Immunic at H.C. Wainwright: Vidofludimus Calcium’s Promise in MS

On Monday, 08 September 2025, Immunic Inc. (NASDAQ:IMUX) presented at the H.C. Wainwright 27th Annual Global Investment Conference, showcasing its innovative approach to treating multiple sclerosis (MS). The company highlighted both the potential and challenges of its lead candidate, vidofludimus calcium, a promising oral therapy targeting both relapsing and progressive MS forms.

Key Takeaways

• Immunic is advancing vidofludimus calcium, a dual-mechanism therapy, through phase III trials for MS.
• Positive phase II results show significant reductions in MRI lesions and disability progression.
• Vidofludimus calcium could potentially capture a multi-billion dollar market in MS treatment.
• The company aims to make it the first oral disease-modifying therapy for both MS types.
• Top-line data from ongoing trials are expected by late 2026.

Operational Updates

• Phase II EMPhASIS Study: Completed with positive outcomes in relapsing-remitting MS, showing a 76% reduction in cumulative active lesions and an 80% reduction in gadolinium-enhanced lesions at 24 weeks.
• ENSURE I and ENSURE II Trials: Currently in phase III for relapsing-remitting MS, with over 1,100 patients enrolled in each. Results are anticipated by late 2026.
• CALIBRATE Study: Exploratory phase II program in progressive MS demonstrated a 24% reduction in time to 24-week confirmed disability worsening.

Future Outlook

• Immunic targets a $23 billion market with a 2-4% annual growth, focusing on both relapsing and progressive MS.
• Vidofludimus calcium aims to be the first oral therapy approved for both MS types, with a projected $1-2 billion opportunity in relapsing MS and over $2 billion in progressive MS.
• The company expects a favorable benefit-risk profile, emphasizing safety and tolerability.

Financial Results

• While specific financial results were not discussed, Immunic anticipates significant financial gains contingent on successful trial outcomes and market penetration.

For more detailed insights, readers are encouraged to refer to the full transcript below.

Full transcript - H.C. Wainwright 27th Annual Global Investment Conference:

Daniel Smith, Equity Research Associate, H.C. Wainwright: Good afternoon, everyone, and thank you for joining the 27th annual H.C. Wainwright Global Investment Conference 2025. My name is Daniel Smith, and I’m an H.C. Wainwright Equity Research Associate in Biotechnology. With that said, let me introduce our presenter for the session. I’d like to welcome Jason Tardio, President and COO of Immunic, Inc., who are developing small molecule therapies for chronic inflammatory and autoimmune diseases. Immunic trades on the NASDAQ under the ticker IMUX. Jason, the floor is yours.

Jason Tardio, President and COO, Immunic, Inc.: Thank you, Daniel, and thank you to H.C. Wainwright for having us today. I’m very fortunate to introduce to many of you Immunic, Inc., an exciting company developing small molecule therapies for a number of autoimmune and inflammatory-related conditions. Before I get started, just please consider our cautionary note regarding forward-looking statements during the course of the presentation. As I’ve mentioned, Immunic, Inc. is a clinical-stage biopharma company with a focus on developing unique small molecule therapies for individuals living with chronic inflammatory and autoimmune-related diseases. We have two products currently in clinical development. IMU-856 is a phase II-ready asset. It’s a modulator of a target called SIRT6 that aims to regenerate the gut wall and barrier function in patients suffering from gastrointestinal-related diseases. We have proof-of-concept data with that respective asset in celiac disease. In that respective data set, we actually retrospectively saw a dose-dependent increase of endogenous GLP-1.

We’ll be further developing that respective asset again in a number of GI-related conditions. The focus of the presentation today will be vidofludimus calcium. This is our phase III molecule that’s in development for relapsing forms of multiple sclerosis. Let’s get into just a quick overview of the unmet need in multiple sclerosis. MS is a chronic autoimmune condition that ultimately leads to significant physical and cognitive disability progression in individuals living with this disease. Even though there are 15+ available therapies approved today, the majority of which are only approved for the relapsing or inflammatory aspect of the disease, none of these medicines are stopping this chronic accumulation of disability. That’s for good reason. We know that multiple sclerosis is a disease of both neuroinflammation and neurodegeneration.

The 15+ medicines available today are only addressing this inflammatory cascade of the disease that’s highlighted in the light blue on this schematic. Within neuroinflammatory disease, patients have relapses. Sometimes they fully recover from those relapses, oftentimes, they don’t. Over time, they get accumulation of disability that’s linked to relapses or inflammatory disease. This is what’s called relapse-associated worsening, or RAW. The available therapies today are all addressing this one way or another. This concept of RAW drives about 50% of the totality of disability accumulation early in the disease. The other 50% is driven by what’s highlighted in the dark blue aspect of this schematic, which is an underlying smoldering neurodegeneration or neurodegenerative component of the disease that’s present from day one. We know that early on in the disease, the other 50% of disability accumulation is driven by this process called PIRA.

This is progression that’s independent of relapse activity or independent of inflammatory disease activity. None of the available therapies today are addressing the neurodegenerative aspect of the disease and providing true neuroprotective benefits. The beautiful thing about vidofludimus calcium is that it is a dual mechanistic approach to address the full aspect of multiple sclerosis. It’s a highly selective inhibitor of an enzyme called dihydroorotate dehydrogenase (DHODH), which we know is a known proven mechanistic approach to address neuroinflammation. It’s also the first and only medicine in development for multiple sclerosis that activates a target called nuclear receptor-related protein 1 (NRR-1). How does the mechanism work? Potent activation of NRR-1 provides both direct and indirect neuroprotective benefits, directly by preventing neurons from cell death, indirectly by reducing the activation of both microglial and astrocytes.

From a DHODH inhibition perspective, we know that vidofludimus calcium selectively targets both hyperactive B and T cells that are implicated in multiple sclerosis. In doing so, it provides a potent anti-inflammatory effect. An interesting note here is this mechanism also provides broad-spectrum antiviral benefits. We know that in multiple sclerosis, the viral trigger for the disease is Epstein-Barr virus. During the course of the disease, Epstein-Barr virus can be reactivated. There is recent data to support that reactivation of this virus during the course of the disease can lead to many of the debilitating symptoms associated with MS, such as fatigue and others. We have data that supports that vidofludimus calcium also prevents reactivation of Epstein-Barr virus via its selective DHODH inhibition.

While DHODH inhibition is a very known mechanistic approach to address MS, activating and targeting NRR-1 has only become an interesting target over the last 10 to 15 or so years. Here is what we know about NRR-1. We know that in patients with relapsing or remitting multiple sclerosis, compared to healthy controls, NRR-1 is downregulated. We also know that in preclinical animal models that activation of NRR-1 delays the onset of multiple sclerosis. Furthermore, we know amongst MS patients alone that lower levels of NRR-1 have been correlated with a more aggressive pathology and clinical parameters of the disease. Probably the most interesting piece of data that links NRR-1 to a potential neuroprotective benefit in multiple sclerosis has to do with pregnancy.

We know that in pregnancy, especially during the second and third trimesters, pregnancy itself is very neuroprotective in that women who have multiple sclerosis that become pregnant have cessation of disease activity. They have no relapses. They have no disability progression. They have no new MRI lesions. A group out of Italy sought to understand biologically why this may be happening. What they found is that there were 347 transcripts that were differentially expressed in relapsing MS patients compared to healthy controls. Furthermore, when they compared women with multiple sclerosis who became pregnant, they found that eight of those respective genes reverted to healthy controls during pregnancy and that NRR-1 was one of those genes. Lots of data support a potential role for NRR-1 activation in multiple sclerosis. We know preclinically that vidofludimus calcium is and does specifically bind to and strongly activate NRR-1.

We know that it also, in doing so, induces a greater than twofold induction of target gene expression. We also know in preclinical models that vidofludimus calcium via NRR-1 activation improves neuronal survival. Lots of data support not only the role of NRR-1 in MS, but how vidofludimus uniquely activates this respective target. We sought a very comprehensive development program, first in relapsing remitting multiple sclerosis. We ran a phase II EMPhASIS study in 268 patients. This was a dose-finding study. We looked at vidofludimus calcium 10, 30, and 45 milligrams compared to placebo. Like most relapsing MS phase II studies, the primary endpoint in this respective study was focal MRI activity. We also looked at clinical outcomes and other biomarker outcomes in addition to safety and tolerability. What you’re seeing here on this slide is the primary and key secondary endpoint.

We see on the left-hand side a 76% reduction, very rapid and robust at week 24, with vidofludimus calcium 30 milligrams in reducing cumulative combined unique active lesions compared to placebo. On the right-hand side, we see nearly an 80% reduction with vidofludimus calcium in reducing gadolinium-enhanced lesions again at week 24. Both of these data points are very highly statistically significant. What was interesting is as early as week 24, we began to see clear separation between the active therapy arm of vidofludimus calcium compared to placebo at confirmed disability worsening events. We see here 1.6% of patients on vidofludimus calcium having confirmed disability worsening at 24 weeks compared to 3.7% of patients on placebo, representing greater than a 50% benefit. This was a clear indication to the team here at Immunic, Inc.

that there’s something else going on with vidofludimus calcium above and beyond its impact on neuroinflammation and further supporting our belief via NRR-1 activation that there’s real neuroprotective properties with this respective medicine. This is data we’ve released recently. This is looking at an open-label extension from this phase II data set. We have followed over 70% of original patients randomized to the study now, still on therapy out to three years or close to three years, 144 weeks. What we see is still very, very low percentages of patients with confirmed disability worsening, with less than 8% of patients on vidofludimus calcium reporting confirmed disability again at week 144. It’s also important to note that the medicine continues to be very safe and very well tolerated out to this extension period.

During the course of the phase II study, we also saw very significant reductions in biomarkers, specifically in the reduction of serum neurofilament light chain. Highlighted here on this respective slide, as you can see, is a very clear dose-dependent reduction in serum neurofilament light, which in MS has been linked to a correlate for future disability worsening. We see here an 18% reduction at the 30 milligram dose and a 26% reduction at the 45 milligram dose of vidofludimus calcium. The safety and tolerability profile of this medicine is quite unique. From the phase II study, we see comparable treatment emergent events between vidofludimus calcium 30 milligrams and 45 milligrams compared to placebo. Compared to, if you will, the first-generation non-selective inhibitor of DHODH teriflunomide, we don’t see treatment emergent adverse events such as liver enzyme elevations. We don’t see an increase of alopecia.

The selective nature of our inhibition of that enzyme clearly has, we believe, safety and tolerability benefits. As highlighted here, we’ve had very low discontinuation rates. Only 2.8% of patients on vidofludimus calcium in the phase II EMPhASIS study discontinued. You compare that to many of the marketed products here again, including Aubagio teriflunomide at almost 20%, Tecfidera at roughly 16%, and others. There is a clear difference between many of the marketed products and the very, very low discontinuation rates associated with vidofludimus calcium. The medicine is very safe. To date, we’ve seen no increased risk of serious infections like progressive multifocal leukoencephalopathy, no increased risk of leukopenia and neutropenia, no hepatotoxicity, no increased risk of malignancies. We believe this will be a true differentiator of our medicine versus many of the available products today.

In summary, from the phase II EMPhASIS study, the primary and key secondary MRI endpoints looking at reduction in focal MRI activity was met with high statistical significance. We also had clear evidence supporting clinical benefit with positive signals on annualized relapse rate, time to relapse, and confirmed disability progression. As mentioned in the previous slide, clear biomarker data confirmed the objective effect of vidofludimus calcium on axonal damage with a dose-dependent reduction in serum neurofilament light chain. The medicine, again, was very safe and very well tolerated. From these data, we moved into a confirmatory phase III program. This is an ongoing set of studies, the ENSURE I and ENSURE II, which are twin identically designed studies looking at vidofludimus calcium 30 milligrams compared to placebo. The primary endpoint will be time to first relapse.

Both of these respective studies are fully enrolled with 1,100 plus patients in each of the respective studies. We expect top-line data from both of these studies in late 2026. The ENSURE program that is ongoing alongside the completed phase II EMPhASIS study confirmed the significant impact of vidofludimus calcium on the neuroinflammatory or relapsing forms of the disease. We also sought to understand whether or not vidofludimus calcium could have an impact on the more neurodegenerative-driven disease in progressive multiple sclerosis. We embarked upon an exploratory phase II program called the CALIBRATE study. This looked at 467 patients up to the age of 65, randomized to receive either vidofludimus calcium 45 milligrams compared to placebo. This was an all-comer study in which we looked at patients with progressive MS and non-active SPMS.

As highlighted here, almost 60% of patients had non-active secondary progressive MS, about 33% of patients had primary progressive MS, and a small portion had active SPMS. In the important clinical outcomes of time to 24-week confirmed disability worsening, which would be the primary endpoint of any phase III study, we saw very robust reduction in the total population, 24% on vidofludimus calcium compared to placebo, 31% reduction in the primary progressive MS subsegment compared to placebo, and 19% reduction in the non-active SPMS compared to placebo, and a nearly 34% reduction in the active SPMS group compared to placebo. There is only one product currently approved for primary progressive multiple sclerosis. That’s Ocrevus or ocrelizumab from Roche. Their phase III program, the ORATORIO study, showed a 25% benefit. Again, reminder here, the CALIBRATE study with vidofludimus calcium in a similar patient population showed a 31% benefit.

Interestingly enough, 27% of patients in the ORATORIO study had inflammatory disease activity at baseline. When you removed those 27% of patients from the data analysis, the 25% benefit was reduced to 16%. We also looked at the data from CALIBRATE to see whether or not we saw a similar signal or whether or not the robustness of our data remained consistent. When you remove the 17.8% of patients with inflammatory disease at baseline, our 31% benefit remains consistent. You see here a 33% benefit in the total population, a 34% benefit in the PPMS population, and a nearly 30% benefit in the non-active SPMS, clearly highlighting that the benefits here are not only being driven by anti-inflammatory benefits, but more so, we believe, are being driven by neuroprotective benefits and a true impact on the neurodegenerative aspect of the disease.

In addition to reducing confirmed disability worsening, we also looked at whether or not vidofludimus calcium compared to placebo could have an impact in change from baseline in EDSS score. You see here, at week 60, we begin to see a statistically significant difference between the active arm and placebo at change from baseline in EDSS score, further giving us confidence of the neuroprotective benefit with vidofludimus calcium. The safety and tolerability profile remains consistent to what we’ve seen to date, with really no differences in treatment emergent adverse events with vidofludimus calcium at 45 milligrams compared to placebo, very, very safe and very well tolerated. From a commercial perspective, we believe there’s a large opportunity here that vidofludimus calcium has the potential to be the first and only oral disease-modifying therapy approved for both relapsing and progressive multiple sclerosis. We know this is a large market.

It’s a $23 billion market growing about 2% to 4% year over year. This will quickly become a $30 billion market. We believe that vidofludimus calcium can continue to show success in both relapsing and progressive disease. The benefit of being the first and only oral disease-modifying therapy, we think, has blockbuster potential. The oral segment of the market is where vidofludimus calcium will compete, and we believe it will compete quite strongly. It represents 40% of total prescriptions today and will continue to represent 40% of prescriptions or nearly 40% of prescriptions over the next 10 years or so. Lots of patients can benefit from this medicine: newly diagnosed patients, patients switching due to disability worsening, due to safety or tolerability concerns, and certainly patients that are older with immunosuppressing concerns. We believe that this would be a wonderful medicine to switch to. The commercial opportunity is quite large.

We believe in relapsing disease alone, again, in which we’ll have data late next year. We believe it’s a $1 billion to $2 billion opportunity. If we continue to show success in progressive disease, we believe it’s a $2 billion plus opportunity in each of those respective indications. As a reminder, the ENSURE I and ENSURE II programs are both fully enrolled, and we expect data in Q4 of 2026. In summary here, we believe vidofludimus calcium has the potential to transform the oral MS market. It’s the first and only dual mechanistic approach to address the full spectrum of the disease. NRR-1 activation provides direct neuroprotective benefits. Highly selective inhibition of DHODH provides anti-inflammatory benefits. We believe it will have a best-in-class benefit-risk profile, driving great efficacy but balanced with wonderful safety and tolerability.

If we continue to show success on the development front in both relapsing and progressive disease, we believe this is a multi-billion dollar opportunity. With that, I want to thank you for your time today. We really appreciate it. We’ll end the presentation there.

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