World MS Day Special: Immunic reveals new hope for progressive MS

What It Covers

Immunic Therapeutics CEO Daniel Witt joins Beyond Biotech on World MS Day to discuss IMU-838, an oral therapy targeting the NR1 nuclear receptor with potential neuroprotective effects in both relapsing and progressive MS, with phase three readouts expected by end of 2025 across 2,221 enrolled patients.

Key Questions Answered

• •IMU-838 dual mechanism: IMU-838 inhibits DHODH (the same target as approved MS drug Tecfidera) but also activates the NR1 nuclear receptor, producing direct neuroprotection beyond standard immunosuppression. Patients and clinicians should understand this distinction: existing MS drugs suppress inflammation but do not directly protect neurons from cell death, leaving progressive patients without effective options.
• •Progressive MS gap in treatment: Secondary progressive MS currently has zero approved treatments. IMU-838's NR1 activation mechanism positions it as a candidate for primary and secondary progressive MS, where neurodegeneration continues despite inflammation cooling. Patients transitioning off anti-CD20 therapies — a process taking one to two years for B-cell recovery — represent a specific high-need population.
• •Phase two CALIBR trial disability improvement signal: The CALIBR phase two study in progressive MS patients recorded a statistically significant increase in confirmed disability improvement (CDI) — meaning measurable reversal of disability, not merely slowing progression. This outcome is rare in MS trials, which typically measure worsening, and serves as the scientific rationale for the planned phase three progressive MS study.
• •Anti-CD20 therapy limitations create switching opportunity: Drugs like Ocrevus deplete B-cells effectively but cannot be used indefinitely — declining IgG levels force physicians to discontinue treatment. IMU-838's non-immunosuppressive profile and antiviral properties make it a candidate switch therapy for patients coming off B-cell depletion, addressing a structural gap in long-term MS disease management.
• •Phase three readout timeline and financing: The ENSURE-1 and ENSURE-2 trials, enrolling 2,221 relapsing MS patients combined, are expected to read out by end of 2025. Immunic raised $200 million in February 2025 (first tranche) with a potential additional $200 million tranche to fund NDA submission and commercial launch preparation, providing a defined financial runway through regulatory filing.