Rhythm Pharmaceuticals (RYTM) investor relations material

Study design and patient population

• Open-label phase II trial enrolled 18 Prader-Willi syndrome (PWS) patients aged 6–65 with severe obesity and comorbidities, treated for up to 52 weeks.

• Dose was escalated up to 5 mg/day for adults and 3 mg for those under 12, with most tolerating 4–4.5 mg; primary endpoints were safety and tolerability.

• Most patients were on multiple concurrent medications, mainly atypical antipsychotics and growth hormone; no GLP-1s were used.

• Eight patients reached Month 3 and five reached Month 6 at data cut-off; 17 of 18 remain on active therapy, indicating good compliance.

• Initial patients had high medical complexity, often ineligible for other therapies due to poorly controlled diabetes or lymphedema.

Efficacy results

• Six of eight patients at Month 3 and three of five at Month 6 achieved BMI reductions; some exceeded 5% BMI reduction at six months.

• DEXA scans and body composition analyses showed significant fat mass reduction, sometimes not fully reflected in BMI changes.

• Meaningful reductions in hyperphagia were observed in most patients, as measured by HQ-CT, with improvements seen early and sustained.

• Patients and families reported improved energy, mood, and exercise capacity, even without weight loss.

Safety and tolerability

• Setmelanotide was well tolerated; most common adverse events were skin hyperpigmentation (up to 27.8%) and injection site reactions (up to 22.2%).

• Other reported adverse reactions included nausea, headache, and depression; hyperpigmentation was generally not a concern for patients.

• No deaths, serious adverse events, or events leading to drug withdrawal were reported.

• Safety monitoring included skin exams, depression screening, and growth assessment in pediatric patients.