The Comprehensive Impact of Lanifibranor: Addressing the Full MASH Spectrum Through Intra - and Extrahepatic Mechanisms of Action October 8, 2025 Property of Inventiva │ Forward Looking Statement This presentation contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Statements that are not historical facts, included in this presentation are forward-looking statements. Certain of these statements, forecasts and estimates ...

Core Points - Inventiva has appointed Andrew Obenshain as the new CEO, succeeding co-founder Frédéric Cren, who has led the company since its inception in 2012 [1][2][3] - The leadership transition is part of a strategic decision to support Inventiva's growth, particularly in preparing for potential commercialization in the U.S. market for metabolic dysfunction-associated steatohepatitis (MASH) [2][3] - The company is currently evaluating lanifibranor in a pivotal Phase 3 clinical trial, which is crucial for its future development and potential market entry [4] Company Overview - Inventiva is a clinical-stage biopharmaceutical company focused on developing oral therapies for MASH, a progressive chronic liver disease [4] - The company is publicly listed on Euronext Paris and Nasdaq, indicating its established presence in the financial markets [5] Leadership Insights - Andrew Obenshain brings over 20 years of experience in drug development and commercialization, having previously served as CEO of bluebird bio and held senior roles at Shire and Genzyme/Sanofi [3][4] - Frédéric Cren expressed pride in the company's transformation from a private biotech to a recognized leader in the MASH field, highlighting the achievements made under his leadership [3]

Core Points - Roche has signed a definitive merger agreement to acquire 89bio for a total equity value of approximately $2.4 billion, with a potential total deal value of up to $3.5 billion [1][2] - The acquisition includes a tender offer to purchase all outstanding shares of 89bio at $14.50 per share in cash, along with a contingent value right (CVR) that could yield payments of up to $6 per share based on specific milestones [1][2] - The deal is expected to close in Q4 2025, pending customary closing conditions and regulatory approvals [2] Company Strategy - Roche aims to strengthen its portfolio in cardiovascular, renal, and metabolic diseases through this acquisition, particularly focusing on the potential of pegozafermin as a transformative treatment for metabolic dysfunction-associated steatohepatitis (MASH) [3][4] - The lead product, pegozafermin, is a fibroblast growth factor 21 (FGF21) analogue currently in late-stage trials for MASH with advanced fibrosis, which could offer best-in-disease efficacy for moderate to severe patients [4][5] Regulatory and Advisory Details - Pegozafermin has received priority medicines (PRIME) status from the European Medicines Agency (EMA) [5] - Citi acted as the financial adviser for Roche, while Sidley Austin served as legal adviser; Moelis & Company and Centerview Partners were financial advisers for 89bio, with Gibson, Dunn & Crutcher as legal adviser [5]

Company Overview - Altimmune is focused on developing a GLP-1 glucagon dual receptor agonist for the treatment of serious liver diseases, specifically MASH [1] - The drug, named pemvidutide, is designed to have direct effects on the liver while also providing metabolic benefits [1] Mechanism of Action - Glucagon has a direct effect on the liver, while GLP-1 contributes to metabolic benefits such as weight loss [2] - The optimal approach to treating MASH involves targeting the liver directly [2]

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]