• Vertex Pharmaceuticals for rare genetic obesity diseases.
• BioMarin Pharmaceutical for genetic obesity disorders.

• IMCIVREE: A commercial-stage therapeutic for the treatment of rare genetic diseases of obesity, including pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1, leptin receptor (LEPR) deficiency obesity, Bardet-Biedl syndrome, and Alström syndrome.
• setmelanotide: A therapeutic currently in Phase II clinical trials for various genetic obesities, such as POMC or LEPR heterozygous deficiency, SH2B1 deficiency, and MC4 receptor deficiency.

• Patients diagnosed with specific rare genetic deficiencies that lead to early-onset severe obesity, including pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1, and leptin receptor (LEPR) deficiency obesity.
• Individuals with rare genetic syndromes that are associated with obesity, such as Bardet-Biedl syndrome and Alström syndrome.
• Patients with a broader range of other rare genetic obesity disorders currently under investigation, such as POMC or LEPR heterozygous deficiency obesities, steroid receptor coactivator 1 deficiency obesity, SH2B1 deficiency obesity, MC4 receptor deficiency obesity, Smith-Magenis syndrome obesity, POMC epigenetic disorders, and other MC4R disorders.

David Meeker, M.D. President and Chief Executive Officer

Dr. David Meeker was appointed President and Chief Executive Officer of Rhythm Pharmaceuticals in July 2020. Prior to joining Rhythm, he served as President and CEO of KSQ Therapeutics for approximately three years. Before KSQ, Dr. Meeker was the Executive Vice President and Head of Sanofi Genzyme, the global business unit of Sanofi focused on rare diseases, multiple sclerosis, oncology, and immunology. He joined Genzyme in 1994 as Medical Director and progressed through various leadership roles, including Chief Operating Officer and Chief Executive Officer, leading the launch of several treatments for rare genetic diseases such as Aldurazyme®, Fabrazyme®, and Myozyme®. Earlier in his career, Dr. Meeker was Director of the Pulmonary Critical Care Fellowship at the Cleveland Clinic and an Assistant Professor of Medicine at Ohio State University.

Hunter Smith Chief Financial Officer and Treasurer

Hunter Smith serves as the Chief Financial Officer and Treasurer of Rhythm Pharmaceuticals. He previously held the role of interim President and CEO of Rhythm Pharmaceuticals before Dr. Meeker's appointment. Mr. Smith's past experience includes serving as an Independent Director and Audit Chair of Aeglea Biotherapeutics Inc. through its reverse merger with Spyre Therapeutics. He also served as a Director for Genessee & Wyoming Inc. from 2015 until its acquisition by Brookfield Infrastructure Partners in December 2019. Mr. Smith is also on the Board of Directors of Vanqua Bio.

Jennifer Chien Executive Vice President, Head of North America

Jennifer Chien is the Executive Vice President, Head of North America at Rhythm Pharmaceuticals.

Yann Mazabraud Executive Vice President, Head of International

Yann Mazabraud holds the position of Executive Vice President, Head of International at Rhythm Pharmaceuticals.

Pamela Cramer Chief Human Resources Officer

Pamela Cramer is the Chief Human Resources Officer for Rhythm Pharmaceuticals.

Rhythm Pharmaceuticals (RYTM) faces several key risks, primarily stemming from its concentrated product portfolio and the inherent challenges of the biopharmaceutical industry focused on rare diseases.

Key Risks to Rhythm Pharmaceuticals (RYTM)

1. High Dependence on IMCIVREE (setmelanotide)
   Rhythm Pharmaceuticals' revenue is almost entirely reliant on its lead commercial product, IMCIVREE (setmelanotide). While IMCIVREE is a first-in-class treatment for rare genetic obesity disorders, this heavy dependence creates a significant single point of failure. Any setbacks in its commercialization, such as unexpected adverse events, intensified competition, or issues with market access and reimbursement, could severely impact the company's financial health. For instance, IMCIVREE has known side effects including depression and suicidal ideation, disturbance in sexual arousal, skin hyperpigmentation, and injection site reactions, which could affect patient acceptance and adherence. The company's near-term strategy also hinges on the upcoming FDA decision for an expanded indication of IMCIVREE for acquired hypothalamic obesity, with a Prescription Drug User Fee Act (PDUFA) goal date of March 20, 2026. A regulatory delay or rejection for this or other potential indications could lead to a sharp sell-off in the stock and deplete the company's cash runway.

2. Clinical Development and Regulatory Approval Risks for Pipeline Candidates
   Beyond IMCIVREE, Rhythm Pharmaceuticals' future growth relies on the successful development and regulatory approval of its pipeline candidates. Setmelanotide is also in Phase II clinical trials for various other indications, and the company is developing other investigational MC4R agonists like bivamelagon and RM-718, as well as preclinical small molecules for congenital hyperinsulinism. The biopharmaceutical industry inherently faces substantial risks in clinical trials, with many candidates failing to progress due to lack of efficacy or unacceptable safety profiles. Even if trials are successful, there's no guarantee of regulatory approval. For example, Rhythm is preparing parallel submissions in Japan for setmelanotide for acquired hypothalamic obesity, indicating the global nature of these regulatory challenges. Failure to advance these programs would limit future revenue streams and long-term viability.

3. Sustained High Operating Expenses and Cash Burn Rate
   Rhythm Pharmaceuticals has consistently incurred operating losses since its inception, with an accumulated deficit of $1.4 billion as of December 31, 2025. While the company has held a robust cash position (approximately $416.1 million as of September 30, 2025), its sustained high operating expenses create constant pressure on its cash runway. The company projected this capital to be sufficient to fund planned operations for at least 24 months from September 30, 2025, extending into late 2027, but this relies on consistent revenue growth and controlled spending. Continued operating losses necessitate ongoing capital infusion, which could lead to further dilutive financing for shareholders or strain existing financial resources, especially if clinical milestones are not met or IMCIVREE's revenue growth is slower than anticipated.

Rhythm Pharmaceuticals (RYTM) is positioned for significant revenue growth over the next 2-3 years, driven by the expansion of its lead product IMCIVREE (setmelanotide) into new indications and markets, as well as continued penetration in its existing approved uses. The company's pipeline development also presents future opportunities for revenue generation.

Here are 3-5 expected drivers of future revenue growth for Rhythm Pharmaceuticals:

• Expansion into Acquired Hypothalamic Obesity (HO) with IMCIVREE: The anticipated U.S. launch of IMCIVREE for acquired hypothalamic obesity, following a PDUFA goal date of March 20, 2026, is a major expected driver. Positive Phase 3 data for this indication has been reported, and analysts express confidence in its potential to significantly expand Rhythm's addressable market and accelerate revenue growth.
• Increased Patient Penetration and Utilization of IMCIVREE in Existing Approved Indications: Rhythm Pharmaceuticals continues to see consistent growth in the number of patients receiving reimbursed IMCIVREE therapy for its already approved indications, such as Bardet-Biedl Syndrome (BBS) and pro-opiomelanocortin (POMC) or leptin receptor (LEPR) deficiency obesities. This growth is further supported by an expanded label to include children as young as 2 years old in these approved indications.
• Geographic Expansion and Market Access for IMCIVREE: The company is actively pursuing international expansion for IMCIVREE. Efforts to secure reimbursement and broaden access in regions outside the U.S., including positive developments in the UK and France, and planned operational build-out in Japan, are expected to contribute to revenue growth.
• Advancement and Potential Commercialization of Pipeline Assets: Beyond the current indications and acquired hypothalamic obesity, Rhythm Pharmaceuticals has several promising pipeline candidates. This includes the ongoing Phase 3 EMANATE trial for setmelanotide in other genetically caused MC4R pathway diseases (with topline data expected in Q1 2026), the Phase 2 trial of setmelanotide in Prader-Willi Syndrome (with six-month data expected in the first half of 2026), and the development of an oral MC4R agonist, bivamelagon, which is advancing towards Phase 3. These programs represent potential new revenue streams within the next 2-3 years and beyond.

Share Issuance

• In July 2025, Rhythm Pharmaceuticals completed an upsized public offering of 2,367,647 shares of common stock at $85 per share, generating net proceeds of approximately $189.2 million.
• The company's shares outstanding have shown an increasing trend, with 0.061 billion shares outstanding in 2024, representing a 5.76% increase from 2023. This followed a 10.65% increase in 2023 from 2022, and a 5.08% increase in 2022 from 2021.

Inbound Investments

• In April 2024, Rhythm Pharmaceuticals secured $150 million in gross proceeds from the sale of Series A convertible preferred stock to existing shareholders, including Perceptive Advisors LLC and its Discovery Fund, with the transaction closing on April 15, 2024.
• This $150 million financing is intended to support the company's clinical development programs, commercial activities, and general corporate purposes, extending its cash runway into 2026.
• On September 30, 2024, Perceptive Advisors LLC significantly increased its stake in Rhythm Pharmaceuticals by acquiring an additional 1,988,631 shares at $52.39 each.

Outbound Investments

• Rhythm Pharmaceuticals has acquired Xinvento.

Capital Expenditures

• Proceeds from the $150 million preferred stock financing in April 2024, along with existing capital, were expected to fund the company's operating expenses and capital expenditure requirements into 2026.
• Increased operating expense guidance for 2026, ranging from approximately $385 million to $415 million, signals higher future investments.
• These anticipated higher investments are primarily focused on next-generation MC4R agonists, the commercial launch for acquired hypothalamic obesity, and the build-out of Japanese operations.