IMMUNIC, INC. (IMUX) GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - IMMUNIC INC

All right. Good afternoon, everyone. Welcome to Guggenheim's third annual healthcare innovation conference. My name is Yatin Suneja, one of the biotech analysts here at the firm. It is my pleasure to introduce our next presenting company in Munich. From the company, we have two executives here. We have Eric Lundgren, who is the chief executive officer, and then we have Jason Tardio, who's the president and chief operating officer. Eric, I'm going to pass it on to you. Maybe perhaps make some opening comments. Tell us about what we should be focused on in the next, let's say, a few months or so. And then we'll go into some of the Q&A that I have prepared for you. Yeah, for sure. Thanks for having us, first of all. I think it's a really exciting time for us. We have two pivotal trials reading out in December. So we're right around the corner, right on the threshold of that data. These are two studies called INSURE-1 and INSURA-2, and they would, if they're positive, result in an NDA filing and approval in relapsing multiple sclerosis. So I'd say our priorities really are preparing for that readout, building the commercial launch apparatus and infrastructure to support it. And then we just announced last week Progressive MS study, a third pivotal trial in Progressive MS called the Protect MS study that we're initiating right now, expecting the first patient in the first half of next year. Got it. Maybe first question is on the corporate side and the commercial side. So you just joined recently, right, Eric? And then you have a new CMO, there's a board chair. Jason, you've been here for a while. So maybe just talk about how are you building from a corporate standpoint? How should we think about the commercial angle? Because, you know, if the data are positive, you could be finding NDA and you could be pretty close to commercial relatively soon. So talk about those two. Yeah. I mean, I think I joined in June. I joined following 19 years at Genentech Roche. I got sort of the reason I'm probably here is I was a part of launching Ocrelizumab, which is the most prescribed MS medicine in the world today. And it was quite an experience to transform the MS market with the introduction of anti-CD20s. That was a decade ago, though. And I think I came because the unmet needs today are extremely clear in MS. They're as clear today as they were then. And I Think the market is ripe for disruption again. And that's where I think this is allowing us to sort of lean in. And as you said, I mean, I'm not the only new person. Our board, not only our board chair, multiple board members have turned over. we've had the ability to bring in a bunch of executive and team level talents, which is really a reflection of this pivot from a development stage to pre-commercial stage company. And I'd say that's, and with the board changes, the remit strategically has also become CRISPR, which ist about this is an MS company focused on commercializing our lead asset. And that's where we are. Jason, how about you? Yeah, from a commercial perspective we're actively preparing. Once we have successful data in December, it will be an accelerated effort to scale and ramp the company. But we're not waiting for that. We've put a lot of work in place to validate our initial strategic assumptions around go-to-market strategy. We have begun to hire key leadership roles on the commercial side of the business, a VP of marketing. Today, We just had a new vice president of patient advocacy start at the company. We've built out the medical affairs organization and begun to deploy a series of medical science liaisons that are out there educating the market. So we're doing a lot of work now. And, of course, you know, if we have successful data in December, we'll accelerate those efforts. Got it. Very good. Very helpful. Then let's just talk about the product or Vitafil-MS. What is the mechanism? I think one part of the mechanism, I think investors and even the physician community know, but it's the neuroprotective side of it, which is the NeuroOne activation. It's not very well known. What do you get a sense, like how familiar are sort of KOLs with this mechanism? I'd say KOLS are quite excited about the NeurOne activation side of our story. Just to sort of back up, though, VitaFluidinous Calcium is a once-daily oral tablet, it. And it really has two underlying mechanisms, as you said, Yadin. There's DHO-DH inhibition, which is a proven pathway in relapsing MS, more on the neuroinflammatory side. But there's really nothing approved today that's neuroprotective. And that's where NeuroOne comes in. Neuro One upregulates a series of genes that are associated with neuronal repair, resilience, and survival. And if you understand the underlying disease mechanism in MS, there's sort of two underlying processes. One is sort of an autoimmune or neuroinflammatory disease component, hyperactive T and B cells effectively. That's what everything approved in MS targets, either through modulation or suppression. Nothing is working on neurons directly and nothing is really working in the CNS compartment directly. And that's where the NIR1 piece of beta-flutimus calcium comes into play. So if approved, it would be the only therapy that is working directly on neurons. And the largest unmet need in MS today are medicines that create a meaningful impact on disability progression. And to do that effectively, you need to reach beyond relapse control and MRI control. control, you need to sort of get into that neuroprotective space. And Vitaflumus calcium is a great shot on goal at that. All right. What sort of preclinical and clinical evidence you have produced to sort of prove this new one activation thesis? Yeah. So we have got a huge set of pre-clinicle data. We shared some of it at the MS meeting in Toronto just a few weeks ago. But, you know, we're very confident. we're binding to, activating NIR1. We can see this in in vitro models. You can see neuronal survival against challenge. You Can see that that effect goes away when you knock out NIR 1. So we're very confident that this is a direct NIR-1 component as opposed to the dhodh sort of piece of our mechanism. So we have a quite robust set of preclinical findings. But I think the piece that gets us most exciting is actually in the clinical findings so from our we had a phase two study in progressive MS which was called the caliper study relatively large phase two steady 467 patients and while it wasn't powered for clinical outcomes the clinical outcomes on progression both in terms of slowing the worsening of the disease but also patients improving on their disability um was very interesting uh and and very compelling to us especially in a patient population that is had no evidence of neuroinflammatory disease driving processes so this is sort of the holy grail in ms drug development at the moment is being able to move the needle in that hardest to treat population and we saw some very exciting i wouldn't say they're confirmatory of anything it's phase two findings nominal all that stuff but it gives us confidence going into a phase three study to prove it out got it got it so then with regard to the phase three studies that are going to read out relatively soon can you maybe recap the design how are they powered what are the benchmarks that we need to be paying attention to yeah so they're they're kind of twin studies so the same same exact protocol running sort of on parallel tracks they read out at the same time And sure one and two in total. We're talking about two thousand two hundred twenty one patients. So massive studies really large Thirty make dose once daily of Vita fluid miscalcium versus placebo And the primary endpoint is time to first relapse. So it's a relapse study and then there's a you know a series the normal slate of MRI and other relapse related endpoints and then we pull the studies to Look at a bunch of progression related Got it. How would you characterize, like, a win here? What would you need to show? And maybe if you want to recap the emphasis of what you saw in the emphasis. So emphasis was our phase two study in relapsing disease, 260-some-odd patients. Seven. 67? Yeah. Thank you. And, I mean, the answer, we haven't guided to a specific number for the insurer, but I would love to recapitulate what we saw in emphasis. We saw a 42% risk reduction on relapse in that study, and we saw a very compelling safety and tolerability profile. And we even asked about that, but I mean, safety and tolerabilty really are essential components of treatment selection in MS. It's impossible to overstate how meaningful that is. It's a chronic disease. Neurologists are typically quite conservative. and there are limitations on that side of the equation for everything that's approved today in MS so it's a huge area of white space for differentiation is on safety and tolerability yeah since you I mean I'll come back to efficacy but since you touched on the safety so we can address that I mean if you see the data across all the patient it seems very benign from a safety standpoint but when you see higher efficacy orals you know they have either tolerability issues or let's say the BTKs. So maybe both of you talk about profile that you expect. And then from a commercial standpoint, if BTK has come on the market, how will the safety differentiation shake out? Yeah. Let me start and then I'll let Jason handle the differentiation. I think from a safety perspective, we have a pretty robust safety database, 3,500 odd patients. Some folks have been on for up to seven years. So for where we are in development, I'd say quite a robust read. I'd also note that a placebo-controlled study is the highest bar you can possibly set on safety and tolerability. And as you said, I joined the company in June. The first thing I looked at when I was doing my due diligence on the company was the safety and tolerance. And I've seen everything in MS for the last dozen years or so, and I've never seen anything like this. And it's quite impressive. It takes care of a bunch of, or at least sort of knock on wood somewhere. Thus far, we don't see any evidence of many of the either tolerability or serious safety issues that have plagued MS treatments. So we see a very clean liver profile. We see a very, very clean infection profile. We don't anything at all in terms of GI tox issues that are so prevalent with MS treatments today and lead to so much discontinuation of therapy. Abagio or teraflutamide, which is also a DHO-DH inhibitor but is sort of a first generation version, has a bunch of off-target effects that are quite limiting. Alopecia, embryo fetal tox, a bunch of things, some liver issues as well. All of those seem to have been cleaned up with the chemistry. And I think that sets us up with, again, a highly differentiated profile. Yeah, I think what I would add there is if you look across the oral disease modifying therapy class, to Eric's point, there's benefit-risk trade-offs. And so what we think fetal flutamase calcium may offer to the market is the best in oral class benefit-risk. And that's versus the currently marketed products and certainly versus any potential BTK inhibitor that may or may not make it to the marketplace. And I should remind you that it's a very sizable portion of the market. The oral class still makes up roughly 25% to 30% of all prescriptions. And so it's an meaningful segment. It's a segment that's ripe for innovation, and we hope to deliver that with data in December. And also, I think, Jason, maybe you and I had discussed it a while back. I think your product, Orvido, has a much shorter half-life versus teripunamide. Can you talk about that dynamic? Is that something that physicians care about, you know, the reversibility of the effect? Certainly. And so just to ground everyone here, the half-life of VitaFluidomus calcium is about 30 hours compared to, you Know, upwards of 16 to 19 days, if you will, for terafluidomide. I mean, the serum half-Life of these medicines is vastly different. Our medicine is out of the system within less than 10 days. On teraflutamide, it can stay circulating in the bloodstream for over two years in some patients. And so as per their label, it mandates activated charcoal to rapidly eliminate that. And so when you think about the disease, the disease of young women, that's certainly a differentiator. And we think it's going to allow us to be possibly used in a population where, you know, terafutamate had limitations. Got it. So now I want to go back on the safety side, at least in terms of the Ensure 1 and 2 studies. So a couple of things. So I think in October of 2024, there was an interim analysis, and then IDMC said, continue, no change. What is the implication or read through, or how should we read that? And then, you know, I think you are doing a pooled analysis also of different endpoints, whether it's CDI or CDW. What should we be expecting there? yeah on the interim question i mean i think that the idmc was asked two questions um they unblinded the data and looked at it and the questions were is the study futile yes or no no the answer was no it's not futile and then the second was are the powering assumptions that went into the study initially adequate um to to to see a result or should the sponsor change the protocol I'll add more power to the study. And the answer was continue unchanged. That analysis was done at about half of the expected event rate, so about halfway through the study, so what's the read-through? I think the read through was they said continue. And that's somewhat encouraging, and here we are today sitting right on the cusp of the final answer. So I don't think there's much more that you can say than that. It's encouraging. I think that that's a data point. I think the other data points I look to are the emphasis study directly. The baseline demographics are very consistent between the phase 2 and the phase 3 enrolled population. And then the other piece in relapsing MS in particular, gadolinium enhancing lesions is an extraordinarily effective predictor in phase 2 of what your clinical outcomes in phase 3 are going to be when you look at meta-analyses. One of the nice things in MS is you have a lot of studies to do big meta-analyses on, and that has always been consistently the case. So if you see a GAD lesion impact of 50% or more, you're pretty much in safe zone in terms of your primary outcome in the phase three. We had a 76% reduction in GAD legion. So we were well, well above that sort of general rule of thumb benchmark. So we feel that the phase three is largely de-risked on the primary outcome. And again, I'll knock on wood just because I don't want to attempt the clinical trial gods too much. Yeah, and then with regard to the pooled progression endpoints, what will be included? How would you define sort of success in these? Yeah, so we look at the, because progression in relapsing studies are relatively rare events, You pool the studies together. We're not the only ones to do this. Pretty much every MS program does this in relapsing disease. And then they're hierarchically sort of evaluated. So we've done something a little bit novel with our stats plan. And we put an endpoint called net clinical benefit at the top. Net clinical benefit is still using the EDSS scale, which is the gold standard for how progression is followed and measured. in MS patients. But it's using a general pairwise comparison. So it's basically getting more out of the same scale. So typically, you're going to look at disability, slowing disability progression is the kind of most standard endpoint utilized. This does that as well. But it's also looking at and valuing if someone stays stable versus a person on the control arm that worsens, that's a win. If someone gets better versus someone that stays stable or gets worse, that is a win, and so you get a lot more data out of it. This is a way of doing these analyses that's been used in oncology studies, and it's being explored in epilepsy studies, and so it's a way to use the gold standard tool, but to just get more signal out of it. So that's where it comes in. And how would you characterize the phase two to phase three translation from an effect standpoint um i mean would you expect any deterioration from what you show in emphasis that's one and then the second is where we get more pushback from investors is that look you have these high efficacy orals you know maybe btks at some point will play in that mix why would somebody give up on the efficacy yeah um well well on the read-through um i think you know you you can look at the baseline characteristics and i think the the read through is we've we've moved as many as as few variables as you possibly can and so i think um i i i don't have much to add to that other than i think we've we've got a pretty clean clean read through we hope and we would love to see it be in that zone there's often a little drift off of a phase two to a phase three it can actually drift in either direction and ii think we have plenty of room based on where we landed in the phase two 42 risk reduction on relapses which we think paired with our safety and tolerability profile as Jason said is a best-in-class total risk benefit package so we can drift around that a little bit and I think we're very viable commercially got it got it maybe then go on the commercial side like are there segments of patients that you would target how large is the market and how quickly you'll be able to even file for approval yeah I mean the way that we look at the market is just as a reminder the relapsing market in the United States is a large market, $70 billion. Today, it's going to grow to be a $25 billion market as we get into the 2030s. The other thing to remember is that there's 300,000 patients treated today with a disease-modifying therapy in relapsed MS. It's a dynamic market, which approximately 90,000 of those 300,00 are actively looking for something new on an annual basis. These are individuals coming in and initiating therapy. These individuals that are switching therapies. And so it's not a zero-sum or a one-size-fits-all. The market itself, you know, patients have this 30- or 40-year journey on a disease-modifying therapy. Andso what you really want is a medicine that's going to meet that patient at different points in their potential journey, whether that's, you know, when they're initiating therapy, whether it's when they'RE switching therapy, whether it'S when they'Re older. AndSo the way that we look at the market is that, Again, it only takes about a 4% to 5% total market share capture to drive a billion dollars in sales. And so what we do is we look at the value proposition of Vita-Futimus calcium, a uniquely novel mechanistic approach to address both aspects of the disease, as we discussed, a selective inhibitor of DHODH for anti-inflammatory properties, an activator, the only medicine in development that activates NIR1 for neuroprotective properties. We've driven great efficacy results to date, balanced with what we think could be best in disease safety and tolerability. That's a profile that we think is a winner. And so, again, you asked a little bit about high efficacy therapies, et cetera. Efficacy is certainly an important consideration, but it's not the only attribute that clinicians and patients alike think about when they're making treatment selections. What they're looking at is the holistic picture. So what does efficacy look like compared to safety, compared to tolerability, compared to convenience? If you take all of these factors into place here, again, we believe VitaFloodim's calcium is going to offer a highly differentiated medicine, specifically within the oral class. And we think we have a commercial winner on our hands. Got it. And I'd say the other big conversation in the MS community today is, how long is too long to be on an anti-CD20? So anti-cd20s have become the dominant sort of mechanistic sort of class, right, anywhere. It's about 50% of the market is on an anti-CD20 today. It's more than that in terms of treatment initiation of a treatment-naive patient. Probably 70%, 75% of patients are going to start on an an anti CD20. But the thing is, as Jason said, people are going live with managing their MS for 30 or 40 years. And pretty much all the doctors I talk to, there's not a consensus view, but it's somewhere around three years, between three years and eight years, depending on the doctor and probably depending on the patient across from them, where they're starting to say, that's too much risk now. There's too risk for opportunistic infection or other issues. And so you're not gonna be on an anti-CD20 forever. And if you think about the market today, again, I was a part of launching Ocrevus ten years ago. It was ten years in March that that medicine launched. It's been the dominant medicine for the last six years. There's a lot of patients that have been on anti-cd20s continuously for really long time and there is not a therapy available today that makes sense as a as a switch to off of an anti cd20 because most of the medicines today are either immunosuppressors or have infection risk or have tolerability issues that are going to limit patient acceptance or have PML associated risk which is like the big scary side effect in MS. And that's where Vito, I think, is such a natural, easy fit right out of the gate. It's a huge need. Every doctor you talk to that has more than a handful of patients in their clinic that they're treating for MS is going to talk about it. And we see an immediate opportunity to slide in there. Got it. And then how quickly you'll be able to file, and would you want to launch it on your own in the U.S.? Absolutely. Yeah, we are planning to launch It on our own. And you asked in the beginning about some of the board changes, and that's really what that was about, is about pivoting to being a commercial company and building ourselves. That's the remit of the Board. That's what we are building and planning to do. In terms of filing, middle of next year would be the goal for filing. and then you know so middle of 28 is sort of the general guidance around launch got it I think last week you did an R&D day on the progressive MS side perhaps would you like to recap number one the finding in caliper and what the path forwarded and the timelines of the phase three study yep so caliper was our phase two study in progressive MS as I said some very exciting findings I should note, the primary endpoint of that study was whole-brain atrophy, and it missed on that, actually. So just to be very transparent about that, it's been subsequently shown in meta-analyses that whole-brain atrophy is an incredibly poor predictor of the clinical outcomes. And so it's a little bit of a disappointment that the company had made that the primary end point. Nevertheless, there were a bunch of other findings in that study that were incredibly encouraging, both on the imaging side, so certain regions of the brain and volume changes, and then in particular on an endpoint called slowly expanding lesions, which is thought to be a real marker of this sort of smoldering progressive component of the disease where we had a nominal statistical benefit on cells. But the clinical outcomes were what really caught my eye, in particular in a subset of patient, large group of the patients, about 85% of the patients, who had no relapses and no GAD-enhancing lesions at baseline, so no evidence of any sort of inflammatory component happening with them. And we saw consistent directional benefit across worsening and improvement in those patients. And if you're seeing that, that is something that has never really been shown before. So this is a nominal finding in a Phase II study. So it's not confirmatory of anything, but it does give us a lot of enthusiasm to charge into a phase three, which is what we announced last week. This is a study called the PROTECT-MS study, and it's going to be about 1,400 patients looking at a non-active progressive patient population. And what is the timeline for it? So we're initiating it now, first patient randomized first half of next year, and It will be about a three-year study. got it got it maybe then final question how is the financial health of the company the capital position yeah good you know there was a big financing event that you're well aware of but it was a Big Pipe that that was announced in February of this year there's a second component of the pipe that has the potential to convert warrants to cash and equity in within 30 days of the public disclosure of the insure one and two studies so that's coming up that that would yield another 200 million of cash for us, which gives us runway into the back half of 28. Well, very good, gentlemen. Thank you so much. Thank you, so much! All right. Thank you.