Multiple sclerosis (MS) treatment could be on the brink of a significant breakthrough thanks to innovative research by Immunic Therapeutics.
Speaking to Fierce Pharma, CEO Daniel Vitt shares insights into the firm’s lead asset, vidofludimus calcium, an oral small molecule with potential to address both relapses and disease progression in MS patients.
During the conversation, Vitt explains that while current treatments effectively manage relapses in MS, patients still experience disability worsening over time. Vidofludimus calcium offers a novel approach by combining two mechanisms – Nurr1 activation and DHODH inhibition. This dual action not only targets inflammatory and antiviral processes, but also addresses the underlying neurodegenerative aspects of MS.
The potential of vidofludimus calcium extends beyond relapsing MS to progressive forms of the disease, where treatment options are limited. Here, Vitt highlights promising interim results from Immunic’s CALLIPER trial, showing a 20% reduction in neurofilament light chain (NFL) levels in progressive MS patients – a strong indicator of potential efficacy in slowing disability worsening.
With ongoing twin Phase 3 trials in relapsing MS (ENSURE-1 & ENSURE-2) and a Phase 2 trial in progressive MS (CALLIPER), Immunic is positioning itself to potentially transform MS treatment. The company's approach could offer new hope for patients across the spectrum of MS, particularly those with progressive forms who currently have few therapeutic options.
Tune into the full discussion to learn more!
Stephanie Butler:
Welcome everyone. I am Stephanie Butler. I am with Fierce Pharma, and I'm here with Daniel Vitt, PhD, who's the CEO and President of Immunic Therapeutics. So, welcome Daniel.
Daniel Vitt:
Hi, Stephanie.
Stephanie Butler:
So, I want to start by talking about autoimmune diseases. We know that they are dramatically increasing every year, and I'd love to hear you tell me a little bit more about why you think that is and what we can do about it.
Daniel Vitt:
I think there are several reasons for increasing numbers of autoimmune diseases in general, and the two indications which are most interesting for us are celiac disease and multiple sclerosis, of course, specifically. So, first of all, I think environmental factors play an important role, and we know that exposure to antigens at a specific time of your life is a little bit of a predisposition of getting more likely some autoimmune diseases later in your life. What is interesting is, and I'll come back to that in a minute, in the case of multiple sclerosis, for example, it has to do likely with Epstein-Barr virus infections and the question, at what time of your life you first are exposed to that virus for example. Another point we should not underestimate is that we really have better diagnostic tools now. So, the numbers are also increasing because we know that people have autoimmune diseases which were believed to be something else, some psychiatric things or whatever, and turned out to really be autoimmune diseases. A good example is ulcerative colitis, which in the earlier times was really not known to be an autoimmune disease.
Stephanie Butler:
So, there are already MS drugs on the market that address relapses, but what makes your work on vidofludimus calcium stand out among all these other medications and how is it addressing unmet needs?
Daniel Vitt:
Let's start what's really needed from the patient point of view, so we need to look through the eyes of a patient. So, if a patient shows up at the doctor's office with some symptoms, for example, it could be some cognitive things happening patients don't understand, and you have a diagnosis of multiple sclerosis, maybe of relapsing MS, which is the most frequent diagnosis in that case, then I think today, as you said, there are a couple of drugs which can address these relapses specifically, so relapsing MS in particular. And this is something which evolved since 1993, since interferons have been introduced as the first treatments for relapses. And since then, I think the world really improved significantly. I think the latest big step was really the introduction of anti-CD20 antibodies with Ocrevus being available now for patients.
So, you can think that's a done deal, so we can treat the relapses. The problem is, and this is I think what also we should know and we should take more into the focus of development, is that, if you ask patients with multiple sclerosis on a treatment regarding how are you doing, for example, in the two-year, three-year, or five-year timeframe, patients recognize that they still progress. So, despite you're on a treatment with an efficacious relapse therapy, patients are still progressing and the first question is why? And the second question would be, what can we do? And I think here vidofludimus comes into play because what we believe is that vidofludimus with its mode of action to be a Nurr1 activator, on top of its activity as a DHODH inhibitor, offers a new mode of action, which could really target the underlying neurodegenerative process, which is ongoing despite or independent of the relapses.
Stephanie Butler:
So, since we're starting to talk about the science, where and how did you first come in contact with vidofludimus and what makes this oral small molecule so unique?
Daniel Vitt:
I think it's a typical story of a small molecule development because you start somewhere and you end up totally different at the end. Initially, it was the idea that we can design, using computers, better, more selective DHODH inhibitors. DHODH, it's an important enzyme. It's a very nice target. It's a metabolic enzyme which is involved specifically in metabolically over-activated cells. So, it's a nice target. It was used at treating RA and also Aubagio in the MS space is known to be a DHODH inhibitor. So, it was quite successful work. It was done, optimized and really was a molecule identified, which does not have any kinase inhibition things, no toxic effects on the typical things, no liver tox, no neutropenia, lymphopenia and these kind of things. So, that was where it evolved.
Going further, I think in development, we found that the drug has pretty unique properties and we decided to go into multiple sclerosis and also knowing that the drug has some additional features, and we didn't know exactly what was the reason for these differences we have seen. And just two years ago, we found out that vidofludimus calcium is a very potent activator of a nuclear receptor protein called Nurr1, which is linked to potential neuroprotective features. And it's expressed in the brain, it's expressed in neurons, but also microglia, for example, an interesting target. It was known for a while, but there was no molecule which was active on activation of it so far.
Stephanie Butler:
It's always fascinating how these things come into development and how you find where they fit best. So, as we're already talking about your lead asset, what is the current status of the recruiting activities, especially in the ongoing Phase 3 trials in relapsing MS? Is everything on track?
Daniel Vitt:
Yeah.
Stephanie Butler:
Okay, good.
Daniel Vitt:
I think it could answer the question just with yes.
Stephanie Butler:
But I'd like a little more.
Daniel Vitt:
I think it's never easy because when we started the study, just a couple of weeks later, the war in Ukraine started, which, as you may know, was affecting most big studies in the world. So, since then the team was continuously working really on making sure to have enough sites, to motivate sites to recruit, we have a lot of countries, so this study is really a global study. It runs around the world, and we have so many sites involved and really great connection with investigators in all of these different sites. So, it is a good time to thank the team for the hard work and really –
Stephanie Butler:
Definitely.
Daniel Vitt:
Making sure recruitment is on track. And it's on track right now.
Stephanie Butler:
That is really good to hear. But it seems like we're going to have to wait a little bit longer and be patient for more data. But April 2025, I think is your next major development milestone with the expected Phase 2 data in progressive MS. So, tell us why this indication and readout are so important for you and what can we expect next?
Daniel Vitt:
Good point. And I think we need to build a little bit of a bridge from RMS to PMS. So, I think that I told you that vidofludimus calcium is a Nurr1 activator. That also means it could work in patients which don't have relapses. And these patients are progressive MS patients, so they don't have relapses. So, they're progressing. And that's the reason why, for example, for secondary progressive MS, there's no treatment approved. The scientific rationale took also an interest in that and that was one of the reasons why we started the Phase 2 study in the different forms of progressive MS. And as you said, the data is now coming up. So, the study was fully enrolled last August already.
Stephanie Butler:
Oh, wow.
Daniel Vitt:
And we're now heading into the data next April. It takes that long because we are observing the patients for 120 weeks. It's a pretty long time -
Stephanie Butler:
That's a long time.
Daniel Vitt:
But we really want to see to what extent is disability worsening stopped or halted or slowed down in those patients.
Stephanie Butler:
So, you have three MS trials going on right now, right? The twin Phase 3 trials and also in the RMS and also the Phase 2 trial in PMS. So, which study are you currently focusing on more with your energy and resources? And which do you think is the indication with the higher and more urgent need from your point of view?
Daniel Vitt:
We love all our kids, so we really love the RMS and the PMS studies, and I think they have different skills.
Stephanie Butler:
Like children.
Daniel Vitt:
Like children. So, the RMS clearly is something which the whole study was designed based on a wonderful, very successful Phase 2 study, the EMPhASIS study, which was completed in 2021. And we're just repeating what we have obtained there in a broader number of patients. So, all in all, each of the ENSURE studies is planned to recruit 1,050 patients. So, together 2,100 patients to really have a bulletproof data set here to get approval. So, the whole concept is: let's demonstrate, let's confirm what we have seen and to get approval for the drug. So, really, we try to reduce any operational or performance risks from that study. So, this is the approval track. And I think the RMS patients also deserve a drug with that wonderful safety profile.
Stephanie Butler:
That's true.
Daniel Vitt:
The drug is really well tolerated. The compliance is very high among the patients, so that's good. But PMS, it's a little bit different. PMS, as I said, there's one treatment approved for primary progressive MS, which is Ocrevus. There's no drug approved for non-relapsing secondary progressive MS, and those patients really deserve also a treatment. So, what can we do? So, once the patient progressed to secondary progressive MS, and here I think we are excited about the data we have generated so far based on the mode of action, but also clinical data.
So, I need to share some data from last year in October: We did an interim analysis in the CALLIPER study, and we really, on a group level, read out a biomarker called NFL, neurofilament light chain. And we ourselves were very impressed about the reduction of NFL in the treated group compared with the placebo group. So, for example, in the so far untreatable population, we have seen a 20% reduction of NFL compared to placebo. That's a strong signal. And I think, if you look on the literature and the experience with NFL as a biomarker, we believe that lower NFL predicted better future disability outcome, which I think we can take as a good signal that likely the drug works and we can expect a positive read out next April.
Stephanie Butler:
Those are some really exciting developments. I can't wait to see what the future holds. I think we're going to see a lot going forward and in the coming years. So, thank you, Daniel. Really exciting and really enjoyed speaking with you and hearing more about what you're working on.
Daniel Vitt:
Thank you. It was a big pleasure talking to you.
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