obesity

A Study of MET233 in Combination With MET097 in Individuals With Obesity or Overweight With or Without Diabetes (clinicaltrials.gov) - P1 | N=132 | Recruiting | Sponsor: Metsera

New P1 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

VESPER-2: A Study to Evaluate the Efficacy and Safety of Once-Weekly MET097 in Adults With Obesity or Overweight and T2DM (clinicaltrials.gov) - P2 | N=125 | Recruiting | Sponsor: Metsera

New P2 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Metsera Reports Fourth Quarter and Full Year 2024 Financial Results and Continued Portfolio Progress (GlobeNewswire) - "VESPER-1, a 28-week Phase 2b clinical trial, is designed to assess the efficacy and tolerability of different titration-free weekly doses of MET-097i. The trial includes 239 participants with obesity or overweight without type 2 diabetes. The last participant in VESPER-1 was enrolled in December 2024, with preliminary data expected in mid-2025....VESPER-3 is a planned Phase 2b clinical trial designed to evaluate the efficacy and tolerability of multiple monthly doses of MET-097i after multiple weekly doses with and without titration. Preliminary results are expected by year-end 2025 or early 2026."

P2b data • Obesity

This Study Will Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of MET097 in Adult Participants With Overweight or Obesity (clinicaltrials.gov) - P1/2 | N=262 | Active, not recruiting | Sponsor: Metsera

New P1/2 trial • Genetic Disorders • Obesity

CenExel Supports Metsera, Inc. in Successful Phase II Trial of MET-097 for Obesity and Metabolic Diseases (ACCESSWIRE) - "CenExel is pleased to announce its partnership with Metsera, Inc., a clinical-stage biopharmaceutical company dedicated to advancing treatments for obesity and metabolic diseases, in support of its recent Phase 2a and Phase 2b clinical trials of MET-097. MET-097 is an ultra-long-acting injectable, fully-biased GLP-1 receptor agonist designed to address the growing global challenge of obesity."

Commercial • Obesity

VESPER-1: A Phase 2b Study to Examine the Safety and Efficacy of Once-Weekly MET097 (clinicaltrials.gov) - P2 | N=225 | Active, not recruiting | Sponsor: Metsera | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

A 16-week Phase 2b Study to Examine the Safety and Efficacy of Four Different Regimens of Once-Weekly MET097 (clinicaltrials.gov) - P2 | N=225 | Recruiting | Sponsor: Metsera

New P2 trial • Genetic Disorders • Obesity