Okay, great. Good afternoon, everyone, and welcome to Oppenheimer's 35th Annual Healthcare Life Science Conference. My name is Andreas Argyrides. I'm one of the Senior Biotech Analysts at Oppenheimer, and today I have the pleasure to be joined by the management team from Immunic Therapeutics. I have Daniel Vitt, CEO, and Jason Tardio, COO. Guys, welcome and thank you. Quick intro here, background on Immunic. Immunic's lead asset, vidofludimus calcium, formerly known as IMU-838, is a neuroprotective, anti-inflammatory, antiviral small molecule that activates NR1, the nuclear receptor 1, and selectively inhibits DHODH. Vidofludimus calcium, we'll call it Vito, is being primarily evaluated in Phase II studies for progressive multiple sclerosis expected to read out in April, and 2 Phase III studies for relapsing multiple sclerosis expected to complete in 2026. Thank you both again for joining us.
Thanks for being here.
Yeah, perfect. Thanks, guys. Maybe what we'll do is we'll start with a, you guys can walk us through a brief overview of the company and discuss some of the recent progress, and then we can dive into specific questions.
Yeah, thank you, Andreas, for having us here today. Let's kick it off here. As you said, we have exciting times ahead of us. We have vidofludimus calcium in advanced development, and it's important to know that we have, on the one hand, Phase III program ongoing, where recruitment goes well, and we anticipate completion of the studies next year already. That's important work for the company. On top of that, we have the progressive MS study reading out in April of this year, which I think underlines the potential of the drug to be neuroprotective and to address maybe the most important unmet medical need in all of the forms of multiple sclerosis.
Maybe to allow me that initial thought here, if we are asked what is unique about the asset, I think, and you mentioned neuron activation, I think we need to change the view a little bit and look through the eyes of the patient. If you're a 25-year-old patient diagnosed with multiple sclerosis, the question is, what does it mean to you? What is your feeling there? I think the biggest unsolved problem in the MS space is still, can we slow down the worsening of the disability? Can we stop the loss of independence of patients over time? This is our goal, this is our aim in all of the studies we're running, to deliver something better for patients in all of the forms of MS. With our vidofludimus calcium or Vito, we have the right tool in hand.
Okay, great. Maybe to that point that you just alluded to, Vito has shown promising activity in relapsing and progressive MS. Maybe you can walk us through a little bit more on the differentiation of the mechanism compared to existing MS treatments, and then maybe also the impact this could have on disease progression.
Right, this is directly linked, of course. This drug is the first neuron activator in advanced development. Neuron is a target which is involved in neuronal survival, but also neuroprotection directly in the neurons themselves, but also in the neurotoxic environment in the brain. This is expressed in microglia cells and so forth. This is a new thing. We need to know for multiple sclerosis, the neuroprotection is key in all of the different forms of multiple sclerosis. The current drugs so far were all focusing on slowing down the relapses. In relapsing MS, you have both ongoing, you have this relapse activity, which is linked to inflammatory activity in the brain. You can see that in the MRI. On top of that, there is this motoring disease, which is linked to the disability progression.
This is the thing, as I said in the beginning, this is the thing that patients are afraid of, and we want to stop that. With all modes of action, I think we have, maybe for the first time, the opportunity to go beyond just stopping relapses and to target this underlying independent disability worsening of the patients.
Yeah, I might add to that, Andreas, again, if you think about multiple sclerosis, really it's a disease, as Daniel has mentioned, of both neuroinflammation and neurodegeneration. Ideally, you'd like a mechanism that addresses both facets of the disease. The unique thing about vidofludimus calcium is it's the only dual mechanistic approach, right? Potent NR1 activation is going to provide neuroprotective benefits, and highly selective inhibition of DHODH is a known improvement anti-inflammatory approach to that specific aspect of the disease. Disability accumulation happens in two different ways in multiple sclerosis. You have disability accumulation that's associated with relapse-associated worsening or inflammatory-associated worsening. Especially early in the disease, that accounts for about 50% of the total accumulation of disability. There are 15 or so medicines approved today that, to some degree or another, all have an impact on relapse-associated worsening.
What Daniel alluded to is that the other component of MS, this smoldering neurodegenerative component that is constant in there from day one, there's no medicines today that's really addressing neuroprotective benefits through this destructive neurodegeneration that's just constantly happening. A potent NR1 activator like vidofludimus calcium will provide neuroprotective benefits. If in doing so, you'll account for the other 50% of the accumulation of disability progression. This is really where the unmet need lies. We're truly excited about our mechanism. It's a unique approach, and we believe a differentiated approach.
Fantastic. Just for clarity, in looking at the competitive landscape, are there other NR1 activators out there, or is this the sole?
I think there's one drug which is claiming to be a NR1 activator as well. It's a chloroquine derivative, dimerization thing called chloroquine. But that's developed. It's just committed phase I.
Correct.
We don't know much about it.
Standalone is the most advanced one that is out there. That is.
Oh, by far, I think, yes.
Very clear differentiator, yeah. Very exciting. How, I guess, as the story evolved, you've come to realize that this was part of the mechanism of Vito. Okay, maybe we can then segue into the Phase II CALLIPER trial readout in progressive MS in April. Maybe walk us through kind of some expectations. How should we think about that readout from in and of itself? What would be it? Is it considered a success? On top of that, any potential read-throughs into RMS?
I think the most important thing is it's a Phase II study, which was designed to demonstrate, to underline the neuroprotective potential of the molecule. Because in these patients, in progressive MS patients, you usually should not have relapses, and you should not have ongoing inflammatory lesions in the MRIs. If we see an effect here on the amount of disability worsening, if you see a protection here, that's a success. Therefore, the key answer to your question, what is a success, would be if we see a protective effect on a clinical endpoint of disability worsening, confirmed disability worsening. It's a Phase II study. We have, and this is good, we have several different subforms of progressive MS in this study. 2/3 of the patients suffer from non-active secondary progressive MS. That sounds better than it is.
It is the untreatable form of multiple sclerosis. Once a patient progresses and has no longer relapses and also has no longer visible flares or lesions in the brain, but still on the disability scale is worsening, this is called non-active MS. This is an indication where currently there's no drug. A huge unmet medical need. Another 30% of patients in this study have primary progressive MS. These are patients which never show a typical relapse pattern, but are diagnosed with multiple sclerosis, and they worsen also. Some of those really quickly worsen on the disability scale. This is pure neurodegeneration if you will. Those two form the main basis of the study. We have another 8% of patients in this study which have so-called active secondary progressive MS.
This is just a subform, which is a little bit in between relapsing MS and non-active secondary progressive MS. These patients typically have no relapses, but still, you may have seen some inflammatory lesions in the MRI prior to being, for example, included in such a clinical study. Therefore, going back to the endpoint, if we see an effect on improving the disability progression here in one of the subgroups, this is a winner. Now, the question you may ask us is, what amount of benefit should we see there? We asked the question to our KOLs and advisors on the clinical side. I think my take was always that 10% is maybe not enough, 20% is a clear win, and 15% is, I think, what we heard, the hurdle we need to jump over to perceive that as a medically meaningful improvement of the disability scale.
This is just a hazard ratio. It could mean for an individual patient, quite a dramatic long prolongation of the time without worsening of disability.
Sure. How should we think about how these results are going to inform a Phase III design?
I think this.
In terms of, sorry, in terms of endpoints specifically.
Yeah, okay. First of all, the purpose of the study is to educate a Phase III study.
Yeah.
It could be either in non-active secondary progressive, but could also be in primary progressive or both. It's at the end a question of the data and the cost of the studies going further and the potential partnership being available further. As I said, since the clinical endpoint is the most important one, also the regulators want to see in the Phase III study a benefit on disability worsening. I think clearly the expectation is from the regulators that we show a benefit on confirmed disability worsening as the primary endpoint for Phase III studies, which is obvious. I think this is why we have that as the key secondary endpoint in the current Phase II study.
Can you remind those listening in what treatments there are for progressive MS out there today?
There's only one therapy currently approved that's for the subtype of primary progressive multiple sclerosis. That's Ocrevus or ocrelizumab. There's nothing currently approved for non-active secondary progressive MS today.
It's a big opportunity for Vito in this particular case.
Absolutely. As I said earlier, the same mechanism plays a role in relapsing MS. If we show a benefit here, we really will expect a halo effect on the RMS because if patients know that this treatment can slow down disability worsening, they want to go on it. I think this is really something if I would be a patient, I would say, yeah, I should try. Since the last two or three years, there were so many papers on so-called PIRA, so progression independent relapse activity in relapsing MS patients, which is a contribution of that non-focal inflammatory smoldering neurodegeneration. I think this is now believed that PIRA is somehow equivalent to what we see as disability worsening in secondary patients.
Great. That's a good segue into my next question here on the ongoing Phase III INSURE programs in RMS. What can we expect to get an update from the trial? What do you expect to see in the data? It's a broad question, but maybe walk us through, if you want to give a quick background on the design and then kind of what we're looking to see from there.
For the insurance studies in relapsing MS, you mean, yeah?
Yes.
I think the insurance studies were built to cover two main aspects. One is to give us the most likely approval, especially in the United States. The study was a very conservative design starting from our emphasis Phase II studies, which were super successful with very, very good P values of 0.0001 and really showed a very nice effect on the anti-inflammatory activity of the drug. We decided Phase III to confirm what we've seen in Phase II, just on a bigger patient base with 1,050 patients per study. For the Phase III, the primary endpoint is time to first relapse. A classical, one of the endpoints, one of the two endpoints you can choose for a relapse-related therapy. I think that's the one thing. The second thing we wanted to show is the neuroprotection once again.
For this, we agreed with the FDA that we can pull the data from the two identical insurance studies on a disability endpoint to strengthen the statistical power of this data set to be able to demonstrate in a statistical fashion that the drug has that neuroprotective potential in relapsing MS as well. These are the two goals. The first is to convince the regulators to get us approval.
The second is for the patient and the doctors to convince them this is the right treatment to, for example, start right away at the very beginning with or the right switch option for a patient who was on another therapy and needed a new alternative because of lack of efficacy or safety issues with the home treatment. These are the two main goals of the study. We will read out a ton of other data, but I think this is the important piece. These are the things where everybody will agree.
You recently announced from an interim look that the study could continue as is, no upsizing of the study. Maybe just give us a sense of what that means, how do we interpret it? I guess, are there any other further updates until we get readout?
First of all, the interim analysis was planned to make sure we are on track. A big pharma usually does not do that. What would they change? For us, it is important because it is our most important study. We just want to make sure we do not miss the primary endpoint with just a couple of patients on statistical significance with a P value of 0.051 at the end.[crosstalk]
Therefore, we implemented that interim analysis, which was checking for, it is a more technical thing, checking for futility, which of course was not futile. It was not a surprise, honestly. The question was really, do we need to upsize the trial to keep our statistical power of the study? The answer was no, you do not need to upsize. The interpretation is very simple. We go ahead and we read all the final data. There is no other data coming out of that study report.
Okay, fair enough. I was trying to get you to say a little bit more, but no, obviously, it is very straightforward there. It was a positive update. Maybe let's look at Vito in the context of other MS, the MS treatment landscape, and the competition from some other emerging MS therapies. Maybe you can talk about the BTK inhibitors and just give us a sense of what we're looking at from that competitive landscape perspective.
Sure, I'll take that question. Thank you, Andreas. From a competitive perspective, there's no other product in late-stage development like vidofludimus calcium. You've mentioned the BTK inhibitors. Many of the legacy MS companies have taken bets on the BTK inhibitors. We've had reported results over the course of the last, let's call it, about 12 months or so, first from German marketing of Merck KGaA with evobrutinib, in which those two respective studies in relapsing disease failed to meet the primary endpoint. More recently, this past fall, Sanofi reported results from tolebrutinib, their BTK inhibitor. Again, the two studies in relapsing disease failed to meet the primary endpoint. In full transparency, they did meet the primary endpoint in a non-relapsing secondary progressive MS patient population.
The reason I share these data is because clearly there's now an open window of opportunity for vidofludimus calcium in the relapsing forms of multiple sclerosis, the largest segment of the market. We don't foresee any BTK inhibitor finding a path forward. There are two others that are continuing in development for relapsing forms of the disease. Their relapsing studies are almost identical in design to the two products I just mentioned. We suspect that there's going to be a very, very high bar for them to overcome to see success. Given this, we think that there's an open road here for vidofludimus calcium. Again, the relapsing MS category represents about 900,000 patients in the major markets currently diagnosed. Interestingly enough, only 500,000 of those 900,000 are currently on therapy.
Even with 15+ available therapies in that segment of the market, there's clearly unmet needs. The available products are not meeting the needs of both the treating clinician and the patient base. We think the profile of vidofludimus calcium with a wonderful efficacy profile balanced with investing disease, we believe safety and tolerability profile will be an option to push a number of those 400,000 patients off the sideline and back onto therapy. In addition to that, as Daniel had mentioned, none of the available products really address the full spectrum of MS. They're mainly potent anti-inflammatory medicines, but none of them are anti-inflammatory and neuroprotective. Given this dual mechanistic approach with vidofludimus calcium, again, activator of NR1 will provide neuroprotective benefits. Highly selective inhibition of DHODH will provide potent anti-inflammatory benefits.
We believe that we'll have the opportunity to be the first product to really address both aspects of disability progression. Again, relapse-associated worsening, but also progression that's independent of relapse or independent of inflammatory activity. Lastly speaking, this product will compete within the oral disease modifying class. This is a class of medicines that represents 40% of total prescriptions today. Our forecast and independent objective forecast support that that's going to remain high. About 35%-40% of total prescriptions, even out to the next 10 years, will come from the oral disease modifying therapy class. This makes sense. Patients like the convenience of just taking a pill every day. This is the area that vidofludimus calcium is going to play. This is the area that we believe vidofludimus calcium is going to compete quite strongly.
Every single available disease modifying therapy in the oral class today comes with trade-offs, namely safety trade-offs. There's black box warnings for serious infections like progressive multifocal leukoencephalopathy. There's black box warnings for hepatotoxicity, black box warnings for increased malignancy signals. We don't see any of this with vidofludimus calcium. When you think about a positive benefit risk profile, we believe vidofludimus will have the best benefit risk profile within this area. Therefore, we expect to compete quite heavily.
Fantastic. Thanks for all that color. Very, very helpful. Before I switch gears to the pipeline, maybe just quickly your thoughts about partnerships for MS in the US and potentially globally.
We've mentioned the BTK inhibitors. We've mentioned that many of the legacy MS companies have had some recent failures there. You can imagine that's certainly accelerated interest in vidofludimus calcium. We have ongoing discussions not only with legacy MS companies, but other companies that are especially neuroscience players that recognize the large opportunity within MS. Recall, Andreas, this is a $23 billion market today. It's going to grow 2%-4% year over year. As we head into the 2030s, this will be a $30 billion plus overall market. It doesn't take much to drive a blockbuster. If you can capture 5% of total share just in the U.S. alone, you have a billion-dollar product. Clearly, there are companies in neuroscience that are not in MS today that have an interest of getting into this space.
As one would expect, the legacy MS companies have looked at this profile and have recognized that it's a differentiated asset in relapsing disease and potentially could be the only oral that has both a relapsing and a progressive indication. There is a lot of interest. We'll continue to have those discussions, and we'll update you and the markets as appropriate.
I mean, if the data are positive, what would be a question, a hurdle, or how could of not achieving that 5% penetration? What are some of the things? I mean, it seems like a novel mechanism that's safe and that has this kind of dual benefit is almost on its way to a blockbuster before it gets to the market, given how unique it is. What would be any thoughts to kind of some of the reasons why or questions around that? I mean, if the data are positive.
Actually, since you asked the question, I was questioning my, what could it be? I have no idea what could stop us from doing that. Basically, it is there's only maybe technical failures or something like that which could hold us or stop us for some time. I think if the world is turning in a normal way, it should be there. It should have that share. It should be successful, at least in the base case, RMS case. If PMS comes out in a positive way, the sky's the limit, I think it could be a game changer because if you're really in all of the MS forms, it makes it so easy for doctors to prescribe. It makes it easy to understand how it works.
There is one thing we are currently working on, another assessment of our ongoing open-label extension from the Phase II EMPhASIS study in RMS, because there are still a couple of patients on open-label extension. To see how they react, what they believe about the drug is also amazing. I think we are convinced that we have really a drug which the patients love. This is maybe the most important thing heading into such a market where patients are treated for decades and they need protection from progression.
Okay, great. We're five minutes remaining. It's been a great discussion so far. Maybe I'll just ask a quick one before we wrap it up on IMU-856. Can you summarize, I guess, the phase one data in celiac disease and then talk about where it could fit in some other GI indications like IBD and graft versus host disease?
Maybe just starting with the phase I study in celiac disease was awesome. It was just 30 patients, but we achieved statistical significance on histology protection against gluten challenge. For celiac disease patients, good news, there is a new mode of action, CERTAN6 modulation, which has shown histological protection, but also a functional improvement even above the baseline level. For example, we could improve the uptake of vitamin B12 in the patients. This is something with 30 patients. It is a great data point. I think this molecule is really even better than that because it deserves to be developed in other indications as well. The main reason is it is different from the current paradigms in GI, which are all against inflammation. Everybody is trying to shut down inflammation or immune system. We do not do that. This mode of action is more a repair kit.
Yeah, you give it to patients and it should fix the epithelial layer in the gut. Fixing the gut leakage, restoring proper function, fixing the villous structure there and everything. We think that that's a cool approach. If it works beyond celiac disease and with this group of guts, I think it's likely it works elsewhere as well. There's a lot you can do with it. Just imagine what's all going on in the gut. There's all this interplay between nutrients, the immune system, and everything, and the microbiome. This could be a very great drug in a lot of different indications. For us, the next step would be a Phase II study. Could be in celiac disease, could also be in a different indication.
Okay, fantastic. We have about a minute left. I want to thank you both for a really intriguing discussion and thanks for the overview. We're going to look forward to the upcoming results. We'll be paying attention quite closely. If any investors listening in have questions, please feel free to reach out to me. If you'd like to speak with a company, we're happy to facilitate those discussions as well. Daniel, Jason, thank you again, and looking forward to continuing our conversations this year.
Thank you, Andreas. It was a pleasure.
Thank you.