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

Amylin receptors as therapeutic targets in obesity: Emerging peptide-based strategies. (PubMed, Vascul Pharmacol) - "The article is a review of the emerging preclinical and clinical data regarding the application of peptide-based amylin receptor agonists (AMYRAs), including pramlintide and cagrilintide, KBP-series DACRAs, and investigational drugs, including ZP8396 and amycretin. Of particular interest, amylin-derived medications can have advantages over weight loss but definite disease-modifying action remains to be determined. Taken together, AMYRAs represent a potential category of therapeutics with promising disease-modifying effects that goes beyond weight loss, providing fresh perspectives for precision obesity management by 2030."

Journal • Review • Genetic Disorders • Metabolic Disorders • Obesity • CALCR

Zealand Pharma Announces Financial Results for the First Nine Months of 2025 (GlobeNewswire) - "Achieved key milestone in the petrelintide Phase 2 ZUPREME-1 trial in people with overweight and obesity, with the last participant completing the 28-week primary endpoint visit, paving the way for 42-week topline data in H1 2026; Approaching Phase 3 data in H1 2026 with survodutide, following last participant last visit in the 76-week SYNCHRONIZE trial in people with overweight and obesity without type 2 diabetes; Zealand Pharma is excited to outline a catalyst-rich 2026 at its upcoming Capital Markets Day on December 11, highlighting its ambition to become a generational biotech company driving the next wave of innovation in obesity."

Clinical data • Obesity • Type 2 Diabetes Mellitus

Petrelintide, amylin analog. (GlobeNewswire) - "In November 2025, enrollment of all trial participants has been completed in ZUPREME-2, the Phase 2 trial evaluating petrelintide versus placebo in people with overweight or obesity and type 2 diabetes."

Enrollment closed • Obesity • Type 2 Diabetes Mellitus

Development of Petrelintide: a Potent, Stable, Long-Acting Human Amylin Analogue. (PubMed, J Med Chem) - "This was enabled through optimization of chemical stability while retaining in vitro and in vivo potency. Petrelintide is in clinical development as a potential treatment for weight management."

Journal • Genetic Disorders • Obesity

'We have the will': Roche unveils strategy to become 'top 3' obesity company (FierceBiotech) - "...CT-388—into a phase 3 study in the first half of next year....The company is eyeing peak sales of more than $3 billion for both CT-388 and petrelintide, according to Roche’s presentation"."

New P3 trial • Sales projection • 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

Effects of the novel long-acting amylin analogue petrelintide on body weight and waist circumference by sex in a phase 1 trial (EASD 2025) - "Petrelintide treatment resulted in clinically relevant reductions in BW and WC; women appeared to respond better, with a retained favorable tolerability profile. A phase 2 obesity trial with petrelintide is ongoing."

P1 data • Metabolic Disorders • Obesity

Pharmacokinetics of Petrelintide Following Administration to Participants With Impaired Renal Function (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Zealand Pharma

New P1 trial • Renal Disease

Upcoming events next 12 months (GlobeNewswire) - "In the first half of 2026, Zealand Pharma expects to report topline results from the Phase 2 ZUPREME-1 trial and complete the Phase 2 ZUPREME-2 trial with petrelintide...Zealand Pharma and Roche expect to initiate Phase 2 with petrelintide/CT-388 in the first half of 2026...In the second half of 2025, Zealand Pharma expects to initiate a Phase 2 trial in a dedicated obesity-related comorbidity....Topline data from SYNCHRONIZE-1 and SYNCHRONIZE-2, the Phase 3 trials with survodutide in people with overweight or obesity without and with type 2 diabetes, respectively, are expected in the first half of 2026."

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

Upcoming events next 12 months (GlobeNewswire) - "In the first half of 2026, Zealand Pharma expects to report topline results from the Phase 2 ZUPREME-1 trial and complete the Phase 2 ZUPREME-2 trial with petrelintide...Zealand Pharma and Roche expect to initiate Phase 2 trials with petrelintide/CT-388 in the first half of 2026...In the second quarter of 2025, Zealand Pharma expects to announce topline results from Part 2 of the Phase 1b trial evaluating higher doses of dapiglutide over 28 weeks of treatment, with subsequent initiation of a Phase 2 trial expected in the second half of 2025. Zealand Pharma will present the results from Part 1 of the Phase 1b trial at the American Diabetes Association’s 85th Scientific Sessions in Chicago, Illinois in June 2025....Topline data from SYNCHRONIZE-1 and SYNCHRONIZE-2, the Phase 3 trials with survodutide in participants with overweight or obesity without and with type 2 diabetes, respectively, are expected in the first half of 2026."

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

Discovery of BGM1812, a Novel Dual Amylin and Calcitonin Receptor Agonist for Obesity Treatment. (PubMed, J Med Chem) - "In both in vivo and in vitro studies, BGM1812 showed significantly enhanced efficacy. This finding provides valuable insights into the SAR of petrelintide and highlights the potential of BGM1812 as a promising obesity drug candidate."

Journal • Genetic Disorders • Obesity

BGM1812, a Novel Amylin Analog, Enhances Receptor Agonism and Induces Superior Weight Loss in Preclinical Models (ADA 2025) - "Introduction and Objective: Amylin receptor agonists (e.g. petrelintide and cagrilintide) have shown promise for weight management...This study evaluates BGM1812's pharmacological properties, weight loss efficacy, and potential synergy with a GLP-1/GIP dual agonist (BGM0504) in diet-induced obese (DIO) rats. Receptor activation: cAMP assays measured EC50 for amylin and calcitonin receptor activation... BGM1812 demonstrates superior receptor activation, robust weight loss effects, and synergistic potential with GLP-1/GIP dual agonism, supporting its development as a next-generation amylin analog for obesity treatment."

Late-breaking abstract • Preclinical • Metabolic Disorders • Obesity

Effects of the Novel Long-Acting Amylin Analogue Petrelintide on Body Weight and Waist Circumference by Sex in a Phase 1 Trial (ADA 2025) - "Petrelintide treatment resulted in clinically relevant reductions in BW and WC; women appeared to respond better, with a retained favorable tolerability profile. A phase 2 obesity trial with petrelintide is ongoing."

P1 data • Metabolic Disorders • Obesity

Safety, tolerability, and clinical effects of petrelintide: a long-acting amylin analog (ECO 2025) - "Treatment with petrelintide appeared safe, was well tolerated, and resulted in clinically meaningful body weight reductions of up to 8.6% after 16 weeks. GI AEs were predominantly mild, transient in nature and occurred during dose escalation. These results underline the potential of petrelintide as an anti-obesity treatment, with efficacy comparable to GLP-1 receptor agonists but with better tolerability."

Clinical • Genetic Disorders • Obesity

Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME 2) (clinicaltrials.gov) - P2 | N=216 | Recruiting | Sponsor: Zealand Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Zealand Pharma announces closing of collaboration and license agreement with Roche (GlobeNewswire) - "Zealand Pharma A/S...announces that all closing conditions in the collaboration and license agreement with Roche announced on March 12, 2025 have been satisfied, including regulatory conditions, and the agreement has become effective."

Licensing / partnership • Obesity

Inside the deal: Roche and Zealand Pharma’s $5.3 billion obesity drug gambit (cnbc) - "The ballooning obesity drug market may have a new contender after Roche struck a $5.3 billion deal to develop Danish biotech Zealand Pharma’s “next generation” weight loss candidate. The deal, announced in March and set to close in the second quarter, marks the Swiss pharma’s latest bid to compete with weight loss heavyweights Novo Nordisk and Eli Lilly, after building out its obesity treatment portfolio over recent years....The Roche-Zealand deal will see the two companies co-develop and co-commercialize petrelintide as both a standalone treatment and as a combo-therapy with Roche’s lead incretin asset CT-388. Under the terms, Zealand will receive upfront cash payments of $1.65 billion, with the potential for milestone payments taking the total to up to $5.3 billion, depending on phase 3 trials and sales development."

Licensing / partnership • Obesity

Phase II Clinical Trial to Evaluate the Efficacy and Safety of NV01-A02 in Children With Autism Spectrum Disorder (clinicaltrials.gov) - P2 | N=105 | Recruiting | Sponsor: Neuroventi Inc.

New P2 trial • Autism Spectrum Disorder • Genetic Disorders

Zealand Pharma begins mid-stage trial for obesity drug candidate in people with type 2 diabetes (Reuters) - "Danish biotechnology company Zealand Pharma...said on Thursday it had enrolled the first patient in a mid-stage trial with its weight-loss drug candidate petrelintide in people with overweight or obesity and type 2 diabetes....The company said in a statement that completion of enrolment of around 200 participants in its so-called Phase 2b ZUPREME-1 trial is expected in the second half of this year."

Trial status • Obesity • Type 2 Diabetes Mellitus

Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME 2) (clinicaltrials.gov) - P2 | N=216 | Not yet recruiting | Sponsor: Zealand Pharma

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

ZUPREME-1: Once-weekly Petrelintide Versus Placebo for Obesity or Overweight with Co-morbidities (clinicaltrials.gov) - P2 | N=494 | Active, not recruiting | Sponsor: Zealand Pharma | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

Zealand Pharma announces completion of enrollment in the Phase 2b ZUPREME-1 trial of petrelintide in people with overweight or obesity (GlobeNewswire) - "Zealand Pharma remains on track to initiate the Phase 2b ZUPREME-2 trial of petrelintide in people with overweight or obesity and type 2 diabetes in the first half of 2025....Zealand Pharma A/S....today announced that the last participant has been enrolled and randomized to active treatment or placebo in ZUPREME-1, a global Phase 2b trial in people with obesity or overweight with weight-related comorbidities comparing once-weekly subcutaneously administered petrelintide, a long-acting amylin analog, versus placebo with regards to effects on body weight, safety, and tolerability."

Enrollment closed • New P2b trial • Obesity • Type 2 Diabetes Mellitus

Zealand Pharma and Roche enter collaboration and license agreement to co-develop and co-commercialize petrelintide as a future foundational therapy for people with overweight and obesity (GlobeNewswire) - "Zealand Pharma...announces a global collaboration and license agreement with Roche...to develop petrelintide, Zealand Pharma’s amylin analog with best-in-class potential, as a foundational therapy for weight management, while rapidly expanding into related indications. The two companies will co-develop and co-commercialize petrelintide and combination products with petrelintide, including a fixed-dose combination product of petrelintide and CT-388, Roche’s lead incretin asset and potential best-in-class GLP-1/GIP receptor dual agonist....As part of this agreement, Zealand Pharma will receive upfront cash payments of USD 1.65 billion, including USD 1.4 billion due upon closing and USD 250 million over the first two anniversaries of the collaboration. Zealand Pharma is also eligible for development milestones of USD 1.2 billion, primarily linked to initiation of Phase 3 trials with petrelintide monotherapy, and sales-based milestones of USD 2.4 billion..."

Licensing / partnership • Obesity

Highlights of the year and key events anticipated in 2025 (GlobeNewswire) - "In December 2024, the company subsequently initiated ZUPREME-1, a large, comprehensive Phase 2b trial in people with overweight or obesity and anticipates completion of participant enrolment in the first half of 2025. The company also expects to expand the development program of petrelintide by initiating ZUPREME-2, a Phase 2b trial in people with overweight or obesity and type 2 diabetes in the first half of 2025."

Enrollment status • New P2b trial • Obesity • Type 2 Diabetes Mellitus

ZUPREME-1: Once-weekly Petrelintide Versus Placebo for Obesity or Overweight With Co-morbidities (clinicaltrials.gov) - P2 | N=480 | Recruiting | Sponsor: Zealand Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity