Madrigal Pharmaceuticals (NasdaqGS:MDGL) FY Conference December 02, 2025 04:15 PM ET Company ParticipantsBill Sibold - CEOMardi Dier - CFOConference Call ParticipantsMike DiFiore - AnalystMike DiFioreLet's get started.Bill SiboldLet's get started.Mike DiFioreBut welcome, everybody. Those of you who don't know me, I'm Mike DiFiore. I'm one of the biotech analysts covering Madrigal and Evercore. But pleasure to have the management team from Madrigal here. Bill, Mardi, welcome. Thanks so much for making it dow ...

Summary of Madrigal Pharmaceuticals Conference Call Company Overview - **Company**: Madrigal Pharmaceuticals (NasdaqGS:MDGL) - **Product**: Rezdiffra, a treatment for MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease) Key Industry Insights - **Market Opportunity**: There is a significant unmet need in the MASH market, with over 20 failed attempts by the industry to find a solution before Madrigal's success with Rezdiffra [2][3] - **Patient Population**: The diagnosed patient population in the U.S. is approximately 1.5 million, with the F2 and F3 indications accounting for about 525,000 patients. The target prescriber base is narrowed down to 14,000, leading to an actionable patient population of 315,000 [6][7] - **Current Treatment Penetration**: Currently, only about 10% of the identified patient population is being treated, indicating substantial growth potential [6][7] Product and Pipeline Development - **Rezdiffra's Profile**: The product is positioned as a foundational therapy for MASH, with a once-a-day oral dosage that is effective and well-tolerated, which is considered a "holy grail" in the industry [11] - **Sales Forecast**: Initial sales in 2024 are projected to be under $200 million, but the potential market size for Rezdiffra could reach $5 billion to $10 billion as penetration increases [3][12][15] - **Intellectual Property**: Madrigal has secured intellectual property for Rezdiffra until 2045, allowing ample time for market development [3] Competitive Landscape - **Comparison with Competitors**: Madrigal's focused approach contrasts with competitors like Novo, which have multiple indications and broader product lines. Madrigal's strategy is to engage directly with specialists, enhancing their market presence [18][19] - **Market Dynamics**: The company is observing the market entry of competitors and is prepared to adapt its strategy accordingly. The focus remains on building a strong presence in the specialty market [19][20] Sales and Marketing Strategy - **Adoption Rates**: Initial adoption rates in specialty clinics are reported to be as high as 80%, attributed to effective white-glove service and support for prescribers [21][24] - **Patient Adherence**: The persistence rate for patients on Rezdiffra is reported to be around 90% at the 12-month mark, significantly higher than the industry benchmark of 60-70% for well-tolerated oral medications [24][25] - **Sales Force Strategy**: The company has built a dedicated sales force to educate and support prescribers, which is crucial for navigating the complexities of specialty drug prescriptions [22][23] Financial Projections - **Gross Unit Projections**: For 2026, Madrigal anticipates gross unit sales to be in the high 30s percentage range, with a disciplined approach to contracting with commercial payers [29][30] - **Market Mix**: The revenue mix is expected to be 50-55% from commercial payers, 30-35% from Medicare, and the remainder from Medicaid and government sources [34] Research and Development - **Ongoing Studies**: The Maestro Outcomes study is ongoing, focusing on F4 cirrhosis patients, with confidence in positive outcomes based on previous open-label trial results [45][46] - **Patient Enrollment Criteria**: The study is designed to enroll patients with specific platelet counts, differentiating it from other ongoing studies that may include less severe populations [48][49] Conclusion - **Long-term Vision**: Madrigal aims to maintain its leadership in the MASH market for decades, supported by a robust pipeline and a strong foundational product in Rezdiffra [15][16]

Core Insights - Sagimet Biosciences is advancing its clinical trials for denifanstat and TVB-3567, targeting metabolic dysfunction and acne treatment, respectively [1][2][5] Clinical Development - A Phase 1 pharmacokinetic trial for the combination of denifanstat and resmetirom is ongoing, with data readout expected in the first half of 2026 [1][11] - The trial aims to evaluate the safety, tolerability, and potential drug-drug interactions of the combination in approximately 40 healthy adult participants [5] - Sagimet has initiated a Phase 1 trial for TVB-3567, another FASN inhibitor, aimed at treating acne [2][5] Corporate Updates - Ascletis Pharma has completed its pre-New Drug Application consultation with China's NMPA for denifanstat, planning to submit an NDA for moderate-to-severe acne vulgaris treatment [1][5] - Recent promotions within the company include Marie O'Farrell as Chief Scientific Officer and Liz Rozek as Chief Legal & Administrative Officer [5] Financial Performance - As of September 30, 2025, the company reported cash, cash equivalents, and marketable securities totaling $125.5 million [11] - Research and development expenses for the third quarter of 2025 were $9.7 million, a decrease from $12.7 million in the same period of 2024 [11] - The net loss for the third quarter of 2025 was $12.9 million, compared to a net loss of $14.6 million in the third quarter of 2024 [11][17] Market Context - MASH (metabolic dysfunction associated steatohepatitis) affects over 265 million people globally, with limited approved treatments for non-cirrhotic stages [9] - The U.S. acne market includes over 50 million individuals, with a significant need for effective chronic management options [10]

Financial Data and Key Metrics Changes - Total cash as of September 30 was $211 million, representing a 60% increase from the beginning of the year [11] - R&D expenses for Q3 2025 were $15 million, down from $19.8 million in Q3 2024, primarily due to the timing of CRO development costs [12] - Net loss for Q3 2025 was $19 million or $0.21 per share, compared to a net loss of $22.8 million or $0.32 per share in Q3 2024 [13] Business Line Data and Key Metrics Changes - Direct costs related to Pemvidutide development in Q3 2025 included $9.2 million, with $3.7 million for the IMPACT phase 2b trial, $3.4 million for AUD and ALD startup costs, and $1.3 million for CMC [12] Market Data and Key Metrics Changes - Market research indicated that 70%-80% of surveyed physicians expressed a high likelihood to prescribe Pemvidutide based on its product profile [7] - Positive feedback from payers suggested broad coverage expectations across the EU for Pemvidutide [8] Company Strategy and Development Direction - The company is preparing for a scheduled end-of-phase two meeting with the FDA to review the proposed phase three MASH program [2][15] - Pemvidutide is positioned as a promising therapeutic candidate for MASH, AUD, and ALD, leveraging its dual mechanism of action [3][5] - The company aims to design a flexible phase three trial to adapt to potential regulatory changes regarding endpoints [20][21] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strength of the 24-week data supporting the upcoming discussions with the FDA [18][19] - The company anticipates continued weight loss and improvements in NITs at the 48-week mark, reinforcing the efficacy of Pemvidutide [20][35] Other Important Information - The company has raised $127 million through various capital sourcing options to support key development milestones [11] - A $400 million shelf registration and a new $200 million ATM facility were filed to enhance financial flexibility [12] Q&A Session Summary Question: Upcoming 48-week data from the phase two IMPACT trial - Management indicated that the end-of-phase two meeting with the FDA was based on the 24-week data, and the 48-week data would be submitted later [18][19] Question: Probability of using NITs or AI-based histological reading - Management noted ongoing discussions and increasing interest in NITs, with flexibility built into the phase three design to adapt to regulatory changes [25] Question: Advantages of AI-based biopsy reading - AI provides a more comprehensive evaluation of fibrosis with less variability compared to traditional histology, which is subject to human error [25][26] Question: Clinically meaningful endpoint for the RECLAIM trial - The primary endpoint for the RECLAIM trial is the number of heavy drinking days per week, with a focus on assessing changes from baseline [28][31] Question: Competitive positioning against Retatrutide - Management believes Pemvidutide's dual mechanism of action provides a competitive advantage in the MASH space compared to Retatrutide [64][65] Question: Progress on the oral formulation of Pemvidutide - The company is advancing its oral formulation program and plans to share more data as it progresses [70]

Market Overview - The MASH (Metabolic Associated Steatotic Hepatitis) space is experiencing significant growth due to recent regulatory approvals of two drugs for treatment, addressing a substantial unmet medical need [2] - The approval of Rezdiffra last year and the recent approval of sema are expected to enhance market expansion and increase diagnosis rates among MASH patients [2] Patient Impact - There are millions of MASH patients, but a large majority remain undiagnosed and untreated, indicating a critical opportunity for market growth and patient care improvement [2]

Group 1: Financial Performance - The company achieved a revenue of 713 million CNY, representing an increase of 11.02% compared to the same period last year [3] - Medical device business revenue reached approximately 482 million CNY, growing by 13.8% [3] - The net profit attributable to shareholders was approximately 74 million CNY, with a year-on-year growth of about 20.99% after excluding stock incentive expenses and exchange losses [3] Group 2: Business Operations - The company focuses on management-style medical services, primarily in the liver disease sector, including drug production, diagnostic equipment development, and related medical services [3] - Echosens has installed a total of 977 units of its products globally [3] - The company is currently collaborating with Novo Nordisk to promote early diagnosis and treatment of Metabolic Associated Steatotic Hepatitis (MASH) [3] Group 3: Market Trends and Strategies - The approval of semaglutide for MASH is expected to enhance awareness and treatment options in the industry [3] - The company has stable internal shareholding and strategic plans, indicating no adjustments to its operational strategies [4] - E-commerce channels for traditional Chinese medicine have shown significant growth, with a year-on-year increase of 59.23% [4] Group 4: Future Outlook - The company's mission is to "keep every family away from liver cancer," focusing on a closed-loop management strategy to reduce liver cancer incidence [5] - There is confidence in the industry outlook and the company's development trajectory, supported by a clear organizational and shareholding structure [5]

Core Insights - Novo Nordisk's weight loss drug Wegovy (semaglutide 2.4mg) has received FDA accelerated approval for a new indication: treatment of adults with metabolic-associated fatty liver disease (MASH) and moderate to severe liver fibrosis (F2-F3) [1][2] - This marks the first time GLP-1 has officially entered the fatty liver treatment space, highlighting its potential in addressing multiple metabolic disorders [1][7] Group 1: Market Dynamics - The approval of Wegovy for MASH has led to a significant increase in Novo Nordisk's stock price, while Madrigal Pharmaceuticals, which recently launched Rezdiffra as the first FDA-approved MASH drug in nearly 40 years, has faced substantial stock pressure [2][4] - Wegovy is viewed as a "platform drug" with broad metabolic benefits, making it more attractive to healthcare providers compared to specialized drugs like Rezdiffra, which may require combination therapies [2][3] Group 2: Diagnostic Opportunities - The approval of MASH treatments has created a pressing need for effective diagnostic tools to identify patients among the millions at risk, as MASH often presents with no symptoms in early stages [3][4] - Companies like Furuya Co., which provide non-invasive diagnostic devices like FibroScan, are positioned to benefit from the increased demand for screening tools essential for identifying high-risk patients [3][4] Group 3: Market Potential and Challenges - The global MASH patient population exceeds 250 million, with projections indicating that the MASH drug market could surpass $30 billion by 2030 [4] - Despite the market potential, the MASH field has been historically challenging for drug development, often referred to as a "graveyard" for pharmaceutical companies due to complex disease mechanisms and diagnostic difficulties [4][5] Group 4: Clinical Trial Insights - The ESSENCE trial, a pivotal study for Wegovy, demonstrated significant efficacy, with 36.8% of participants showing improvement in liver fibrosis without worsening fatty liver disease, compared to 22.4% in the placebo group [5][6] - Safety profiles for Wegovy align with previous studies in weight loss and diabetes, indicating a low discontinuation rate due to adverse events, primarily gastrointestinal [6][10] Group 5: Future Directions - The approval of MASH indications for GLP-1 drugs like Wegovy represents a strategic expansion into chronic diseases driven by obesity, aiming to consolidate treatment approaches under a unified GLP-1 framework [7][8] - The industry is shifting towards a new paradigm of "quality weight loss," focusing on preserving muscle mass while reducing fat, with potential innovations in combination therapies targeting muscle protection [8][9]

Core Insights - The FDA approval of semaglutide for treating metabolic dysfunction-associated steatotic liver disease (MASH) marks a significant milestone, potentially elevating GLP-1 drugs to a dominant position in the pharmaceutical market [1][5][6] - The MASH market is projected to reach $32.2 billion by 2030, driven by a growing patient population and significant unmet medical needs [3][6] - The entry of GLP-1 into the MASH market raises questions about its impact on existing and pipeline MASH therapies, whether it will disrupt the market or serve as a complementary treatment [7][8] Group 1: Market Potential - MASH is a large and growing market, with an estimated 351 million patients globally in 2020, expected to rise to 486 million by 2030 [3] - The approval of semaglutide is expected to accelerate the growth of the MASH market, which has been historically challenging for drug development [3][6] - The first approved MASH drug, Madrigal's Rezdiffra, achieved sales of $317 million within its first year, indicating strong market potential [6] Group 2: Clinical Evidence - In clinical trials, semaglutide demonstrated significant efficacy, with 36.8% of patients showing improvement in liver fibrosis compared to 22.4% in the placebo group [5] - The drug also showed a 62.9% rate of fatty liver disease resolution without worsening fibrosis, compared to 34.3% in the placebo group [5] Group 3: Competitive Landscape - Over 60 GLP-1 related drugs are currently in development for MASH, indicating a highly competitive environment [7] - The market dynamics may shift as companies explore combination therapies, with approximately 25% of Rezdiffra patients already using it in conjunction with GLP-1 treatments [8] - The future of the MASH market will depend on how GLP-1 drugs perform against existing therapies and whether they can coexist or dominate the market [7][8] Group 4: Future Outlook - The potential of GLP-1 drugs extends beyond MASH, with ongoing research exploring their efficacy in various conditions, including neurodegenerative diseases and metabolic disorders [10][11] - The innovation landscape in pharmaceuticals is evolving, with GLP-1 representing a significant shift that may redefine treatment paradigms across multiple therapeutic areas [11][12]

Regulatory Approval & Market Expansion - FDA approves Novo Nordisk's weight loss drug Wegovy for MASH (Metabolic dysfunction-associated steatohepatitis), a liver condition affecting an estimated 5% of the US population [2][3] - MASH indication could add almost $2 billion in peak sales for Novo Nordisk, addressing a market with limited existing treatment options [4] - Wegovy treats the underlying metabolic drivers of MASH, demonstrating benefits beyond weight loss [4] Pricing & Accessibility - Novo Nordisk will offer Ozempic, its diabetes drug, for $4.99 per month for out-of-pocket payers [5] - This pricing strategy expands the Novocare direct-to-consumer platform, which already sells Wegovy [5] - The $4.99 price point aims to compete with compounded versions of GLP-1 drugs [9] Drug Information - Ozempic and Wegovy share the same active ingredient, with Wegovy indicated for weight loss and Ozempic for diabetes [6] - While dosages may vary, the active ingredient and side effects are the same for both drugs [7][8] - Approximately 98% of people with diabetes have insurance coverage for Ozempic [8]

Core Insights - Sagimet Biosciences has made significant progress in developing therapeutics for metabolic dysfunction associated steatohepatitis (MASH) and acne, with denifanstat meeting all primary and secondary endpoints in a Phase 3 clinical trial in China [2][5] - The company has initiated a Phase 1 clinical trial for TVB-3567, a new FASN inhibitor for acne treatment in the U.S., and plans to evaluate a combination of denifanstat and resmetirom in a Phase 1 trial in late 2025 [2][11] Recent Corporate Highlights - Denifanstat's Phase 3 trial in China involved 480 patients and demonstrated a treatment success rate of 33.2% compared to 14.6% for placebo, with significant reductions in total lesion count and inflammatory lesions [5] - The Phase 1 trial for TVB-3567 is designed to assess safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy participants, including those with acne [4][11] Financial Results - As of June 30, 2025, the company reported cash and cash equivalents of $135.5 million, with research and development expenses of $7.2 million for the quarter, up from $6.3 million in the same period in 2024 [11][12] - The net loss for the three months ended June 30, 2025, was $10.4 million, compared to $8.1 million for the same period in 2024 [11][12] Industry Context - Acne affects over 50 million people annually in the U.S., and there has been limited innovation in treatment options over the past 40 years, highlighting the potential market opportunity for new therapies like denifanstat [4][14] - MASH is a progressive liver disease impacting over 115 million people globally, with only one recently approved treatment in the U.S., indicating a significant unmet medical need [13]