Financial Performance & Guidance - Rhythm Pharmaceuticals reported Q3 2025 product revenue of $51.3 million, compared to $33.3 million in Q3 2024[51] - The company experienced a 10% quarter-over-quarter growth in patients on reimbursed therapy globally[49] - Q3 2025 operating expenses totaled $98.5 million, including $18.8 million in stock-based compensation expense[52] - Rhythm anticipates non-GAAP operating expenses for 2025 to be between $295 million and $315 million, including R&D expenses of $150 million to $165 million and SG&A expenses of $145 million to $150 million[52] - As of September 30, 2025, Rhythm Pharmaceuticals held $416.1 million in cash, cash equivalents, and short-term investments[51] IMCIVREE & Pipeline Updates - Steady growth in global IMCIVREE sales in Q3 2025 was primarily driven by Bardet-Biedl syndrome (BBS)[10] - The FDA accepted the sNDA for setmelanotide in acquired hypothalamic obesity (HO) for Priority Review, with a PDUFA goal date of December 20, 2025[10] - A German investigator-led study showed that over 80% of BBS patients on setmelanotide exhibited either resolution of MASLD or stabilization at grade S1 after six months of therapy[12] - The same study showed 100% of patients (N=26) with both BBS and metabolic dysfunction-associated steatotic liver disease (MASLD) showed improvement[12] Strategic Initiatives & Market Access - Rhythm Pharmaceuticals estimates the U S prevalence of acquired hypothalamic obesity to be approximately 10,000 patients[15] - IMCIVREE is available in >25 countries outside the United States[36] - Rhythm estimates the European prevalence of acquired hypothalamic obesity to be approximately 10,000 patients[40] - Rhythm estimates the prevalence of acquired hypothalamic obesity in Japan to be approximately 5,000 to 8,000[43]

Core Insights - Rhythm Pharmaceuticals reported continued momentum in the third quarter of 2025, highlighted by FDA acceptance of the supplemental new drug application (sNDA) for acquired hypothalamic obesity and steady growth from Bardet-Biedl syndrome (BBS) commercial efforts [2][5] Financial Performance - Revenue from global sales of IMCIVREE (setmelanotide) was $51.3 million for Q3 2025, a 6% increase from Q2 2025, primarily driven by growth in patients and sales for BBS treatment [3][9] - U.S. revenue accounted for $38.2 million (74% of product revenue), marking a 19% sequential increase, while international revenue was $13.1 million (26% of product revenue), reflecting a 21% decrease [3][9] - The company recorded a one-time charge of $3.2 million in Q3 2025 due to a final reimbursed price agreement for IMCIVREE in France [3][9] - R&D expenses were $46.0 million in Q3 2025, up from $37.9 million in Q3 2024, mainly due to increased headcount and stock-based compensation [10] - SG&A expenses rose to $52.4 million in Q3 2025 from $35.4 million in Q3 2024, driven by higher costs associated with expanding operations and marketing [11] - The net loss attributable to common stockholders was $54.3 million for Q3 2025, compared to a net loss of $45.0 million in Q3 2024 [12] Clinical Developments - Rhythm expects to report preliminary results from the Phase 2 trial of setmelanotide in Prader-Willi syndrome in Q4 2025 [5][13] - A recent observational study indicated that setmelanotide treatment improved measures of metabolic dysfunction-associated steatotic liver disease (MASLD) and kidney function in BBS patients [6][7] Upcoming Milestones - The FDA's PDUFA goal date for the sNDA for setmelanotide in acquired hypothalamic obesity is set for December 20, 2025 [5][7] - The company anticipates completing enrollment in the Phase 1 trial evaluating RM-718 in Q1 2026 and announcing topline data from various ongoing trials in early 2026 [13] Cash Position - As of September 30, 2025, the company had approximately $416.1 million in cash, cash equivalents, and short-term investments, compared to $320.6 million at the end of 2024 [8][20]

Commercial Readiness for Acquired Hypothalamic Obesity September 24, 2025 ® © Rhythm® Pharmaceuticals, Inc. All rights reserved. Forward-looking Statements This presentation contains certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, and that involve risks and uncertainties, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical progress of our products and product candidates, including setmel ...

Financial Performance & Outlook - Rhythm Pharmaceuticals reported $48.5 million in net product revenue from global sales in Q2 2025, a 29% sequential growth[60] - The company's cash, cash equivalents, and short-term investments totaled $291 million as of June 30, 2025[59,62] - Rhythm anticipates non-GAAP operating expenses for 2025 to be between $285 million and $315 million, including SG&A expenses of $135 million to $145 million and R&D expenses of $150 million to $170 million[63] - A public offering of common stock closed July 11, 2025, resulting in net proceeds of $189.2 million[59] Clinical & Regulatory Updates - Rhythm is on track to complete U S and EU regulatory submissions for setmelanotide in acquired hypothalamic obesity (HO) in Q3 2025[10,33] - Phase 3 trial data showed a -16.5% BMI change from baseline in the setmelanotide arm (n=81) compared to a +3.3% BMI change in the placebo arm (n=39), resulting in a placebo-adjusted difference in BMI reduction of -19.8% (P<0.0001)[21,22,23,24] - Bivamelagon achieved statistically significant BMI reductions at all doses in a 14-week, Phase 2 trial, with reductions of -2.68% (200mg), -7.69% (400mg), and -9.31% (600mg) compared to a +2.18% increase in the placebo group[25] Commercial Performance & Strategy - The company saw a 38% increase in cumulative prescribers from Q2 2024 to Q2 2025 and a 9% increase from Q1 2025 to Q2 2025 for IMCIVREE prescriptions in patients with Bardet-Biedl syndrome (BBS)[40] - IMCIVREE prescriptions for patients aged 2-12 years accounted for 40% of Q2 2025 prescriptions[43]

Core Insights - Rhythm Pharmaceuticals reported a net product revenue of $48.5 million from global sales of IMCIVREE® (setmelanotide) for Q2 2025, marking a 29% increase sequentially from Q1 2025, primarily driven by sales for Bardet-Biedl syndrome (BBS) [6][9] - The company presented strong Phase 2 and Phase 3 data demonstrating the efficacy of bivamelagon and setmelanotide for treating acquired hypothalamic obesity [2] - Rhythm strengthened its balance sheet with a public offering that raised approximately $189.2 million in net proceeds [5] Financial Performance - Revenue from global sales of IMCIVREE was $48.5 million for Q2 2025, compared to $29.1 million for Q2 2024 [9] - R&D expenses increased to $42.3 million in Q2 2025 from $30.2 million in Q2 2024, attributed to higher drug formulation and clinical trial costs [10] - SG&A expenses rose to $45.9 million in Q2 2025 from $36.4 million in Q2 2024, driven by increased headcount and marketing costs [11] - The net loss attributable to common stockholders was $48.0 million for Q2 2025, compared to a net loss of $33.6 million for Q2 2024 [14] Clinical Development Highlights - U.S. and EU regulatory submissions for setmelanotide in acquired hypothalamic obesity are on track for completion in Q3 2025 [5] - The Phase 2 trial of bivamelagon met its primary endpoint with significant BMI reductions [5] - Data from the Phase 3 TRANSCEND trial showed a 19.8% placebo-adjusted difference in BMI reduction [5] Upcoming Milestones - Rhythm plans to host an event on September 24, 2025, to discuss its global launch strategy for setmelanotide [7] - The company anticipates completing enrollment in the Phase 1 trial for RM-718 in Q1 2026 and announcing topline data from various ongoing trials in early 2026 [12] Cash Position - As of June 30, 2025, the company had cash, cash equivalents, and short-term investments of approximately $291.0 million, not including the $189.2 million raised from the public offering [8][21]

Business Highlights - Rhythm Pharmaceuticals is on track to complete U S and EU regulatory submissions for setmelanotide in acquired hypothalamic obesity (HO) in Q3 2025[9] - The company experienced solid patient demand growth for IMCIVREE (setmelanotide) in Q1 2025[9] - Data readout for the Phase 2 trial of oral bivamelagon in acquired HO is expected in Q3 2025[9] - Rhythm Pharmaceuticals expects its current cash runway to extend into 2027[9] Clinical Trial Results (Setmelanotide in Acquired HO) - The Phase 3 trial showed a statistically significant BMI reduction of 16 5% in the setmelanotide arm compared to baseline[13] - The placebo-adjusted difference in BMI reduction from baseline was 19 8% (P<0 0001)[14] - Significant BMI reductions were observed in both adults (16 3%) and children (16 8%) treated with setmelanotide[18] - A vast majority of patients with acquired HO completed the Phase 3 trial and transitioned to an extension study[27] Financial Performance (Q1 2025) - Net product revenue was $37 7 million, compared to $26 0 million for the three months ended March 31, 2024[63] - Cash, cash equivalents, and short-term investments totaled $314 5 million as of March 31, 2025[63] - The company anticipates non-GAAP operating expenses between $285 million and $315 million for 2025[66]

Core Insights - Rhythm Pharmaceuticals reported a net product revenue of $37.7 million from global sales of IMCIVREE (setmelanotide) for the first quarter of 2025, representing an increase from $26.0 million in the same quarter of 2024 [5][7] - The company has a cash position of approximately $314.5 million as of March 31, 2025, which is expected to support operations into 2027 [6][13] - Rhythm is on track to complete U.S. and EU regulatory submissions for setmelanotide in acquired hypothalamic obesity in the third quarter of 2025 [2][4] Financial Performance - Revenue from global sales of IMCIVREE was $37.7 million for Q1 2025, with $24.5 million (65%) generated in the U.S. and $13.2 million (35%) from international sales [5][7] - The number of patients on reimbursed therapy increased by 14% in Q1 2025 compared to Q4 2024, indicating strong demand for IMCIVREE [5] - R&D expenses decreased to $37.0 million in Q1 2025 from $128.7 million in Q1 2024, primarily due to the absence of in-process research and development costs related to the acquisition of bivamelagon [8] - SG&A expenses increased to $39.1 million in Q1 2025 from $34.4 million in Q1 2024, attributed to increased headcount and marketing efforts [9] Clinical Developments - The pivotal Phase 3 TRANSCEND trial of setmelanotide met its primary endpoint with a -19.8% placebo-adjusted BMI reduction in patients with acquired hypothalamic obesity [4][10] - Topline data from the Phase 2 trial of oral MC4R agonist bivamelagon is expected to be announced in Q3 2025 [2][4] - Rhythm has initiated a Phase 2 trial of setmelanotide in patients with Prader-Willi syndrome, with the first patients dosed on April 7, 2025 [10] Upcoming Milestones - Rhythm anticipates submitting a supplemental New Drug Application to the FDA and a Type II variation request to the European Medicines Agency for setmelanotide in the third quarter of 2025 [10] - The company plans to announce topline data from the bivamelagon Phase 2 trial in acquired hypothalamic obesity in Q3 2025 [10] - Enrollment in the setmelanotide Phase 2 trial in Prader-Willi syndrome is expected to be completed in the second half of 2025 [10]

Core Viewpoint - Rhythm Pharmaceuticals, Inc. will host a live conference call on May 7, 2025, to report its first quarter 2025 financial results and provide a corporate update [1]. Company Overview - Rhythm Pharmaceuticals is a commercial-stage biopharmaceutical company focused on rare neuroendocrine diseases [4]. - The company's lead product, IMCIVREE® (setmelanotide), is an MC4R agonist approved by the FDA for treating obesity and maintaining weight reduction in patients aged 2 years and older with specific genetic conditions [4][5]. - Setmelanotide is also authorized by the European Commission and the UK's MHRA for similar indications in adults and children [4][6]. - Rhythm is advancing a clinical development program for setmelanotide in other rare diseases and is exploring investigational MC4R agonists and small molecules for congenital hyperinsulinism [4]. Product Indications - In the U.S., setmelanotide is indicated for reducing excess body weight in patients with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or specific genetic deficiencies [5]. - In the EU and UK, it is indicated for obesity treatment and hunger control associated with genetically confirmed BBS or loss-of-function biallelic POMC, PCSK1, or LEPR deficiencies [6]. Safety and Adverse Reactions - Common adverse reactions (≥20% incidence) include skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection [15]. - Serious hypersensitivity reactions have been reported, and the drug is contraindicated in patients with prior serious hypersensitivity to setmelanotide [7][12].