RM-718 / Rhythm Pharma - LARVOL DELTA

Anticipated Upcoming Milestones (GlobeNewswire) - "Receive a decision from the FDA on our sNDA (anticipated to be received by the PDUFA goal date of December 20, 2025) for setmelanotide in conditions associated with acquired hypothalamic obesity; Complete enrollment in the Phase 1, Part C trial evaluating the weekly, MC4R agonist RM-718 in patients with acquired hypothalamic obesity in the first quarter of 2026; Announce topline data in the 12-patient Japanese cohort of the setmelanotide Phase 3 trial in acquired hypothalamic obesity in the first quarter of 2026; Announce topline data in the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases in the first quarter of 2026; Complete enrollment in the setmelanotide Phase 3 trial substudy in congenital hypothalamic obesity in the first half of 2026; and Pending further feedback from U.S. and European regulatory agencies, initiate a pivotal Phase 3 trial evaluating bivamelagon in acquired hypothalamic obesity in 2026."

Clinical data • New P3 trial • PDUFA • Trial status • Hypothalamic Injury-associated Obesity • Obesity

Second Quarter and Recent Clinical Development Highlights (GlobeNewswire) - "Today, Rhythm announced that it has enrolled the first patient with hypothalamic obesity in Part C of its Phase 1 trial evaluating RM-718, a weekly-administered melanocortin-4 receptor (MC4R) agonist....Complete enrollment in the Phase 1, Part C trial evaluating the weekly, MC4R agonist RM-718 in patients with acquired hypothalamic obesity in the first quarter of 2026."

Trial status • Hypothalamic Injury-associated Obesity • Obesity

Rhythm Pharmaceuticals Reports First Quarter 2025 Financial Results and Business Update (GlobeNewswire) - "Submit a supplemental New Drug Application to the FDA and a Type II variation request to the European Medicines Agency for setmelanotide for the treatment of patients with acquired HO in the third quarter of 2025; Announce topline data from the bivamelagon Phase 2 trial in acquired HO in the third quarter of 2025; Complete enrollment in the setmelanotide Phase 2 trial in PWS in the second half of 2025; Complete enrollment in the Phase 1, Part C trial evaluating the weekly, MC4R agonist RM-718 in patients with acquired HO in the second half of 2025."

EMA filing • FDA filing • P2 data • Trial status • Obesity • Prader–Willi syndrome

Rhythm Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Business (GlobeNewswire) - "Begin enrolling the first patients with congenital HO in a 34-week substudy of setmelanotide being conducted under the protocol for its global Phase 3 trial in the first quarter of 2025; Begin enrolling the first patients with Prader-Willi syndrome (PWS) in a 26-week, open-label Phase 2 trial evaluating setmelanotide in the first quarter of 2025; Begin enrolling patients with acquired HO in Part C of the Phase 1 trial evaluating the weekly, MC4R agonist RM-718 in the first quarter of 2025; Announce top-line data in the Phase 3 trial evaluating setmelanotide in acquired HO in the second quarter of 2025; Announce topline data from the Phase 2 trial of bivamelagon in acquired HO in the second half of 2025; and Announce top-line data in the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases in the first half of 2026."

Enrollment status • P2 data • P3 data: top line • Hypothalamic Injury-associated Obesity • Metabolic Disorders • Obesity • Prader–Willi syndrome

A Study of RM-718 in Healthy Subjects and in Patients With HO (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Rhythm Pharmaceuticals, Inc. | Trial completion date: Jun 2025 ➔ Jul 2026 | Trial primary completion date: Jun 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

Rhythm Pharmaceuticals Announces Preliminary Fourth Quarter and Full Year 2024 Net Product Revenues, Pipeline Advancements and Upcoming Milestones (GlobeNewswire) - "Rhythm is on track to complete enrollment in the Phase 2 trial evaluating bivamelagon, an oral MC4R agonist, in acquired HO in the first quarter of 2025...Following acceptance of a protocol amendment, Rhythm expects to begin dosing patients with acquired HO in Part C of the Phase 1 trial evaluating RM-718, a weekly MC4R agonist, in the first quarter of 2025."

Enrollment status • Trial status • Metabolic Disorders • Obesity

A Study of RM-718 in Healthy Subjects and in Patients With HO (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Rhythm Pharmaceuticals, Inc. | N=90 ➔ 120

Enrollment change • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

Design of a Phase 1 Trial of Once-Weekly RM-718, a Selective Melanocortin-4 Receptor Agonist, in Patients With General or Hypothalamic Obesity (ENDO 2024) - "Abstract is embargoed at this time."

Clinical • P1 data • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

Hyperphagia and Body Weight Gain Are Reduced With Once-Weekly Treatment With RM-718, a Selective Melanocortin-4 Receptor Agonist, in Zucker Obese Rats (ENDO 2024) - "Abstract is embargoed at this time."

Preclinical • Obesity

Hyperphagia and Body Weight Gain Are Reduced With Once-Weekly Treatment With RM-718, a Selective Melanocortin-4 Receptor Agonist, in Zucker Obese Rats (ENDO 2024) - "The MC4R agonist setmelanotide (SET) reduced weight and hunger in patients with proopiomelanocortin deficiency, leptin receptor deficiency, Bardet-Biedl syndrome, and hypothalamic obesity (HO); however, reversible skin hyperpigmentation occurs via residual MC1R activation. Three weeks of RM-718 QW, a selective MC4R agonist with potential to avoid MC1R-related hyperpigmentation, resulted in stable weight and food intake reduction and improved insulin sensitivity similar to sustained-release SET QW. A Phase 1 trial of RM-718 QW in healthy patients with obesity and patients with HO is planned.Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins."

Preclinical • Bardet–Biedl Syndrome • Diabetes • Genetic Disorders • Hypothalamic Injury-associated Obesity • Inherited Retinal Dystrophy • Obesity • Ophthalmology • POMC-null Obesity • LEP • LEPR

A Study of RM-718 in Healthy Subjects and in Patients With HO (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Rhythm Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

A Study of RM-718 in Healthy Subjects and in Patients With HO (clinicaltrials.gov) - P1 | N=90 | Not yet recruiting | Sponsor: Rhythm Pharmaceuticals, Inc.

New P1 trial • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity