Rhythm Pharmaceuticals Fourth Quarter, Full Year 2024 Financial Results and Business Update February 26, 2025 ® © Rhythm® Pharmaceuticals, Inc. All rights reserved. On Today's Call ® ® 3 David Meeker, MD Chair, President and CEO ® 2 • David Connolly, Executive Director of Investor Relations and Corporate Communications • David Meeker, MD, Chair, President and Chief Executive Officer • Jennifer Lee, Executive Vice President, Head of North America • Yann Mazabraud, Executive Vice President, Head of Internatio ...

Company Performance - Rhythm Pharmaceuticals reported a quarterly loss of $0.72 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.69, and compared to a loss of $0.70 per share a year ago, indicating an earnings surprise of -4.35% [1] - The company posted revenues of $41.83 million for the quarter ended December 2024, surpassing the Zacks Consensus Estimate by 2.19%, and showing a significant increase from year-ago revenues of $24.23 million [2] - Over the last four quarters, Rhythm Pharmaceuticals has surpassed consensus EPS estimates two times and topped consensus revenue estimates three times [2] Stock Outlook - The stock has underperformed the market, losing about 8.8% since the beginning of the year, while the S&P 500 has gained 1.3% [3] - The current consensus EPS estimate for the coming quarter is -$0.71 on revenues of $39.32 million, and for the current fiscal year, it is -$2.52 on revenues of $183.18 million [7] Industry Context - The Medical - Biomedical and Genetics industry, to which Rhythm Pharmaceuticals belongs, is currently ranked in the top 24% of over 250 Zacks industries, indicating a favorable outlook compared to the bottom 50% [8] - Empirical research shows a strong correlation between near-term stock movements and trends in earnings estimate revisions, suggesting that industry performance can materially impact stock performance [5][8]

Financial Performance - Preliminary unaudited net revenues from global sales of IMCIVREE were approximately $42 million for Q4 2024 and $130 million for FY 2024, representing a 26% quarter-over-quarter increase from Q3 2024[8][10]. - 74% of Q4 2024 revenues and 73% of FY 2024 revenues were generated from the U.S. market[10]. - The company plans to report fourth quarter and full year 2024 financial results in late February 2025[10]. Clinical Trials and Development - The ongoing Phase 3 trial for setmelanotide in acquired hypothalamic obesity is expected to report topline data in H1 2025[8][21]. - Enrollment in the supplemental Japanese cohort of the Phase 3 trial for setmelanotide has been completed[8]. - Rhythm Pharmaceuticals is advancing clinical development for setmelanotide in Prader-Willi syndrome and genetically-defined MC4R pathway diseases[6][8]. - The company is driving life-cycle management with bivamelagon and RM-718, with plans to initiate a new Phase 2 trial for setmelanotide in Prader-Willi syndrome in Q1 2025[6][8][21]. - Rhythm Pharmaceuticals has completed enrollment in two substudies in the Phase 3 EMANATE trial for genetically-caused MC4R pathway diseases[8]. - The Phase 3 Hypothalamic Obesity Trial has completed enrollment, with data expected in H1 2025[51]. - Enrollment for the Phase 3 EMANATE trial was completed in Q4 2024, with topline data expected in H1 2026[78]. - The ongoing SIGNAL trial is a 14-week Phase 2 open-label trial evaluating Bivamelagon in patients with hypothalamic obesity, with enrollment expected to complete in Q1 2025[68]. - A 34-week substudy in congenital hypothalamic obesity is expected to begin enrollment in Q1 2025, leveraging the existing Phase 3 trial infrastructure[61]. - The company plans to initiate an exploratory Phase 2 trial of setmelanotide for Prader-Willi syndrome (PWS) in Q1 2025, targeting up to 20 patients aged 6 to 65 years[92]. Treatment Efficacy - Setmelanotide achieved a mean percent reduction in BMI of -17.7% from baseline at Month 12[37]. - All patients in the study experienced a decrease in obesity severity, with three out of eleven pediatric patients achieving normal weight at one year[42]. - In a real-world study, the mean BMI reduction was -5.6% at Month 1 and -12.8% at Month 3 for adult patients with acquired hypothalamic obesity[49]. - In the DAYBREAK Phase 2 trial, a mean BMI change of -12.4% was observed from baseline among 32 patients on continuous setmelanotide therapy, with 84% achieving or maintaining a >5% BMI reduction[85]. - The DAYBREAK trial's primary endpoint is the proportion of patients achieving a BMI reduction of ≥5% from baseline in response to setmelanotide at the end of Stage 1[81]. - The company reported that 27 out of 32 patients on setmelanotide achieved or maintained a >5% BMI reduction, with a p-value of 0.001 indicating statistical significance[85]. - The pediatric baseline BMI for participants in the DAYBREAK trial was recorded at 2.5 (SD: 0.3), with a range of 1.83 to 2.97[82]. - The company reported positive real-world data from a French early-access program, indicating Setmelanotide may be an effective treatment for congenital hypothalamic obesity[55]. Market Potential and Unmet Needs - The estimated U.S. prevalence of hypothalamic obesity is approximately 29,000 patients, with a significant unmet medical need[17][27]. - The EMANATE trial aims to address a potential market of over 6,000 patients with heterozygous POMC/PCSK1 deficiency and 4,000 with heterozygous LEPR deficiency[76]. - Setmelanotide is being developed for congenital hypothalamic obesity, which has no approved therapies and an estimated prevalence of over 1,000 patients in the U.S. and Europe[54]. - The U.S. prevalence of Bardet-Biedl syndrome (BBS) is estimated to be between 4,000 and 5,000 patients, with a similar number in Europe[101]. - IMCIVREE, the first FDA- and EMA-approved therapy for BBS, has shown steady growth in net product revenues since its launch, reaching $33.3 million in Q1 2023[99]. Financial Position - The company has sufficient cash, cash equivalents, and short-term investments of $298.4 million as of September 30, 2024, to fund operations into 2026[19]. - The company is actively expanding its market presence in the U.S. and Europe, with ongoing patient identification efforts and genetic sequencing data to support its initiatives[101].

Core Insights - Rhythm Pharmaceuticals reported a fourth quarter 2024 net revenue of $41.8 million from global sales of IMCIVREE, marking a 26% increase sequentially from the third quarter of 2024, primarily driven by sales for the treatment of Bardet-Biedl syndrome (BBS) [5][8] - The FDA approved an expanded label for IMCIVREE to include children as young as 2 years old, enhancing the market potential for the drug [5][6] - The company raised approximately $75 million in gross proceeds through its ATM equity offering program, extending its cash runway into 2027 [2][5] Financial Performance - For the full year 2024, net product revenues from IMCIVREE totaled $130.1 million, compared to $77.4 million in 2023 [8] - Research and development (R&D) expenses for Q4 2024 were $41.2 million, up from $29.9 million in Q4 2023, driven by increased costs related to the acquisition and development of bivamelagon [9] - Selling, general, and administrative (SG&A) expenses were $38.1 million for Q4 2024, compared to $32.4 million in Q4 2023, reflecting higher headcount and marketing costs [10] Business Developments - The company is on track to report topline data from its Phase 3 trial evaluating setmelanotide in acquired hypothalamic obesity in Q2 2025 [4][12] - Enrollment was completed in the Phase 2 trial of oral MC4R agonist bivamelagon for acquired hypothalamic obesity [4][12] - Rhythm announced a strategic partnership with Trispera Pharma Solutions in Turkey, expanding its international reach [5] Cash Position - As of December 31, 2024, the company had cash, cash equivalents, and short-term investments of approximately $320.6 million, an increase from $275.8 million as of December 31, 2023 [7][15] - The cash balance does not include approximately $34.7 million from stock sales under the ATM program executed in January 2025 [7] Upcoming Milestones - Rhythm anticipates several key milestones in 2025, including the announcement of topline data from various clinical trials and the initiation of new trials for conditions such as Prader-Willi syndrome [13][14]

Core Viewpoint - Rhythm Pharmaceuticals, Inc. is set to report its fourth quarter and full year 2024 financial results on February 26, 2025, and will also provide a corporate update [1] Group 1: Upcoming Events - Rhythm Pharmaceuticals will host a live conference call and webcast at 8:00 a.m. ET on February 26, 2025, to discuss financial results [1] - David Meeker, M.D., will participate in a fireside chat at the TD Cowen 45th Annual Health Care Conference on March 3, 2025, at 1:10 p.m. ET [2] Group 2: Company Overview - Rhythm Pharmaceuticals is a commercial-stage biopharmaceutical company focused on rare neuroendocrine diseases [4] - The company's lead product, IMCIVREE® (setmelanotide), is approved by the FDA for treating obesity and hunger control in patients with specific genetic conditions [4][5] - Setmelanotide is also authorized by the European Commission and the UK's MHRA for similar indications [4][6] Group 3: Product Indications - In the U.S., setmelanotide is indicated for patients aged 2 years and older with syndromic or monogenic obesity due to specific genetic deficiencies [5] - In the EU and UK, it is indicated for obesity and hunger control associated with genetically confirmed conditions in adults and children aged 2 years and above [6] Group 4: Limitations and Contraindications - Setmelanotide is not indicated for obesity due to benign variants or other types of obesity not related to specific genetic deficiencies [7][8] - Serious hypersensitivity reactions have been reported, and the drug is contraindicated in patients with prior serious hypersensitivity to it [9] Group 5: Warnings and Precautions - Patients may experience disturbances in sexual arousal, depression, and hypersensitivity reactions [10][11][12] - Skin hyperpigmentation and the development of new melanocytic nevi have been observed, necessitating regular skin examinations [13] Group 6: Adverse Reactions - Common adverse reactions (≥20% incidence) include skin hyperpigmentation, injection site reactions, nausea, headache, and depression [15]

Core Viewpoint - Rhythm Pharmaceuticals, Inc. is actively engaging in the healthcare sector by participating in the Oppenheimer 35th Annual Healthcare Life Sciences Conference, highlighting its commitment to addressing rare neuroendocrine diseases through its lead asset, setmelanotide [1][2][3]. Company Overview - Rhythm Pharmaceuticals is a commercial-stage biopharmaceutical company focused on transforming the lives of patients with rare neuroendocrine diseases [3]. - The company's lead product, IMCIVREE® (setmelanotide), is an MC4R agonist approved by the FDA for reducing excess body weight and maintaining weight reduction in patients aged 2 years and older with specific genetic obesity conditions [3][4]. - Setmelanotide has also received authorization from the European Commission and the UK's Medicines & Healthcare Products Regulatory Agency for similar indications [3][5]. Product Indications - In the U.S., setmelanotide is indicated for patients with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or deficiencies in POMC, PCSK1, or LEPR [4]. - 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, including PCSK1 and LEPR deficiencies [5]. Clinical Development - Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases and is also exploring investigational MC4R agonists LB54640 and RM-718, along with a preclinical suite of small molecules for congenital hyperinsulinism [3]. Safety Information - Common adverse reactions associated with setmelanotide include skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection, with an incidence of 20% or more [12].

Group 1 - Rhythm Pharmaceuticals, Inc. (RYTM) shares have increased by 0.3% over the past four weeks, closing at $56.52, with a mean price target of $71.42 indicating a potential upside of 26.4% [1] - The mean estimate consists of 12 short-term price targets with a standard deviation of $6.87, where the lowest estimate is $60 (6.2% increase) and the highest is $80 (41.5% increase) [2] - Analysts show a strong consensus that RYTM will report better earnings than previously estimated, which is a positive indicator for potential stock upside [4][9] Group 2 - The Zacks Consensus Estimate for the current year has risen by 2.3% over the past month, with one estimate increasing and no negative revisions [10] - RYTM holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates, suggesting a strong potential upside [11] - While consensus price targets may not be reliable for predicting exact gains, they can provide a directional guide for price movement [12]

Company Overview - Rhythm Pharmaceuticals, Inc. (RYTM) shares increased by 5.5% to close at $57.52, supported by high trading volume compared to normal sessions, following a 2.7% decline over the past four weeks [1] Financial Performance - The company reported preliminary net revenues of approximately $42 million for Q4 2024 and around $130 million for the full year 2024 from worldwide sales of Imcivree (setmelanotide), which may have contributed to the recent share price increase [2] - The upcoming quarterly report is expected to show a loss of $0.72 per share, reflecting a year-over-year change of -2.9%, while revenues are anticipated to be $36.23 million, marking a 49.5% increase from the same quarter last year [3] Earnings Estimates - The consensus EPS estimate for Rhythm Pharmaceuticals has been revised 1% higher in the last 30 days, indicating a positive trend that typically correlates with stock price appreciation [4] - The stock currently holds a Zacks Rank of 2 (Buy), suggesting favorable market sentiment [4] Industry Context - Rhythm Pharmaceuticals is part of the Zacks Medical - Biomedical and Genetics industry, where another company, Ultragenyx (RARE), saw a 3.2% increase to $41.28, despite a -8.8% return over the past month [4] - Ultragenyx's consensus EPS estimate has changed by +1.5% to -$1.28, representing a +15.8% change from the previous year, and it currently holds a Zacks Rank of 3 (Hold) [5]

Core Insights - Rhythm Pharmaceuticals reported preliminary unaudited net revenues of approximately $42 million for IMCIVREE (setmelanotide) in Q4 2024, marking a 26% increase from Q3 2024, and approximately $130 million for the full year 2024, compared to $77.4 million in 2023 [1][3] - The company is on track to report topline data from a global Phase 3 trial for setmelanotide in acquired hypothalamic obesity in the first half of 2025 [1][4] - Rhythm has completed enrollment in a supplemental Japanese cohort for the Phase 3 trial and plans to initiate a new Phase 2 trial for Prader-Willi syndrome in early 2025 [1][12] Financial Performance - Preliminary unaudited net revenues for Q4 2024 are expected to be approximately $42 million, a 26% increase sequentially from Q3 2024 [3] - Full-year 2024 revenues are projected at approximately $130 million, significantly up from $77.4 million in 2023 [3] - U.S. sales contributed approximately 74% of Q4 revenues and about 73% of full-year revenues [3] Clinical Development Pipeline - The Phase 3 trial for acquired hypothalamic obesity is progressing, with topline data expected in the first half of 2025 [4] - Enrollment for a 34-week substudy in congenital hypothalamic obesity is anticipated to begin in Q1 2025 [5] - The Phase 3 EMANATE trial has completed enrollment, with independent data readouts expected for each genetic cohort [6] Upcoming Milestones - Rhythm plans to initiate a Phase 2 trial for Prader-Willi syndrome, enrolling up to 20 patients, with a focus on safety and tolerability [12] - The company expects to report topline data from the Phase 3 EMANATE trial in the first half of 2026 [6]

Core Viewpoint - Rhythm Pharmaceuticals has received FDA approval for an expanded indication of IMCIVREE (setmelanotide) to treat obesity in children as young as 2 years old, specifically for those with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed pro-opiomelanocortin (POMC), PCSK1, or LEPR deficiencies [5][22][29] Company Overview - Rhythm Pharmaceuticals is a commercial-stage biopharmaceutical company focused on rare neuroendocrine diseases, headquartered in Boston, MA [3][7] - The company is committed to advancing care and precision medicines that address the root causes of these diseases [7] Product Information - IMCIVREE is the first and only precision medicine targeting the hypothalamic MC4R pathway, addressing hyperphagia and obesity in patients with BBS and POMC, PCSK1, or LEPR deficiencies [14] - The drug is indicated for long-term weight reduction in patients aged 2 years and older [17][22] Clinical Development - Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases and investigational MC4R agonists [3] - Results from the Phase 3 VENTURE trial indicate significant and sustained reductions in weight and hunger [31] Market Impact - The approval is seen as a significant advancement for the BBS community, providing a targeted treatment option for children suffering from insatiable hunger and obesity [15] - Approximately 4,000 to 5,000 people in the U.S. are affected by BBS, while POMC, PCSK1, and LEPR deficiencies affect around 600 to 2,500 individuals [16]