Rhythm Pharmaceuticals Second Quarter 2025 Financial Results and Business Update August 5, 2025 ® © Rhythm® Pharmaceuticals, Inc. All rights reserved. On Today's Call ® ® 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 International • Hunter Smith, Chief Financial Officer Forward-looking ...

[Executive Summary & Business Update](index=1&type=section&id=Executive%20Summary%20%26%20Business%20Update) [Company Overview & Strategic Highlights](index=1&type=section&id=Company%20Overview%20%26%20Strategic%20Highlights) Rhythm Pharmaceuticals, a commercial-stage biopharmaceutical company, reported strong Q2 2025 results, highlighting significant progress in its MC4R agonism platform and global mission to treat rare neuroendocrine diseases - Rhythm Pharmaceuticals is a commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases[1](index=1&type=chunk) - The company has made significant progress in advancing its melanocortin-4 receptor agonism platform[2](index=2&type=chunk) - Global commercial sales of IMCIVREE achieved **double-digit growth in Q2 2025**[2](index=2&type=chunk) - Strengthened the balance sheet through an upsized common stock offering in July 2025[2](index=2&type=chunk) - Presented strong Phase 2 and Phase 3 data demonstrating potential efficacy of bivamelagon and setmelanotide for acquired hypothalamic obesity[2](index=2&type=chunk) [Second Quarter Business Highlights](index=1&type=section&id=Second%20Quarter%20Business%20Highlights) Global sales of IMCIVREE reached $48.5 million for the second quarter of 2025, representing a 29% sequential increase, primarily driven by sales for Bardet-Biedl syndrome (BBS), and the company completed an upsized public offering in July, raising approximately $189.2 million in net proceeds IMCIVREE Net Product Revenue (Q2 2025) | Metric | Q2 2025 Revenue | Sequential Change (from Q1 2025) | | :----- | :-------------- | :------------------------------- | | Global Sales | $48.5 million | +29% | | U.S. Sales | $32.0 million (66% of product revenue) | +31% | | Non-U.S. Sales | $16.5 million (34% of product revenue) | +24% | - Revenue increase primarily driven by sales of IMCIVREE for the treatment of patients with Bardet-Biedl syndrome (BBS)[3](index=3&type=chunk) - On July 11, 2025, Rhythm closed an upsized public offering of common stock, raising approximately **$189.2 million in net proceeds**[4](index=4&type=chunk) [Clinical Development & Upcoming Milestones](index=2&type=section&id=Clinical%20Development%20%26%20Upcoming%20Milestones) Rhythm announced positive Phase 2 data for bivamelagon and pivotal Phase 3 TRANSCEND trial data for setmelanotide, both showing statistically significant BMI reductions in acquired hypothalamic obesity, with key upcoming milestones including regulatory submissions for setmelanotide in acquired hypothalamic obesity in Q3 2025 and further trial data disclosures in late 2025 and early 2026 - Enrolled the first patient with hypothalamic obesity in Part C of its Phase 1 trial evaluating RM-718, a weekly-administered melanocortin-4 receptor (MC4R) agonist[6](index=6&type=chunk) Setmelanotide Phase 3 TRANSCEND Trial Data (Acquired Hypothalamic Obesity) | Metric | Result | | :----- | :----- | | Placebo-adjusted difference in BMI reduction | -19.8% (N=120) | | Consistent BMI reductions across subgroups | Observed across age (<12, 12-17, <18, and 18+ years) and sex (-16.3% female; -16.8% male) | Bivamelagon Phase 2 Trial Data (Acquired Hypothalamic Obesity) | Cohort | BMI Reduction from Baseline (14 weeks) | p-value | | :----- | :------------------------------------ | :------ | | 600mg (n=8) | -9.3% | 0.0004 | | 400mg (n=7) | -7.7% | 0.0002 | - Bivamelagon safety and tolerability results were consistent with MC4R agonism and mechanism of action[6](index=6&type=chunk) - New, real-world data showed consistent improvements in BMI, BMI-Z, and hunger scores in patients with acquired and congenital hypothalamic obesity treated with setmelanotide[6](index=6&type=chunk) - Anticipated completion of U.S. FDA sNDA and EU EMA Type II variation request for setmelanotide in acquired hypothalamic obesity in **Q3 2025**[6](index=6&type=chunk) - Preliminary results from the setmelanotide Phase 2 trial in Prader-Willi syndrome expected in the second half of 2025[6](index=6&type=chunk) - Rhythm plans to host an investor event, 'Commercial Readiness for Acquired Hypothalamic Obesity,' on September 24, 2025, to review its global launch strategy for setmelanotide[7](index=7&type=chunk) - Upcoming milestones for Q1 2026 include completing enrollment in RM-718 Phase 1 Part C, announcing topline data for the setmelanotide Phase 3 Japanese cohort and EMANATE trial, and completing enrollment in the setmelanotide Phase 3 substudy in congenital hypothalamic obesity[12](index=12&type=chunk) - Pending regulatory alignment, a pivotal Phase 3 trial evaluating bivamelagon in acquired hypothalamic obesity is expected to initiate in 2026[12](index=12&type=chunk) [Financial Results](index=3&type=section&id=Financial%20Results) [Second Quarter 2025 Financial Performance](index=3&type=section&id=Second%20Quarter%202025%20Financial%20Performance) Rhythm Pharmaceuticals reported a net product revenue of $48.5 million for Q2 2025, a significant increase from Q2 2024, however, R&D and SG&A expenses also rose, leading to an increased net loss of ($48.0) million for the quarter [Cash Position](index=3&type=section&id=Cash%20Position) Cash, Cash Equivalents and Short-Term Investments | Metric | June 30, 2025 | Dec. 31, 2024 | | :----- | :------------ | :------------ | | Total | $291.0 million | $320.6 million | - The quarter-end cash position does not include approximately **$189.2 million in net proceeds** from a public offering of common stock that closed on July 11, 2025[8](index=8&type=chunk) - The cash position includes **$40 million** subsequently paid by the Company to LG Chem, Ltd. in July 2025 as part of the acquisition of bivamelagon[8](index=8&type=chunk) [Revenue](index=3&type=section&id=Revenue_Q2) Net Product Revenue (Q2) | Metric | Q2 2025 | Q2 2024 | YoY Change | | :----- | :------ | :------ | :--------- | | Net Product Revenue | $48.5 million | $29.1 million | +66.7% | [Operating Expenses (R&D, SG&A)](index=3&type=section&id=Operating%20Expenses%20(R%26D%2C%20SG%26A)_Q2) Operating Expenses (Q2) | Metric | Q2 2025 | Q2 2024 | YoY Change | | :----- | :------ | :------ | :--------- | | R&D Expenses | $42.3 million | $30.2 million | +40.0% | | SG&A Expenses | $45.9 million | $36.4 million | +26.1% | - R&D increase primarily due to increased costs associated with drug formulation and development (CMC) for RM-718 and bivamelagon, increased clinical trial costs, and higher headcount[10](index=10&type=chunk) - SG&A increase primarily due to higher costs associated with additional headcount to support expanding business operations and establish international commercial operations, increased marketing and promotion costs, and increased professional services costs[11](index=11&type=chunk) [Other income (expense), net](index=4&type=section&id=Other%20income%20(expense)%2C%20net_Q2) Other Income (Expense), Net (Q2) | Metric | Q2 2025 | Q2 2024 | YoY Change | | :----- | :------ | :------ | :--------- | | Other income (expense), net | ($1.0) million | $8.7 million | N/A (shift from income to expense) | - The Q2 2024 figure included a non-recurring gain of **$8.9 million** on settlement of a forward contract[13](index=13&type=chunk) - The increase in other expense was partially due to non-cash interest expense associated with the accretion of deferred royalty obligation and the liability payable to LG Chem, Ltd., offset by foreign currency gains[13](index=13&type=chunk) [Net Loss](index=4&type=section&id=Net%20Loss_Q2) Net Loss Attributable to Common Stockholders (Q2) | Metric | Q2 2025 | Q2 2024 | YoY Change | | :----- | :------ | :------ | :--------- | | Net Loss | ($48.0) million | ($33.6) million | +42.9% | | Net Loss Per Share (Basic & Diluted) | ($0.75) | ($0.55) | +36.4% | [Year to Date 2025 Financial Performance](index=4&type=section&id=Year%20to%20Date%202025%20Financial%20Performance) For the six months ended June 30, 2025, net product revenue grew significantly to $86.2 million, and while SG&A expenses increased, R&D expenses decreased year-over-year due to a non-recurring acquisition cost in 2024, resulting in a reduced net loss of ($98.8) million [Revenue](index=4&type=section&id=Revenue_YTD) Net Product Revenue (YTD) | Metric | YTD 2025 | YTD 2024 | YoY Change | | :----- | :------- | :------- | :--------- | | Net Product Revenue | $86.2 million | $55.0 million | +56.6% | [Operating Expenses (R&D, SG&A)](index=4&type=section&id=Operating%20Expenses%20(R%26D%2C%20SG%26A)_YTD) Operating Expenses (YTD) | Metric | YTD 2025 | YTD 2024 | YoY Change | | :----- | :------- | :------- | :--------- | | R&D Expenses | $79.3 million | $158.9 million | -50.1% | | SG&A Expenses | $85.0 million | $70.8 million | +20.0% | - The decrease in R&D expenses was primarily due to the non-recurrence of **$92.4 million** in-process research and development costs associated with the acquisition of bivamelagon in Q1 2024[16](index=16&type=chunk) - The increase in SG&A expenses was primarily due to higher costs associated with additional headcount to support expanding business operations and establish commercial operations in international regions, and increased marketing and promotion costs[17](index=17&type=chunk) [Other income (expense), net](index=4&type=section&id=Other%20income%20(expense)%2C%20net_YTD) Other Income (Expense), Net (YTD) | Metric | YTD 2025 | YTD 2024 | YoY Change | | :----- | :------- | :------- | :--------- | | Other income (expense), net | ($3.4) million | $7.5 million | N/A (shift from income to expense) | - The YTD 2024 figure included a non-recurring gain of **$8.9 million** on settlement of a forward contract[18](index=18&type=chunk) - The increase in other expense was partially due to non-cash interest expense associated with the accretion of the deferred royalty obligation and the liability payable to LG Chem, Ltd[18](index=18&type=chunk) [Net Loss](index=4&type=section&id=Net%20Loss_YTD) Net Loss Attributable to Common Stockholders (YTD) | Metric | YTD 2025 | YTD 2024 | YoY Change | | :----- | :------- | :------- | :--------- | | Net Loss | ($98.8) million | ($174.9) million | -43.6% | | Net Loss Per Share (Basic & Diluted) | ($1.56) | ($2.89) | -46.0% | [Financial Guidance](index=5&type=section&id=Financial%20Guidance) For the full year 2025, Rhythm anticipates Non-GAAP Operating Expenses to be between $285 million and $315 million, and the company expects its current cash position, combined with proceeds from the July 2025 offering, to fund operations for at least 24 months 2025 Financial Guidance | Metric | Range | | :----- | :---- | | Non-GAAP Operating Expenses | $285 million to $315 million | | GAAP SG&A expenses | ~$135 million to $145 million | | GAAP R&D expenses | ~$150 million to $170 million | - Non-GAAP Operating Expenses are defined as GAAP operating expenses excluding stock-based compensation and fixed consideration related to in-licensing[20](index=20&type=chunk)[39](index=39&type=chunk) - Rhythm expects its cash, cash equivalents, and short-term investments as of June 30, 2025, combined with the net proceeds from the July 2025 offering, to be sufficient to fund planned operations for at least 24 months[21](index=21&type=chunk) [Product Information & Safety](index=5&type=section&id=Product%20Information%20%26%20Safety) [About Rhythm Pharmaceuticals](index=5&type=section&id=About%20Rhythm%20Pharmaceuticals) Rhythm Pharmaceuticals is a commercial-stage biopharmaceutical company based in Boston, MA, focused on rare neuroendocrine diseases, with its lead asset, IMCIVREE® (setmelanotide), an MC4R agonist approved in the U.S., EU, and UK for specific genetic forms of obesity, including Bardet-Biedl syndrome (BBS), POMC, PCSK1, or LEPR deficiency, and the company is also developing bivamelagon and RM-718, and preclinical small molecules for congenital hyperinsulinism - Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases[24](index=24&type=chunk) - Rhythm's lead asset is IMCIVREE® (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity[24](index=24&type=chunk) - Setmelanotide is approved by the FDA, European Commission (EC), and UK's MHRA for specific genetic forms of obesity (BBS, POMC, PCSK1, or LEPR deficiency)[24](index=24&type=chunk) - Rhythm is advancing a broad clinical development program for setmelanotide, as well as investigational MC4R agonists bivamelagon and RM-718, and a preclinical suite of small molecules for congenital hyperinsulinism[24](index=24&type=chunk) [IMCIVREE® (setmelanotide) Indication & Usage](index=6&type=section&id=Setmelanotide%20Indication%20%26%20Usage) IMCIVREE (setmelanotide) is indicated in the U.S. for reducing excess body weight and maintaining weight reduction in adult and pediatric patients (2 years and older) with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed POMC, PCSK1, or LEPR deficiency, with similar indications existing in the EU and UK - In the U.S., setmelanotide is indicated to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed POMC, PCSK1, or LEPR deficiency[26](index=26&type=chunk) - In the European Union and the United Kingdom, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, PCSK1, or LEPR deficiency in adults and children 2 years of age and above[27](index=27&type=chunk) - In the EU and UK, setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology[27](index=27&type=chunk) [Important Safety Information](index=6&type=section&id=Important%20Safety%20Information) IMCIVREE has specific limitations, contraindications, warnings, and precautions, including risks of sexual arousal disturbances, depression/suicidal ideation, hypersensitivity reactions, skin hyperpigmentation, and risks associated with benzyl alcohol preservative in neonates, with common adverse reactions including skin hyperpigmentation, injection site reactions, nausea, and headache [Limitations of Use & Contraindications](index=6&type=section&id=Limitations%20of%20Use%20%26%20Contraindications) - Setmelanotide is not indicated for obesity due to suspected POMC, PCSK1, or LEPR deficiency with variants classified as benign or likely benign[32](index=32&type=chunk) - Not indicated for other types of obesity not related to BBS or POMC, PCSK1, or LEPR deficiency, including general (polygenic) obesity[32](index=32&type=chunk) - Contraindicated in patients with prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE[28](index=28&type=chunk) [Warnings and Precautions](index=6&type=section&id=Warnings%20and%20Precautions) - Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred; patients should seek emergency medical attention for erections lasting longer than 4 hours[29](index=29&type=chunk) - Depression and Suicidal Ideation: Monitor patients for new onset or worsening depression or suicidal thoughts/behaviors; consider discontinuing IMCIVREE if clinically significant or persistent symptoms occur[30](index=30&type=chunk) - Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported; advise patients to promptly seek medical attention and discontinue IMCIVREE if suspected[31](index=31&type=chunk) - Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Perform a full body skin examination prior to initiation and periodically during treatment[33](index=33&type=chunk) - Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: IMCIVREE is not approved for use in neonates or infants[34](index=34&type=chunk) [Adverse Reactions](index=7&type=section&id=Adverse%20Reactions) - Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection[35](index=35&type=chunk) [Use in Specific Populations](index=7&type=section&id=Use%20in%20Specific%20Populations) - Treatment with IMCIVREE is not recommended when breastfeeding[36](index=36&type=chunk) - Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus[36](index=36&type=chunk) [Additional Information](index=8&type=section&id=Additional%20Information) [Forward-Looking Statements](index=8&type=section&id=Forward-Looking%20Statements) This section contains forward-looking statements regarding the safety, efficacy, and clinical progress of products, potential regulatory approvals, commercial growth, estimated market size, future data announcements, business strategy, financial performance, and sufficiency of funds, all of which are subject to numerous risks and uncertainties - Statements regarding the safety, efficacy, potential benefits, and clinical design or progress of products (setmelanotide, bivamelagon, RM-718) are forward-looking[38](index=38&type=chunk) - Expectations surrounding potential regulatory submissions, progress, or approvals (e.g., sNDA to FDA, Type II variation to EMA) and their timing are forward-looking[38](index=38&type=chunk) - The commercial growth of IMCIVREE, estimated market size, and addressable population for drug products are forward-looking[38](index=38&type=chunk) - Future announcement of data from ongoing clinical trials (e.g., Japanese cohort, congenital hypothalamic obesity substudy, EMANATE, RM-718, Prader-Willi syndrome) is forward-looking[38](index=38&type=chunk) - Anticipated financial performance, including estimated Non-GAAP Operating Expenses for 2025, and the sufficiency of cash to fund operations are forward-looking[38](index=38&type=chunk) - Forward-looking statements are subject to numerous risks and uncertainties, including clinical trial enrollment, regulatory approvals, competition, data analysis, pricing, reimbursement, international operations, commercialization, liquidity, and key personnel retention[38](index=38&type=chunk) [Non-GAAP Financial Measures](index=8&type=section&id=Non-GAAP%20Financial%20Measures) The press release includes Non-GAAP Operating Expenses, defined as GAAP operating expenses excluding stock-based compensation and fixed consideration related to in-licensing, presented as a supplemental performance indicator for investors and analysts, though it may not be comparable across companies and has limitations as an analytical tool, and a quantitative reconciliation to GAAP operating expenses is not provided due to the inherent uncertainty of stock-based compensation expenses - Non-GAAP Operating Expenses are defined as GAAP operating expenses excluding stock-based compensation and fixed consideration related to in-licensing[39](index=39&type=chunk) - This non-GAAP measure is a supplemental measure of performance, not required by or presented in accordance with U.S. GAAP, and should not be considered an alternative to GAAP operating expenses[39](index=39&type=chunk)[40](index=40&type=chunk)[41](index=41&type=chunk) - Management uses this non-GAAP financial measure for planning, evaluating operational strategies, and assessing business expansion capacity[41](index=41&type=chunk) - A quantitative reconciliation of forecasted Non-GAAP Operating Expenses to forecasted GAAP operating expenses is not provided due to the inability to calculate stock-based compensation expenses with confidence without unreasonable efforts[42](index=42&type=chunk) [Conference Call Information](index=5&type=section&id=Conference%20Call%20Information) Rhythm Pharmaceuticals hosted a live conference call and webcast on August 5, 2025, at 8:00 a.m. ET to discuss Q2 2025 financial results and business activities, with an archived webcast available on the company's investor relations website - Rhythm Pharmaceuticals hosted a live conference call and webcast on August 5, 2025, at 8:00 a.m. ET to review its second quarter 2025 financial results and recent business activities[22](index=22&type=chunk) - An archived webcast is available under 'Events and Presentations' in the Investor Relations section of the Rhythm Pharmaceuticals website[23](index=23&type=chunk) [Condensed Consolidated Financial Statements](index=10&type=section&id=Condensed%20Consolidated%20Financial%20Statements) [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) This section presents the unaudited condensed consolidated statements of operations and comprehensive loss for the three and six months ended June 30, 2025, and 2024, detailing revenues, costs and expenses, loss from operations, other income/expense, net loss, and net loss per share Condensed Consolidated Statements of Operations and Comprehensive Loss (Selected Data) | Metric (in thousands) | Three months ended June 30, 2025 | Three months ended June 30, 2024 | Six months ended June 30, 2025 | Six months ended June 30, 2024 | | :-------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Product revenue, net | $48,502 | $29,078 | $86,220 | $55,045 | | Total revenues | $48,502 | $29,078 | $81,206 | $55,045 | | Cost of sales | $5,543 | $2,947 | $9,191 | $5,753 | | Research and development | $42,308 | $30,194 | $79,281 | $158,858 | | Selling, general, and administrative | $45,947 | $36,415 | $85,034 | $70,797 | | Total costs and expenses | $93,798 | $69,556 | $173,506 | $235,408 | | Loss from operations | ($45,296) | ($40,478) | ($92,300) | ($180,363) | | Total other (expense), net | ($999) | $8,696 | ($3,413) | $7,509 | | Net loss | ($46,632) | ($32,261) | ($96,130) | ($173,633) | | Net loss attributable to common stockholders | ($47,981) | ($33,563) | ($98,801) | ($174,935) | | Net loss per share, basic and diluted | ($0.75) | ($0.55) | ($1.56) | ($2.89) | | Weighted-average common shares outstanding | 63,684,359 | 61,011,824 | 63,373,489 | 60,577,691 | [Condensed Consolidated Balance Sheets](index=11&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This section provides the unaudited condensed consolidated balance sheets as of June 30, 2025, and December 31, 2024, detailing assets, liabilities, convertible preferred stock, and stockholders' equity Condensed Consolidated Balance Sheets (Selected Data) | Metric (in thousands) | June 30, 2025 | Dec. 31, 2024 | | :-------------------- | :------------ | :------------ | | Cash and cash equivalents | $135,586 | $89,137 | | Short-term investments | $155,444 | $231,428 | | Total current assets | $360,680 | $374,200 | | Total assets | $372,733 | $392,273 | | Total current liabilities | $129,455 | $115,517 | | Total liabilities | $239,150 | $227,724 | | Series A convertible preferred stock | $145,491 | $142,820 | | Total stockholders' equity | ($11,908) | $21,729 | | Total liabilities, convertible preferred stock and stockholders' equity | $372,733 | $392,273 |

"Rhythm has made significant progress in advancing our melanocortin-4 receptor agonism platform and executing on our global mission to transform the lives of patients with rare neuroendocrine diseases," said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. "This quarter, we presented strong Phase 2 and Phase 3 data that demonstrated the potential efficacy of both bivamelagon and setmelanotide, respectively, as treatment options for patients with acquired hypothalamic obesity." ...

Wall Street expects a year-over-year decline in earnings on higher revenues when Rhythm Pharmaceuticals, Inc. (RYTM) reports results for the quarter ended June 2025. While this widely-known consensus outlook is important in gauging the company's earnings picture, a powerful factor that could impact its near-term stock price is how the actual results compare to these estimates. The stock might move higher if these key numbers top expectations in the upcoming earnings report, which is expected to be released ...

Core Viewpoint - Rhythm Pharmaceuticals, Inc. is set to report its second quarter 2025 financial results and provide a corporate update on August 5, 2025, highlighting its focus on rare neuroendocrine diseases and the development of its lead asset, setmelanotide [1][4]. Company Overview - Rhythm Pharmaceuticals is a commercial-stage biopharmaceutical company dedicated to transforming the lives of patients with rare neuroendocrine diseases [4]. - 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 [4][5]. - Setmelanotide is also authorized by the European Commission and the UK's MHRA for similar indications in adults and children [4][6]. Upcoming Events - Rhythm Pharmaceuticals will host a live conference call and webcast on August 5, 2025, at 8:00 a.m. ET to discuss its financial results [1]. - Alastair Garfield, Chief Scientific Officer, and David Connolly, Head of Investor Relations, will participate in a fireside chat at the Canaccord Genuity 45th Annual Growth Conference on August 13, 2025, at 12:30 p.m. ET [2]. 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 [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, including PCSK1 and LEPR deficiencies [6]. Clinical Development - Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases and is also exploring investigational MC4R agonists, bivamelagon and RM-718, along with a preclinical suite of small molecules for congenital hyperinsulinism [4].

Core Insights - Rhythm Pharmaceuticals presented new data on acquired hypothalamic obesity at the Endocrine Society's Annual Meeting (ENDO 2025), highlighting the efficacy of setmelanotide and bivamelagon in reducing body mass index (BMI) in affected patients [1][2][3]. Group 1: Clinical Data and Efficacy - The Phase 2 SIGNAL trial demonstrated that bivamelagon, a daily oral MC4R agonist, achieved statistically significant and clinically meaningful reductions in BMI over 14 weeks [2]. - The Phase 3 TRANSCEND trial showed setmelanotide resulted in a -9.3% BMI reduction in the 600mg cohort, -7.7% in the 400mg cohort, and -2.7% in the 200mg cohort, with a placebo cohort showing a 2.2% increase in BMI [4][5]. - A placebo-adjusted difference of -19.8% in BMI reduction was observed across 120 participants, with significant reductions noted in various age and sex subgroups [5][6]. Group 2: Patient Impact and Future Potential - The data from the trials suggest that both bivamelagon and setmelanotide could become transformative therapeutic options for patients with acquired hypothalamic obesity, potentially establishing a new standard of care [2][4]. - Rhythm estimates that there are between 5,000 to 10,000 individuals living with hypothalamic obesity in the U.S., indicating a significant patient population that could benefit from these treatments [11]. Group 3: Company Overview - Rhythm Pharmaceuticals is a commercial-stage biopharmaceutical company focused on rare neuroendocrine diseases, with its lead asset, setmelanotide, approved for treating obesity related to specific genetic conditions [9][12]. - The company is advancing a broad clinical development program for setmelanotide and other investigational MC4R agonists, indicating a commitment to expanding treatment options for patients with rare diseases [9].

Core Insights - Rhythm Pharmaceuticals presented new data on acquired hypothalamic obesity at the Endocrine Society's Annual Meeting (ENDO 2025), highlighting the efficacy of setmelanotide and bivamelagon in reducing body mass index (BMI) in affected patients [1][2][3] Group 1: Clinical Data and Efficacy - The Phase 3 TRANSCEND trial demonstrated significant BMI reductions with setmelanotide, showing a -9.3% reduction in the 600mg cohort, -7.7% in the 400mg cohort, and -2.7% in the 200mg cohort, while the placebo cohort experienced a 2.2% increase [4][5] - A placebo-adjusted difference of -19.8% in BMI reduction was observed across 120 participants, with significant reductions noted in various age and sex subgroups [5][6] - Bivamelagon, a daily oral MC4R agonist, also showed statistically significant BMI reductions in a Phase 2 trial, indicating its potential as a transformative treatment option for patients with acquired hypothalamic obesity [2][3] Group 2: Patient Population and Market Potential - Acquired hypothalamic obesity is a rare condition affecting an estimated 5,000 to 10,000 individuals in the U.S., with similar prevalence in Japan and the E.U. [11][10] - The condition is characterized by rapid weight gain and hyperphagia due to damage to the hypothalamic region of the brain, often following brain tumors or their treatment [10][11] - The presentations at ENDO 2025 underscore the potential for MC4R-targeted therapies to become the standard of care for this patient community if approved [2][3]

Core Insights - Rhythm Pharmaceuticals (RYTM) shares increased by 36.6% following the announcement of positive top-line data from a Phase II study of the oral melanocortin-4 receptor (MC4R) agonist, bivamelagon, for treating acquired hypothalamic obesity [1][7]. Company Overview - Rhythm Pharmaceuticals is focused on developing treatments for obesity-related conditions, specifically acquired hypothalamic obesity, which is characterized by rapid weight gain and uncontrollable hunger due to hypothalamic damage [2][4]. - The company also markets setmelanotide, another MC4R agonist, under the brand name Imcivree for chronic weight management in patients with specific genetic conditions [4]. Study Results - The Phase II study demonstrated that bivamelagon resulted in statistically significant reductions in body mass index (BMI) after 14 weeks of treatment, with reductions of 9.3%, 7.7%, and 2.7% for the 600mg, 400mg, and 200mg doses, respectively [3][8]. - In contrast, the placebo group experienced a BMI increase of 2.2% over the same period [8]. - Patients receiving bivamelagon also reported a mean decrease of over 2.8 points in peak hunger scores on a standardized 10-point scale, indicating effective management of excessive hunger [9]. Future Development Plans - Following the encouraging Phase II results, Rhythm Pharmaceuticals plans to engage with regulatory authorities in the U.S. and EU to discuss the design of a Phase III study for bivamelagon [10]. - The company aims to request an end-of-phase II meeting with the FDA to pursue a registrational path for bivamelagon [11].

Company Overview - Rhythm Pharmaceuticals, Inc. (RYTM) shares increased by 36.6% in the last trading session, closing at $89, with notable trading volume compared to typical sessions [1] - The stock had previously experienced a 3.3% loss over the past four weeks [1] Recent Developments - The stock's rally followed the announcement of positive top-line data from a phase II study of the investigational oral melanocortin-4 receptor (MC4R) agonist, bivamelagon, for patients with acquired hypothalamic obesity [2] - The study results indicated statistically significant and clinically meaningful reductions in body mass index after 14 weeks of treatment with bivamelagon [2] Financial Expectations - The company is projected to report a quarterly loss of $0.64 per share, reflecting a year-over-year change of -16.4% [3] - Expected revenues for the upcoming report are $43.76 million, which represents a 50.5% increase from the same quarter last year [3] - The consensus EPS estimate for the quarter has remained unchanged over the last 30 days, indicating that stock price movements may not continue without trends in earnings estimate revisions [4] Industry Context - Rhythm Pharmaceuticals is part of the Zacks Medical - Biomedical and Genetics industry, which includes other companies like EyePoint Pharmaceuticals (EYPT) [5] - EYPT shares closed 10.2% higher at $10.96, with an 8% return over the past month [5] - EYPT's consensus EPS estimate for the upcoming report has also remained unchanged at -$0.67, representing a -15.5% change from the previous year [6]

Group 1 - Rhythm Pharmaceuticals, Inc. announced the pricing of its upsized public offering of 2,058,824 shares at a price of $85.00 per share, with expected gross proceeds of approximately $175 million [1] - The offering includes a 30-day option for underwriters to purchase an additional 308,823 shares at the same public offering price [1] - The offering is expected to close on or about July 11, 2025, subject to customary closing conditions [1] Group 2 - Morgan Stanley, BofA Securities, Stifel, and Wells Fargo Securities are acting as joint book-running managers for the offering, with Canaccord Genuity and Citizens Capital Markets as lead managers [2] - The offering is made pursuant to a shelf registration statement on Form S-3 filed with the SEC, which became effective on March 2, 2023 [3] - A preliminary prospectus supplement and accompanying prospectus have been filed with the SEC and are available on the SEC's website [3]