Summary of Immunic Conference Call Company Overview - **Company**: Immunic - **Key Product**: Vidofludimus calcium, a drug in development for treating multiple sclerosis (MS) Industry Context - **Market**: Multiple Sclerosis (MS) treatment landscape, which includes various therapies with differing safety and efficacy profiles Key Points 2026 Outlook - 2026 is expected to be transformative for Immunic with the phase 3 readout of ENSURE-1 and ENSURE-2 studies planned for the end of the year [1] - NDA submission for vidofludimus calcium is planned for the following year [1] Drug Mechanism and Safety Profile - Vidofludimus calcium is designed as a safer and more selective DHODH inhibitor compared to Aubagio, avoiding off-target activities that lead to side effects [3][4] - The drug activates the nuclear receptor Nurr1, providing neuroprotective effects and solid anti-inflammatory activity [3][7] - Safety data indicates that vidofludimus calcium has a favorable liver toxicity profile compared to teriflunomide, with liver enzyme elevations comparable to placebo [10] - The elimination half-life of vidofludimus calcium is approximately 30 hours, allowing for quicker clearance compared to teriflunomide, which has a half-life of 10-19 days [11] Clinical Data and Efficacy - In the EMPhASIS study, vidofludimus calcium showed a 57% lower rate of confirmed disability progression compared to the control group [13] - The CALLIPER study indicated a 31% reduction in confirmed disability worsening in primary progressive MS (PPMS) patients [16] - The primary endpoint for upcoming studies will be time to first relapse, with secondary endpoints including confirmed disability progression and improvement [20] Market Positioning - Vidofludimus calcium aims to capture the oral medication segment, which constitutes 35%-40% of all prescriptions in the U.S. for MS [26] - The drug is positioned to address unmet needs in patients transitioning from CD20 therapies, which have serious infection risks [30] - The company believes that vidofludimus calcium will offer a best-in-class benefit-risk profile, particularly for patients preferring oral administration [27] Future Plans - A confirmatory study for PPMS is expected to start in the second half of the year, with an estimated duration of 3.5-4 years for enrollment and data readout [38] - The company anticipates significant market potential, estimating a multi-billion dollar upside for the PPMS indication [41] Conclusion - Immunic is optimistic about the upcoming data and believes that vidofludimus calcium could provide a new treatment option for individuals living with MS, addressing both relapsing and progressive forms of the disease [40][41]

Core Insights - Immunic, Inc. presented significant data on vidofludimus calcium's therapeutic potential for multiple sclerosis (MS) at the 41st Congress of ECTRIMS, highlighting its ability to improve disability outcomes in progressive MS and its neuroprotective properties [1][2][5] Clinical Development - Phase 2 CALLIPER trial data showed a statistically significant 24-week confirmed disability improvement in progressive MS, with consistent results across various subgroups, supporting the drug's neuroprotective potential [1][2][5] - Long-term data from the phase 2 EMPhASIS trial indicated high rates of patients remaining free from confirmed disability worsening, demonstrating favorable safety and tolerability over treatment durations of up to 5.5 years [1][2][5] - Top-line data from the twin phase 3 ENSURE trials in relapsing MS is expected by the end of 2026, with the potential to address a significant market need in progressive MS [1][2][5] Financial Performance - Research and Development (R&D) expenses for Q3 2025 were $20.0 million, a decrease from $21.4 million in Q3 2024, primarily due to reduced external development costs [4][6] - General and Administrative (G&A) expenses increased to $6.0 million in Q3 2025 from $4.4 million in Q3 2024, driven by higher personnel costs [9] - The net loss for Q3 2025 was approximately $25.6 million, compared to a net loss of $24.4 million in Q3 2024, reflecting an increase in weighted average common shares outstanding [9][10] Intellectual Property - The company received a Notice of Allowance from the U.S. Patent and Trademark Office for a key patent covering dose strengths of vidofludimus calcium for the treatment of progressive MS, potentially extending market exclusivity into 2041 [2][5] Market Opportunity - With only one approved therapy currently available for primary progressive MS, vidofludimus calcium presents a significant opportunity in an underserved multi-billion-dollar market [2][5]

Core Insights - Immunic, Inc. presented significant data on vidofludimus calcium at the ECTRIMS Congress, highlighting its potential to improve disability in progressive multiple sclerosis (PMS) patients [1][2] - The CALLIPER trial demonstrated a statistically significant reduction in confirmed disability worsening (24wCDW) and improvement (24wCDI) in the overall PMS population, with a notable two-fold probability over placebo [2][4] - Long-term data from the EMPhASIS trial showed high rates of patients remaining free of confirmed disability worsening, indicating favorable safety and tolerability [1][9] Group 1: CALLIPER Trial Findings - Vidofludimus calcium reduced the risk of 24wCDW by 23.8% in the overall PMS population and by 33.7% in patients without gadolinium-enhancing lesions [4][7] - The treatment demonstrated consistent trends in reducing disability progression across various outcomes and subgroups, supporting its neuroprotective potential [5][7] - The results from the CALLIPER trial were selected for the 'Best of ECTRIMS 2025' slide deck, underscoring their significance [2][10] Group 2: EMPhASIS Trial Insights - In the EMPhASIS trial, 92.3% of patients remained free of 12-week confirmed disability worsening (12wCDW) and 92.7% remained free of 24-week confirmed disability worsening (24wCDW) at week 144 [9][13] - The trial indicated low discontinuation rates and a favorable long-term safety profile, with no new safety signals observed [9][13] - Cumulative data from up to 5.5 years of treatment reinforced the drug's tolerability and safety [9][13] Group 3: Mechanism and Future Potential - Vidofludimus calcium acts as a Nurr1 activator, which may represent a novel mechanism to prevent neurodegeneration in MS [2][5] - The drug's unique dual mode of action combines neuroprotective, anti-inflammatory, and anti-viral effects, positioning it as a potential differentiated oral therapy in the multi-billion-dollar MS market [2][15] - The company is advancing vidofludimus calcium into phase 3 studies for PMS, with top-line data from ongoing trials expected by the end of 2026 [2][16]