Immunic (NASDAQ:IMUX) executives outlined their multiple sclerosis (MS) development strategy and commercial thinking for vidofludimus calcium during a session at the Leerink Partners Global Healthcare Conference, emphasizing what they described as a differentiated mechanism that combines anti-inflammatory effects with potential neuroprotection.
Dual mechanism highlighted: Nurr1 activation and DHODH inhibition
CEO Daniel Vitt said what matters most to patients with MS is neuroprotection, because patients “are afraid of progression.” He described vidofludimus calcium as activating Nurr1, a nuclear receptor he said is “directly involved in neuroprotection,” while also inhibiting DHODH, an “established anti-inflammatory mechanism in multiple sclerosis.”
Phase II data review: EMPhASIS in relapsing MS
Vitt and COO/Chief Commercial Officer Jason Tardio discussed Immunic’s Phase II EMPhASIS trial in MS, which Vitt called “very successful.” He said the study confirmed anti-inflammatory activity using MRI-based endpoints, citing p-values of less than 0.0001 and 0.0002 on suppression of inflammatory lesions.
Vitt cited the following MRI reductions:
- 76% reduction in cumulative active lesions
- 78% reduction in gadolinium-enhancing lesions
He said these effects were seen with both 30 mg and 45 mg doses, and that the company selected 30 mg for Phase III relapsing MS (RMS) studies. A 10 mg dose showed “borderline activity,” according to Vitt.
Management also pointed to biomarker and disability-related signals. Vitt said the company observed dose-dependent reductions in neurofilament light chain (NfL), and “a numerical reduction of disability progression” measured by confirmed disability worsening (CDW) of more than 50% in the small Phase II study over a half-year treatment period.
Tardio added that Immunic saw a 20% reduction in serum NfL at the 30 mg dose and a 26% reduction at the 45 mg dose, and noted that serum NfL reduction is correlated with future disability progression in MS.
On safety and tolerability, Vitt and Tardio said the profile appeared comparable to placebo in EMPhASIS. Tardio contrasted this with side effects seen with Aubagio/teriflunomide—citing GI toxicity, alopecia (around 15% in that product), and liver enzyme elevations—and said Immunic has not seen those signals to date. He added that liver enzyme changes (ALT/AST) were comparable to placebo in the company’s data so far, while cautioning that “you never know what the FDA is gonna do.”
Phase III RMS program: twin ENSURE studies and timing
Vitt said Immunic initiated two identical Phase III “twin” trials—ENSURE—in 2021 in relapsing MS. He said the program enrolled 1,100 patients and has been fully enrolled since mid-2024. The primary endpoint is time to first relapse, while secondary endpoints include MRI measures, NfL, and disability progression.
Vitt said an interim futility analysis was conducted in late 2024 when about half of events had occurred. The independent data monitoring committee (IDMC) was unblinded and advised that the trial was not futile and recommended continuing “as planned,” without increasing study size under three potential upsizing scenarios the company had contemplated.
Management said both Phase III studies are expected to read out by the end of this year. Vitt said the statistical assumptions included 90% power and a hazard ratio effect size of 0.67 for time to first relapse.
Commercial view: oral segment and sequencing off anti-CD20s
On market opportunity, Tardio argued that RMS remains “not solved for,” citing the need to address disability accumulation biology and to offer safer, better tolerated therapies. He said Immunic is focused on two segments in RMS:
- Oral therapies: Tardio said oral drugs represent about 35%–40% of total MS prescriptions, and he characterized current oral options as having safety trade-offs. He said Immunic believes it can offer a better benefit-risk profile.
- Patients sequencing off anti-CD20 therapies: Tardio said anti-CD20s carry serious infection warnings, and he estimated that 5%–10% of U.S. patients need to discontinue and sequence off these therapies annually due to serious infections. He said B-cell repletion can take roughly two years after stopping, limiting use of immunosuppressive therapies during that period. He described vidofludimus calcium as an immunomodulator (not immunosuppressant), neuroprotective via Nurr1, and “antiviral” via DHODH inhibition, positioning it as a potential option for those patients.
Tardio said that segment alone could represent a $1 billion opportunity in the U.S. and described a “multi-billion-dollar opportunity” in RMS overall. On pricing, he said it is “way too early” for Immunic to discuss specifics, but noted that the average wholesale acquisition cost (WAC) of branded oral MS therapies is about $110,000 in the U.S., with typical annual price increases of around 5%, implying the class could be $120,000–$125,000 WAC by the time of launch.
Progressive MS: CALLIPER data and plans for a PPMS Phase III
Vitt and Tardio also focused on progressive disease, which they called a major unmet need. Vitt said primary progressive MS (PPMS) typically lacks relapses and often shows limited active inflammatory lesions, estimating about 15% of patients have such lesions. He noted that only one therapy is approved for PPMS—Ocrevus—adding that benefit in that setting appears linked to inflammation and younger age based on details from ORATORIO discussed during the session.
Vitt described Immunic’s Phase II CALLIPER study in progressive MS, which enrolled PPMS and non-active secondary progressive MS (SPMS) patients, and reported a reduction of confirmed disability progression: 24% overall and 31% in the PPMS subgroup (based on 130 PPMS patients). He said that when excluding patients with baseline gadolinium lesions, the PPMS reduction increased from 31% to 34%, and non-active SPMS improved from 20% to 30%.
Vitt also said the company observed statistically significant confirmed disability improvement (CDI), citing a hazard ratio of 2.44, which he described as a 2.4 times higher likelihood of CDI versus placebo.
Looking ahead, Vitt said Immunic plans to start a pivotal PPMS study, with a design he said would be similar to recent programs such as Sanofi’s tolebrutinib, using 24-week confirmed disability progression as the primary endpoint. He estimated enrollment of roughly 800 to 1,000 patients in an event-driven design, and said Immunic observed a hazard ratio of 0.7 in Phase II, which could inform planning. He estimated a study duration of about 3.5 to 4 years if assumptions hold, and said the company hopes to activate the study in the second half of this year after an IDMC meeting, noting feasibility work is underway.
Tardio framed the PPMS market as sizable, citing Roche’s public comments that about 35% of Ocrevus global sales are from PPMS; he said Ocrevus had $9 billion in global sales last year, implying over $3 billion attributable to PPMS. He argued that a tablet with a comparable safety/tolerability profile and a meaningful disability progression benefit could represent a significant commercial opportunity in the segment.
About Immunic (NASDAQ:IMUX)
Immunic, Inc is a clinical-stage biopharmaceutical company focused on developing novel oral therapies to treat chronic inflammatory and autoimmune diseases as well as certain cancers. The company’s research strategy centers on small-molecule immunology, aiming to offer targeted treatments with improved safety and tolerability profiles. By modulating key signaling pathways within the immune system, Immunic seeks to address underlying disease mechanisms and achieve durable therapeutic benefits for patients.
Immunic’s lead product candidate, vidofludimus calcium (IMU-838), is an oral selective dihydroorotate dehydrogenase (DHODH) inhibitor in Phase 2 clinical development for conditions including ulcerative colitis, Crohn’s disease and relapsing multiple sclerosis.
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