Summary of Madrigal Pharmaceuticals (MDGL) FY Conference Call - August 12, 2025 Company Overview - **Company**: Madrigal Pharmaceuticals (MDGL) - **Product**: ResDiffera, a treatment for NASH (Non-Alcoholic Steatohepatitis) Key Industry Insights - **NASH Market**: The NASH market is expected to grow significantly, with Madrigal positioned as a leader due to its first approved drug in this space. - **Patient Population**: Approximately 245,000 patients with F4C (compensated cirrhosis) and 315,000 patients with F2F3 NASH are targeted, with a focus on deeper penetration in the F4C group due to their higher medical needs. Core Points and Arguments 1. **Patent Protection**: A new US patent extends protection until February 2045, providing a significant competitive advantage and allowing for strategic planning of future pipelines [3][17][18]. 2. **Sales Performance**: The company reported $213 million in sales for the last quarter, annualizing to over $800 million, with 80% of top targets prescribing ResDiffera [5][6]. 3. **Patient Adoption**: Over 23,000 patients are currently on therapy, indicating strong adoption and positive feedback from healthcare providers [5][6]. 4. **Clinical Efficacy**: Positive feedback from hepatologists indicates that ResDiffera is exceeding expectations in improving liver stiffness and other health metrics [9][10][11]. 5. **Commercial Strategy**: The company is focused on long-term education for providers and patients, ensuring understanding of NASH and the benefits of ResDiffera [13][14][15]. 6. **Combination Therapy**: The recent acquisition of an oral GLP-1 to combine with ResDiffera is expected to enhance efficacy by reducing liver fat and improving patient outcomes [35][36][37]. 7. **Market Positioning**: ResDiffera is positioned as a first-line therapy in EASL guidelines, with a strategic approach to launch in Germany and other European countries [49][50]. Additional Important Insights - **Real-World Data**: The company is leveraging real-world data from the US launch to inform its European strategy, aiming for a smooth rollout [51]. - **Off-Label Use**: There is some off-label use of ResDiffera in F4 patients, but the company is cautious about this until further study results are available [31][32]. - **Future Studies**: The Maestro Outcomes study is expected to provide further validation of ResDiffera's efficacy in 2027, which will be crucial for market confidence [26][30]. This summary encapsulates the key points discussed during the conference call, highlighting Madrigal Pharmaceuticals' strategic initiatives, market positioning, and the promising outlook for ResDiffera in the NASH treatment landscape.

Financial Data and Key Metrics Changes - Madrigal Pharmaceuticals reported net sales of $213 million for Q2 2025, representing a 55% increase quarter-over-quarter [13][37] - The annualized net sales for ResDiffera are now exceeding $800 million [13][37] - R&D expenses decreased to $54.1 million from $71.1 million year-over-year, primarily due to lower clinical trial costs [38] - SG&A expenses increased to $196.9 million from $105.4 million year-over-year, driven by higher commercial launch activities [38] Business Line Data and Key Metrics Changes - ResDiffera's quarterly run rate has surpassed $200 million, positioning it among the best specialty launches in the last decade [6][13] - The number of patients on ResDiffera increased to over 23,000, up from more than 17,000 at the end of Q1 2025 [13][14] - Physician penetration reached 80% among the top 6,000 target prescribers, with 60% of a broader 14,000 target prescriber base having written prescriptions by the end of Q2 [15][16] Market Data and Key Metrics Changes - The U.S. market for ResDiffera is expected to expand with the upcoming international launch in Germany, targeting approximately 370,000 diagnosed patients across Europe [26][28] - The company is preparing to expand into compensated NASH cirrhosis (F4C), which could potentially double ResDiffera's market opportunity in the U.S. [31] Company Strategy and Development Direction - Madrigal is focused on maximizing ResDiffera's value and expanding its leadership in the NASH market through geographic expansion and new indications [5][8] - The company has secured a new U.S. patent extending protection for ResDiffera until February 2045, enhancing its long-term growth potential [7][10] - A promising oral GLP-1 asset has been licensed to complement ResDiffera, with plans to enter clinical trials in the first half of next year [25][120] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strong demand for ResDiffera and the potential for continued patient growth despite upcoming competition from GLP-1 therapies [56][57] - The company anticipates that the launch of semaglutide will raise awareness and drive broader screening, ultimately benefiting ResDiffera [22][23] - Management emphasized the importance of maintaining a disciplined approach to gross-to-net dynamics, expecting it to remain within the typical range for specialty medicines [48][49] Other Important Information - Madrigal has entered into a $500 million senior secured credit facility to support its ongoing launch and business development activities [40][41] - The company is preparing for a potential launch in Europe, with a focus on Germany as the first market [26][28] Q&A Session Summary Question: Can you expand on gross-to-net and inventory dynamics? - Management noted that gross-to-net will be choppy early in the launch, with expectations for more impact from contracting in the second half of the year [45][48] Question: How do you foresee maintaining growth with GLP-1 market entry? - Management expects strong demand to continue and is actively engaging with payers to establish partnerships, while also preparing for various scenarios regarding GLP-1 pricing and access [54][58] Question: Can you provide details on the new oral GLP-1 selection process? - The selection process was systematic, focusing on favorable chemical properties and pharmacokinetics, leading to the choice of SYH-2086 as a promising candidate for combination therapy [66][68] Question: What is the competitive landscape regarding GLP-1s? - Management believes that the familiarity with GLP-1s in the market will facilitate combination use, and they are focused on leveraging ResDiffera's unique profile to maintain a competitive edge [128][130]

Financial Data and Key Metrics Changes - The launch of ResDiffera has been described as outstanding, with over 17,000 patients on the product by March 2025, compared to almost zero a year prior [6][7] - The company reported that over 80% of commercial lives were covered by payers at the six-month mark post-launch [6] - The company anticipates robust growth for 2025, with expectations for gross to net discounts typical for specialty medicines [44][45] Business Line Data and Key Metrics Changes - The company is focusing on expanding its prescriber base, with over 70% of targeted prescribers having written prescriptions for ResDiffera [9] - The company is currently at 5% penetration of the identified 315,000 diagnosed patients, indicating significant room for growth [8][9] - The management noted that the product is becoming standard of care, which is expected to facilitate further adoption [11] Market Data and Key Metrics Changes - The company sees favorable market dynamics in the NASH space, with a potential patient population that is many multiples of the diagnosed patients [8] - The anticipated approval of semaglutide is viewed as a market growth opportunity rather than a direct threat [31][32] Company Strategy and Development Direction - The company is optimistic about extending its intellectual property (IP) into the 2040s and is actively pursuing new IP to enhance its position [23][24] - The focus on lifecycle management includes ongoing trials and exploring distinct populations for potential new indications [24][26] - The company is strategically positioned to leverage its existing product while selectively pursuing business development opportunities [65][66] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the product's performance and its acceptance in the market, noting positive feedback from prescribers and patients [36][37] - The company is well-prepared for the European launch, with a strong team in place and high anticipation from the treating community [78][79] - Management believes that the competitive landscape will not hinder their growth, as they maintain a strong product profile [30][31] Other Important Information - The company has a strong balance sheet with $848 million in cash and only $115 million in debt, providing ample capacity for future initiatives [69] - The management emphasized the importance of time in building familiarity with the product among prescribers and patients [11] Q&A Session Summary Question: What are the expectations for reauthorization? - Management believes reauthorization will not be a challenge, as criteria are fair and based on physician assessments of patient stabilization or improvement [21][22] Question: How does the company plan to manage competition? - The company is focused on gross to net strategies and has begun contracting for access, anticipating competition while maintaining a long-term view [42][44] Question: What is the company's approach to business development? - The company is selectively looking for opportunities to enhance its pipeline without risking its current strong position [66][70] Question: How does the company view the upcoming European launch? - Management is optimistic about the European launch, noting that the market is better prepared than the U.S. was at launch [75][78] Question: What is the anticipated impact of MFN on pricing in Europe? - The company is optimistic that Europe will recognize innovation and is prepared to approach pricing based on unfolding information [84]

Summary of Oligos Therapeutics Conference Call Company Overview - **Company**: Oligos Therapeutics - **CEO**: Lawrence Blatt - **Focus**: Development of therapies for chronic hepatitis B (HBV) and other conditions Key Points on Pipeline and Products - **Pipeline Status**: Transitioning into Phase II studies, particularly for ALG184, a capsid assembly modulator for chronic hepatitis B treatment [2][49] - **Other Products**: - ALG184 for chronic hepatitis B [2] - ALG-nine for NASH, with completed Phase II study and ongoing outlicensing discussions [3] - Coronavirus protease inhibitor funded by external sources [3] Chronic Hepatitis B Insights - **Prevalence**: Approximately 300 million people infected globally [5] - **Current Treatments**: - Nucleoside analogs block virus replication but do not fully suppress HBV DNA, leading to disease progression [5][6] - Pegylated interferons can achieve functional cures in a subset of patients [6] - **Clinical Data**: - Study in Taiwan showed 4% of patients on nucleoside analogs developed hepatocellular carcinoma over five years [6] - Incomplete suppression of HBV DNA correlates with poor outcomes [8][10] ALG184 Mechanism and Efficacy - **Mechanism**: ALG184 blocks encapsulation of pre-genomic RNA and transport of rcDNA into the nucleus, effectively suppressing all viral markers [11] - **Clinical Trial Results**: - In a Phase 1b study, 60% of E antigen positive patients achieved HBV DNA levels below 10 international units by week 48, and 100% by week 96 [17] - E antigen negative patients also showed rapid reductions in HBV DNA [18] - **Comparison with Standard Care**: ALG184 demonstrated superior efficacy compared to Gilead's TAF and TDF in achieving undetectable HBV DNA levels [19] Safety and Regulatory Pathway - **Safety Profile**: No emergence of resistant variants or significant toxicity observed over two years of treatment [25][26] - **Regulatory Guidance**: FDA and other regulatory bodies have indicated that chronic suppression is an acceptable endpoint for approval [57][58] Market Potential - **Economic Burden**: The cumulative cost of HBV to the healthcare system is estimated at $45 billion, highlighting the need for effective treatments [45] - **Market Differentiation**: ALG184 is positioned as a once-daily oral therapy, contrasting with injectable therapies that are difficult to administer and store [41][48] - **Potential Revenue**: The U.S. market potential for ALG184 exceeds $1 billion, with significant interest from payers due to the economic burden of untreated HBV [46][48] Future Milestones - **Upcoming Studies**: Initiation of Phase II study (B Supreme) expected soon, with interim analysis planned for 2026 [49][66] - **Data Presentation**: Off-therapy data from the Phase 1b study will be presented at ASLD [50] Conclusion - **Positioning**: ALG184 is expected to replace nucleoside analogs as the standard of care for chronic HBV suppression and serve as a backbone for future functional cure therapies [37][48]

Summary of Altimmune (ALT) 2025 Conference Call Company Overview - **Company**: Altimmune, focusing on treatments for metabolic diseases, particularly NASH (Non-Alcoholic Steatohepatitis) and obesity [1][2] Key Industry Insights - **NASH and Obesity**: The company emphasizes the dual approach of treating both NASH and obesity, as a significant percentage (80-90%) of NASH patients are either obese or overweight [6][29] - **Pembutide**: A dual receptor agonist (GLP-1 and glucagon) that targets both liver health and weight loss, positioning it uniquely in the market [5][7] Core Points and Arguments - **Phase Two Data**: Anticipation for the upcoming Phase Two data readout, which is expected to demonstrate significant efficacy in treating NASH and obesity [4][26] - **Placebo Effect Management**: The company is implementing rigorous methodologies to minimize the placebo effect in trials, including a three-panel read for biopsy analysis [15][17] - **Statistical Analysis**: Plans to present data using ITT (Intention to Treat), completer analysis, and imputation methods to provide a comprehensive view of treatment efficacy [19][21] - **Endpoints**: Focus on three primary endpoints: weight loss, NASH resolution, and fibrosis improvement, with expectations of statistical significance across all [26][34] Financial Position - **Cash Reserves**: Altimmune reported $150 million in cash, sufficient to fund operations through the end of 2026, supporting the Phase Three program initiation [50][54] Future Development Plans - **Phase Three Design**: The company is preparing for a Phase Three trial that will emphasize early efficacy indicators and potentially reduce patient numbers required for NDA submissions [48][56] - **Partnership Strategy**: While open to partnerships, Altimmune is prepared to advance its NASH program independently, focusing on the serious nature of the disease rather than entering the competitive obesity market alone [54][57] Additional Indications - **Alcohol Use Disorder (AUD) and Alcohol Liver Disease (ALD)**: Altimmune is pursuing trials for AUD and ALD, which share similar pathophysiological characteristics with NASH. The market for these conditions is largely untapped, with only 2% of AUD patients currently receiving treatment [60][68] Market Opportunity - **Unmet Medical Need**: Both AUD and ALD represent significant market opportunities due to the lack of effective treatments and the high prevalence of these conditions [68][69] Conclusion - Altimmune is strategically positioned to address significant unmet needs in the metabolic disease space, with a strong focus on innovative treatment approaches and a robust financial foundation to support its development pipeline [50][68]

Summary of Akero Therapeutics (AKRO) Conference Call Company Overview - **Company**: Akero Therapeutics (AKRO) - **Focus**: Development of Afruxifirman (EFX) for the treatment of liver fibrosis and NASH (Non-Alcoholic Steatohepatitis) Key Industry Insights - **FGF21 Mechanism**: EFX operates through two mechanisms: it reduces liver fat (anti-steatotic) and acts as a direct antifibrotic by inhibiting collagen synthesis in hepatic stellate cells [3][4] - **Comparative Efficacy**: EFX has shown faster and more effective results in reducing liver fat compared to GLP-1 agents, with significant fibrosis responses observed in just 24 weeks [4][5] - **Regulatory Landscape**: The approval of Madrigal's Resifera has shifted investor confidence, demonstrating that the FDA is willing to approve drugs for NASH without requiring biopsies [9][10] Clinical Data Highlights - **Phase 2B Symmetry Study**: 39% of patients on EFX showed one or more stage improvement in fibrosis compared to 15% on placebo after 96 weeks, marking a significant breakthrough in treatment [11][12] - **Historical Context**: Prior to EFX, no agent had demonstrated statistically significant improvement in fibrosis in the NASH population, challenging the long-held belief that cirrhosis is irreversible [13][14] - **Mortality Implications**: Improvement in fibrosis could potentially extend life expectancy significantly for patients with cirrhosis, with a 50% five-year mortality rate without a transplant [15][16] Future Outlook - **Long-term Efficacy**: Data suggests that longer dosing periods enhance the efficacy of EFX, with expectations of continued improvement beyond the initial study endpoints [19][20] - **Regulatory Pathway**: Akero anticipates filing for regulatory approval in the first half of 2027, with a focus on both pre-cirrhotic and cirrhotic populations [33][34] - **Combination Therapies**: The potential for combining EFX with GLP-1 agents is promising, as both classes target different aspects of NASH pathology [40][41] Safety and Tolerability - **Safety Profile**: Rates of decompensation were low in the Symmetry study, with incidents of ascites being classified as incidental findings rather than clinical events [36][38] - **Combination Studies**: Initial studies combining EFX with GLP-1 agents showed no significant increase in gastrointestinal side effects, indicating a favorable tolerability profile [44][45] Market Considerations - **Payer Dynamics**: As treatment options expand, payers are likely to require non-invasive monitoring of patient progress, moving away from biopsy requirements [56][57] - **Market Competition**: The FGF21 class is data-driven, and the accumulation of clinical evidence will be crucial for distinguishing between competing therapies [52][53] Conclusion - **Clinical Benefit Focus**: The overarching goal for Akero is to demonstrate clear clinical benefits through ongoing studies, with a strong emphasis on both histological and clinical outcome measures [60]

Financial Data and Key Metrics Changes - The company ended Q1 2025 with $150 million in cash, cash equivalents, and short-term investments, an increase from $132 million at the end of 2024, primarily due to $35 million raised from the ATM facility [22][20] - R&D expenses for Q1 2025 were $15.8 million, down from $21.5 million in the same period of 2024, with $9.2 million specifically related to pemidutide development [22][24] - General and administrative expenses rose to $6 million from $5.3 million in Q1 2024, mainly due to increased non-cash stock compensation [23] Business Line Data and Key Metrics Changes - The company is focused on the development of pemidutide, with significant progress in the NASH program, including the upcoming readout of the IMPACT Phase 2b MATCH trial [8][12] - The trial enrolled 212 participants with biopsy-confirmed F2F3 NASH, enhancing the study's power [12] Market Data and Key Metrics Changes - The company is expanding into alcohol use disorder (AUD) and alcohol liver disease (ALD), with plans for Phase II trials in these areas [9][10] - The market research indicates that a drug like pemidutide, which reduces alcohol consumption and liver inflammation, would be well-received by patients and physicians [18] Company Strategy and Development Direction - The company aims to establish pemidutide as a foundational treatment across multiple fibrotic liver diseases, focusing on NASH, AUD, and ALD [10][19] - The strategic partnership with Hercules Capital for a $100 million credit facility is intended to support the ongoing development of pemidutide [9][20] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving the trial's key efficacy and safety objectives for pemidutide, which could become the first therapy to achieve statistical significance on NASH endpoints at 24 weeks [8][13] - The company anticipates 2025 to be a transformative year, with significant milestones expected from the IMPACT trial and the initiation of Phase II trials for AUD and ALD [19][24] Other Important Information - The company is preparing for an end-of-Phase II meeting with the FDA in Q4 2025, which will discuss the potential for accelerated approval in F4 cirrhosis [78][79] - The company has a large safety database for pemidutide, which may allow for more efficient trial designs in Phase III [73] Q&A Session Summary Question: Can you provide commentary on the distribution of F2 and F3 in the Phase 2b population? - Management indicated that the demographics of the final qualifying population are similar to other studies, but precise numbers will be presented later [28][29] Question: What is the ideal population for pemidutide post-IMPACT? - The focus is on treating NASH with obesity, as a significant percentage of NASH patients are obese, which is a key factor in the treatment strategy [30][31] Question: How are you handling study discontinuations? - Management reported satisfaction with the discontinuation rates and stated that data will be available at the time of the readout [36] Question: How important is weight loss in this study? - Weight loss is crucial, as it addresses comorbidities associated with NASH, and the company aims to achieve clinically meaningful weight loss [40][41] Question: What are the expected placebo responses for fibrosis and NASH resolution endpoints? - Management noted that placebo responses have varied historically, but they expect to control the placebo response effectively in their trial [87][88] Question: Will you discuss NASH F4 cirrhosis with the FDA? - The company intends to discuss F4 with the FDA and believes they will be successful in this area [78][79] Question: Can you confirm the cash runway with the Hercules facility? - The facility will provide $15 million upfront, with additional tranches available, potentially extending the cash runway into Q3 2026 [81][82]

Summary of Altimmune (ALT) Conference Call Company Overview - **Company**: Altimmune - **Focus**: Development of GLP-1 glucagon dual agonist, pembidutide, for multiple indications including NASH (Non-Alcoholic Steatohepatitis) and obesity [7][8] Core Points and Arguments - **Drug Mechanism**: Pembidutide leverages a dual mechanism of action targeting both the liver and weight loss, crucial for treating NASH, where 80% of patients are also obese [8][9] - **Clinical Data**: - Phase 2b data for NASH is expected soon, with a focus on liver health and weight loss [8] - Previous Phase II studies showed a 15.6% weight loss at 48 weeks and a 20% reduction in LDL cholesterol, indicating potential synergy with statins [24][25] - Class-leading liver fat reduction of 76% at 24 weeks, the highest among drugs in development for NASH [26][41] - **Safety Profile**: Over 500 subjects have been exposed to pembidutide, confirming its safety for glycemic control and cardiovascular health, with no major adverse cardiovascular events reported [22][23] - **Regulatory Engagement**: The FDA has acknowledged the safety profile and glycemic control of pembidutide, which is designed to be glucose neutral [18][22] Industry Context - **Resurgence of Glucagon**: The importance of glucagon in obesity and metabolic diseases is being recognized, with multiple companies exploring its benefits [12][14] - **Market Positioning**: Pembidutide is positioned as a comprehensive solution for NASH, combining weight loss and direct liver effects, unlike other agents that only address one aspect [62] Additional Insights - **Patient Selection and Study Design**: The IMPACT trial is designed with 190 subjects, focusing on a 1.8 mg dose compared to placebo, with a robust methodology to minimize bias in biopsy readings [27][28] - **Long-term Effects**: The combination of glucagon and weight loss is expected to yield compounding benefits over time, enhancing treatment outcomes for NASH patients [39][43] - **Future Indications**: Altimmune plans to explore pembidutide for alcohol use disorder (AUD) and alcoholic liver disease (ALD), leveraging its ability to reduce cravings and heal liver inflammation [63][64] Financial Position - **Cash Position**: At the end of 2024, Altimmune expects to have approximately $132 million, sufficient to support ongoing and upcoming milestones, including new indications [68] Upcoming Events - **Earnings Call**: A full update on data and financials is expected in the upcoming earnings call, with significant data anticipated in the second quarter [66][68]