Financial Data and Key Metrics Changes - Rhythm Pharmaceuticals reported global revenue of $51.3 million for Q3 2025, a sequential increase of 6% from $48.5 million in Q2 2025 [28] - The number of patients on reimbursed therapy increased by 10% globally during the quarter [28] - Year-over-year, net product revenues increased by $18 million, or 54%, compared to Q3 2024 [32] Business Line Data and Key Metrics Changes - InSibiri sales reached $51.3 million, driven predominantly by Bardet-Biedl Syndrome (BBS), with a 10% increase in the number of patients on reimbursed therapy [4][28] - The proportion of prescriptions for pediatric versus adult patients began to normalize, with 50% of new patients being adults, 22% adolescents, and 28% pediatrics [16] Market Data and Key Metrics Changes - In the U.S., $38.2 million or 74% of Q3 net revenue was generated, while $13.1 million or 26% came from international markets [28] - International revenue decreased by $3.4 million quarter-over-quarter, but patients on reimbursed therapy increased at a low double-digit percentage [30] Company Strategy and Development Direction - The company is preparing for the launch of InSibiri for hypothalamic obesity, pending FDA approval, with a PDUFA date set for December 20, 2025 [5][11] - Rhythm is focused on engaging with physicians and payers to establish InSibiri as a foundational treatment for acquired hypothalamic obesity [20] - The company aims to complete enrollment of the RM-718 weekly phase 2 study in HO patients during Q1 2026 and initiate a phase 3 study with Bivamelagon next year [12][13] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming launch of InSibiri for hypothalamic obesity, highlighting strong growth in BBS and promising regulatory dialogues [5][11] - The company anticipates that the upcoming data readouts and regulatory approvals will position it for sustained long-term growth [4][5] Other Important Information - Rhythm raised approximately $189 million in net proceeds from a follow-on equity offering completed in July 2025, ending Q3 with $416.1 million in cash [28] - The company expects to have sufficient cash to fund planned operations for at least 24 months [34] Q&A Session Summary Question: Can you share your latest thinking on the trial design for your phase 3 HO study? - The HO trial will be a double-blind randomized controlled trial, with expectations for a full year of data [39] Question: Can you provide more details on the efficacy endpoints for Prader-Willi syndrome? - Success will be defined by a BMI percent change, with a target of a 5% threshold in BMI decrease in 52 weeks [45] Question: What are the drivers behind the changes to the ongoing Prader-Willi trial? - The trial was extended to allow patients to continue beyond the initial six months if they wish, and there is a possibility of adding additional sites [51] Question: How should investors think about the launch curve in hypothalamic obesity? - The company has a solid foundation based on learnings from the BBS launch, but the process of getting patients diagnosed may take time [60][62] Question: What is the anticipated gross to net in HO relative to BBS? - The gross to net mix is uncertain, but the company expects to work through reimbursement processes similar to those for BBS [66]

Rhythm Pharmaceuticals Conference Call Summary Company Overview - **Company**: Rhythm Pharmaceuticals (NasdaqGM:RYTM) - **Focus**: Development of treatments for rare diseases, specifically targeting acquired hypothalamic obesity (HO) [1][2] Industry Context - **Condition**: Acquired hypothalamic obesity (HO) is characterized by significant weight gain due to injury to the hypothalamus, often following surgeries for benign tumors like craniopharyngiomas [18][19] - **Market Need**: There are currently no approved therapies for HO, representing a significant unmet medical need [20][31] Key Points from the Call Commercial Readiness - Rhythm Pharmaceuticals is preparing for the launch of its drug, setmelanotide, with a PDUFA date set for December 20, 2023 [3][17] - The company has a solid global foundation with over 350 employees across 15 countries and availability in more than 25 countries [18] Clinical Data and Efficacy - **Phase 2 and Phase 3 Trials**: Setmelanotide has shown promising results, with a 19.8% placebo-adjusted BMI reduction in the phase 3 trial [14][24] - **Patient Response**: Nearly all patients in the trials exhibited some level of response, with 80% losing 5% or more of their body weight [25][26] - **Safety Profile**: The drug's side effects are consistent with MC4R agonist-related effects, primarily nausea and vomiting [29][30] Patient Experience and Challenges - Patients with HO face multiple medical issues, including neuroendocrine dysfunction and obesity, leading to a complex treatment landscape [20][54] - The average patient experiences significant weight gain post-injury, with some doubling their body weight within two years [60][61] - The psychological impact of HO is profound, as patients often mourn their previous active lifestyles [57][58] Regulatory and Market Strategy - Rhythm Pharmaceuticals is actively engaging with regulatory bodies to ensure timely access to treatments for patients [17][62] - The company is also conducting claims analysis and engaging with healthcare providers to better understand the epidemiology of HO, adjusting patient estimates to around 10,000 in the U.S. [32] Future Directions - The company is exploring additional therapeutic options, including oral formulations and combination therapies with GLP-1 agonists, to enhance treatment efficacy [15][28][66] - There is a strong emphasis on early diagnosis and intervention to improve patient outcomes [11][12] Additional Insights - The complexity of HO requires a multifaceted approach to treatment, including behavioral modifications and environmental restrictions [66] - The need for better diagnostic criteria for HO is highlighted, as current methods may overlook patients who gain weight rapidly post-injury [73][74] This summary encapsulates the critical aspects of the conference call, focusing on Rhythm Pharmaceuticals' strategic positioning, clinical advancements, and the broader implications for the treatment of acquired hypothalamic obesity.