Great. Thanks very much. It's my pleasure to be moderating this chat with the Immunic team, and we'll keep this mostly conversational with Q&A. Here we have Daniel and Jason from the team, so maybe I can have one of you guys, Daniel, if you want to kick it off and just sort of give a brief snapshot of what 2026 looks like for Immunic, you know, ahead of some key data coming up in RMS, and then we can do Q&A. How does that sound? Yeah. Thank you, Paul, and happy to kick it off here with the 2026 outlook. I think 2026 is a transformative year for the company, just raised money earlier this year, heading into the phase III readout of our two phase III studies, the ENSURE-1 and ENSURE-2 studies, at the end of the year. Also in parallel to that, already preparing NDA submission planned for next year and so forth. Great. Awesome. How would you like to kind of set things up as it relates to the RMS study and the vidofludimus calcium program? Maybe I think a little bit of a background on the drug, the historical context on this drug being sort of similar to Aubagio, but having its own nuanced differences. I think that would be probably the best setup. With that, we can kind of ask some more offshoot questions on sort of data, differentiation, you know, plans beyond RMS. I think that would be a good level set if that works for you. Wonderful. Maybe I kick it off with a bit of a history on vidofludimus calcium because I think it's the best of two worlds, basically here. Initially designed as a safer and more selective DHODH inhibitor, compared to Aubagio. It's specifically not hitting protein kinases, which I think are believed to be the main reasons for a couple of side effects of Aubagio. The drug was developed, and during development we found out that it is also a very potent activator of a nuclear receptor called Nurr1. I think this, when I say the best of two worlds, is really making a unique molecule with a direct neuroprotective mode of action by Nurr1 activation and a very solid selective anti-inflammatory activity by DHODH inhibition without the pitfall of having kinase inhibition like Aubagio has. Right. From a practical perspective on the safety side, you know, Aubagio is a commercially successful product, but there's been a collection of, you know, safety nuances that maybe have capped its uptake to some degree, right? You've got, embryo-fetal toxicity, hepatotoxicity. You know, maybe talk about like what your expectation is, for your drug as it relates to like what of this you can avoid, and how you want to try to prove that out in the upcoming phase III readout. Well, actually so far, I think clearly these effects were... Effects were. These effects were really related mainly to the off-target activity of Aubagio in the development there, hitting the Aurora A kinase and EGFR kinases. What you know about Aubagio is that, for example, the hair loss, neutropenia, lymphopenia, they all things are expected to originate from the kinase inhibition. We know so far vidofludimus calcium is really a uniquely safe and well-tolerated product. I think this is one of the key strengths of the molecule. We think that also with this clean DHODH inhibition profile that we avoid actually most of those, if not all of those, going forward. On top of that, I think the Nurr1 activation makes it also a very safe tolerated direct neuroprotective molecule. Yeah. I would just add. Yeah. Really quickly here, Paul, related to specifically, I think the hepatotoxicity and embryo-fetal toxicity associated with teriflunomide, which I call the first-generation non-selective inhibitor of DHODH. Just a couple additional thoughts. You know, data is going to speak. At the end of the day, the data we've generated to date with vidofludimus calcium, specifically to liver enzyme elevations and changes, either you know, 3x, 5x, 10x increase on ALT or AST, has been comparable to placebo. We think we have strong data that suggests a highly differentiated liver tox profile versus teriflunomide or even the first generation product, which was leflunomide. We will share that data with the regulators and hope for the best. From an embryo tox perspective, again, we've generated very interesting data to date in animals, of course. We're continuing to generate additional data that may provide a differentiated profile. One last note I think specific to embryo tox as well is you have to remember that the half-life and elimination half-life of these medicines are vastly different, right? Teriflunomide has a very long elimination half-life from like 10-19 days. It takes approximately three months to reach steady state with that medicine. The product can actually stay in the blood for up to two years in some patients. Versus vidofludimus calcium, we have elimination half-life of approximately 30 hours. We reach steady state in five-eight days and typically the medicine clears within 10 days. Again, we think we have advantages that are very distinct and different that may offer a compelling argument with the regulators as to why we don't need some of these safety warnings. You know, the data will speak. Yep. Okay, great. Thank you, Jason. That's great context. Maybe talk a little about the Nurr1 angle. Like how was this discovered, and why is this biologically significant? Yeah. I think first of all, it goes back to the clinical trials. As I said, initially developed as a clean DHODH inhibitor, we have seen already in the EMPhASIS study, phase II study in relapsing MS patients that the drug has hints of neuroprotection. It has two things. On the one hand, the clinical side, we have seen a very low rate of confirmed disability progression there. Actually 57% less than in the control group. Also we have seen a dose-dependent reduction of NFL. Intrigued by these data points and also good open label extension data from that study, we worked together with a couple of academic groups, and we found that investigating nuclear receptor profiles, actually we found that the drug is a potent activator of Nurr1. Saying potent, really up to 5-fold target gene expression increase with the drug. This is unique, this is new, and no other product was ever seen and shown to have such a strong effect on Nurr1 activation until that time point. That has driven our work there forward. On, and color to that, we also know from, for example, gene expression analysis that Nurr1 is a known potential target for MS. Because, for example, it was shown that in pregnant women during pregnancy with suffering from multiple sclerosis that Nurr1 is one of the key targets which is upregulated during pregnancy. It's known that during pregnancy, the disease activity and also progression goes down in these patients. There is also a known medical history about around Nurr1 activation in MS patients. Yeah. Yep. Okay. Makes sense, Daniel. Do you think having this secondary mechanism is going to lead to differentiation on efficacy in the upcoming RMS readout? If so, what are the key endpoints where you see the greatest opportunity for Nurr1 to have an impact? Clearly, yes. I think we believe that this drug has direct neuroprotective effect based on the Nurr1 activation. The recent CALLIPER data we published last year underlines that also to translate into a clinical benefit with, just to remind you, in PPMS, a subset of that study, we have seen a 31% reduction of confirmed disability worsening in the patients. Really something outstanding and unique for these indications. Linking the mode of action of Nurr1 activation with the clinical activity. We think we should see effects in all of the clinical studies going forward that started in EMPhASIS where we have seen, for example, in the open label extension phase, that there is this very slow rate of disability progression here. Also specifically low rates of PIRA in that study. We also think that the ENSURE studies should give us data underlining again or confirming again that the drug has these effects on lowering confirmed disability progression as maybe the most important clinical outcome for the patients. Yeah. Okay. Yeah, I mean, the progressive MS data is obviously super encouraging. But can you prove out this kind of neuroprotective concept on efficacy in an actively relapsing population? Like, how do you kind of separate the two in this type of trial? Is it in a subgroup, or is it something where the read-through is gonna be more limited? I think this is, of course, mixing in the relapsing MS, mixing with the relapse associated worsening. Right. You're correct. This is both there. I think the totality of data should also give us a hint that the drug has these effects. We will have the subgroup analysis of the PIRA as well, but that's not powered for statistical benefit of course, because it will be a smaller set of n of patients there. I think I'm expecting a lot from also having a look on the PIRA effect of the drug here. Because usually, as you know, 50% of the contribution of disability is coming from PIRA also in relapsing MS population. There should be something we can see. Yeah. Yeah. Okay. Great. Maybe as it relates to just efficacy and kind of putting the upcoming relapsing MS data into context, like maybe talk about the selection of the primary endpoint. It's a little bit different than some of the older studies that just looked at ARR. Maybe more broadly, like can we make cross-trial comparisons here between a contemporary RMS study and some of the studies that were done for Aubagio or other drugs that were done 15, 20 years ago? Like how are we gonna be able to understand beyond statistical success what like a clinically compelling outcome would be? What you said is also true, the baseline characteristics have changed over the years. It's maybe somehow a little bit limited. The primary endpoint here is a pretty straight one. It's time to first relapse using Kaplan-Meier analysis. It's basically the same medical data we are evaluating compared to ARR. It's just a different way to look at the same thing. It has an advantage from the ethical point of view, and I think it's a more modern state-of-the-art endpoint for such a study. We also will report ARR as a secondary endpoint. I think other secondary endpoints of this study includes, as I mentioned before, confirmed disability progression, but also confirmed disability improvement. That's also part of our list of things we're measuring, MRI endpoints. Of course, you can compare. You can compare with other studies of course, but the question is what is the most important thing here? I think the totality of data is important here. First of all, to achieve a statistically significant primary endpoint outcome for both studies, and then followed by good secondary outcome measures as well. Yeah. Okay. Any thought on like a numerical effect size, that you feel like would kind of be the floor or what you sort of need to see on relapse rate reduction or slowing of disability to be compelling commercially in what's become obviously a more crowded market? Well, no, I don't think it makes sense to guide here for any expected minimum thresholds here. I think it's the totality of data which matters. The balance between the relapse effect, the safety, and the disability effect, because they all matter for selection of the treatment for a treating physician. I think we- Yeah. ... can we expect good data from all of those three. I think maybe the most important thing on relapses is to achieve statistical significance because you want to get it approved. This is a discussion with the regulators there. And to demonstrate the drug has these effects. It doesn't make a big difference if it's 5% or 10% less or more on these things. That doesn't make a big difference from a commercial point of view. Whereas I think every percentage point you can have on slowing down disability, that's important, and that's helpful, and it will help us to differentiate from other products as well. But I- Yeah. ... will not give a guidance here on expected, numbers here, on percentages here. I think I expect good data. Let's see what's coming out here. Yeah. Okay. Fair enough. Commercially, the market in MS has obviously changed a lot. I remember back when I first did, you know, research in this area, there was kind of this attitude of using the safest drugs first, saving the more efficacious products for later in the disease, and that hasn't flipped across the board. Right? You see a lot of OCREVUS used early on now, right, which is believed to be the most efficacious drug in RMS. In the context of this landscape, which has sort of changed somewhat philosophically, and then you also have, you know, oral drugs that are generic. Like where do you see your drug fitting in? Like, who do you think are the early adopters, and what is kind of the key niche you think over time? There's a couple of different patient populations, you know, that make a lot of sense for a medicine like vidofludimus calcium. Clearly, first and foremost, for those individuals that just prefer an oral route of administration, we want to be in the consideration set there, and we expect to win. This is still with the success of the CD20s, the oral segment is still a considerable and meaningful, you know, overall contributor to the total prescription base, with roughly 35%-40% of all prescriptions today in the United States still being for oral disease-modifying therapies. When you think about this class of medicines, all of the existing approved therapies come with, you know, trade-offs from a safety perspective. They have serious infection risks like progressive multifocal leukoencephalopathy, which can lead to death. They have increased risk of malignancies. They have drug-induced liver injury or hepatotoxicity, among others. There's this constant trade-off as you think about the value proposition of these medicines. We think vidofludimus calcium will offer a best-in-oral-class benefit risk profile. You know, Daniel talked a little bit about the differences of this molecule, we think will show strong efficacy across relapses, disability, and MRI. You balance that with what we think will be a best-in-class safety and tolerability profile. We think we have a compelling story to win that patient when an oral route of administration is what's desired. As we think about the CD20s, a couple of things to note. These are highly effective medicines, but largely just on inflammation associated with the disease. They do a very good job of squashing relapses, and focal MRI activity. Still, over 30% of patients on CD20 class of medicines continue to progress, and this is for good reason. They have disability progression and accumulation because those medicines have little to no effect on the neurodegenerative component of the disease or this PIRA, this progression that's independent of relapse activity. Given the neuro- Right. ... one activation with vidofludimus calcium, we think that we will have an effect there. That's a clear difference. I think one last patient segment specific to the CD20 is that we seek to go after, and we think that there's an enormous unmet need in the market, are those patients that need to sequence off of a CD20 therapy. Remember, these medicines via their mechanism broadly deplete B cells, and this comes with serious infection risk. Prolonged B cell depletion, the longer you're on these therapies, there's an incremental risk for this serious infection. When these patients get an infection, you must immediately stop the CD20. It takes over two years to replete B cells. The market doesn't have a clear path today to sequence these patients from that class to something safe and something that will be effective. Given that vidofludimus calcium is an immunomodulator, not an immunosuppressant therapy, we think it makes a lot of sense for this population. Again, we've talked about the potential benefits in neuroprotection on staving off disability progression and of course, the safety and tolerability. We think that represents a wonderful segment as well. In summary here, we think we'll offer a best-in-oral-class benefit risk profile, and we expect to compete heavily within that segment of the market. For the CD20 patients, we know that a considerable amount of these patients continue to progress when they need to switch due to that progression. We think Nurr1 activation is a wonderful solution. Of course, when those patients need to sequence away from that class of medicines because of safety and infection risk, we think vidofludimus as an immunomodulator with great neuroprotection, will be the medicine to switch to. Yeah. Yep. Okay. Great. Do you want to briefly touch upon your plans in progressive MS? Maybe talk a little bit again about the phase II CALLIPER data and just kind of how you're now thinking about going into phase III. Sure. The phase II CALLIPER study was an exploratory phase II study in which we looked at all comers with progressive disease. We had roughly close to 60% of patients with non-active SPMS, about 30% of patients with primary progressive MS, and a small percentage with active SPMS. The real goal of this study was to determine whether or not vidofludimus calcium could have a clinically meaningful impact on delaying confirmed disability progression in this very tough-to-treat, high unmet need population. Indeed, we showed that. We showed a 24% reduction in time to 24-week confirmed disability progression in the total cohort, including a 31% reduction for the PPMS sub-segment. This is very, very compelling data. I think furthermore, we also showed some differentiation on change from baseline with a statistically significant separation from placebo beginning at week 60 and continuing throughout the 120 weeks of the study. We showed more than a two, almost a 2.5x increase in potential confirmed disability improvement on the medicine as well compared to placebo. And again, this is in the total cohort, but also in the subsets of both PPMS and non-active SPMS. All signs are very encouraging about the potential impact of this medicine in a progressive population. Of course, there's an enormous unmet need within both the non-active SPMS and PPMS segment, and that's why we've signaled here that in the second half of the year, we look forward to kicking off confirmatory study initially in primary progressive MS. Yep. Okay. That's great. How long do you think a study like that will take to conduct? How much of that is, I guess, in your control from, like, an execution perspective? Yeah, we've done a lot of work. We've done a feasibility work. I mean, again, we have advantages here in that we ran a phase II study in this population, so we have existing relationships with investigators and clinical sites throughout the world, which I think gives us a bit of an advantage versus maybe some of the competitors. We anticipate, you know, given our current assumptions, that it may take anywhere from three and a half-four years to fully enroll and read out the study. Of course, you know, you'll need about a year to submit the application and then wait for approval. We estimate, again, let's call it roughly four years to execute the study and deliver data, and then another year to submit the application and garner the approval. Okay. Great. Thanks, Jason. Well, we're coming towards the end here. Anything else you'd like to convey or get across ahead of your big RMS readout that's coming up? Yeah. A couple of thoughts. You know, there is still enormous unmet need in multiple sclerosis in both clearly the progressive side with little to no treatment options, but there is still unmet need in the relapsing side, and this disease is not solved for. As I've mentioned, over 30% of patients on the CD20 therapies continue to have disability progression. There's a need for novel mechanistic approaches that address neuroprotection, and we believe vidofludimus calcium via its Nurr1 activation will do just that. Furthermore, there's a need for just safer and more tolerable medicines. Remember, this is a chronic disease. Patients have to be on these therapies for life. Almost all the currently approved therapies come with some serious trade-offs, again, largely related to safety risk and safety concerns. There needs to be continued evolution here about how we think about safety and tolerability within the space. We believe we clearly have done a lot of work to understand this segment of the market. We believe there's considerable opportunity for a new entrant, a new novel and unique entrant like vidofludimus calcium. If the data shows us what we think the data will show us, we think it's a blockbuster opportunity in relapsing disease alone. Of course, if we continue to show success in progressive disease, we can replicate the data that we showed in the CALLIPER study last spring. That's significant. We're talking multi-billion dollar upside for our PPMS indication down the road. We're very excited about what we have, and we're very excited to see the data, and hopefully we'll be able to deliver a new option for individuals living with MS. Awesome. Well, great, guys. Thank you. Always great to see you, and yeah, good conversation. We look forward to the data very soon. Thank you. Yeah. Thank you, Paul, for having us on. Awesome. All right. Thank you guys. Appreciate it.