ConversationDavid ConnollyHead of Investor Relations & Corporate Communications Good morning, everybody. Thank you for joining us today. I'm Dave Connolly, IR here at Rhythm Pharmaceuticals. Before we begin the speaking program, I'll just remind you that this event may include remarks concerning future expectations, plans and prospects, which constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important f ...

ConversationDavid ConnollyHead of Investor Relations & Corporate Communications Good morning, everybody. Thank you for joining us today. I'm Dave Connolly, IR here at Rhythm Pharmaceuticals. Before we begin the speaking program, I'll just remind you that this event may include remarks concerning future expectations, plans and prospects, which constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important ...

Rhythm Pharmaceuticals Conference Call Summary Company Overview - **Company**: Rhythm Pharmaceuticals (NasdaqGM:RYTM) - **Focus**: Development of treatments for rare diseases, specifically targeting acquired hypothalamic obesity (HO) [1][2] Industry Context - **Condition**: Acquired hypothalamic obesity (HO) is characterized by significant weight gain due to injury to the hypothalamus, often following surgeries for benign tumors like craniopharyngiomas [18][19] - **Market Need**: There are currently no approved therapies for HO, representing a significant unmet medical need [20][31] Key Points from the Call Commercial Readiness - Rhythm Pharmaceuticals is preparing for the launch of its drug, setmelanotide, with a PDUFA date set for December 20, 2023 [3][17] - The company has a solid global foundation with over 350 employees across 15 countries and availability in more than 25 countries [18] Clinical Data and Efficacy - **Phase 2 and Phase 3 Trials**: Setmelanotide has shown promising results, with a 19.8% placebo-adjusted BMI reduction in the phase 3 trial [14][24] - **Patient Response**: Nearly all patients in the trials exhibited some level of response, with 80% losing 5% or more of their body weight [25][26] - **Safety Profile**: The drug's side effects are consistent with MC4R agonist-related effects, primarily nausea and vomiting [29][30] Patient Experience and Challenges - Patients with HO face multiple medical issues, including neuroendocrine dysfunction and obesity, leading to a complex treatment landscape [20][54] - The average patient experiences significant weight gain post-injury, with some doubling their body weight within two years [60][61] - The psychological impact of HO is profound, as patients often mourn their previous active lifestyles [57][58] Regulatory and Market Strategy - Rhythm Pharmaceuticals is actively engaging with regulatory bodies to ensure timely access to treatments for patients [17][62] - The company is also conducting claims analysis and engaging with healthcare providers to better understand the epidemiology of HO, adjusting patient estimates to around 10,000 in the U.S. [32] Future Directions - The company is exploring additional therapeutic options, including oral formulations and combination therapies with GLP-1 agonists, to enhance treatment efficacy [15][28][66] - There is a strong emphasis on early diagnosis and intervention to improve patient outcomes [11][12] Additional Insights - The complexity of HO requires a multifaceted approach to treatment, including behavioral modifications and environmental restrictions [66] - The need for better diagnostic criteria for HO is highlighted, as current methods may overlook patients who gain weight rapidly post-injury [73][74] This summary encapsulates the critical aspects of the conference call, focusing on Rhythm Pharmaceuticals' strategic positioning, clinical advancements, and the broader implications for the treatment of acquired hypothalamic obesity.

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

Company Overview - Terns Pharmaceuticals is a small-cap, clinical-stage biotech company focused on developing therapies for metabolic dysfunction and obesity-related conditions, with key candidates including TERN-601 and TERN-501 [3][4][6] - TERN-601 is an oral GLP-1 candidate currently in mid-stage studies, with a 12-week phase 2 clinical trial initiated for weight loss, expecting data in the fourth quarter [3][6] Pipeline and Development - Terns Pharmaceuticals is also developing TERN-501 for metabolic dysfunction-associated steatohepatitis and as a potential combination therapy to enhance GLP-1 medicines [1] - TERN-701 is another candidate in a phase 1 study for cancer therapy, with data readout anticipated in the fourth quarter [1] Market Context - The anti-obesity market is rapidly growing, attracting significant attention from both large and small pharmaceutical companies, with the potential for substantial financial returns [5] - Oral medications like TERN-601 could address patient preferences and lower manufacturing costs compared to subcutaneous injections, which may enhance market competitiveness [2][3] Competitive Landscape - Terns Pharmaceuticals faces competition from other biotech firms developing oral GLP-1 medicines, making it crucial to deliver strong results for TERN-601 to impress the market [2][6] - The success of Terns Pharmaceuticals is heavily reliant on the progress of TERN-601, with potential stock volatility if mid-stage studies do not yield positive results [6]

Group 1 - The presentation is part of the Morgan Stanley Global Healthcare Conference, highlighting the participation of Rhythm Pharmaceuticals [1] - David Meeker, President and CEO of Rhythm Pharmaceuticals, is introduced as a key speaker [1][2]

Company Overview - Rhythm Pharmaceuticals is led by David Meeker, who serves as the President and CEO [1]. - The company is being presented at the Morgan Stanley Global Healthcare Conference, indicating its engagement with investors and the healthcare community [1]. Conference Context - The presentation is part of a larger event, the Morgan Stanley Global Healthcare Conference, which focuses on biotech and healthcare sectors [1][2]. - The introduction of David Meeker suggests a focus on sharing insights about the company's strategy and performance to an audience that may not be familiar with Rhythm Pharmaceuticals [2].

Rhythm Pharmaceuticals FY Conference Summary Company Overview - **Company**: Rhythm Pharmaceuticals (NasdaqGM:RYTM) - **Event**: FY Conference held on September 09, 2025 Key Industry Insights - **Focus on Melanocortin-4 Pathway**: The company emphasizes the significance of the melanocortin-4 (MC4) pathway in regulating satiety and energy expenditure, particularly in patients with genetic defects affecting this pathway [2][3] - **Rare Disease Market**: Rhythm Pharmaceuticals is targeting rare diseases, specifically Bardet-Biedl syndrome (BBS) and acquired hypothalamic obesity (HO), with a focus on understanding and diagnosing these conditions [3][4] Core Points and Arguments - **Bardet-Biedl Syndrome (BBS)**: - Approved in June 2022, with an estimated patient population of 4,000 to 5,000 in the U.S. - Potential revenue opportunity estimated at $300 million to $500 million based on patient uptake [8][9] - **Acquired Hypothalamic Obesity (HO)**: - Estimated patient population of 5,000 to 10,000 in the U.S., with growing confidence in these numbers due to fieldwork and claims analysis [9][10] - Japan shows a higher prevalence of HO, with an estimated 5,000 to 8,000 patients, presenting a significant growth opportunity [9][14] - **Clinical Trial Results**: - The phase 3 TRANSCEND study showed a 16% decrease in BMI in the treated group, with a placebo-adjusted effect of 19.8% [19][20] - Consistent responses across different age groups, indicating the treatment's effectiveness regardless of the time since the initial injury [21] - **Regulatory Engagement**: - Positive interactions with the FDA, with a PDUFA date set for December 2025, indicating a strong likelihood of approval [26] Additional Important Insights - **Next-Generation MC4 Receptor Agonists**: - Two new programs are in development: an oral formulation (bivamelagon) and a weekly injectable (RM-718), both designed to minimize side effects like hyperpigmentation [36][39] - The company aims to provide a comprehensive portfolio of treatment options for patients [39] - **Prader-Willi Syndrome**: - Ongoing phase 2 study with a focus on weight loss as the primary endpoint, aiming for a 5% weight loss target based on FDA guidelines [48][55] - The trial design considers the unique challenges of Prader-Willi, including behavioral aspects that may affect treatment outcomes [49][50] - **Market Dynamics**: - The company is building its sales force and increasing disease awareness among healthcare providers to support upcoming product launches [28][31] - The Japanese market is becoming increasingly accessible due to regulatory changes, enhancing the potential for quicker patient access to new treatments [14][15] Conclusion Rhythm Pharmaceuticals is strategically positioned in the rare disease market, focusing on innovative treatments for conditions linked to the melanocortin-4 pathway. The company is optimistic about its growth prospects, driven by strong clinical data, regulatory support, and expanding market opportunities in both the U.S. and Japan.

Financial Data and Key Metrics Changes - Rhythm Pharmaceuticals reported a strong year, with significant advancements in their drug development pipeline, particularly for IMCIVREE, which addresses obesity and hyperphagia [2][4] - The company has a solid patent position, with composition of matter patents expiring in 2032 and formulation patents extending to 2034 in the U.S. [4] Business Line Data and Key Metrics Changes - The company has successfully launched IMCIVREE for Bardet-Biedl syndrome (BBS) and is preparing for the launch of IMCIVREE for hypothalamic obesity (HO) [2][6] - The management expressed optimism about the potential for IMCIVREE in HO, anticipating a more gradual launch compared to BBS due to the nature of the patient population [10][12] Market Data and Key Metrics Changes - The management highlighted the difference in patient demographics between BBS and HO, noting that HO patients are more likely to be treated by endocrinologists, which could facilitate a quicker adoption of the drug [10][12] - The potential market for HO is significant, with estimates suggesting a population size of 5,000 to 10,000 patients, leaning towards the higher end of that range [15] Company Strategy and Development Direction - Rhythm Pharmaceuticals is focused on expanding its drug development pipeline, including next-generation compounds like bivamelagon and RM-718, while also exploring other genetic conditions [5][49] - The company aims to leverage its existing knowledge and experience from BBS to enhance the launch and adoption of IMCIVREE in HO [10][12] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing development of treatments for complex conditions like Prader-Willi syndrome, despite the challenges associated with the patient population [8][34] - The company is optimistic about the future of its drug pipeline, particularly in the context of addressing unmet medical needs in rare diseases [6][58] Other Important Information - The management is actively engaging with payers to ensure smooth reimbursement processes for IMCIVREE, building on the positive experiences from BBS [26][27] - There is a focus on understanding the complexities of patient backgrounds in ongoing trials, particularly for Prader-Willi syndrome, to ensure effective treatment outcomes [44][45] Q&A Session Summary Question: What is the trajectory of the launch for IMCIVREE in HO compared to other indications? - Management indicated that the launch for HO may be more gradual than for BBS, but the overall opportunity remains significant due to the concentrated patient population [10][12] Question: Are there any label considerations for IMCIVREE in HO? - Management noted that including hyperphagia in the label is critical for differentiating the drug, especially for Medicare coverage [21][22] Question: How is the company preparing for the upcoming analyst day? - The company plans to share insights from experts and provide updates on patient numbers and market potential for HO [31][32] Question: What are the challenges faced in the Prader-Willi trials? - Management acknowledged the complexity of the Prader-Willi patient population and the need for a robust study design to capture the drug's efficacy [34][36] Question: How does the company view the potential of next-generation compounds? - Management expressed a commitment to advancing both bivamelagon and RM-718, with plans to initiate phase 3 trials as soon as possible [49][50]

Financial Data and Key Metrics Changes - Rhythm Pharmaceuticals reported a strong year, emphasizing the positive developments in their science and biology over the past 12 months [2] - The company highlighted the importance of their formulation patents, which extend to 2034 in the U.S., providing a competitive edge [4] Business Line Data and Key Metrics Changes - The approval of IMCIVREE for Bardet-Biedl syndrome (BBS) in June 2022 has created a profitable business opportunity, with expectations of steady revenue from this ultra-rare disease [3] - The company is optimistic about the launch of IMCIVREE for hypothalamic obesity (HO), anticipating a more rapid uptake compared to BBS due to the concentration of patients with endocrinologists [8][11] Market Data and Key Metrics Changes - The management noted that the HO patient population is expected to be larger than initially estimated, with growing confidence in the higher end of the prevalence range [13][31] - The competitive landscape for Prader-Willi syndrome is highlighted, with the recent approval of DCCR creating a well-organized patient community eager for effective treatments [10][11] Company Strategy and Development Direction - Rhythm Pharmaceuticals plans to continue executing on current business lines while exploring new genetic opportunities and other avenues for drug development [6][48] - The company is focused on developing next-generation drugs, including bivamelagon and RM-718, with plans to enter phase 3 trials for HO as soon as possible [46][47] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the future, emphasizing the need to educate and energize the medical community around HO treatment options [9][12] - The company is aware of the challenges in developing drugs for complex conditions like Prader-Willi syndrome but remains committed to pursuing these opportunities [7][32] Other Important Information - The management is actively working on pre-commercial activities with payers, indicating a smooth interaction thus far with no anticipated pushback [25][26] - The company is also exploring the potential for new treatment centers for HO, similar to existing centers for other rare diseases [15][16] Q&A Session Summary Question: What is the expected trajectory for the launch of IMCIVREE for HO? - Management anticipates a more gradual launch compared to BBS but believes the overall opportunity is significant due to the concentration of patients with endocrinologists [8][11] Question: Are there any label considerations for the HO approval? - Management is hopeful to include hyperphagia in the indication statement, which could enhance the drug's marketability, especially with Medicare considerations [19][20] Question: How is the company preparing for the upcoming analyst day? - The company plans to share insights from experts and provide updates on patient numbers and market dynamics for HO [30][31] Question: What are the challenges faced in the Prader-Willi trials? - Management acknowledged the complexity of the Prader-Willi population and the need for a robust development plan to address these challenges [32][41] Question: How does the company view the competitive landscape for hyperphagia treatments? - Management believes that while there are multiple companies pursuing hyperphagia treatments, their focus will remain on weight loss as the primary endpoint [44]