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]

Financial Data and Key Metrics Changes - The company is preparing for a significant data readout for its NASH drug candidate, pemidutide, expected by the end of the current quarter, which is crucial for future development plans [27][20]. - The highest dose in the MOMENTUM trial showed a weight loss of 15.6% at 48 weeks, indicating strong efficacy compared to competitors [30]. Business Line Data and Key Metrics Changes - The company is focusing on the dual mechanism of action of pemidutide, which combines weight loss with direct effects on liver health, positioning it uniquely in the market [15][18]. - The upcoming Phase 2b trial for NASH is designed to control placebo responses, which have been problematic in previous trials, aiming for a more accurate assessment of drug efficacy [12][14]. Market Data and Key Metrics Changes - NASH is now the leading cause of liver transplantation in the U.S., with a growing prevalence linked to the obesity epidemic, highlighting a significant unmet medical need [10][11]. - The company is expanding its pipeline to include Alcohol Use Disorder (AUD) and Alcoholic Liver Disease (ALD), both of which have critical unmet needs and overlap with obesity-related conditions [38][42]. Company Strategy and Development Direction - The company aims to treat serious conditions resulting from obesity rather than pursuing a pure obesity indication, which is becoming increasingly competitive and price-sensitive [36][39]. - The strategy includes leveraging a large safety database from previous trials to support the development of AUD and ALD treatments, enhancing the overall market opportunity [43][41]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming data readout and the potential for a Phase III program to start in early 2026, contingent on positive results [20][40]. - The company believes that the combination of metabolic and liver health benefits will allow it to cover a broad spectrum of patients with NASH and related conditions, improving treatment options [60][61]. Other Important Information - The company has noted that the weight loss profile of pemidutide is expected to be comparable to semaglutide at 48 weeks, with potential for even greater efficacy beyond that timeframe [24][25]. - The design of the IMPACT trial includes unique features aimed at controlling placebo responses, which could lead to more reliable results [12][14]. Q&A Session Summary Question: Can you tell us about the unmet need in NASH? - Management highlighted that there is only one approved drug for NASH with modest effects, and the condition is increasingly prevalent due to obesity, creating a significant need for more effective treatments [10][11]. Question: What are the expectations around the upcoming Phase 2b trial? - The company plans to have its end of Phase 2 meeting after the 24-week readout, focusing on the primary endpoint of biopsy results at that time [20][21]. Question: How does the company view the competitive landscape for obesity treatments? - Management indicated that the obesity market is changing, and the company is focusing on serious diseases related to obesity rather than solely on obesity itself, which is becoming a price-sensitive market [36][39]. Question: What are the key differentiators of pemidutide compared to other treatments? - The company believes that pemidutide's dual action of promoting weight loss while directly affecting liver health sets it apart from other drugs in development [15][18]. Question: What is the timeline for the AUD and ALD studies? - The AUD study has just started, and initial data readouts are expected by the end of next year, with the ALD study anticipated to begin in the third quarter [45][41].

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]

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 [22] - R&D expenses were $15.8 million for Q1 2025, down from $21.5 million in the same period of 2024 [22] - The net loss for Q1 2025 was $19.6 million, or $0.26 per share, compared to a net loss of $24.4 million, or $0.34 per share, for Q1 2024 [23] Business Line Data and Key Metrics Changes - The company is focused on the development of pemidutide, with significant R&D investments directed towards its clinical trials [8][22] - The IMPACT Phase 2b MATCH trial has enrolled 212 participants, enhancing the study's power compared to the original target [12] Market Data and Key Metrics Changes - The company is expanding into alcohol use disorder (AUD) and alcohol liver disease (ALD), both of which have significant unmet medical needs [8][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 [17] Company Strategy and Development Direction - The company aims to establish pemidutide as a foundational treatment across multiple fibrotic liver diseases, including NASH, AUD, and ALD [10][18] - The upcoming readout of the IMPACT Phase 2b MATCH trial is expected to be a transformative event for the company, with plans for Phase III trials in NASH following successful results [24] 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 [7][13] - The company anticipates 2025 to be a transformative year, with significant milestones expected in clinical development [24] Other Important Information - The company has entered into a credit facility with Hercules Capital for up to $100 million, providing flexibility to support the development of pemidutide [8][20] - The facility includes a $15 million upfront funding and additional tranches available based on milestones [21] 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 will be similar to other studies, but precise numbers cannot be disclosed yet [28] 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] 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 [38] Question: How important is weight loss in the study? - Weight loss is crucial, as it impacts the treatment of NASH patients, and the company aims to achieve clinically significant weight loss [41] Question: Will you consider taking a higher dose into Phase III? - The company is strongly considering the 2.4 mg dose for Phase III due to its expected better weight loss outcomes [49] Question: What is the expected range of placebo responses? - The company anticipates a placebo response range of 7% to 13% based on historical data and the trial's design [90] Question: Will you discuss NASH F4 cirrhosis with the FDA? - The company intends to discuss F4 with the FDA and believes it can be successful in this area [80]