8-K: Immunic's Vidofludimus Calcium Shows Promise in MS Trials

Immunic, Inc. announced positive data for vidofludimus calcium in progressive and relapsing-remitting multiple sclerosis at the 41st ECTRIMS Congress.

Summary

• Immunic presented key vidofludimus calcium data in an oral and four poster presentations at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) held September 24-26, 2025.
• The Phase 2 CALLIPER trial in progressive multiple sclerosis (PMS) demonstrated statistically significant 24-week confirmed disability improvement (24wCDI) with an over two-fold probability over placebo in the overall study population (Hazard Ratio (HR) 2.441, p=0.034).
• In the overall PMS population (n=467), vidofludimus calcium reduced the risk of 24-week confirmed disability worsening (24wCDW) by 23.8% versus placebo (HR 0.762).
• Among PMS patients without gadolinium-enhancing (Gd+) lesions at baseline, vidofludimus calcium reduced the risk of 24wCDW by 33.7% overall (HR 0.663).
• The increase in mean Expanded Disability Status Scale (EDSS) in the overall PMS population was reduced statistically significantly (p<0.05) at 60, 72, 84, 96, and 108 weeks, with p<0.01 at 120 weeks.
• Long-term data from the Phase 2 EMPhASIS trial in relapsing-remitting multiple sclerosis (RRMS) showed high rates of patients remaining free of 12-week (92.3%) and 24-week (92.7%) confirmed disability worsening at week 144.
• The EMPhASIS open-label extension (OLE) period demonstrated a favorable long-term safety and tolerability profile for up to 5.5 years, with an annualized discontinuation rate of approximately 6.4% and no new safety signals.
• Preclinical data supports vidofludimus calcium's Nurr1 activation as a novel mechanism to prevent neurodegeneration in MS, showing reduced T cell infiltration into the CNS and increased Nurr1 target gene expression.

Sentiment

Score: 8

Explanation: The filing presents strong positive clinical data for vidofludimus calcium in both progressive and relapsing-remitting MS, including statistically significant disability improvement and reduction in worsening, along with a favorable safety profile. This de-risks a potential Phase 3 program and positions the drug well in a high-need market.

Positives

• Statistically significant 24-week confirmed disability improvement (24wCDI) in the Phase 2 CALLIPER trial for progressive MS, showing an over two-fold probability over placebo (HR 2.441, p=0.034).
• Consistent positive signals for slowing disability progression (24wCDW) across disability endpoints, patient populations, and subgroups in the CALLIPER trial, including in patients without baseline inflammatory lesions.
• Significant reduction in the risk of 24wCDW in the overall progressive MS population (23.8%) and a more pronounced reduction in patients without Gd+ lesions (33.7%).
• Statistically significant reduction in the increase of mean EDSS at multiple time points up to 120 weeks in the CALLIPER trial.
• Long-term data from the Phase 2 EMPhASIS trial in relapsing-remitting MS showed high rates of patients remaining free of 12-week (92.3%) and 24-week (92.7%) confirmed disability worsening at week 144.
• Favorable long-term safety and tolerability profile for vidofludimus calcium, with low discontinuation rates (approximately 6.4% annualized) and no new safety signals observed over 5.5 years of treatment.
• Preclinical data supports vidofludimus calcium's Nurr1-mediated neuroprotective activity, suggesting a novel mechanism to prevent neurodegeneration in MS.
• The CALLIPER results were selected for the 'Best of ECTRIMS 2025' slide deck, highlighting their significance.

Risks

• Increasing inflation, tariffs, and macroeconomic trends could impact operations.
• The Ukraine-Russia conflict and the conflict in the Middle East may affect planned and ongoing clinical trials.
• Uncertainties exist regarding the ability to project future cash utilization and reserves needed for contingent liabilities and business operations.
• The availability of sufficient financial and other resources to meet business objectives and operational requirements is a risk.
• Results from earlier preclinical studies and clinical trials may not be predictive of future clinical trial outcomes.
• Changes to the size of the target markets for the company's products or product candidates could occur.
• Risks are associated with the protection and market exclusivity provided by Immunic's intellectual property.
• Risks related to the drug development and regulatory approval process are inherent.
• The impact of competitive products and technological changes could affect market position.

Future Outlook

Vidofludimus calcium has the potential to become a differentiated oral therapy in the multi-billion-dollar MS market due to its unique neuroprotective, anti-inflammatory, and anti-viral profile, along with clean safety and tolerability observed in clinical trials. The CALLIPER trial data supports advancing vidofludimus calcium into Phase 3 studies for progressive MS, as 24wCDW is an accepted regulatory endpoint. Top-line data for the fully enrolled twin Phase 3 ENSURE trials in relapsing multiple sclerosis (RMS) is expected by the end of 2026. The company is also developing IMU-856, targeting Sirtuin 6 (SIRT6), to restore intestinal barrier function for gastrointestinal diseases, and IMU-381, a next-generation molecule in preclinical testing for gastrointestinal diseases.

Management Comments

• "Having such a broad presence at the prestigious ECTRIMS Congress is a major achievement for Immunic and underscores both the strength of our clinical and preclinical data and the potential of vidofludimus calcium to transform the oral MS therapy landscape." Daniel Vitt, Ph.D., Chief Executive Officer of Immunic.
• "The CALLIPER results, also selected for the Best of ECTRIMS 2025 slide deck, highlight vidofludimus calcium's neuroprotective potential and its promise to slow disease progression in patients with or without focal inflammation." Daniel Vitt, Ph.D., Chief Executive Officer of Immunic.
• "We believe that, since 24wCDW is an accepted regulatory endpoint to demonstrate clinical benefit in PMS, this evidence of clinical activity merits further investigation and de-risks a potential phase 3 program." Daniel Vitt, Ph.D., Chief Executive Officer of Immunic.
• "In the phase 2 CALLIPER trial of vidofludimus calcium in progressive multiple sclerosis patients, we observed consistent trends suggesting a reduction in disability progression across multiple outcomes, patient populations, and subgroups, including those without gadolinium-enhancing lesions at baseline." Robert J. Fox, M.D., Coordinating Investigator of the CALLIPER trial.
• "These findings support the hypothesis that Nurr1 activation may represent a novel mechanism to prevent neurodegeneration in MS." Robert J. Fox, M.D.
• "Overall, the CALLIPER trial data support advancing vidofludimus calcium into phase 3 studies for PMS." Robert J. Fox, M.D.

Industry Context

The announcement positions vidofludimus calcium as a potentially transformative oral therapy in the multi-billion-dollar multiple sclerosis market, particularly addressing the high unmet medical need in progressive MS. The drug's unique dual mode of action, combining neuroprotective, anti-inflammatory, and anti-viral effects, and its novel Nurr1 activation mechanism, could differentiate it from existing treatments and contribute to slowing neurodegeneration, a critical aspect of MS progression.

Comparison to Industry Standards

• The filing highlights that 24-week confirmed disability worsening (24wCDW) is an "accepted regulatory endpoint to demonstrate clinical benefit in PMS," indicating that the positive results from the CALLIPER trial meet a recognized standard for advancing to Phase 3 studies.

Stakeholder Impact

• Shareholders: Positive impact due to strong clinical data, de-risking of future trials, and potential for a differentiated product in a large and high-need market.
• Patients (MS): Offers "much needed hope" for progressive MS patients and the potential for a new, effective, and well-tolerated oral therapy.
• Medical Community: Provides new data supporting Nurr1 activation as a novel mechanism for neuroprotection in MS, potentially influencing treatment paradigms.

Next Steps

• Advance vidofludimus calcium into Phase 3 studies for progressive multiple sclerosis, supported by the CALLIPER trial data.
• Await top-line data by the end of 2026 for the fully enrolled twin Phase 3 ENSURE trials in relapsing multiple sclerosis (RMS).
• Continue development of IMU-856, targeting Sirtuin 6 (SIRT6), for gastrointestinal diseases.
• Continue preclinical testing of IMU-381, a next-generation molecule, for gastrointestinal diseases.

Key Dates

Recommendation

The reported Phase 2 CALLIPER trial results for vidofludimus calcium in progressive multiple sclerosis are highly encouraging, demonstrating statistically significant confirmed disability improvement and a reduction in disability worsening. This, coupled with consistent positive signals across subgroups and a favorable long-term safety profile from the EMPhASIS trial, significantly de-risks the drug's path to Phase 3 and potential market approval. The drug's unique dual mechanism of action and its targeting of a high unmet medical need population in the multi-billion-dollar MS market suggest substantial commercial potential. These strong clinical outcomes warrant a "strong buy" recommendation for long-term investors.

Keywords

Immunic, IMUX, Vidofludimus Calcium, IMU-838, Multiple Sclerosis, MS, Progressive MS, Relapsing-Remitting MS, Clinical Trials, Phase 2, CALLIPER, EMPhASIS, ECTRIMS, Neuroprotection, Nurr1 Activator, DHODH Inhibitor, Biotechnology, Autoimmune Diseases, Inflammatory Diseases, Drug Development