Good morning, everyone. Thank you for joining in the room and on the webcast. My name is Faisal Khurshid. I'm one of the senior biotech analysts here at Leerink Partners. We are here in Miami at the 2025 Leerink Partners Global Healthcare Conference. Really pleased to have with us today the management team of Immunic. Here with me on stage is Dr. Daniel Vitt, CEO of the company. Daniel, why don't you start with kind of teeing up for us or introducing yourself and the company and kind of explaining what's in store for 2025? I know we have a really exciting catalyst coming up. You know, kind of counting down the days now. Yeah. Thank you, Faisal, for. I'll find my questions. you for the nice introduction. Yeah, great to be here today at the conference. Yeah, let me shortly introduce the company. Immunic, and I was a co-founder of Immunic in 2016. Our mission is to develop safer, better drugs and more efficient drugs for chronic inflammation, autoimmune diseases, and specifically oral drugs. We think there is a high unmet need. That brings me directly to our lead product, vidofludimus calcium, which is a perfect example for that. This molecule is really, on the safety tolerability side, a game changer for the MS field. We progressed that molecule from phase one now into phase three studies in relapsing MS. That's the first thing. On top of that, we also have a phase two study ongoing in progressive MS, which will read out actually in a couple of weeks or maybe days. April is coming. So we give guidance that we read out in April. OK, great. Let's talk about that because I think that is the new exciting thing kind of coming up. Can you just remind us quickly the design of the CALLIPER study? Yeah, as I said, the molecule is safe, but the key differentiator for the molecule is its activation of nuclear receptor 1. That gives us a molecule which has the potential to really stop progression or slow down progression in patients. That's a problem in relapsing MS. As we all know, it came up last couple of years that there is this progression independent relapse activity in our MS. In progressive MS, it's certainly an interesting thing because these patients just have progression. This is their obvious key unmet medical need. Therefore, we designed a study to test which patients benefit from the drug. This phase two study, the CALLIPER study, has three different patient populations. All in all, 467 patients. 60% of the patients have secondary progressive MS. This is the non-active secondary progressive MS. These patients don't have inflammation. They don't have relapses. Thirty percent of the patients or 32% of the patients suffering from primary progressive MS in the study. It's also a, I forgot to say, in SPMS, there's no drug approved right now. This is a totally white space. That's the 60%. That's the 60%. That's the tolerable. That's tolerable, a little bit. We'll get to it. We'll get to that. It's an important difference there because I think we really focus on these non-inflammatory patients only, which are the right definition of SPMS. Yeah. In PPMS, I think there's also a high unmet need. Ocrevus is approved for that, so Ocrelizumab, anti-CD20 therapy in a two-year infusion. That is mainly available for younger patients because of the B-cell depletion. I think it always needs to be decided by the doctors what's the right time to prescribe it and to use it because, as we all know, it can lead to increased infections and therefore somehow also has some limitations. I think we want to address the whole space of progressive MS. We are testing here what sub-indication is the most promising for the drug. Yeah. That's helpful on kind of the patient segments. You recently disclosed some of the baseline characteristics of the population you enrolled. Can you kind of tell us what are the biggest highlights of what you disclosed from the baseline characteristics? In particular, how is this population different from some of the studies that have read out like the tolebrutinib in non-active SPMS and the Ocrevus study in primary progressive? Right, right. The most important thing is that if you have an anti-inflammatory drug and it has some neuroprotective effects, as we have and others also believe they have, I think you have these two different effects you can have in a patient. If a patient you include in the study still has active inflammation, they benefit from the anti-inflammatory treatment as well. This gives a little bit of a challenge on reading out the clinical signal in such trials. What we know is that in, for example, the tolebrutinib study, we do not know the exact details because Sanofi so far did not publish the details there. We know that they included patients with non-relapsing secondary progressive MS, meaning these patients may still have more inflammatory lesions at baseline. We recently published our baseline numbers, and we really, in this population, we have just the 6% patients with inflammatory activity. I think it can't be lower at the end. This is more really the pure SPMS population at the end. It's important also from a scientific point of view to separate these two signals. These patients and our patient cohort allow us to separate that, which brings me to one important point. What's the purpose of the study? The purpose is really to demonstrate the drug is neuroprotective. Really focusing on can we reduce the rate of disability recently? You had only 6% of your patient population had inflammatory. In the non-active, in the 60% non-active secondary progressive population. In the PPMS, it's a bit more challenging because they don't have relapses from the very beginning. Here, I think usually activities are a little bit higher. We have 16%, something like that, in that population. Compare that with Ocrevus, they had 24%-25%. Yeah. For the tolebrutinib study in the non-active SPMS, what percentage did they have of that inflammatory lesion activity? They didn't tell us. It isn't public. Interesting. Something we maybe Sanofi will publish later. Yeah. They did disclose that they had 16% of the patients had prior relapse activity in the last few years. Is that a comparable number or is that not? They disclosed for the whole study something like 26% inflammatory activity, if I'm getting it right. I don't know the exact numbers, but yeah. Got it. OK. What defines success for you in this phase two readout? I think if patient's doing well, that's the first thing. On a quantitative level, I think reduction of disability. We know that the biggest issue of patients is to keep their individual independence as long as possible. Really, progression, disability worsening, that's the issue. We want to slow down that whole process. A meaningful medical effect here on reducing that, that's our goal of this study. Got it. What number does that translate to? There are maybe two answers to the question. The first is, we asked our advisors, the key people, KOLs in the MS world, what do you think is a success here? What is really good? I think the answer is efficacy, after a little bit of a discussion, was believed to be something like 15% reduction. It has a ratio of 0.85, would be a medically relevant signal. I personally believe that we should be able to show something like 20% improvement. Every percentage point more is better. Yeah. Got it. That's there. Looking on other data, the only data point we really have is the Ocrevus data, which was some kind of 24% for the total population. If you discount the inflammatory subfraction, it's a 19% signal. That's maybe the best thing today. Yeah. You mean when you take that subgroup of just that pure progressive. Yeah, which we have in our study. I think that would be the right comparator for the PPMS. Got it. The correct Ocrevus comparator, to be clear, is that subgroup that had 0.81 on the hazard ratio. Yes. OK, makes sense. How do you think about the tolebrutinib benchmark on disability? Because that was a bit better. It was 0.69, I think. Yeah, they didn't disclose what the subpopulations are. So we can't tell. Do you have a safer draw? It was a good signal, honestly. It was a good signal. If we just look on disability in any patients, the question is, what is the origin of that? If it's really the anti-inflammatory effect, then the real numbers are lower. Right. I can't comment on things I don't know, and it's not public. We will see how the FDA will handle that. Honestly, I think patients deserve maybe the choice of maybe one or two treatments. At the end, I also think the biggest problem of BTK inhibitors are still the liver tox issues, which are not in all of the developments. Clinical hold from the FDA is an issue somehow. We will see how that goes further. Yeah. I mean, this is a disease area, but there's plenty of precedent for safer products being used. Better sales, clearly, yes. Yeah, totally. Especially when it comes to some fatal outcomes, I think. That changes the view of patients and of doctors as well. Yeah. In the progressive MS subtypes, there's not a lot of precedent for kind of properly run phase two studies before phase three. Like a lot of the large pharma development has gone straight into phase three in progressive based on relapsing phase twos. How should investors think about the kind of phase two to phase three translatability? What I mean is, if you achieve this 0.8 hazard ratio in the setting of a phase two, what do you expect when you go to phase three? Should that signal strengthen, weaken, or stay the same? Actually, it should stay the same. This study is big enough. It's big enough to give a solid signal. Got it. Of course, event rates at the end are decisive of the stability and the noise in the data set. I think this study will tell us how to design a successful phase three study. You're right, this is the first industry-sponsored phase two study in progressive MS at all. I think that's the right way to do it because we want to know what the signal is and then to decide what is the right population. For example, it could be that specifically primary progressive are benefiting more or secondary progressive are benefiting more. We don't know that yet. I think we will know that in a couple of weeks from now. Yeah. That's my next question. You have these two major subgroups, right? The non-active secondary progressive, the primary progressive. How are you going to decide which one to push into phase three? Is it even an either/or? How are you thinking about that? The FDA still believes they are separate indications. If we want to get approval, I think we need to run a study. Depending on the data a little bit, we may use the data from the CALLIPER study to convince people that it's approvable. It was not designed as a pivotal study. We will have end of phase two meeting and discussing the data. There's another thing which is also important to mention. We have the phase threes ongoing, the big phase three studies, 1,000 patients each and the ENSURE studies. The holistic view of data may also be a good reason to talk again to the regulators to maybe get an expedited way towards approval. That's something which at the end depends on the data, but there's a way forward. In a classical way, I think with the data we're generating here, it will be very clear and easy to define the right straight strategy for phase three for each of those indications, for primary progressive and for secondary progressive. Got it. Makes sense. Can you just remind us, so the disability outcome in the CALLIPER study is a phase two because in a phase two, you can't actually power that as the primary. You have a phase three. Can you remind us the statistical considerations around it? Like when we're talking about these benchmarks of 0.85 or 0.8 on the hazard ratio, could that be statistically significant? Or is the powering not there to? No, it's not that. I think this study can't be powered for statistical benefit on that clinical outcome. This is the phase three endpoint. If we would have powered it for that, it would be a phase three study. It would be much larger. Therefore, this study is really an exploratory study to educate us what is the effect size and to plan a proper phase three study. Got it. Makes sense. Can you remind us, you had an interim analysis that looked at the NfL biomarker? Yes. Could you explain how and why that gives you confidence on what we're going to see in days to weeks on the full study readout? Yeah. I think NfL is an important achievement of the industry and research globally in the neurology space. It is a protein. I think it's one of the proteins which is disseminating from impaired neurons or dying neurons. Of course, there can be different sources in an individual. The contributions can come from the brain, can come from the CSF, also from the periphery. If you want to use a biomarker, you need to ask yourself, what is it telling me? Is it proven? Luckily, there was a very nice publication from Roche on their successful phase three study, Ocrevus's phase three study ORATORIO. What they did is they rebaselined the patients after one year of Ocrevus treatment. What that led to is the stop of any remaining focal inflammation. More or less, you force your patients to be really just a progressive population. They looked on to what extent is baseline NFL predicting future disability outcome. The clear answer to that, and there actually was nine-year data in that paper, they have shown that with a pretty good hazard ratio of 0.65, something like that, over the time, there was a very clear separation. Lower baseline NfL predicts lower future disability risk. That was a great study, and it was also a big study. I think we can conclude from that NfL is, in this situation, a good predictor. It is maybe not if you have still lesions. In a total population where you have lesions, because they come and go, there is a relapse-remitting profile of the lesions, and it also leads to NfL fluctuation. If you have that, then I think you need to be careful on that. That is why a lot of old publications come to wrong conclusions on the use of NfL in MS. For example, in relapsing MS, it may be used as a diagnostic marker, because you can easily measure these values and see if it is an elevated level of NfL. That's a nice way to think about it. Basically, in your study, because of the type of patients you enrolled, anything you see on NfL, it's not relapse-related NfL release. It's actually related to kind of the disease progression in your view. Exactly. We think that with the numbers we have seen, and it was even statistically significant when we read out 50% of the patients after the first 24 weeks. Remember, this is a 120-week study. It's a huge thing. This was quite impressive. We were really partying around the NfL data. I think for me, it's really the reason why I believe in a positive outcome on the whole clinical data. Yeah, yeah. I want to shift gears a little bit. You mentioned you have the phase 3 ENSURE program going on in relapsing MS data next year. You guys have pulled off a feat of running a phase 3 relapsing MS program as a small company. Can you remind us, you recently had a--no, I say that because investors-- It's a shock. Investors who don't know, they hear this, they're like, oh, this company did a 1,000-plus patient study. 1,000-plus. Yes, yes. I want to talk about you had the interim analysis in December. Can you describe what happened at the interim analysis and how that gives you—yeah, what level of confidence that gives you into the data next year? First of all, pharma companies don't do that. They don't need to do that because they don't care. They just do the study and read out the thing. For us, it's a big thing. It's a big study. It costs a lot of money. I think the very simple idea behind the ENSURE studies was we confirm, we want to confirm in a highly statistically significant way what we have seen in the phase two study, the EMPhASIS RMS phase two study. We had two goals of that study. The first goal is to get an approval of the data package. Very easy. Therefore, the endpoint needs to be relapse reduction. We powered that study to deliver this. It's the most conservative approach you can take. I think the reason why we did it in a way is we didn't want to gamble. We want to make sure we do not run into unsure waters on shortcutting, changing inclusion criteria, and ambitious endpoints, which you maybe just do not achieve because you do not know the whole picture. That was the more conservative part of the planning. The second thing is that we know we have a drug which can be better. This is really based on disability prevention. Therefore, we have established a design where we can pool the data from the two phase 3 studies at the readout point on reading out confirmed disability worsening. This should make a difference for the patients, for the doctors. Statistics for the regulators and the clinical benefit shown in confirmed disability worsening and these other endpoints for doctors and patients, and also the safety for everybody, for the regulators and for the patients. I think we also want to confirm that outstanding safety and tolerability profile of the drug, which has none of the known issues current drugs have. Got it. That data will be next year? That data, so the study completion is projected for next year. What I can confirm here is our recruitment is on track. OK, great. Look forward to details on that. We are about 10 minutes left. I want to talk a little bit about sort of the strategic vision path forward for the company. You founded this and have steered this forward. As you think about the opportunity set available for the drug, obviously MS is a large indication. How do you think about the sort of strategic partnerships for the asset and what that kind of looks like going forward, especially as you're kind of on the doorstep of a phase three readout next year? Yeah. This is the number one question for us as a company, of course, how to handle this value in the context of a challenging capital market. In a normal market, maybe our market cap should be something like a $700 million, $1 billion-ish place. How do we handle that? If you drill it down to the value of the asset, if you just do a classic rNPV evaluation of what we have and look on the competitive space, cleaned up, a lot of competitors got out of studies didn't work out. We have a very interesting, unique asset which is developed in all of the MS indications. It is currently just based on RMS, basically, and Ocrevus and PPM as a $23 billion market in the seven major markets. There are companies which are huge need for next drugs to fill the pipelines. We have a high unmet medical need for stopping disability. We think the value of the asset is much higher than our market cap, substantially higher. How to handle that in this world? I think we still take a double approach. On the one hand, we convinced Jason Tardio last year to join us as Chief Operating Officer with his commercial background in the MS space so that we have the ability to also prepare a potential launch of the drug in either one or more territories. That is still something we think is feasible. Also looking on, as I said, on the value and value development and cash needed for commercial launch and so forth, we think it could also benefit from a partnership. Based on where we are and the data coming out now in April, we started, I think, actually end of last year and during JP Morgan week, a lot of BD discussions with players in the space. We know that most companies have an eye on it right now. I'm pretty optimistic if we continue that we will find a good partner to work with us on leveraging the whole commercial potential of the drug. I think that this would clearly enable us to strengthen the pipeline. We have that wonderful second molecule, IMU-856, where we recently reported some surprising data on the gut repair and the associated incretine change, which was a little bit unexpected thing. We think we want to continue that in maybe celiac disease and maybe also have an eye on weight management there. We have more things in the pipeline on neuroprotection and at earlier stage. There is a lot we can do to establish the company on the next level based on the success of vidofludimus calcium. Yeah. I guess as you're starting to engage in partnership discussions, what's kind of interesting and unique here is that the timing between the two programs, right? A potential partner would have to be kind of on board with a nearer-term commercial launch, but then also on the development side, embarking on a phase three in progressive MS. How does that kind of play into the discussions in terms of that kind of dual remit across the two indications? Everybody loves it. It's the thing you want to have. You have a rock-solid base for a start and a huge upside from a multi-billion opportunity from progressive MS. It's perfect. I think people love it. Also considering PMS is a single phase 3 study, not two studies needed. Size of the study is maybe not larger than a single RMS study. It’s feasible. Also in progressive MS, I think such a study will be easier to recruit, given the unmet need is so high. It's obviously easy to recruit. Yeah. There is a precedent of how these studies are run as well. Yeah. If you own the drug and you bring it to the market, you really can change the world how we treat MS. It is the potential of a real breakthrough. It depends, of course, on the data at the end. I think it has the potential to really change the way we treat MS. Yeah. As you think about the kind of sequencing of the potential value inflection points in the company, you kind of have the phase two CALLIPER readout coming up next month. It is going to be roughly a year and a half, give or take, to the phase three readout, right? That is another. Yeah. We got completion of the phase three studies next year, the first of those in the second quarter, and the second one in the second half of next year. It is still open how the readout goes. I am careful on saying the readout will be at that time point because it depends on the full recruitment of both studies and also whether we do it sequentially or together. There is an open discussion on how we handle that. Got it. Yeah. I guess just to put it broadly, you have the next full readout and then next year phase three, which will obviously be as a phase three readout, there's a potentially big value inflection point. As you're thinking about kind of strategic path forward, how do you think about kind of timing of that, given that you have these two major de-risking events with a kind of gap in between? I think I don't perceive it as a gap. It is close. Given the size of what we're talking about, this is a blockbuster indication and a molecule. I think it deserves the attention we give it to that. There may be more data coming from our other programs, but it has never the same relevance as these two important readouts. Yeah. What I mean by. Yeah. What I mean by. Partnership could be the other thing. If we enter a partnership, this could also change a little bit the view from our point, our shareholders and investors on the one hand, but also of the market, the patients, the doctors. There is a lot. I can imagine there are a lot of things which could happen in the next couple of months. Yeah. Yeah. I guess what I mean is if you're in a situation where you're kind of talking about partnerships, but you know you have another big value inflection point coming up, are you kind of compelled to wait then because you know you have phase three readout kind of on the horizon? Depends a little bit on the funding situation and the market situation. Yeah. I know I'm bugging you on hypotheticals here. Yes, yes. I think in a perfect world, I would go to the very end and launch it. Yeah. There are also reasons to maybe join forces with somebody who has an established marketing organization for the indication. Yeah, I think we need to be just flexible and open-minded. It is always my creed to expect the unexpected. Let's see how that goes further. Got it. Yeah. That makes sense. Yeah. Sorry, I know I'm bugging you on all these hypothetical things. We have the same discussion internally. Glenn and I, we usually talk about it every week. How do we handle that because he managed the cash and how we structured that and what's the price of the money? Yeah. Today it's also a discussion. Yeah, totally. If you raise money from equity side, it's also not cheap. Yeah. Let's talk about that because you have an interesting kind of financing agreement in place. Can you kind of remind the folks listening, how does that work and then what does that fund? First of all, I want to thank BVF for taking the lead last year and supported by Lyrinc at that time to do this PIPE investment in last January. We signed this three-tranched deal with up to $240 million supporting the company. Of course, for the price of dilution, that's unavoidable. I think it was very good for the company and secured the financing. We got the first tranche last year. The second tranche could be invested after the CALLIPER data comes out. The third tranche is a little bit linked to the second tranche execution. We will see. We will see how that goes forward. We published the deal and the terms and so on in the public. That's one of the things which I think it brings the company in a good situation. Also clearly, we want to grow. We want to grow the company. Also, I think we should also give 856, our second molecule in celiac disease and maybe also obesity, an opportunity to show its strength and to generate more data. That is another aspect of what is currently not covered by the funds we have. Yeah. So you'll get that 80 or hopefully you'll get that 80. Can you remind us, does that take you to the phase three readout? Does that also cover any kind of starting up of the phase three in progressive? No. This is not covered. It's a phase three in progressive MS. Look, I don't want to overpromise here things, but I don't think that's a problem. If we have good data on progressive MS, we have good problems to solve because everybody wants to have it. That's something where that's not a problem from my point of view. We will find somebody to work together with us on that. Right. I admire the confidence. Driven by the disability data because this is, as I said, important for PMS, but also supporting the RMS development. Yep. Cool. We are right at time. There is just one question that I always like to wrap this up with. Just to close us out, what do you think investors misunderstand most about the Immunic story? I think they don't get the market size we're working in and how nicely that molecule is positioned as maybe the best development option right now in MS at all. That's maybe because people are mixing up RMS and PMS and really don't understand the real unmet medical need, which is progression, which is 50% of progression is not related to relapses. You have 15 molecules approved in the US, making $23 billion of sales and solving half of the problem. That's maybe in simple words how I see the world. That gives us and maybe others in the future an opportunity to add something medically meaningful on top of that, which could really make it a multi-billion opportunity. If you don't understand that, then you may not get the story. Great. Sounds good. Thank you so much, Daniel, for joining us here. Thank you, folks in the room who dialed in. We look forward to hearing from you in, I guess, a few weeks. Yeah. Thank you for having us here. It's always a pleasure to be here in the conference. All right. Thank you. Thank you.