Rhythm Pharmaceuticals Conference Call Summary Company Overview - **Company**: Rhythm Pharmaceuticals (NasdaqGM:RYTM) - **Focus**: Treatment of rare neuroendocrine disorders, specifically targeting the MC4R pathway - **Key Product**: IMCIVREE (setmelanotide), the first approved agonist of the MC4R pathway, with three current indications and a fourth pending approval for hypothalamic obesity (HO) on March 20, 2026 [2][3] Core Points and Arguments Product and Pipeline - IMCIVREE is approved for three indications, with a significant upcoming indication for hypothalamic obesity [2] - Recent interim phase 2 data in Prader-Willi syndrome shows promise [3] - Two additional pipeline compounds: - Bivamelagon (oral small molecule MC4R agonist) - RM-718 (weekly injectable therapy) [3] Market Dynamics - **Sales Growth**: - $57 million in sales reported last quarter, with a 9% quarter-over-quarter growth for the bulk of the previous year [9] - 10% growth in reimbursed patients and a 7% increase in BBS prescriptions in Q4 [9] - **Patient Population**: - Targeting approximately 1,000 patients in the U.S. for BBS, with a potential peak sales opportunity of $300 million [12] - For HO, estimates suggest upwards of 10,000 patients in the U.S., indicating a larger market potential compared to BBS [13] Clinical Data - HO study showed a 16.5% reduction in BMI for patients on setmelanotide, with a placebo-adjusted difference of 19.8% at 52 weeks [20] - High response rates: 80% of patients had more than a 5% BMI reduction, and 60% had more than a 10% reduction [20] Commercial Strategy - Increased sales force from 16 to 42 representatives in anticipation of the HO PDUFA date [22] - Utilization of claims data to identify potential HO patients, with 2,000 suspected or diagnosed patients identified in targeted physician practices [24] - Challenges include physician awareness and the reimbursement process, particularly for Medicare patients [30] Regulatory and Development Updates - Delay in PDUFA due to additional analysis requested by the FDA regarding BMI Z scores for patients under 18 [36] - Ongoing studies in Prader-Willi syndrome, with interim data showing positive results for patients on setmelanotide [44] Other Important Considerations - The company is navigating the complexities of physician education regarding hypothalamic obesity, which is not widely understood among endocrinologists [26] - The potential impact of Medicare reimbursement policies on the launch trajectory for HO treatment [30] - Cash runway of approximately $418 million, providing at least 24 months of operational funding [51] This summary encapsulates the key insights from the Rhythm Pharmaceuticals conference call, highlighting the company's strategic focus, market opportunities, clinical data, and regulatory challenges.

Core Insights - Rhythm Pharmaceuticals has experienced significant growth, outperforming major companies like Google and Nvidia over the past year, with a consensus price target indicating a potential upside of around 40% [1][2] - The company operates in the biotech sector with a market capitalization of $6.8 billion, focusing on therapies for rare genetic obesity disorders rather than high-profile conditions [4] Company Overview - Rhythm Pharmaceuticals' only approved drug is Imcivree, a first-in-class melanocortin-4 receptor (MC4R) agonist, which treats obesity due to specific genetic deficiencies and Bardet-Biedl syndrome, generating sales of approximately $194 million in 2025, reflecting a year-over-year increase of about 50% [5] - The company is advancing its pipeline with plans to move its oral MC4R agonist bivamelagon into Phase 3 clinical testing in 2026, alongside another candidate, RM-718, currently in Phase 1 testing [6] Competitive Landscape - Competition for Rhythm Pharmaceuticals is limited, with Palatin Technologies being the only notable rival developing MC4R agonists, but it is significantly behind in clinical testing [7] Upcoming Catalysts - Wall Street's optimism is bolstered by multiple upcoming catalysts, particularly the anticipated FDA approval of Imcivree for treating acquired hypothalamic obesity, with a PDUFA date set for March 20, 2026 [8] - Acquired hypothalamic obesity affects an estimated 10,000 patients in the U.S., with additional patient populations in Europe and Japan, representing a market opportunity that is at least 3.7 times larger than the current approved indications for Imcivree [9]

Core Viewpoint - Rhythm Pharmaceuticals reported strong preliminary unaudited net product revenues for IMCIVREE, indicating significant growth in 2025 and outlining future milestones for product development and regulatory approvals [2][3][6]. Financial Performance - Preliminary unaudited net product revenues for Q4 2025 are expected to be approximately $57 million, reflecting an 11% increase from Q3 2025 [3][6]. - Full-year 2025 net product revenues are projected to be around $194 million, a 50% increase compared to $130 million in 2024 [3][6]. - U.S. sales contributed approximately 68% of Q4 revenues and about 69% of full-year revenues for 2025 [3][6]. Upcoming Milestones - The company plans to launch IMCIVREE for acquired hypothalamic obesity in the U.S. pending FDA approval, with a PDUFA goal date set for March 20, 2026 [7]. - Top-line data from the Japanese cohort of the Phase 3 trial in acquired hypothalamic obesity is expected in Q1 2026 [6][8]. - Top-line data from the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases is also anticipated in Q1 2026 [6][8]. Product Development - Rhythm is advancing setmelanotide for Prader-Willi syndrome, with positive preliminary data from a Phase 2 trial showing reductions in BMI and hyperphagia [9]. - The company plans to initiate a pivotal Phase 3 trial for bivamelagon in acquired hypothalamic obesity in 2026, pending feedback from regulatory agencies [10]. - Enrollment in the Phase 1 trial for RM-718 is expected to be completed in Q1 2026 [11].

Core Viewpoint - Rhythm Pharmaceuticals is set to disclose preliminary data from its exploratory Phase 2 trial of setmelanotide in patients with Prader-Willi syndrome (PWS) during a live conference call on December 11, 2025 [1] Company Overview - Rhythm Pharmaceuticals is a commercial-stage biopharmaceutical company focused on 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 syndromes [4][5] - Setmelanotide is also authorized by the European Commission and the UK's Medicines & Healthcare Products Regulatory Agency for similar indications [4][6] - Rhythm is advancing a clinical development program for setmelanotide in other rare diseases and is exploring investigational MC4R agonists and small molecules for congenital hyperinsulinism [4] Conference Call Details - The live conference call and webcast will take place at 8:00 a.m. ET on December 11, 2025, with participants encouraged to join ten minutes early [2] - A webcast of the call will be available on the Rhythm Pharmaceuticals website and archived for 30 days [3] Indications and Usage - In the U.S., setmelanotide is indicated for patients with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS), POMC, PCSK1, or LEPR deficiency [5] - In the EU and UK, it is indicated for obesity and hunger control associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1 and LEPR deficiencies [6] Limitations and Contraindications - Setmelanotide is not indicated for patients with benign or likely benign variants of POMC, PCSK1, or LEPR deficiency, nor for other types of obesity unrelated to these conditions [7][8] Warnings and Precautions - Adverse reactions include skin hyperpigmentation, sexual arousal disturbances, and potential for depression and suicidal ideation [9][10][11] - Serious hypersensitivity reactions have been reported, necessitating caution in prescribing [12] Adverse Reactions - Common adverse reactions (≥20% incidence) include skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection [15]

Rhythm Pharmaceuticals FY Conference Summary Company Overview - **Company**: Rhythm Pharmaceuticals (NasdaqGM:RYTM) - **Event**: FY Conference on November 12, 2025 Key Industry Insights - **Focus on Obesity Treatment**: Rhythm Pharmaceuticals is targeting the MC4 axis for treating various forms of obesity, including genetic and hypothalamic obesity [1][2][3] - **Biological Mechanism**: The MC4 pathway in the hypothalamus regulates satiety and energy expenditure. Disruptions in this pathway can lead to severe obesity [2][3] - **Research Expansion**: The company is exploring additional genetic defects beyond the classic POMC and leptin receptor defects, with a focus on a new M&A trial involving four different genes [3][4] Regulatory Updates - **PDUFA Date Extension**: The FDA extended the PDUFA date for Rhythm's drug by three months due to a major amendment request, which was triggered by new data submissions [6][8][9] - **Commercial Implications**: The delay may provide additional preparation time for the commercial launch of setmelanotide, particularly in the AHO (Adiposity Hyperphagia Obesity) setting [11][12] Market Dynamics - **Patient Population**: The estimated patient population for AHO has increased to approximately 10,000, with ongoing efforts to identify and confirm patients through literature and claims analyses [21][24] - **Comparison with Other Rare Diseases**: The launch dynamics for AHO are expected to differ from Bardet-Biedl syndrome (BBS) and Prader-Willi syndrome (PWS), with AHO having a higher rate of diagnosis but still presenting challenges in patient access and awareness [12][19][20] Competitive Landscape - **Differentiation from GLP-1s**: Rhythm's approach focuses on hormonal replacement via setmelanotide, contrasting with GLP-1s, which trigger weight loss indirectly. Clinical trials indicate that setmelanotide may provide a more significant weight loss response in AHO patients compared to GLP-1s [25][26][27] Future Developments - **Next-Generation Assets**: Rhythm is developing new compounds, including 718, which is designed to be more potent and specific than bivamelagon. The company aims to complete enrollment for the open-label study by Q1 2026 [40][42] Conclusion - **Outlook**: Rhythm Pharmaceuticals is positioned for a promising future with its focus on the MC4 pathway and the upcoming launch of setmelanotide. The company is actively preparing for market entry while navigating regulatory challenges and expanding its understanding of the patient population [45][46]

Financial Data and Key Metrics Changes - Rhythm Pharmaceuticals reported global revenue of $51.3 million for Q3 2025, a sequential increase of 6% from $48.5 million in Q2 2025 [28] - The number of patients on reimbursed therapy increased by 10% globally during the quarter [29] - Year-over-year, net product revenues increased by $18 million, or 54%, compared to Q3 2024 [31] Business Line Data and Key Metrics Changes - Imcivree sales reached $51.3 million, driven predominantly by Bardet-Biedl Syndrome (BBS), with a 10% increase in the number of patients on reimbursed therapy [5][29] - In the U.S., $38.2 million (74% of Q3 net revenue) was generated, while $13.1 million (26% of total revenue) came from international markets [29] - The proportion of prescriptions for pediatric versus adult patients began to normalize, with 50% of new patients being adults, 22% adolescents, and 28% pediatrics [16] Market Data and Key Metrics Changes - The company has established Imcivree in over 25 countries outside the U.S. for BBS and/or POMC lipid deficiencies, with continued growth in patient numbers [22] - In France, an agreement was reached for reimbursement pricing for Imcivree, reflecting the therapeutic benefit for patients [22] - The estimated prevalence of acquired hypothalamic obesity (HO) in Europe is approximately 10,000 patients, making it a significant market opportunity [25] Company Strategy and Development Direction - The company is preparing for the launch of Imcivree in acquired hypothalamic obesity, pending FDA approval, with a PDUFA date set for December 20, 2025 [11][21] - Rhythm is focused on engaging with physicians and educating payers to secure access and support for patients long-term once treatment begins [19] - The company aims to complete enrollment of the RM-718 weekly phase II study in HO patients during Q1 2026 and initiate a phase III study with bivamelagon next year [13][14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming launch of Imcivree for HO, highlighting the strong foundation built from the BBS launch [15][21] - The regulatory dialogue with the FDA and EMA has been productive, keeping the company on track for the upcoming approvals [6][11] - Management noted the importance of understanding the unique needs of patients and their providers as they prepare for the launch [21] Other Important Information - The company raised approximately $189 million in net proceeds from a follow-on equity offering, strengthening its balance sheet [27] - R&D expenses for Q3 were $46 million, up from $37.9 million in the same quarter last year, primarily due to increased CMC work and headcount [32] - SG&A expenses increased to $52.4 million for Q3 2025, reflecting costs associated with the upcoming launch in acquired hypothalamic obesity [32] Q&A Session Summary Question: Can you share your latest thinking on the trial design for your phase III HO study? - Management indicated that the HO trial will be a double-blind randomized controlled trial, with expectations for a full year of data [38][39] Question: Can you provide more details on the efficacy endpoints for Prader-Willi syndrome? - Management stated that success will be defined by a BMI percent change, with a focus on individual patient data rather than mean numbers [42][43] Question: What are the drivers behind the changes to the ongoing Prader-Willi trial? - Management explained that the trial was updated to allow patients to continue beyond the initial six months if they wish, and discussions about adding sites are ongoing [48][49] Question: Any updates on conversations with payers regarding the HO launch? - Management expressed optimism based on feedback from payers and indicated that they will work through the reimbursement process even if specific policies are not in place at the time of approval [52][53] Question: How should investors think about the launch curve in hypothalamic obesity? - Management highlighted the solid groundwork laid from the BBS launch and noted that while there are challenges in diagnosis, they are confident in their execution capabilities [56][58] Question: Will the initial data for Prader-Willi lead to a go/no-go decision for phase III? - Management indicated that all options are on the table, and they may decide based on the strength of the initial data [78][79] Question: How do you expect the German observational study findings to impact prescribing decisions? - Management noted that the study showed significant improvements in liver function, raising the possibility of broader implications for other indications [83][84]

Financial Data and Key Metrics Changes - Rhythm Pharmaceuticals reported global revenue of $51.3 million for Q3 2025, a sequential increase of 6% from $48.5 million in Q2 2025 [28] - The number of patients on reimbursed therapy increased by 10% globally during the quarter [29] - Year-over-year, net product revenues increased by $18 million, or 54%, compared to Q3 2024 [31] Business Line Data and Key Metrics Changes - InSibiri sales reached $51.3 million, driven predominantly by Bardet-Biedl syndrome (BBS), with a 10% increase in the number of patients on reimbursed therapy [5][29] - The U.S. generated $38.2 million (74% of total revenue), while international revenue accounted for $13.1 million (26% of total revenue) [29] - The proportion of prescriptions for pediatric versus adult patients began to normalize, with 50% of new patients being adults, 22% adolescents, and 28% pediatrics [16] Market Data and Key Metrics Changes - Rhythm's international business saw continued success, with InSibiri now available in over 25 countries outside the U.S. [22] - The company reached an agreement with the French Economic Committee for Health Products on reimbursement pricing for InSibiri for BBS and POMC lipid deficiencies [22] - The estimated prevalence of acquired hypothalamic obesity (HO) in Europe is approximately 10,000 patients, making it a significant market opportunity [25] Company Strategy and Development Direction - The company is preparing for the launch of InSibiri in acquired hypothalamic obesity, pending FDA approval, with a PDUFA date set for December 20, 2025 [11][21] - Rhythm aims to establish InSibiri as a foundational treatment for acquired HO and educate payers to secure long-term access for patients [17][19] - The company plans to initiate a phase three study with Bivamelagon and acquired HO next year, with further timing defined after regulatory feedback [14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming launch of InSibiri for acquired HO, highlighting strong engagement with physicians and payers [11][21] - The regulatory dialogue has been productive, with both the FDA and EMA accepting regulatory filings for HO [6] - Management noted that the company is well-positioned for sustained long-term growth, supported by a strong balance sheet and upcoming data readouts [5][28] Other Important Information - Rhythm raised approximately $189 million in net proceeds from a follow-on equity offering completed in July 2025 [27] - The company ended Q3 2025 with $416.1 million in cash, providing at least 24 months of operational runway [28][33] - R&D expenses for Q3 were $46 million, while SG&A expenses were $52.4 million, reflecting increased costs associated with the upcoming launch [32][33] Q&A Session Summary Question: Can you share your latest thinking on the trial design for your phase three HO study? - Management indicated that the HO trial will be a double-blind randomized controlled trial, with expectations for a full year of data [39] Question: Can you give us more insight into the efficacy endpoints for Prader-Willi syndrome? - Management stated that success will be defined by a BMI % change, with a target of a 5% threshold in BMI decrease over 52 weeks [42][45] Question: Can you discuss the drivers behind the changes to the ongoing Prader-Willi trial? - Management explained that the trial was updated to allow patients to continue beyond the initial six months if they wish, and discussions about adding sites were precautionary [49] Question: Any updates on conversations with payers regarding the HO launch? - Management expressed optimism based on feedback from payers and indicated that they would work through the reimbursement process even if specific policies are not in place at the time of prescription [52][66] Question: How should investors think about the launch curve in hypothalamic obesity? - Management noted that while they are confident in execution, the ramp-up may take time due to the need for patient diagnosis and education [56][59]

Financial Performance & Guidance - Rhythm Pharmaceuticals reported Q3 2025 product revenue of $51.3 million, compared to $33.3 million in Q3 2024[51] - The company experienced a 10% quarter-over-quarter growth in patients on reimbursed therapy globally[49] - Q3 2025 operating expenses totaled $98.5 million, including $18.8 million in stock-based compensation expense[52] - Rhythm anticipates non-GAAP operating expenses for 2025 to be between $295 million and $315 million, including R&D expenses of $150 million to $165 million and SG&A expenses of $145 million to $150 million[52] - As of September 30, 2025, Rhythm Pharmaceuticals held $416.1 million in cash, cash equivalents, and short-term investments[51] IMCIVREE & Pipeline Updates - Steady growth in global IMCIVREE sales in Q3 2025 was primarily driven by Bardet-Biedl syndrome (BBS)[10] - The FDA accepted the sNDA for setmelanotide in acquired hypothalamic obesity (HO) for Priority Review, with a PDUFA goal date of December 20, 2025[10] - A German investigator-led study showed that over 80% of BBS patients on setmelanotide exhibited either resolution of MASLD or stabilization at grade S1 after six months of therapy[12] - The same study showed 100% of patients (N=26) with both BBS and metabolic dysfunction-associated steatotic liver disease (MASLD) showed improvement[12] Strategic Initiatives & Market Access - Rhythm Pharmaceuticals estimates the U S prevalence of acquired hypothalamic obesity to be approximately 10,000 patients[15] - IMCIVREE is available in >25 countries outside the United States[36] - Rhythm estimates the European prevalence of acquired hypothalamic obesity to be approximately 10,000 patients[40] - Rhythm estimates the prevalence of acquired hypothalamic obesity in Japan to be approximately 5,000 to 8,000[43]

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.

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]