petrelintide (ZP8396) / Zealand Pharma, Roche - LARVOL DELTA

Zealand Pharma…announces the initiation of the global registrational Phase 3 ZUPREME program, evaluating the efficacy and safety of once-weekly petrelintide versus placebo in people with overweight or obesity (GlobeNewswire) - "The Phase 3a program for petrelintide monotherapy, which is being conducted with Zealand Pharma’s partner Roche, consists of three trials: ZUPREME-3, ZUPREME-4, and ZUPREME-5, evaluating the efficacy and safety of once-weekly petrelintide versus placebo in people with obesity or overweight without type 2 diabetes, people with obesity or overweight with type 2 diabetes, and people with obesity or overweight and established cardiovascular disease, respectively. The three trials are expected to enroll approximately 7,000 participants in total."

New P3 trial • Obesity • Type 2 Diabetes Mellitus

Petrelintide Co-Administered With Enicepatide in People Living With Obesity or Overweight (ZYNERGY) (OBESITY WEEK 2026) - No abstract available

Genetic Disorders • Obesity

Petrelintide for the Treatment of Obesity: Post-Hoc Subgroup Analyses of the Phase 2 ZUPREME 1 Trial (OBESITY WEEK 2026) - No abstract available

P2 data • Retrospective data • Genetic Disorders • Obesity

Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME 2) (clinicaltrials.gov) - P2 | N=221 | Completed | Sponsor: Zealand Pharma | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Petrelintide, a human amylin analog for the treatment of obesity: results from a Phase 2, randomised, double-blind, placebo-controlled trial (ZUPREME 1) (EASD 2026) - P2 | "In this phase 2 trial with a gender-balanced population, petrelintide achieved clinically meaningful weight reduction and improved key cardiovascular risk factors at 42 weeks. Petrelintide demonstrated a GI tolerability profile largely similar to placebo. Hence, petrelintide has the potential to be an effective and very well tolerated treatment for persistent long-term obesity therapy, via a mechanism of action distinct from current therapies."

Clinical • P2 data • Metabolic Disorders • Obesity • CRP

Upcoming events in the second half of 2026 (GlobeNewswire) - "Petrelintide, amylin analog. In H2 2026, Zealand Pharma and Roche expect to initiate registrational Phase 3 trials with petrelintide monotherapy; Petrelintide, amylin analog. In H2 2026, Zealand Pharma expects to report topline results from the Phase 2 ZUPREME-2 trial in people with overweight or obesity and type 2 diabetes; Petrelintide/enicepatide (CT-388), amylin+GLP-1/GIP fixed-dose combination. Zealand Pharma and Roche expect to initiate the Phase 2 ZYNERGY trial in people with overweight or obesity in H2 2026."

New P3 trial • P2 data • Trial status • Obesity • Type 2 Diabetes Mellitus

Beyond GLP-1: Amylin-Based Pharmacotherapy and the Search for Better-Tolerated Weight-Loss Drugs. (PubMed, Pharmacol Res) - "Recent advances in peptide engineering, lipidation, and reversible albumin binding have enabled the development of long-acting amylin-based agents, including cagrilintide, eloralintide, petrelintide and NN1213. We place particular emphasis on the tolerability profile of this drug class and discuss how receptor pharmacology, hindbrain and parabrachial circuitry, species differences, and pharmacokinetic exposure may shape nausea, malaise, and emesis. Understanding how amylin-based therapies dissociate weight-loss efficacy from gastrointestinal intolerance may guide the rational design of next-generation anti-obesity drugs with improved clinical utility."

Journal • Review • Genetic Disorders • Metabolic Disorders • Obesity

Amylin Analogs: The Next Major Class of Weight Loss Therapy: A Review of Experimental Data and Early-Phase Clinical Trials. (PubMed, Diabetes Obes Metab) - "Amylin-based therapies represent a promising addition to the evolving treatment landscape of obesity. Their emerging efficacy as both standalone and combination therapies supports a multi pathway approach to addressing the biological complexity and heterogeneity of the disease."

Journal • Genetic Disorders • Obesity

Pharmacokinetics of Petrelintide in Participants With Impaired Hepatic Function (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Zealand Pharma

New P1 trial

ZYNERGY: A Dose-Finding Study of Petrelintide With Enicepatide (RO7795068) in Adults With Obesity or Overweight (clinicaltrials.gov) - P2 | N=486 | Not yet recruiting | Sponsor: Hoffmann-La Roche | Initiation date: Jun 2026 ➔ Sep 2026

Trial initiation date • Genetic Disorders • Obesity

Petrelintide, a Human Amylin Analog for the Treatment of Obesity: Efficacy and Safety from the Phase 2 Trial, ZUPREME 1 (ADA 2026) - "In a gender-balanced population, petrelintide achieved clinically meaningful weight reduction at 42 weeks in this phase 2 trial, with a GI tolerability profile that was largely similar to placebo. Petrelintide has the potential to be an effective and very well-tolerated treatment for sustained long-term obesity therapy, via a distinct MOA compared to current therapies."

Clinical • Late-breaking abstract • P2 data • Metabolic Disorders • Obesity

HM17321, a Novel UCN2 Analog, Improves Weight Loss Quality in Combination with Amylin Analogs in DIO Rats (ADA 2026) - "Here, we evaluated a novel combination potential of HM17321 and amylin analogs. Combination efficacy of HM17321 and amylin analogs (cagrilintide, petrelintide, and eloralintide) was evaluated in DIO rats. In DIO rats, combination treatment of HM17321 with amylin analogs enhanced FM reduction while promoting LM gain, leading to marked improvement in WLQ. These findings highlight the unique potential of HM17321 to improve body composition during weight loss and support its development both as a monotherapy and as a combination partner for amylin- or incretin-based therapies."

Combination therapy • Late-breaking abstract • Preclinical • Metabolic Disorders • Obesity

Comparison of Conditioned Taste Avoidance Profiles between GLP-1 Peptides, Amylin Peptides, and Small Molecule Amylin Receptor Agonists (ADA 2026) - "Semaglutide showed a higher potency on CTA induction than food intake inhibition, while cagrilintide and petrelintide showed comparable potency on both behaviors. These data demonstrate that CTA in lean rats can be used to differentiate nausea-like behavioral profiles among weight loss compounds. The small molecule amylin receptor agonist ACCG-2728 showed a comparable CTA profile to cagrilintide in this preclinical model."

Late-breaking abstract • Metabolic Disorders

Petrelintide, a Human Amylin Analog for the Treatment of Obesity: Efficacy and Safety from the Phase 2 Trial, ZUPREME 1 (ADA 2026) - "In a gender-balanced population, petrelintide achieved clinically meaningful weight reduction at 42 weeks in this phase 2 trial, with a GI tolerability profile that was largely similar to placebo. Petrelintide has the potential to be an effective and very well-tolerated treatment for sustained long-term obesity therapy, via a distinct MOA compared to current therapies."

Clinical • Late-breaking abstract • P2 data • Metabolic Disorders • Obesity

Petrelintide Elicits Distinct Effects on Eating Pattern and Maintains Locomotor Activity Compared with Semaglutide in Rats with Diet-Induced Obesity (ADA 2026) - "These results suggest that petrelintide vs. semaglutide elicits different effects on eating pattern and increases satiation. Initial reduced locomotor activity in rats dosed with semaglutide could indicate lower tolerability vs."

Preclinical • Metabolic Disorders • Obesity

Long-Acting Amylin Analog Petrelintide Does Not Delay Gastric Emptying (ADA 2026) - P1 | "Introduction and Objective: Native amylin, pramlintide (a short-acting amylin analog) and GLP1 based medications have been shown to delay gastric emptying (GE). Petrelintide does not impact GE either after SD or at steady state in doses up to 9.0 mg. Absence of delayed GE and favorable tolerability profile observed in the phase 1 trials potentially represent a clinically relevant benefit of petrelintide. Phase 2 dose finding trial for weight management is ongoing."

Metabolic Disorders

ZP8396-25077: PHARMACOKINETICS OF PETRELINTIDE FOLLOWING ADMINISTRATION TO PARTICIPANTS WITH IMPAIRED HEPATIC FUNCTION (clinicaltrialsregister.eu) - P1 | N=36 | Not yet recruiting | Sponsor: Zealand Pharma A/S | N=18 ➔ 36

Enrollment change

New data from Phase 2 ZUPREME-1 trial at the American Diabetes Association 2026 Scientific Sessions further support potential of petrelintide to redefine the weight management experience for people living with overweight and obesity (GlobeNewswire) - "In the double-blind, parallel-group, dose-finding ZUPREME-1 trial, 485 adults...were randomized (5:1) to weekly subcutaneous injections of five doses of petrelintide or placebo. The trial met its primary endpoint....Petrelintide led to mean reductions in body weight from baseline to Week 42 of up to 10.7% vs 1.7% for placebo (efficacy estimand; p<0.001). 88-98% of participants successfully escalated to their targeted maintenance dose of petrelintide....Petrelintide was associated with meaningful improvements in key cardiovascular risk factors, with the reductions with petrelintide ranging from 7.9-10.8cm for waist circumference (vs 4.3 cm with placebo), 17-41% for high-sensitivity C-reactive protein (hsCRP) (vs 6% with placebo) and 12-21% for triglycerides (vs 9% with placebo)."

P2 data • Obesity

A Phase II multi-arm trial evaluating enicepatide and petrelintide fixed-dose combinations will be initiated towards mid-2026 to develop a differentiated treatment option (GlobeNewswire)

New P2 trial • Obesity

Roche to present new data advancing its obesity portfolio at the American Diabetes Association’s 2026 Scientific Sessions (GlobeNewswire) - "Late-breaking Phase II data highlight enicepatide’s (CT-388) efficacy and safety, reinforcing its potential to deliver best-in-class weight loss across a broad population of people living with overweight or obesity. Late-breaking data from the Phase II ZUPREME-1 trial showcase petrelintide’s efficacy, safety, and compelling tolerability profile, which has the potential to redefine the weight management experience for people living with overweight or obesity."

Late-breaking abstract • P2 data • Obesity

In diet-induced obese rats, amylin receptor selective drug candidates lead to similar changes in fat mass and fat free mass loss than drug candidates activating both amylin and calcitonin receptors (ECO 2026) - "Studies in rats have shown a fat free mass (FFM) preserving effect of AS compared to the GLP-1 receptor agonist semaglutide or cagrilintide (NS), suggesting improved quality of weight loss...Rats were treated once daily for 20 days (subcutaneous injection) with vehicle, cagrilintide (NS), Compound 48 (WO2022/129254) (AS), GUBAmy (NS), NN1213 (AS), eloralintide (AS/NS) or petrelintide (NS) or with semaglutide... At a matched weight loss, the AMYR agonists tested resulted in similar fat mass and fat free mass changes as semaglutide. AS drug candidates had no preserving effect on fat free mass over NS drug candidates. Conflicts of Interest & Funding: Rune E Kuhre, David H Ipsen, Jesper F Lau, Thomas Kruse, Anna Secher and Kirsten Raun are employed by Novo Nordisk A/S"

Preclinical • Obesity

ASC36, a Once-Monthly Next-Generation Amylin Receptor Agonist Peptide, demonstrated 32-day average observed half-life, 6-fold longer than petrelintide, in NHP model and 91% more relative weight loss than petrelintide in DIO rat model (ECO 2026) - "ASC36 has excellent chemical and physical stability with no fibrillation around neutral pH, allowing for co-formulation with other peptides including ASC35, a GLP-1R/GIPR dual agonist. ASC36's longer observed half-life and greater weight loss demonstrate its potential as a best-in-class once-monthly amylin receptor agonist for the treatment of obesity. Nymble. ClR provides obesity clinical care in the My Best Weight clinic and Beyond BMI clinic and is a co-owner of these clinics."

Preclinical • Genetic Disorders • Obesity

ZP8396-25077: PHARMACOKINETICS OF PETRELINTIDE FOLLOWING ADMINISTRATION TO PARTICIPANTS WITH IMPAIRED HEPATIC FUNCTION (clinicaltrialsregister.eu) - P1 | N=36 | Not yet recruiting | Sponsor: Zealand Pharma A/S

New P1 trial

ZYNERGY: A Dose-Finding Study of Petrelintide With Enicepatide (RO7795068) in Adults With Obesity or Overweight (clinicaltrials.gov) - P2 | N=486 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P2 trial • Genetic Disorders • Obesity

ZP8396-25077: PHARMACOKINETICS OF PETRELINTIDE FOLLOWING ADMINISTRATION TO PARTICIPANTS WITH IMPAIRED HEPATIC FUNCTION (clinicaltrialsregister.eu) - P1 | N=18 | Not yet recruiting | Sponsor: Zealand Pharma A/S

New P1 trial