An unheralded New York–listed biotech is chasing one of neurology’s biggest goals: a pill that not only tamps down the inflammatory flares of multiple sclerosis but also directly protects the brain from the slow, steady damage that leaves many patients disabled.
Immunic Inc (NASDAQ:IMUX) is developing vidofludimus calcium, an oral medicine it says is “first-in-class” because it combines two mechanisms: one to reduce relapses and magnetic resonance imaging (MRI) lesions, and another aimed at shielding neurons from degeneration that accumulates even when flares are quiet.
“The purpose is to treat all forms of multiple sclerosis, and the unique thing about the molecule is this dual mode of action,” says chief executive Daniel Vitt.
“On the one hand, it targets inflammation via inhibition of the enzyme DHODH, which is important for treating relapses. Secondly, it has been shown to be a potent activator of a protein called Nurr1.”
“By activating Nurr1, vidofludimus calcium directly acts to protect neurons from cell death, so it is intrinsically neuroprotective. Every patient with multiple sclerosis can benefit because the goal is to slow down the worsening of physical ability by stopping neurodegeneration, which is important in both relapsing and progressive MS.”
Closer look at MS
Multiple sclerosis is typically discussed in two broad phases. In relapsing forms, patients experience attacks when the immune system mistakenly assaults the insulation around nerve fibers, producing new symptoms and fresh MRI spots.
Over time, many enter a progressive phase marked by slow worsening of movement and cognition, whether or not obvious relapses occur, a form of MS called secondary progressive MS (SPMS). This can also start right from the onset of the disease if patients suffer from primary progressive MS (PPMS).
This hidden accrual is called “smoldering” disease, or “progression independent of relapse activity”, and Immunic argues that new treatments must tackle these processes. Its pill is framed around solving those two problems.
The anti-inflammatory side comes from DHODH inhibition, a way to dial down hyperactivated immune cells that drive relapses and inflammatory brain lesions.
By selectively blocking the DHODH enzyme, vidofludimus calcium slows only the problem cells without shutting down the whole immune system. This helps reduce overshooting inflammation, MRI-detected brain lesions, and relapses.
Guardians of the nervous system
The neuroprotective side targets Nurr1, a nuclear receptor linked to nerve survival and calmer microglia; the latter is often described as the resident “gardeners” or “guardians” of the central nervous system.
Immunic’s data suggest that vidofludimus calcium binds and activates Nurr1 and “improves neuronal survival via Nurr1 activation.” The company notes that, while around 15 anti-inflammatory treatments exist for relapsing MS, none directly target the relapse-independent neurodegeneration driving disability progression.
The ambition is a once-daily pill that both prevents the short-term damage of relapses and slows the deterioration that steadily raises disability scores.
In EMPhASIS, a 268-patient Phase 2 trial in relapsing-remitting MS, vidofludimus calcium met key efficacy and safety endpoints, including strong reduction of MRI lesion activity versus placebo and a dose-dependent drop in serum neurofilament light chain, a marker of nerve injury. Safety was “similar to placebo.”
Compelling data
The company reported a 71%–78% reduction in certain lesion measures over 24 weeks and a numerical signal in preventing confirmed disability worsening during the blinded period.
To probe the progressive form, the 467-patient CALLIPER Phase 2 study enrolled patients with primary or secondary progressive MS who had evidence of ongoing disability progression and, by design, had not relapsed in the prior two years.
Vidofludimus calcium reduced the risk of 24-week confirmed disability worsening by 24% in the overall population, with a 31% risk reduction in PPMS.
“Vidofludimus calcium is able to reduce the risk of disability worsening in patients in a substantial way,” Vitt says. The company also highlighted a 34% reduction among patients without active gadolinium-enhancing lesions, a particularly hard-to-treat group.
“To our knowledge, numerically, this is the most substantial reduction in disability seen so far,” says Vitt. The trial also confirmed favorable safety and tolerability with no new signals, according to the top-line readout.
Human element
Vitt underscores the human element: “Patients are diagnosed maybe at 20 or 25, and then they need to pick a treatment. The elephant in the room is they don’t want to progress; in particular, they want to keep their independence.”
“You don’t want to end up in a wheelchair if you’re that age. Many of the currently approved drugs are good at stopping relapses but really do little or nothing on PIRA, progression independent of relapse activity.”
“The world thought that with the 15 drugs on the market for relapsing MS, we solved the problem, but we only solved 50% of it. We are going beyond that point.”
Two global Phase 3 trials, ENSURE-1 and ENSURE-2, have completed enrollment in relapsing MS, with “time to first relapse” as the primary endpoint and a pooled analysis of disability progression as a secondary endpoint.
In an interim analysis, an independent monitoring board recommended the studies continue as planned, with top-line results expected by the end of 2026.
Safe and convenient
Beyond efficacy, Immunic is leaning on convenience and safety. “This drug has been shown to be very, very safe and well tolerated in all the clinical studies conducted to date, which is also an unmet need in multiple sclerosis,” says Vitt.
Unlike certain treatments, it is a simple pill that avoids injections or infusions, while there are none of the dangerous side effects that have emerged from certain classes of drug.
So, vidofludimus calcium “has the potential to be the first and only oral disease-modifying therapy approved for both relapsing and the different forms of progressive MS, a claim that will hinge on regulatory decisions.
For patients and physicians, the appeal is clear. In today’s relapsing MS market, most drugs target inflammation; in progressive MS, options are sparse and often require infusions.
Changing the calculus
A pill that reduces relapses and slows day-to-day decline, without intensive monitoring, would change the calculus for newly diagnosed patients, those worsening despite therapy, and older patients where broad immunosuppression raises risk concerns.
The ENSURE trials are expected to read out toward the end of next year. That will be the “biggest milestone,” says chief operating officer Jason Tardio. In the meantime, the team will be engaging with regulators, including the US Food and Drug Administration and the European Medicines Agency.
“These end of Phase 2 meetings will help us better understand their perspective on our progressive MS data and, more importantly, on our potential approach forward for a Phase 3 study, most likely initially in primary progressive multiple sclerosis,” Tardio says.
“Those meetings will happen in the latter part of the year and will help to inform next steps for the program.”
From an investors’ standpoint, the prize could be substantial. Immunic estimates the fully de-risked market for vidofludimus calcium could be between $3 billion and $7 billion, firmly in blockbuster territory. Confidence was reinforced in May when the company raised $65 million in an oversubscribed funding round.
Generating value
Immunic’s decision to take vidofludimus calcium into late-stage trials itself is an ambitious, if calculated, move. However, this also gives Immunic more optionality in generating value.
Partnering both pre- and post-Phase 3 ENSURE readout are possible alternatives to continuing the launch of vidofludimus calcium in RMS after hopefully positive data towards the end of 2026.
Vitt comments: “We have a lot of discussions ongoing with pharmaceutical companies as potential partners here. But, it's a question of what is the right time from a pure value perspective.”
For a small New York–listed biotech, the ambition is outsized. If vidofludimus calcium lives up to its promise, Immunic could achieve what has long eluded neurology: a simple pill that not only reins in multiple sclerosis flares but also protects the brain from the steady damage that leaves so many patients disabled.
The MS community, investors and the wider world will no doubt be following the story with great interest.