Rhythm Pharmaceuticals (RYTM) investor relations material

Commercial readiness and strategic foundation

• Significant groundwork laid for setmelanotide launch in acquired hypothalamic obesity (HO), leveraging experience from Bardet-Biedl syndrome (BBS) launches and established relationships with key opinion leaders and healthcare providers.

• Data-driven methods, including claims analysis and field insights, have refined patient identification and targeting, focusing on endocrinologists and pediatric endocrinologists as primary treaters.

• Sales force expanded to 43 territory managers, with scaled patient service teams to support anticipated demand and ensure seamless onboarding and long-term therapy maintenance.

• Educational initiatives, such as unbranded sites and webinars, are underway to raise awareness and support diagnosis among both physicians and patients.

Market opportunity and diagnosis landscape

• Updated prevalence estimate for acquired HO is around 10,000 in the U.S. and Europe, with approximately 500 new cases annually in each region; Japan estimated at 5,000–8,000.

• HO is underdiagnosed due to lack of targeted therapies and overlap with general obesity management; education efforts are leading to increased recognition and differential diagnosis.

• Claims analysis identified about 5,000 endocrinologists managing at least one HO patient, with a top tier of 2,400 managing a larger share.

• Over 2,000 patients in the U.S. are diagnosed or suspected to have acquired HO.

• Market research indicates endocrinologists view HO as a major concern post-injury, second only to pituitary insufficiencies.

Clinical profile and provider feedback

• Setmelanotide demonstrated a statistically significant and clinically meaningful reduction in BMI in Phase 3 trials, with a placebo-adjusted difference of -19.8% (p<0.0001), and 80% of patients losing at least 5% of body weight, 60% losing 10% or more.

• Consistent efficacy and BMI reductions were observed across all age groups and in patients with prior or concomitant GLP-1RA use.

• Setmelanotide led to rapid and significant reductions in hunger scores compared to placebo.

• Safety profile consistent with MC4R agonist class, with nausea and hyperpigmentation as main side effects; most adverse events manageable and not new.

• Providers are highly motivated to prescribe setmelanotide, with 60% indicating they would initiate therapy at diagnosis and 100% of endocrinologists finding a 15% BMI reduction highly compelling.