STIFEL 2026 HEALTHCARE CONFERENCE - IMMUNIC INC

All right. Thanks very much, everybody. Happy to be moderating this chat here with the Munich management team. With me is Eric Lundgren and Jason Tardio. These guys have a somewhat important clinical readout coming up, maybe. But, yeah, no, with that, just to be more serious, maybe I'll have you two guys each just if you want to say any prepared remarks around the setup for the company going into the end of the year with these two RMS readouts. And then, you know, we can dig more into Vita Flumis Calcium. Absolutely. Thanks for having us. Thanks for your interest. I'm Eric Lundgren, the CEO of Immunic. And as Paul indicated, we have a couple very exciting weeks ahead of us. We have two phase three pivotal trials reading out in relapsing MS, the Insure 1 and Insure 2 studies. Those will be reading out in December. And they would be, assuming they're positive, they would the NDA filing enabling. So we're very focused on that. In addition, we are initiating a third phase three study. This one would be in progressive MS. That's called the PROTECT-MS study, getting that off the ground as well. So, we're looking at some very exciting near-term catalysts preparing for NDA filing and doing the commercial build to get ready. Great. Yeah. Well, okay. Maybe we'll get right into it. So you have these two RMS readouts coming up um maybe just like talk about the setup there so you got these two studies like what do you guys disclose in the top line and you know what sort of target product profile are you hoping to reaffirm yeah so i mean i i'd start with what do we see as the big unmet needs in ms and i think there's there's they're many but i draw your attention to two um the first one is really around progression so there's been a ton of innovation in mss over the last 20 years or so But progression remains a very, very difficult place to move the needle on and really the overwhelming unmet need. We think with our lead asset, which is called beta flutamase calcium, it is the it would be the first approvable MS treatment that is neuroprotective in nature. It has two mechanisms. One is on the neuroinflammatory side and one is onthe neurodegenerative side. And so we think we've got a really interesting and unique shot at moving the needle in ways that other MS therapies have been unable to do on progression. So that's sort of unmet need number one. And then the second big unmet needs is really around safety and tolerability. There's a lot of medicines approved. It's really hard for patients to stay on them. And I think we have demonstrated out of a pretty robust safety database to date, 3,500 patients, a very, very unique safety and tolerability profile. And that's going to matter right away because there's a lot of need for medicines that people can start and stay on. And in particular, there's an large bolus of patients, actively treated MS patients that are on anti-CD20s today. Anti-CD20s are the dominant sort of class of treatment in relapsing MS, and they're really wonderful medicines, but you can't ablate people's B cells in perpetuity. And so you need medicines that folks can come off of anti-CD20s and step onto and still confer disease control, hopefully do something on progression, and do so with a safety and tolerability profile that is consummate to the sort of challenge of treating people who are immunosuppressed. Right. Okay. Yeah. So that's that's the thesis there. And then as it relates to this phase three study, you know, maybe talk about the phase two data. And what does that data sort of predict for the most likely efficacy and safety profile to come out in pivotal trials? Yeah. So we had a we ran a pretty robust phase two study in relapsing MS called the emphasis study. It gave us two, three things that give us a lot of confidence going into this. The first is looking at the MRI outcomes. Gadolinium-enhancing lesions are incredibly strong predictors in the phase 2 setting of the clinical outcomes in a phase 3 setting. And we had a very robust 78% reduction in gadolinium enhancing lesions in the fase 2 study. That gives us a tremendous amount of confidence that we not only have an active medicine here, but that it's clinically relevant range for the primary outcome in the phrase 3s. Second is, although they weren't powered, their phase two study wasn't powered for statistical significance on relapses. We did, of course, look at relapsis and we saw that we saw 42 percent risk reduction and relapse as was the point estimate. Not significant, obviously, again, but but that's a really healthy place to be landing in in terms of a read through on the confidence. And then third is the safety and tolerability. And I'll keep coming back to that because I think it's so meaningful. But the safety and tolerability profile was I've looked at everything and I'm asked for the last dozen years. I've never seen anything quite like this in terms of the safety intolerability. And I think it's really highly differentiated. It addresses a lot of the limitations of the currently available therapies. And it's going to be pretty appealing to physicians and the patients. Yep. OK, great. And you also talked at the start about disability being our disability progression being a significant unmet need or maybe progression in general. But to that point, what is your expectation and thesis there around some of the secondary endpoints? Maybe you could also talk about the NIR1 angle and whether or not that angle is likely to manifest in the RMS data. Yeah. So with RMS studies, I think what you what's typically done and we'll do the same is because the event rate is you're powering on relapses and the event rate for progression is less common. So we're going to have these twin studies, same study protocols. So, we will look at the progression endpoints in a pooled fashion. So that's a way to get a little bit more signal. But what I would expect, Paul, is I would expect a numerical advantage. I would to expect to see consistency across. But I do think in an 18-month relapsing study, the biostats are kind of against a screaming p-value, but We'll see. I mean, we're going to give ourselves the absolute best shot at seeing it. We certainly hope to see it. And it doesn't. And if we don't see it, I think it wouldn't mean that we're it wouldn'T. It wouldn't cause me to erode my confidence in NIR1. I think this is a study that's built to look at relapses and MRI and safety. It's certainly not a set of studies built to work at progression. That's why we're gonna run a third study that is built around progression in a progressing population with progression endpoints and power to do it. And what would you define as like a home run safety tolerability profile in phase three? Well, I think I'd look first to are we able to address the main problems that are out there among what we hear from patients? So you want to you want a clean liver liver signal. So that's that's one. You want to address infection imbalances, in particular, serious or opportunistic infection im balances. that would be number two. And then I think you want to look at the day-to-day tolerability issues that are the number one driver of treatment discontinuation amongst the oral treatments that are currently approved in MS. So this is nausea, vomiting, diarrhea, flushing, these types of symptoms. So you want to make sure that you're handling those. And then there's another medicine that was approved about 15 years ago called teraflunomide or which is a DHO-DH inhibitor, which we share that targeting mechanistic pathway with. And they also have alopecia rates like north of 20 percent. That's not a fantastic thing to have in a population of people who are two-thirds female diagnosed around 30 years of age. So we want to be able to clean up some of those issues as well. And we expect to see that based on our phase two data. Okay. Got it. Anything to add, Jason? No, I mean, I think Eric tackled it quite well. I think the thing to remember, again, is all the available oral disease-modifying therapies today come with these Achilles heels. They have a tradeoff on the safety side of things, again. For hepatotox, increased risk of malignancies, increased risks of serious infections like PML. But they also have these acute adverse events that make it very, very difficult for these patients to stay on these therapies. So, again, when clinicians and patients alike think about a disease-modifying therapy in MS, it's around the totality of the attributes. And our belief is that we're going to deliver a highly differentiated oral disease-modern therapy that can potentially deliver the best in oral class benefit risk profile. That's versus the currently marketed products and any future products like PTK inhibitors or others that might be coming to the market. And on that point, Jason, so when we think about, I know your primary endpoint is time to first relapse, but it seems simpler to compare these drugs on ARR. Tell me if you agree or not, but like, are we going to be able, do you think it's gonna be a fair comparison to look at the ARR in this phase three program and compare it to the older Abagio, Tecfidera, Galenia data? Maybe that's one question. And then, you know, also, how would you compare it zu the remibrutinib data given that study has an active control? Yeah, I mean, we should never cross-compare data, first and foremost. Do you think physicians will, though? I mean everyone does, but we should Never because, I mean, think about these studies that were done. If we don't cross- compare data, then I don't have a job. We want you to be gainfully employed. All right, so let's assume we do. I mean in seriousness here, the patient populations from 20 plus, 25, even 15 years ago are so different than the patient populations we're treating today. The relapse rates over time have gone down considerably. As Eric has alluded to, confirmed disability events have gone down considerably because we're identifying patients younger. These are healthier patients that are getting into trial. So it is extremely difficult to try and cross-compare. But what I would tell you collectively speaking, as Eric alluded to. We expect to see relapse reduction on time to first relapse in the 30% range, give or take, if we deliver that with good MRI data, with the safety and tolerability profile that we've seen to date, we think we have a highly competitive and marketed product. And in those ranges of relapse reduction, we'll be highly competitive against these oral products that you just mentioned, the fumarates of the world, the S1P modulators, et cetera. But, again, I go back to the fact that it's not just numerical reduction on efficacy that drives prescription behavior in this category. In fact, when you poll clinicians, whenyou poll patients, what you find is that safety and tolerability is equally important, if not in many instances more important than the overall efficacy profile of medicine. Because, again,, this is a chronic disease. These patients are going to be on these medicines for prolonged periods of time. And of course, like with any medicine, if they can't take the medicine because it's intolerable, then they're never going to benefit from, you know, from the medicine itself. And so it is a holistic picture. And again, we believe vitiflutimous calcium is going to offer a highly differentiated holistic picture, yeah. Okay, so maybe on the commercial side, like, can you talk about who you think are the likely early or just, you know, over time adopters of vitiflitimous calcium, and how would you, like, size each of those populations into market opportunities? Yeah, so we look at the market, and we've identified what we think are three very large and underserved patient populations today. The first, and probably the lowest-hanging fruit, as we would say, are just patients who prefer oral disease-modifying therapies. This remains a sizable percentage of the market. It's about 25 to 30 percent of all prescriptions today are for oral disease modifying therapies. And we've talked about the limitations of the currently marketed products. And so we believe we'll compete quite heavily for a large market share within these patients that just prefer that modality. The second patient segment are patients sequencing off of the anti-CD20 class of medicines. Now, these medicines have transformed the care of MS, specifically on relapsing disease. They own about a 50% share of the market. But what's quite clear today is that you cannot keep someone on a broad B-cell depleting therapy forever. And so what we know is about 10 percent of patients on an anti-CD20 today is actively looking to discontinue that medicine on an annual basis. Another 15 percent of patients on a CD20 today are using extended interval dosing to minimize the safety risks associated with that class. So collectively speaking, that represents 25% of patients on a CD20 or 40,000 patients that are actively going to be looking to sequence away from that class of medicines. We think of vitiflutamase calcium, given that it's an immunomodulator, given its safety profile, given it's antiviral properties, would be a great medicine to switch, especially patients that have infections on that class of medicines, but even those patients that are switching because of progression independence of relapse activity. We believe the NER1 story, the neuroprotective story, or potential impact on neurodegeneration would offer a very, very nice solution. The third segment are just older individuals living with relapsing disease. The innovation over these last 30 years in this space has changed the demographic of what a relapsed patient looks like today. Based on claims analysis, we believe that it's about 40 to 50 percent of all individuals with a diagnosis of relapsing MS today in the United States are aged 55 or older. So why is this important? Well, there's unique treatment considerations for these older patient populations. Immunosenescence begins to kick in, so the body's ability to fight infection just wanes with age. These patients have comorbidities. They're on polypharmacy. So again, you can't have this population on potent immunosuppressant-like therapies. We believe Vitaflutamase, given the profile that we've discussed, will be a very, very smart and powerful medicine for, again, this population. Yeah, the key thing that just for people to understand, I think, is that this is a very heterogeneous patient population and people's needs change over the course of their therapy. So what you need when you're first diagnosed and you're young and your immune system might be really revved up is going to be a little bit different than when you are 55 years old or 52 years old and you've you've kind of gotten your relapses under control for a bit. So I think this is not a sort of one one class takes the whole kind of pie type of a situation. What's true in MS is that novel mechanisms of action are valued. And so we're coming with the first potentially neuroprotective agent ever to be approved in this class. And we think there's going to be a lot of interest in that. Yeah. OK. Makes sense. How do you guys think about building a business here commercially? Maybe talk about like the target call point with physicians, how many reps you need and sort of like, you know, you have experience doing this. Both of you have bigger companies. Like, is this a market that a small emerging biotech can can compete in? Well, I think the answer to that is without a doubt. I think there's a very good recent analog in TG Therapeutics to show that a small, relatively kind of first-time launching company can step into the space and compete quite well. I think a couple of things to remember here. First of all, there's really three active companies competing in the space, right? You have Novartis, you have Roche, and you have TG Therapetics, right. So I think The Space is ripe for another manufacturer like Immunic to step into The Space. The other thing to remember is that there's roughly 3,000 clinicians writing 80% of the volume of prescriptions. So you can be very hyper-targeted on where you're going. We've talked a little bit about the growth segments of the patient populations that we would focus on. You could further segment the market based upon some of these unique populations that these clinicians might be treating. The approach that we plan to take is a targeted approach. We plan, you know, back 20 years ago, Paul, you would have had to hire, you know, 200 to 300 reps, you know, to try and compete in the space. That is clearly not the case today. And so we're not going to, for competitive purposes, talk specifically on the numbers we think, but it's much lower than that. We will have other customer-facing roles that will support the patient and clinician journey in prescribing these medicines like MSLs, TLLs, field reimbursement managers, et cetera. But and I think the last point I'd make is that, you know, as you've mentioned, I come from a background in marketing many of these products. Eric came to us from Genentech. We know this space. We know the top talent in this space and our expectation is we're going to go hire the best of the best to join the company and to really help us market and commercial this product. Yeah. OK, great. Yeah. Maybe just one more question on Revy Brutnib since it comes up so much. I mean, some of the patient segments that you've talked about, Jason, are segments strategically that I'm sure that drug will be positioned in. Like, how do you guys expect physicians to make a choice on what is the right option for, like, a CD20 switch or for an older patient or things like that? I can take the first shot at it. I mean I'd say, first of all, there's plenty of room in the market for Vitaflutamase calcium and Remabrutinib to compete and thrive. I think rimobrutinib will be a successful medicine. I also am very confident Vitaflutimib's calcium will be a successful medication. Some places where I think we might end up seeing some advantage, as a reminder, we haven't unlocked our data yet to take a look at it, so obviously reserve the right to sort of come back to this question once we've seen what we have. But I think they showed up with a relatively clean liver profile. I think that was a big question that the field was curious about, and they deserve credit for that. But they do have a nearly two-to-one imbalance on serious infection risk. They had a pretty strong imbalance on bleeding risks. They have kind of a complicated DDI sort of profile to sort of navigate. And if you think about the patient I just keep thinking about is the one that Jason painted a picture of. So I've been on an anti-CD20 for, let's say, five years. I've depleted my B cells. I've gotten my relapses under control. I haven't had a blip of my MRI in a couple years, but I'm worried about serious infection risk down the line. Am I going to reach for a BTKI, which is still impacting B cells, not depleting them, but still sort of affecting B cells? It has a serious infection imbalance, has some some other hangover kind of questions in the class. Maybe I'm an older patient. I've got some polypharmacy considerations. I just don't think that Remy is going to be the first thing that the patient or the physician reach for in that particular patient. There are others for whom they might. But my point is, I think we can both succeed. And frankly, if, you know, my expectation is that over the 40-year journey that someone is being treated with DMTs and NMS, they'll probably end up seeing rimobrutinib and they'll probably endup seeing vitiflutimus calcium along the way. Right. And that's just where it is. Yep. Okay. You know, with there being generics in this market now, what do you guys think the most likely step edits are to prescribing vitiflitimus calcium when approved? Yeah, so, I mean, there's very good recent analogs around how branded products are treated in this space. In the oral class, for example, just a couple things from an access perspective, there is still very high WAC pricing here, right? So, the average oral disease-modifying therapy in MS is priced today at about $115,000 USD. You know, the gross to net on average is anywhere in the 30 percent range, so there is high net per patient pricing here. All the branded products, you know, are treated the same. They're placed on a specialty category. You know, they have to be prescribed by a specialist. There's usually a prior authorization, usually just to confirm the diagnosis of the disease. And then most plans require a failure of one or two previous therapies. There aren't prescriptive enough to sit here and say you must step through this product A to get to product B. You don't think they'll say generic Abagio? That's always the question. I mean, that's the question we always get. Remember, our medicine is vastly different. We share one of the mechanisms of this product is a DHOH inhibitor, but we do it in a much more selective manner. So the data to date supports a much cleaner and safer profile versus that. Our medicine is a neuro one activator, of which we know abagio or terraformide does not bind to nor activate that target. The chemistry is completely different. The PKPD profile is completely difference. And so I think, you know, you're going to be hard-pressed to find a PBM or a payer plan that's going to say you must fail on this generic product, terflutamide, to get to VitaFloam as calcium. So, again, and the other thing I'll just make mention here is that two points is that, you Know, the branded products in the space today have large, large coverage. It's over 90% coverage across the plants. And even in the categories in which there's generic products on the market, it's about a 50-50 split of use of branded products versus generic. So it's not like, you know, the generics make up 90% of a specific class of medicines, et cetera. Again, we believe that we'll be able to sell through and pull through. I think that there's wind at our back here, Paul. Makes sense. Do you want to talk a little bit about Progressive MS, the data there, and the plan phase three? Yeah, I would love to. So we had an R&D day last week. We were able to sort of roll out some of the specifics around what we're calling the PROTECT-MS study, which is a Phase III study in progressive MS. It's going to be – we're initiating it now, first patient in, expected first half of next year. This is a study of around 1,400 patients. We'll be using a progression endpoint, which is time-to-worsening or a nine-hole PEG test to power it. And, yeah, we think this is extraordinarily exciting. It's on thesis for NIR1. And we have – we're really leaning into this opportunity on the basis of a Phase 2 study that we've conducted called the CALIPER study, which was a large phase two study, 467 patients. And what we saw in that study were a couple things that were really interesting. I should, in transparency, note that the primary endpoint was whole brain atrophy, and it actually missed on whole brain atrophy. This is a phase two steady. The reason whole brain Atrophy was selected is there's not really a good phase two marker that's predictive of phase three success. At the time the study was initiated, people thought maybe whole brain atrophy would be a good marker. It has been subsequently shown in meta-analyses to have really no correlation whatsoever with progression, which is unfortunate for the company that that was the primary endpoint of the study. But you don't throw the baby out with the bathwater because what we saw beyond the primary was a couple of things that were really interesting, including on imaging. So in terms of volume, we looked at sub-regions of the brain that are much more sensitive. So thalamic volume, massive advantage to active treatment. You saw in slowly expanding lesions, which is thought to be a really emerging biomarker that's looking at the smoldering disease. We saw statistical significant impact on cells. And then clinically, we looked at, it's not powered for clinical outcomes, but we saw an impact on worsening. And we also saw an effect on improvement. So people actually improving on the medicine. Last thing I'll say on this is we did a subgroup analysis, a large subgroup though, it was like about 85% of the patients that were not only non-relapsing, but also non-active, meaning at their baseline screening visit, they had no GAD-enhancing lesions. So no evidence that there's an inflammatory process that's going on. And in that population, we saw not only the benefits that we were looking at on progression holding, they actually looked stronger in that sub-cohort of patients. This is hugely meaningful Because if you look at something like Ocrelizumab, which has a label in primary progressive, their original data was largely driven by the opposite cohort, which was a younger GAD lesion kind of based population. The group that no one's been able to really move the needle on is this truly non-active population. And we did. Now, it's a phase two study. So let's not get too over our skis. But it is aligned with a neuroprotective mechanism. And it's either noise that won't hold up in a larger trial or it's some of the most compelling evidence we have of NIR1 as a clinically meaningful target and progressive MS. We're obviously betting on the latter and we're going to chase that that theory down to the ground with a with a big, big powered study to show it. Great. Maybe in the last minute here, do you guys just want to wrap up and touch upon your cash runway into into data? Yeah, sure. So we had a big financing event that happened earlier this year in February that would that that generated 200 millions of proceeds for the company. We've been working through that. That allows us to get aggressive, read out of two phase three studies, plan for a third and bill and start the commercial build. There were some warrants that were a part of that. So there's a tranche to have warrants, that have the opportunity to convert on positive insure one and two data. so coming up right around the corner should that all convert that's another 200 million if that converts that gives us a runway into mid-2028 so i'd say we're in a pretty comfortable position on the balance sheet data and market supporting we'll be looking at different financing options on the back of data as well to strengthen it further yeah great best of luck guys always great to see you all right thank you thanks paul thanks everyone