NCOA1

-- Fourth quarter 2024 net revenue from global sales of IMCIVREE® (setmelanotide) of $41.8 million -- -- On track to report topline data from global Phase 3 trial evaluating setmelanotide in acquired hypothalamic obesity in the second quarter of 2025 -- -- Completed enrollment in the Phase 2 trial of oral MC4R agonist bivamelagon in acquired hypothalamic obesity -- -- FDA approved expanded label for IMCIVREE to include children as young as 2 years old -- -- Raised approximately $75 million in gross proceeds under ATM equity offering program; Cash runway extended into 2027 -- -- Management to host conference call today at 8:00 a.m. ET -- BOSTON , Feb. 26, 2025 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, today reported financial results and provided a business update for the fourth quarter and full year ended December 31, 2024 . “Rhythm delivered solid IMCIVREE global sales growth in the fourth quarter and is poised to drive continued growth in 2025,” said David Meeker , M.D., Chairman, Chief Executive Officer and President of Rhythm. “Our Phase 3 trial in acquired hypothalamic obesity (HO) remains on track as we expect to disclose topline data in the second quarter of 2025. We are well capitalized as we strengthened our balance sheet with approximately $75 million in gross proceeds raised under our ATM program, which extends our cash runway into 2027, enabling us to execute on multiple clinical milestones expected in the year ahead.” Fourth Quarter and Recent Business Highlights Revenue from global sales of IMCIVREE was $41.8 million for the fourth quarter of 2024, an increase of 26% percent on a sequential basis from the third quarter of 2024, primarily driven by sales of IMCIVREE for the treatment of Bardet-Biedl syndrome (BBS). In the fourth quarter of 2024, revenue of $31.7 million , or 76% of product revenue, was generated in the United States , an increase of 36.2% on a sequential basis; revenue of $10.1 million , or 24% of product revenue, was generated outside the United States ; Today, the Company announced that it raised approximately $75 million in gross proceeds from the sale of approximately 1.3 million shares of common stock at a weighted average price of $56.30 under its “at the market” equity offering program (the “ATM Program”) during the fourth quarter of 2024 and in January 2025 ; Today, Rhythm announced that it completed enrollment in the Phase 2 trial evaluating oral MC4R agonist bivamelagon (LB54640) in acquired hypothalamic obesity; Today, Rhythm announced a strategic partnership agreement with Trispera Pharma Solutions in Turkey ; On January 10, 2025 , Rhythm announced that it: Completed enrollment in its supplemental, 12-patient Japanese cohort of the global Phase 3 trial evaluating setmelanotide in acquired HO. Data from this supplemental cohort will serve as the basis for a regulatory submission in Japan ; Completed enrollment in the Phase 3 EMANATE trial of setmelanotide, which is comprised of four substudies: SH2B1 (n=121); POMC and/or PCSK1 (n=79); SRC1 (n=73); and LEPR (n=23). The four-substudy design of this trial allows for independent data readouts and potential registration for each genetic cohort; On December 20, 2024 , the Company announced that the U.S. Food and Drug Administration (FDA) approved an expanded indication for IMCIVREE to include children as young as 2 years old with syndromic or monogenic obesity due to BBS or genetically confirmed pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), deficiency or leptin receptor (LEPR) deficiency; On December 3, 2024 , Rhythm announced that the United Kingdom’s Medicines & Healthcare products Regulatory Agency (MHRA) has expanded the marketing authorization for IMCIVREE to include the treatment of obesity and control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adult and pediatric patients as young as 2 years old and older; and During the annual meeting of the European Society for Paediatric Endocrinology in November 2024 , Rhythm presented new, real-world data that showed four pediatric patients, two with acquired HO and two with congenital HO, achieved >5% weight reduction at three months on setmelanotide. The Company announced plans for a new, 34-week substudy in the ongoing setmelanotide Phase 3 trial in 39 patients with congenital HO aged 4 years and older. Completed enrollment in its supplemental, 12-patient Japanese cohort of the global Phase 3 trial evaluating setmelanotide in acquired HO. Data from this supplemental cohort will serve as the basis for a regulatory submission in Japan ; Completed enrollment in the Phase 3 EMANATE trial of setmelanotide, which is comprised of four substudies: SH2B1 (n=121); POMC and/or PCSK1 (n=79); SRC1 (n=73); and LEPR (n=23). The four-substudy design of this trial allows for independent data readouts and potential registration for each genetic cohort; Anticipated Upcoming Milestones Rhythm expects to achieve the following near-term milestones: Begin enrolling the first patients with congenital HO in a 34-week substudy of setmelanotide being conducted under the protocol for its global Phase 3 trial in the first quarter of 2025; Begin enrolling the first patients with Prader-Willi syndrome (PWS) in a 26-week, open-label Phase 2 trial evaluating setmelanotide in the first quarter of 2025; Begin enrolling patients with acquired HO in Part C of the Phase 1 trial evaluating the weekly, MC4R agonist RM-718 in the first quarter of 2025; Announce top-line data in the Phase 3 trial evaluating setmelanotide in acquired HO in the second quarter of 2025; Announce topline data from the Phase 2 trial of bivamelagon in acquired HO in the second half of 2025; and Announce top-line data in the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases in the first half of 2026. Fourth Quarter and Full Year 2024 Financial Results: Cash Position: As of December 31, 2024 , cash, cash equivalents and short-term investments were approximately $320.6 million , as compared to $275.8 million as of December 31, 2023 . The December 31, 2024 cash balance does not include gross proceeds of approximately $34.7 million from the sale of stock under the Company’s ATM program executed during January 2025 . Revenue: Net product revenues relating to global sales of IMCIVREE were $41.8 million for the fourth quarter of 2024 and $130.1 million for the full year of 2024, as compared to $24.2 million for the fourth quarter of 2023 and $77.4 million for the full year of 2023. R&D Expenses: R&D expenses were $41.2 million in the fourth quarter of 2024 and $238.0 million for the full year of 2024, as compared to $29.9 million in the fourth quarter of 2023 and $135.0 million for the full year of 2023. The year-over-year increase was primarily due to increased costs associated with the acquisition of bivamelagon from LG Chem and its development with certain additional product manufacturing activity, ongoing clinical trials and increased headcount. This increase was partially offset by decreased costs in other trials. SG&A Expenses: SG&A expenses were $38.1 million for the fourth quarter of 2024 and $144.3 million for the full year of 2024, as compared to $32.4 million for the fourth quarter of 2023 and $117.5 million for the full year of 2023. The year-over-year increase was primarily due to increased headcount, marketing and promotions costs and expenses for professional services and partially offset by inventory-related costs that were capitalized as labor and overhead. Other income (expense), net: Other income (expense), net was ($2.1) million for the fourth quarter of 2024 and $5.2 million for the full year of 2024. Net Loss: Net loss attributable to common stockholders was ($44.6) million for the fourth quarter of 2024 and ($264.6) million for the full year of 2024, or a net loss per basic and diluted share of ( $0.72 ) and ( $4.34 ), respectively, as compared to a net loss attributable to common stockholders of ($41.6) million for the fourth quarter of 2023 and ($184.7) million for the full year of 2023, or a net loss per basic and diluted share of ( $0.70 ) and ( $3.20 ), respectively. Financial Guidance: For the year ended December 31, 2024 , the Company had GAAP total operating expenses of $382.3 million , inclusive of $92.4 million associated with the acquisition of the rights to bivamelagon from LG Chem. The Company today reported non-GAAP Operating Expenses for the year ended December 31, 2024 of $250.2 million , which is derived from GAAP total operating expenses of $382.3 million less $39.7 million in stock-based compensation and $92.4 million associated with the acquisition of the rights to bivamelagon from LG Chem. For the year ending December 31, 2025 , Rhythm anticipates approximately $285 million to $315 million in Non-GAAP Operating Expenses. Non-GAAP Operating Expenses are derived from: GAAP total operating expenses, inclusive of: SG&A expenses of approximately $135 million to $145 million ; R&D expenses of approximately $150 million to $170 million ; and Excluding stock-based compensation. SG&A expenses of approximately $135 million to $145 million ; R&D expenses of approximately $150 million to $170 million ; and Excluding stock-based compensation. Non-GAAP Operating Expenses is defined as GAAP operating expenses excluding stock-based compensation and fixed consideration related to in-licensing (see below under "Non-GAAP Financial Measures" for more details). Based on its current operating plans, Rhythm expects that its existing cash, cash equivalents and short-term investments as of December 31, 2024 , and including proceeds from the sale of stock through its ATM program during January 2025 , will be sufficient to fund its operating expenses and capital expenditure requirements into 2027. Conference Call Information Rhythm Pharmaceuticals will host a live conference call and webcast at 8:00 a.m. ET today to review its fourth quarter and full year 2024 financial results and recent business activities. Participants may register for the conference call here. It is recommended that participants join the call ten minutes prior to the scheduled start. A webcast of the call will also be available under "Events and Presentations" in the Investor Relations section of the Rhythm Pharmaceuticals website at https://ir.rhythmtx.com/. The archived webcast will be available on Rhythm Pharmaceuticals’ website approximately two hours after the conference call and will be available for 30 days following the call. About Rhythm Pharmaceuticals Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases. Rhythm’s lead asset, IMCIVREE® (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity, is approved by the U.S. Food and Drug Administration (FDA) to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients 2 years of age and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), deficiency or leptin receptor (LEPR) deficiency. Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists LB54640 and RM-718 , and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA. Setmelanotide IndicationIn the United States , 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 Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). 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, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. In the European Union and the United Kingdom , setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Limitations of Use Setmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign Other types of obesity not related to BBS or POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity Contraindication Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. WARNINGS AND PRECAUTIONS Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention. Depression and Suicidal Ideation: Depression, suicidal ideation and depressed mood have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur. Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE. Skin Hyperpigmentation, Darkening of Pre-existing Nevi , and Development of New Melanocytic Nevi: Generalized or focal increases in skin pigmentation, darkening of pre-existing nevi, development of new melanocytic nevi and increase in size of existing melanocytic nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented lesions. 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. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol preserved drugs. ADVERSE REACTIONSMost common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection. USE IN SPECIFIC POPULATIONS Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus. To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See section 4.8 of the Summary of Product Characteristics for information on reporting suspected adverse reactions in Europe . Please see the full Prescribing Information for additional Important Safety Information. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the safety, efficacy, potential benefits of, and clinical design or progress of any of our products or product candidates at any dosage or in any indication, including, setmelanotide, bivamelagon, and RM-718 ; the potential use of setmelanotide in patients with acquired hypothalamic obesity; our expectations surrounding potential regulatory submissions, progress, or approvals and timing thereof for any of our product candidates; the estimated market size and addressable population for our drug products; the announcement of data from our clinical trials, including our Phase 3 trial evaluating setmelanotide for patients with acquired hypothalamic obesity, the substudy evaluating setmelanotide for patients with congenital hypothalamic obesity, the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases, and the Phase 2 trial evaluating the oral MC4R agonist bivamelagon in acquired hypothalamic obesity; Part C of the Phase 1 trial evaluating RM-718 ; the open-label Phase 2 trial evaluating setmelanotide in patients with Prader-Willi syndrome; the ongoing enrollment in our clinical trials; existing or future collaboration agreements; the Company’s business strategy and plans; our anticipated financial performance and financial position for any period of time, including estimated Non-GAAP Operating Expenses for the year ending December 31, 2025 ; and the sufficiency of our cash, cash equivalents and short-term investments to fund our operations; and the timing of any of the foregoing. Statements using words such as “expect”, “anticipate”, “believe”, “may”, “will”, “aim” and similar terms are also forward-looking statements. Such statements are subject to numerous risks and uncertainties, including, but not limited to, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the ability to achieve necessary regulatory approvals, risks associated with data analysis and reporting, failure to identify and develop additional product candidates, unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, risks associated with the laws and regulations governing our international operations and the costs of any related compliance programs, the impact of competition, risks relating to product liability lawsuits, inability to maintain collaborations, or the failure of these collaborations, our reliance on third parties, risks relating to intellectual property, our ability to hire and retain necessary personnel, general economic conditions, risks related to internal control over financial reporting, and the other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2024 and our other filings with the Securities and Exchange Commission . Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this press release or to update them to reflect events or circumstances occurring after the date of this press release, whether as a result of new information, future developments or otherwise. Non-GAAP Financial MeasuresThis press release includes Non-GAAP Operating Expenses, a supplemental measure of our performance that is not required by, or presented in accordance with, U.S. GAAP and should not be considered as an alternative to operating expenses or any other performance measure derived in accordance with GAAP. We define Non-GAAP Operating Expenses as GAAP operating expenses excluding stock-based compensation and fixed consideration related to in-licensing. We caution investors that amounts presented in accordance with our definition of Non-GAAP Operating Expenses may not be comparable to similar measures disclosed by our competitors because not all companies and analysts calculate this non-GAAP financial measure in the same manner. We present this non-GAAP financial measure because we consider it to be an important supplemental measure of our performance and believe it is frequently used by securities analysts, investors, and other interested parties in the evaluation of companies in our industry. Management believes that investors’ understanding of our performance is enhanced by including this non-GAAP financial measure as a reasonable basis for comparing our ongoing results of operations. Management uses this non-GAAP financial measure for planning purposes, including the preparation of our internal annual operating budget and financial projections; to evaluate the performance and effectiveness of our operational strategies; and to evaluate our capacity to expand our business. This non-GAAP financial measure has limitations as an analytical tool, and should not be considered in isolation, or as an alternative to, or a substitute for operating expenses or other financial statement data presented in accordance with GAAP in our consolidated financial statements. Rhythm has not provided a quantitative reconciliation of forecasted Non-GAAP Operating Expenses to forecasted GAAP operating expenses because the Company is unable, without making unreasonable efforts, to calculate the reconciling item, stock-based compensation expenses, with confidence. This item, which could materially affect the computation of forward-looking GAAP operating expenses, is inherently uncertain and depends on various factors, some of which are outside of Rhythm's control. Corporate Contact: David Connolly Head of Investor Relations and Corporate Communications Rhythm Pharmaceuticals, Inc. 857-264-4280dconnolly@rhythmtx.com Media Contact: Sheryl Seapy Real Chemistry(949) 903-4750sseapy@realchemistry.com Source: Rhythm Pharmaceuticals, Inc.

-- Preliminary unaudited net revenues from global sales of IMCIVREE® (setmelanotide) of approximately $42 million for the fourth quarter of 2024 and approximately $130 million for the full year of 2024 -- -- On track to report topline data from global Phase 3 trial evaluating setmelanotide in acquired hypothalamic obesity in the first half of 2025 -- -- Completed enrollment in supplemental Japanese cohort of Phase 3 trial of setmelanotide in acquired hypothalamic obesity -- -- Completed enrollment in two substudies in Phase 3 EMANATE trial of setmelanotide in genetically-caused MC4R pathway diseases -- -- Plan to initiate new Phase 2 trial exploring setmelanotide in Prader-Willi syndrome -- BOSTON, Jan. 10, 2025 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, today announced preliminary unaudited net revenues from global sales of IMCIVREE® (setmelanotide) for the fourth quarter and full year of 2024, pipeline advancement updates and upcoming milestones. “Rhythm enters 2025 poised for the next level of growth. Over the past two years, we have established the commercial viability of our rare MC4R pathway diseases franchise by demonstrating steady continued growth in an increasing number of countries, and this year we are looking forward to a series of readouts from our robust clinical development pipeline,” said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. “Our Phase 3 trial in acquired hypothalamic obesity (HO) remains on track, and we completed enrollment in the supplemental 12-patient Japanese cohort which will form the basis for a Japanese regulatory filing and the significant opportunity to treat hypothalamic obesity there. We are set to begin our congenital HO substudy with the potential to further expand the opportunity related to injury to and or failure of the hypothalamus to develop. These indications represent significant unmet medical needs and potentially transformative opportunities for Rhythm.” Dr. Meeker continued, “We have completed enrollment of what we believe to be the two most promising substudies in the Phase 3 EMANATE trial. Based on the unmet need and severity of Prader-Willi syndrome (PWS) and learnings from our initial study, we plan to initiate an exploratory Phase 2 study with higher doses of setmelanotide over a longer duration of 6 months. As we previously indicated, 2024 was a year of execution and we expect 2025 will be a year of readouts.” Preliminary Unaudited Fourth Quarter and Full Year 2024 Net Product Revenues Based on preliminary unaudited financial information, Rhythm expects net revenues from global sales of IMCIVREE to be approximately $42 million for the fourth quarter of 2024, an increase of 26% percent on a sequential basis from the third quarter of 2024. Net revenues for the full year of 2024 are expected to be approximately $130 million, compared to $77.4 million for the full year of 2023. The sequential quarter over quarter increase was due to growth in reimbursed patients on therapy and inventory growth in the United States. U.S. sales of IMCIVREE contributed approximately 74% of fourth quarter preliminary unaudited net product revenues and approximately 73% of full-year 2024 revenues. The Company plans to report its fourth quarter and full year 2024 financial results in late February 2025. Pipeline Advancement and Upcoming Milestones Setmelanotide Acquired Hypothalamic Obesity (HO) The Company is on track to report topline data from the pivotal, 120-patient cohorts of its global, Phase 3 trial evaluating setmelanotide in acquired HO in the first half of 2025. Rhythm has completed enrollment in its supplemental, 12-patient Japanese cohort of the global Phase 3 trial evaluating setmelanotide in acquired HO. Data from this supplemental cohort will serve as the basis for a regulatory submission in Japan. Congenital HO Rhythm anticipates enrolling the first patients with congenital HO in a 34-week substudy of the ongoing global Phase 3 trial in the first quarter of 2025. This substudy is independent from the pivotal Phase 3 trial in acquired hypothalamic obesity. Genetically Caused MC4R Pathway Diseases Rhythm completed enrollment in the Phase 3 EMANATE trial, which is comprised of four substudies: SH2B1 (n=121); POMC and/or PCSK1 (n=79); SRC1 (n=73); and LEPR (n=23). The four-substudy design of this trial allows for independent data readouts and potential registration for each genetic cohort. The primary endpoint for each substudy is the difference in mean percent change in BMI from baseline to 52 weeks in setmelanotide arm compared to placebo arm. The Company anticipates reporting topline data from the Phase 3 EMANATE trial in the first half of 2026. Prader-Willi Syndrome (PWS) Today, Rhythm announced it plans to initiate a new, 26-week, open-label Phase 2 trial evaluating setmelanotide for treatment of PWS in the first quarter of 2025. Rhythm plans to enroll up to 20 patients with PWS and obesity aged 6 to 65 years old. Patients will be dose escalated to 5 mg/day, as tolerated. The primary endpoints are safety and tolerability. Key secondary endpoints will assess weight, hyperphagia, behavior and pharmacokinetics. This trial will be conducted at a single site in the United States. PWS is a rare genetic disorder that results in a number of physical, mental and behavioral problems. A key feature of PWS is a constant sense of hunger that usually begins at about 2 years of age. PWS is estimated to affect approximately 400,000 people worldwide and approximately 20,000 people in the United States. Currently, there are no approved therapies for the treatment of PWS that effectively reduce extreme hyperphagia or address low energy expenditure. Bivamelagon (LB54640) Rhythm is on track to complete enrollment in the Phase 2 trial evaluating bivamelagon, an oral MC4R agonist, in acquired HO in the first quarter of 2025. RM-718 Following acceptance of a protocol amendment, Rhythm expects to begin dosing patients with acquired HO in Part C of the Phase 1 trial evaluating RM-718, a weekly MC4R agonist, in the first quarter of 2025. The Company plans to enroll up to 30 patients with acquired hypothalamic obesity for 16 weeks in Part C of this Phase 1 trial. Financial Disclosure Advisory This release contains certain estimated preliminary financial results for the fourth quarter and fiscal year ended December 31, 2024. These estimates are based on the information available to the Company at this time. The Company’s financial closing procedures for the fourth quarter and full year 2024 are not yet complete and, as a result, actual results may vary from the estimated preliminary results presented here due to the completion of the Company’s financial closing and audit procedures. The estimated preliminary financial results have not been audited or reviewed by the Company’s independent registered public accounting firm. These estimates should not be viewed as a substitute for the Company’s full interim or annual financial statements. Accordingly, you should not place undue reliance on this preliminary data. About Rhythm Pharmaceuticals Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases. Rhythm’s lead asset, IMCIVREE® (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity, is approved by the U.S. Food and Drug Administration (FDA) to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients 2 years of age and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), deficiency or leptin receptor (LEPR) deficiency. Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists LB54640 and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA. Setmelanotide Indication In the United States, 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 Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). 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, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. In the European Union and the United Kingdom, setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Limitations of Use Setmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign Other types of obesity not related to BBS or POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity Contraindication Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. WARNINGS AND PRECAUTIONS Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention. Depression and Suicidal Ideation: Depression, suicidal ideation and depressed mood have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur. Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE. Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Generalized or focal increases in skin pigmentation, darkening of pre-existing nevi, development of new melanocytic nevi and increase in size of existing melanocytic nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented lesions. 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. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol preserved drugs. ADVERSE REACTIONS Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection. USE IN SPECIFIC POPULATIONS Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus. To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See section 4.8 of the Summary of Product Characteristics for information on reporting suspected adverse reactions in Europe. Please see the full Prescribing Information for additional Important Safety Information. Forward-looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical progress, potential regulatory submissions, approvals and timing thereof of setmelanotide and other product candidates, including bivamelagon (LB54640) and RM-718; the announcement of data from our clinical trials, including our global Phase 3 trial evaluating setmelanotide in patients with acquired hypothalamic obesity; the ongoing enrollment of patients in our clinical trials; the potential benefits of any of the Company’s products or product candidates for any specific disease indication or at any dosage; expectations surrounding potential clinical trial results, regulatory submissions and approvals our business strategy and plans, including regarding the ongoing commercialization of setmelanotide, expectations surrounding net revenues and sales and reimbursement of IMCIVREE, our anticipated financial performance for any period of time, including preliminary unaudited net product revenues, for the fourth quarter and full year ending December 31, 2024, our participation in upcoming events and presentations; and the timing of any of the foregoing. Statements using words such as “expect”, “anticipate”, “believe”, “may”, “will” and similar terms are also forward-looking statements. Such statements are subject to numerous risks and uncertainties, including, but not limited to, risks relating to our net revenues and anticipated financial results for the fiscal year ended December 31, 2024, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the impact of competition, the ability to achieve or obtain necessary regulatory approvals, risks associated with data analysis and reporting, our ability to successfully commercialize setmelanotide, our liquidity and expenses, our ability to retain our key employees and consultants, and to attract, retain and motivate qualified personnel, and general economic conditions, and the other important factors discussed under the caption “Risk Factors” in Rhythm’s Quarterly Report on Form 10-Q for the three months ended September 30, 2024 and other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise. Corporate Contact: David Connolly Head of Investor Relations and Corporate Communications Rhythm Pharmaceuticals, Inc. 857-264-4280 dconnolly@rhythmtx.com Media Contact: Sheryl Seapy Real Chemistry (949) 903-4750 sseapy@realchemistry.com Source: Rhythm Pharmaceuticals, Inc.

-- Four Pediatric patients treated in French early-access program achieved meaningful weight reduction at three months on setmelanotide therapy -- -- Rhythm announced plans for a new substudy to evaluate setmelanotide therapy in patients with congenital hypothalamic obesity -- BOSTON, Nov. 18, 2024 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, today announced the presentation of new, real-world data that showed four pediatric patients with acquired hypothalamic obesity or congenital hypothalamic obesity achieved >5% weight reduction at three months on setmelanotide, a melanocortin-4 receptor (MC4R) agonist. These data were among five Rhythm-related presentations delivered during the 62nd annual meeting of the European Society for Paediatric Endocrinology (EPSE) in Liverpool, England. “Patients living with hypothalamic obesity – whether acquired or congenital –are mostly refractory to lifestyle programs and anti-obesity medicines that do not address the underlying cause,” said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. “Based on these case reports and insight generated through our pre-approval early-access program for setmelanotide in France, we look forward to exploring the potential efficacy of setmelanotide to offer a new therapy for these patients.” 3-month real-world setmelanotide hunger and weight outcomes in four French pediatric patients with acquired or congenital hypothalamic obesityThe presentation includes results from four case reports of patients <18 years old, two with acquired hypothalamic obesity and two with congenital hypothalamic obesity, at month three on setmelanotide therapy: Congenital hypothalamic obesity: Female, age 15, with septo-optic dysplasia as cause of hypothalamic obesity, achieved a body weight decrease of 9.6% from baseline (94 kg) at month 3 and BMI-Z score change from 3.1 at baseline to 2.8;Male, age 9, with pituitary stalk interruption syndrome (PSIS) as cause of hypothalamic obesity, achieved a body weight decrease of 5.2% from baseline (64 kg) at month 3 and BMI-Z score change from 3.7 at baseline to 3.5; Acquired hypothalamic obesity: Male, age 13, with acquired hypothalamic obesity related to craniopharyngioma resected at age 9, achieved a body weight decrease of 5.6% from baseline (116 kg) at month 3 and 9.5% weight reduction at month 6, and BMI-Z score change from 3.7 at baseline to 3.4 at month six of setmelanotide therapy; andMale, age 13, with acquired hypothalamic obesity related to radiotherapy for juvenile pilocytic astrocytoma, achieved a body weight decrease of 8.3% from baseline (88.3 kg) at month 3 and BMI-Z score change from 3.1 at baseline to 2.8. These patients were treated with setmelanotide at four different hospitals in France under a pre-marketing, early-access authorization program. All four patients remain on therapy, as of November 15, 2024, and there were no new safety signals observed. “These patients present with differences and complexities associated with hypothalamic obesity, but these conditions share the same disrupted MC4R pathway signaling,” said Dr. Ahlam Azar-Kolakez, MD, Endocrinology-Diabetology Department, Reference Center for Endocrine Growth and Developmental Diseases, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris, France. “These real-world results are the first reported evidence of setmelanotide treatment for patients with congenital hypothalamic obesity demonstrating that it may be an effective, targeted therapy for both acquired and congenital hypothalamic obesity despite differences in etiology.” Also today, Rhythm announced plans for a new, 34-week substudy designed to evaluate setmelanotide in 39 patients with congenital hypothalamic obesity aged 4 years and older. Rhythm is seeking approval from the U.S. Food and Drug Administration (FDA) for the independent substudy for congenital hypothalamic obesity as a protocol amendment to the Company’s ongoing Phase 3 trial evaluating setmelanotide in patients with acquired hypothalamic obesity. Rhythm anticipates enrolling the first patients with congenital hypothalamic obesity in the first quarter of 2025. The substudy in congenital hypothalamic obesity is independent from Rhythm’s pivotal Phase 3 trial in acquired hypothalamic obesity. The Company remains on track to disclose topline data from that pivotal trial in the first half of 2025. About Congenital Hypothalamic ObesityCongenital hypothalamic obesity is a rare disease caused by certain inborn brain abnormalities that may impair the function of the MC4R pathway, which regulates satiety or food intake and energy expenditure. The hallmark features of this disease include hyperphagia and early-onset, refractory obesity that is often linked to an impairment in the MC4R pathway associated with several pituitary deficiencies. Rare diseases that may cause congenital hypothalamic obesity include septo-optic displasia (or de Morsier syndrome), optic nerve hypoplasia, multiple pituitary hormone deficiency (also known as combined pituitary hormone deficiency) and pituitary stalk interruption syndrome. Each of these diseases is considered rare, and between 12% and 40% of patients with these diseases may have congenital hypothalamic obesity. Rhythm’s preliminary estimate of the prevalence of congenital hypothalamic obesity is in excess of 1,000 patients in the United States with a similar prevalence in Europe. Additional Presentations at ESPE 2024In a poster entitled, “Evaluating Setmelanotide Treatment for 12 Months in Pediatric Age Groups With Rare Melanocortin-4 Receptor Pathway–Related Obesity: Efficacy in Weight Reduction and Safety Outcomes,” presenters highlighted the importance of early intervention in young patients with rare MC4R pathway diseases. A cross-sectional analysis of 50 patients aged 2 to 17 years with rare MC4R pathway diseases who participated in one of five different clinical trials of setmelanotide was presented showing that patients regardless of age achieved clinically meaningful weight reductions, and that children between 2 and 5 years old achieved a greater absolute BMI Z reduction. Additionally, the Company delivered three oral presentations based on analyses of more than 5,000 sequencing samples from the Company’s European genetic testing program for individuals with suspected rare MC4R pathway diseases, Rare Obesity Advanced Diagnosis or ROAD®. Genetic testing of individuals with early-onset obesity can help improve disease etiology understanding and identify patients who may benefit from specialized care. Highlights from these three presentations included: 1.74% of individuals tested carried a biallelic variant in one of 22 tested genes related to Bardet-Biedl syndrome (BBS), and the frequency in Turkey was 5.82%, potentially due to consanguinity rates;22.5% of tested individuals with early-onset obesity carried a variant classified as pathogenic, likely pathogenic or of unknown significance (VUS) of one or more genes closely associated with MC4R pathway function: SIM1, SEMA3 family, PLXNA family, POMC, PCSK1, LEPR, SH2B1 and NCOA1; and4.9% of tested individuals carried a biallelic or heterozygous pathogenic, likely pathogenic or VUS variant in one or more of these genes: ALMS1, BBS, MAGEL2, PHIP, or TBX3 genes. These genes are associated with certain debilitating syndromes. All of the Rhythm-related presentations from ESPE 2024 are available here: https://hcp.rhythmtx.com/publications-presentations/. About Rhythm PharmaceuticalsRhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases. Rhythm’s lead asset, IMCIVREE® (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity, is approved by the U.S. Food and Drug Administration (FDA) for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. The EC has also authorized setmelanotide for control of hunger and treatment of obesity in children as young as 2 years old, living with BBS or POMC, PCSK1, or LEPR deficiency. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists LB54640 and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA. Setmelanotide IndicationIn the United States, setmelanotide is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to POMC, PCSK1 or LEPR deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1 or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS) or BBS. In the European Union, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. In Europe, setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Limitations of UseSetmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benign.Other types of obesity not related to POMC, PCSK1 or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity. ContraindicationPrior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. WARNINGS AND PRECAUTIONS Skin Pigmentation and Darkening of Pre-Existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred because of its pharmacologic effect. Full body skin examinations prior to initiation and periodically during treatment should be conducted to monitor pre-existing and new pigmentary lesions. Heart rate and blood pressure monitoring: In Europe, heart rate and blood pressure should be monitored as part of standard clinical practice at each medical visit (at least every 6 months) for patients treated with setmelanotide. Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Patients who have an erection lasting longer than 4 hours should seek emergency medical attention. Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Patients should be monitored for new onset or worsening depression or suicidal thoughts or behaviors. Consideration should be given to discontinuing setmelanotide if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur. Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue setmelanotide. Pediatric Population: The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated. In Europe, the prescribing physician should monitor growth (height and weight) using age- and sex-appropriate growth curves. Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs. ADVERSE REACTIONSMost common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection. USE IN SPECIFIC POPULATIONS Lactation: Not recommended when breastfeeding.To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See section 4.8 of the Summary of Product Characteristics for information on reporting suspected adverse reactions in Europe. Please see the full U.S. Prescribing Information and EU Summary of Product Characteristics for additional Important Safety Information. Forward-looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical progress, potential regulatory submissions, approvals and timing thereof of setmelanotide and other product candidates; the timing of results from our global Phase 3 trial evaluating setmelanotide in patients with acquired hypothalamic obesity; the planned new substudy to the ongoing Phase 3 trial evaluating setmelanotide in patients with acquired hypothalamic obesity that would add and evaluate patients with congenital hypothalamic obesity and the timing of enrollment for the substudy; the potential benefits of any of the Company’s products or product candidates for any specific disease indication or at any dosage, including the potential benefits of setmelanotide for patients with acquired hypothalamic obesity or congenital hypothalamic obesity, POMC, PCSK1, or LEPR variants or genetically confirmed Bardet-Biedl syndrome (BBS); expectations surrounding potential clinical trial results, regulatory submissions and approvals; our participation in upcoming events and presentations, the content thereof and the timing of any of the foregoing . Statements using words such as “expect”, “anticipate”, “believe”, “may”, “will” and similar terms are also forward-looking statements. Such statements are subject to numerous risks and uncertainties, including, but not limited to, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the impact of competition, the ability to achieve or obtain necessary regulatory approvals, risks associated with data analysis and reporting, our ability to successfully commercialize setmelanotide, our liquidity and expenses, our ability to retain our key employees and consultants, and to attract, retain and motivate qualified personnel, and general economic conditions, and the other important factors discussed under the caption “Risk Factors” in Rhythm’s Quarterly Report on Form 10-Q for the three months ended September 30, 2024 and other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise. Corporate Contact:David ConnollyHead of Investor Relations and Corporate CommunicationsRhythm Pharmaceuticals, Inc.857-264-4280dconnolly@rhythmtx.com Media Contact:Sheryl SeapyReal Chemistry(949) 903-4750sseapy@realchemistry.com