Core Insights - Inventiva, a clinical-stage biopharmaceutical company, announced the publication of results from the Phase 2b NATIVE clinical trial and preclinical study on lanifibranor for treating metabolic dysfunction-associated steatohepatitis (MASH) [1][10] Group 1: Clinical Trial Results - The Phase 2b NATIVE trial demonstrated that lanifibranor can reduce liver sinusoidal endothelial cell (LSEC) capillarization, which is associated with fibrosis and inflammation in patients with MASH [2][3] - CD34 staining in liver biopsies indicated a higher density in patients with MASLD or MASH compared to those without, and treatment with lanifibranor for 24 weeks resulted in a dose-dependent reduction in CD34 staining [3][6] - Histological evaluations showed that LSEC capillarization occurs early in the disease, suggesting that lanifibranor may help prevent progression to cirrhosis [6][7] Group 2: Mechanism of Action - Lanifibranor acts as a pan-PPAR agonist, targeting all three PPAR isoforms, which may contribute to its anti-fibrotic and anti-inflammatory effects [9] - Preclinical models indicated that lanifibranor not only reverses capillarization but also normalizes intrahepatic vascular resistance and portal vein pressure, outperforming single PPAR agonists [4][7] Group 3: Company Overview - Inventiva is focused on developing oral therapies for MASH and is currently evaluating lanifibranor in the pivotal Phase 3 NATiV3 clinical trial [10] - The FDA has granted Breakthrough Therapy and Fast Track designations to lanifibranor, highlighting its potential in treating MASH [9]

Efficacy Highlights - Pemvidutide demonstrated statistically significant MASH resolution without worsening of fibrosis, reaching up to 59.1% at 24 weeks[55] - Fibrosis improvement without worsening of MASH was observed in up to 34.5% of patients at 24 weeks[55] - Liver fat content was reduced by up to 62.8%[55] - Patients experienced weight loss of up to 6.2% which continued through 24 weeks without plateauing[55] Safety and Tolerability - The trial showed potentially best-in-class tolerability with a low discontinuation rate of less than 1% due to adverse events in subjects receiving pemvidutide[55] - There were no heart rate increases or differences in cardiac adverse events between the pemvidutide and placebo groups[55] Additional Benefits - Pemvidutide maintained HbA1c levels regardless of diabetes status[55] - The trial observed statistically significant improvements in non-invasive tests of fibrosis[55] - Alanine Aminotransferase (ALT) was significantly reduced in ITT Analysis, with reductions of -34.4 IU/L in the 1.2 mg group and -34.6 IU/L in the 1.8 mg group compared to -10.0 IU/L in the placebo group[40]

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]