All right, good morning everyone. Welcome to Guggenheim's Emerging Outlook, Biotech Summit 2026. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim. I'm joined here with my colleague Eddie Hickman, and we will moderate the next session here. It is my pleasure to welcome our next presenting company, ProMIS Neurosciences. From the company, we have a few executives here, but we will be chatting here with Chief Executive Officer Neil Warma. Neil, very exciting time, and ProMIS, you're gonna have some key data coming up this year, well-financed now as well. So why don't you make some opening comments, tell us about the story, what are some of the upcoming catalysts, and then we'll moderate the discussion.
Thanks, Yatin. Thanks, and thanks for the introduction. Always happy to be at the Guggenheim conferences, Eddie. Always great to see you as well, and thanks for hosting us today. Yeah, as you say, Yatin, it's a really kind of exciting time for us at ProMIS. For those of you who are kind of new to the story, ProMIS, publicly traded company, ticker is PMN on the Nasdaq exchange. We're focused on the treatment of neurodegenerative diseases, primarily in the dementia space. So we've got product candidates for the treatment of Alzheimer's, ALS, Parkinson's, Lewy body dementia. But it is, as you say, it's really a kind of an exciting time for us. We're coming off the back of, I guess, two really important milestones for the company relatively recently. Our lead product, PMN 310, is currently in the clinic for the treatment of Alzheimer's disease.
The milestones we've delivered, I'm pleased to say, on target and on time, was the completion of enrollment in the phase 1b study that we're running. So we completed enrollment in the middle of December last year. We are oversubscribed. We enrolled a total of 144 patients in our phase 1b study in Alzheimer's, Alzheimer's disease. So that was a key milestone for us. The second milestone, which is also very important, which we achieved just a couple of weeks ago, was the really a transformational financing for the company. We were oversubscribed for that too, but we raised a total of up to $175 million, really with an A-list of, of investors coming into that as well. It was led by Janus, Ally Bridge, participation by Wellington, Deep Track, Great Point, TrailsEdge. So a really superb syndicate. So fully enrolled in the study and fully financed through data.
As Yatin, as you said, it's really important a year for us. I think, I think it'll be a kind of a watershed year for our Alzheimer's patients in general and certainly for ProMIS. We have data coming up, kind of an interim analysis, kind of a qualitative look at the trial data, in around the middle of this year. And then we've got final top-line results towards the end of this year. So we're excited about that. And I think, you know, probably the best decision we made was in the design of the phase 1b, the ongoing study. And we have quite a robust phase 1b study and, as I said, enrolled 144 patients. It's a 12-month study, so monthly dosing for 12 months in early Alzheimer's disease. It's dose escalation trial, placebo-controlled, randomized study. So it really is a robust study.
What was important to us was to design a study that would give us a definitive answer as to whether this truly differentiated antibody works in Alzheimer's disease. So we should find that out over the next several months. As I said, it's nice to be in the same year where data comes out. It's nice to be fully funded through data. It's, again, very important to have a differentiated asset, which we believe we do. We believe we have kind of the only antibody drug candidate in development that selectively targets the most toxic species of these amyloid beta protein, and that being the toxic oligomers. So we're excited to be potential for best-in-class with data readout later this year, kind of months away, so to speak, and fully financed.
Got it. Thank you for that. So we'll go into the nitty-gritty of the trial and the study. Can you just also talk about, because it's something really unique that you're trying to prove here, right, going after these toxic oligomers. So what is this EpiSelect platform? Because it seems like you this is your antibody you're trying to prove. So just orient our investor, you know, what is this EpiSelect? How did you come up with this hypothesis? And then Eddie can moderate, like, the next session.
Yeah, thanks, Yatin. That is an important point. This is all proprietary to ProMIS Neurosciences. It is a platform company, and it's generated a number of highly selective antibodies. It's really based on the brilliance and the efforts of our founding scientist, Dr. Neil Cashman. Dr. Cashman is one of the foremost leaders in understanding how misfolded proteins drive a number of different diseases. So our whole premise, I mean, ProMIS, is protein misfolding. The platform is derived on designing antibodies. This is kind of, I won't get into necessarily the science, but it's a unique way, a differentiated way of designing antibodies, looking at being able to predict how proteins misfold and then identifying a unique binding site on that conformational epitope to which antibodies are designed against.
So it's a fundamentally different way of designing antibodies, which is why we can say we're selective to the toxic oligomers. Others have certainly tried but have not quite gotten there. But we have a very different way of doing this. So from this Epielect platform, we have a highly selective antibody for these toxic oligomers, for amyloid beta protein. We have a highly selective, antibody targeting misfolded forms of TDP-43, critical for ALS, misfolded forms of alpha-synuclein, which we're going after for Lewy body dementia and Parkinson's.
The EpiSelect platform, again, is truly proprietary to ProMIS and has enabled us to generate even beyond those two or three candidates a kind of pipeline of candidates, which once we demonstrate proof of concept in Alzheimer's disease at the end of the year, that kind of shows proof of concept across the entire platform and kind of validates the candidates coming behind it.
Yeah, for those in the room who aren't as familiar, can you walk us through a little bit about what we know about these toxic oligomers and why they are, you know, sort of the focus of your research and focus of your company and what preclinical data you've shown so far as to how PMN 310 acts on these oligomers?
Sure, Eddie. It's an important question. We get that obviously, we get that question a lot. I think, you know, a couple of decades ago, the focus was on these, kind of plaque formations, you know, the plaque that builds up in the brains in Alzheimer's patients. And that was the focus that people thought that was driving kind of cognitive decline in Alzheimer's disease. But we've shown in over I mean, over the years, as Dr. Altstiel likes to say, even back when Alzheimer's day and over the years, the link to plaque clearance and cognitive decline has really not been proven. And now we know there's drugs that completely eliminate plaque, and the patients continue to decline. So the link between, you know, cognitive decline and plaque has been, you know, I won't say disproven, but the link has moved away.
There's been a lot of research and understanding from our side, but also from others, that it's these kind of upstream, low molecular weight, highly toxic oligomers that are really driving cognitive decline. What we know and what the literature and the, you know, thousands of publications show is that these oligomers are especially toxic to the neurons, but specifically the synapses. So you get this destructive, you know, this destructive process created by the oligomers attacking the synapses that drives cognitive decline. Then over the years, the challenge has been as people understand that, it's like, well, how do you design an antibody that can hit the oligomers but avoid other forms of the same protein? I mean, there's multiple species of amyloid beta. So how can you hit one and not the others? That's been the challenge with other antibodies that have tried.
I mean, lecanemab was designed to go after these toxic species, but it also binds monomers. It also binds plaque. There's other drugs out there that have been tried to be selective, but again, they all cross-react. And that comes back to our EpiSelect platform, that we have a very fundamentally different way of designing antibodies that allows us to selectively target only the oligomers. And we've put that kind of to the test, really, over the past years to prove to ourselves, to prove to FDA, to prove to the investors, that we seem to be the only company now that has a selectively targeting oligomer. And we've done multiple assays where we've done side-by-side analysis looking at really all the drugs on the market and in development, you know, who binds plaque and who does not.
Consistently, PMN 310 was the only antibody out of all of them that did not bind plaque. You know, we did a robust tox study where we dosed mice for half a year, 26 weeks, up to 800 mg per kilogram, just to see if we had any, any bleeding, microhemorrhage in the mice brain. Because one of the things we know with drugs that bind plaque, not only is there no kind of tremendous benefit cognitively, but drugs that bind and clear plaque are also associated with ARIA. You know, and this is this significant side effect. In ARIA, you get either swelling or bleeding in the brain. So not only is plaque not that relevant anymore, it also has a serious side effect. So there's, you know, there's good reasons to, even from an efficacy, but certainly from a safety perspective, to try to avoid plaque.
Again, monomers are beneficial. You don't want to hit those. The challenge also is that they are much higher concentration, plaque and monomers, than the oligomers. So if you're delivering drug that cross-reacts with all species, it gets soaked up by the off-target species and very little gets to the oligomers. Whereas our drug, PMN310, all of it's designed to avoid monomers, avoid plaque, and only hit the oligomers. So we're expecting much reduced liability with respect to ARIA and improved efficacy as well, given the selective targeting.
Great. And you've shown both of those in mice models so far, comparing sort of the binding of different antibodies that are commercial and in development to plaque.
Correct. And we've shown lack of plaque binding kind of across the board in multiple different preclinical studies. And then we've also shown, you know, preclinical animal models, you know, as predictive as they can be, but, you know, very strong efficacy in the animal models as well in improving cognitive benefit.
Great. So, yeah, moving towards, you know, the phase 1b study, which you've over-enrolled, talk to us a little bit about who these patients are that you enrolled, which types of patients you were targeting, and, yeah, we'll go from there.
Yeah, sure. As I said, you know, it was an interesting decision and probably the best decision. And when, you know, with Dr. Altstiel, our Chief Medical Officer, having, you know, he was currently a practicing neurologist treating Alzheimer's patients, but importantly, ran CNS at Pfizer for years. So Larry's kind of, you know, we stepped back, you know, a couple of years ago now and said, we, as I said at the outset, we need a study that's going to give us a definitive answer. And other companies had kind of done a three-month, 30-patient, kind of quick and dirty biomarker study, and that doesn't really tell you much. So for us, it was like, you know, the direction to the team was design a study that's going to give us an answer.
So that we came up with the Precise AD trial, you know, 100+ patients over 12 months so we can get a clear clinical signal at the end of it as to whether the antibody, you know, works with clinical outcomes in addition to safety and biomarkers. So we embarked on this study about a year ago, kind of towards the beginning of last year. It's a placebo-controlled, double-blind, randomized study. It really is a very robust phase 1b study. It's probably one of the more robust 1b studies kind of out there. The goal, as I said, was to get to, you know, as much of a definitive answer as we could over three ascending doses. So we're at 5, 10, and 20 mg per kilogram. We are enrolling patients, kind of early Alzheimer's patients. So these are patients with MCI, mild cognitive impairment due to Alzheimer's disease.
We wanted to have a relatively homogeneous patient population coming into this that we screen for the presence of Alzheimer's disease. And then the endpoints that we're looking at are really three buckets. One is biomarker. We've got a relatively robust panel of biomarkers that we're looking at. And biomarkers are relatively well understood in Alzheimer's disease. So biomarkers endpoint, bucket number one, safety in ARIA. Again, one of our claims going forward is we expect to significantly reduce ARIA liability in the Alzheimer's patient population, which again is critical because ARIA is very challenging to manage with the two drugs on the market. So if we can eliminate, reduce ARIA liability, that will be significant. Then the other bucket of endpoints, as I mentioned, is the clinical signal. We want to be able to kind of connect the dots, if you will, between biomarkers, safety, and clinical outcome.
So CDR sum of boxes, ADAS-Cog. So the FDA-approved clinical endpoints are important for us. So a 12-month study, three ascending doses in a very kind of robust clinical study. So we're, you know, we're very pleased. And now data is coming, as I said, this year, mid-year, we'll have an interim analysis towards the end of the year, the final top-line results.
Yeah. So I want to start with ARIA and the sort of tolerability and safety question first is, you know, where in this patient population, what is the sort of average ARIA rate outside of taking any antibodies? And sort of what is the range that you'd expect to be in that would differentiate you from something like lecanemab or donanemab?
Yeah, good question, Eddie. It's important to note that, you know, we're not saying we're going to eliminate all ARIA. Our expectations are to eliminate all ARIA because we know there is an underlying rate of spontaneous, if you will, ARIA in placebo patients. We've seen that in other studies. We're expecting to be similar to that of placebo. What we've kind of benchmarked against are the other studies, the large studies that were undertaken by Eisai and Lilly, so with donanemab and lecanemab. What they saw, their placebo rate was in the range of 9% to 14%. Overall ARIA in the placebo populations were in the range of 9% to 14%. That's kind of our expectations that we should be with ARIA-H and ARIA-E kind of in that similar range.
Again, I think, and we've heard this before from KOLs and from pharma companies, that if we deliver ARIA, you know, similar to placebo, which is far better than what the drugs in the market are showing, then that would be a huge win, which I believe. Because the management of ARIA, it's not just the serious side effect issue of potential bleeding and swelling on the brain. It's also managing these patients, monitoring these patients.
It's a significant undertaking to be able to conduct the surveillance and monitoring of these patients on a regular basis, which is why the two products on the market have, you know, a large black box warning with respect to ARIA. It's why the, you know, the expectations around the revenue have been a little bit lower than expected. Because management of ARIA, again, in addition to the seriousness to the patient, is substantial challenge.
When ARIA does show up in what's expected to be a drug-induced, drug-mediated manner, like when does it usually, you know, manifest? And what have your interim safety looks, you know, shown you so far in the study?
Interesting. We've looked at that. You know, as I said, for the other studies, when do we typically see ARIA in other trials? And interestingly, over 90% of all cases of ARIA for the other products in the market occur in the first six months. I think it's about 70% in the first three months. Over 90% of ARIA, if it occurs, occurs in the first six months. So that's important for us. So the trial design that we put in place, we kind of front-loaded the MRIs to be able to, you know, really see if we can detect any ARIA. Because it's critical to us to be able to really, you know, power the study. And we're 95+% powered to detect a single case of ARIA if one exists.
So front-loading the MRI just to really push and see if we can see ARIA is what we've done in our study because we know 90%+ come in that first six months. And what we've said publicly and what we're kind of really pleased with the kind of where we are to date and again, we started dosing, you know, about a year ago. So many of the patients have completed 12 months of dosing. Many have completed six months of dosing. And we're kind of really pleased to date that we've seen no treatment-related serious adverse events in the trial thus far. So the safety signal, if you will, and this, you know, the SAEs, the serious adverse events include serious cases of ARIA.
So we're really pleased, Eddie, as to and again, there's still dosing to go and, you know, we need to be careful what we say here. But we're really pleased with the safety signal to date with respect to SAEs, none related to treatment so far. Interestingly as well, we were expecting, you know, kind of a relatively significant dropout rate. Looking at other trials that have come before us, there was probably a, you know, 28% to 30% dropout rate in patients. And our dropout rate, our retention, if you will, has far exceeded expectations. So what we're seeing from the trial investigators is a lot of enthusiasm to the product.
I think knowing that there's the potential here for significantly reduced ARIA, a lot of the PIs in the trial are kind of rushing to bring their patients in, which is why we saw over-enrollment. I think the patients are kind of encouraged that potentially we've got something here that doesn't come with this serious side effect issues. So they want to stay involved in the study. So kind of early, I guess we're midway here. But yeah, signals from the trial to date are quite encouraging.
That's great. Thanks for that. Then, you know, moving to the biomarker data coming, you know, around mid-year, obviously, you know, you hope to show, you know, maybe something on the ARIA front that differentiates it. Let's talk about these biomarkers. Which biomarkers are sort of most important to the mechanism of PMN310? Then maybe if you could talk a little bit about the paper that came out at the end of last year about sort of how we should think about those biomarkers reading through to potential cognitive data later in the year.
Yeah, very good question. I mean, as I said, the biomarkers are a lot of them are fairly well understood with respect to Alzheimer's. And to quote Larry, you know, we try not to pick our favorite child in the kind of identification of which is the most important biomarker. Because I think, you know, collectively, the entire panel tells a really important or paints a really important picture around the biology of the disease. So our panel collectively will be important. I know there's a lot of, you know, there is a lot of interest in p-tau217. And that's one that measures disease progression. So we certainly will look at that, as have others. You know, p-tau243 measures downstream tau phosphorylation. Again, very critical, really important to us as well, as I mentioned, the synaptotoxicity of the oligomers.
So measuring synaptic biomarkers is going to be really critical. Neurogranin, post-synaptic, SNAP-25, pre-synaptic, those biomarkers will be critical. NfL, neurofilament light, is going to be important to us. GFAP. So there's a range of biomarkers that are going to be absolutely critical. So I think holistically or on a whole, it's going to tell us a really important picture. We've got a whole panel of Alamar biomarkers we're looking at. So we're really comprehensive in our look at biomarkers. But yes, you're right, Eddie. There are a few that have been noted. We kind of co-authored a publication with Pentara, probably one of the leading biostats groups out there, superb, looking at the predictiveness, if that's the word, predictability of p-tau217 on clinical outcome.
And it was the first time that they or we showed collectively that p-tau217 is a very strong predictor of clinical benefit and clinical outcome. So that's a kind of a good signal and a good connection there. And for the interim analysis, you know, we'll be looking at, again, collectively, this is a qualitative look on kind of trends in biomarker movement. So we'll have the safety kind of picture, if you will.
And then combined with that will be, are we seeing a downward trend? Because most of these Abeta 42/40, being the only exception, most of these biomarkers, if they're showing a beneficial drug effect, will show a decrease in the biomarkers. Abeta 42/40 will show an increase. It's inversely related. But we want to see a downward trend at the interim analysis showing that there is a drug effect. It is working combined with, you know, terrific safety. And that'll be, I think, that'll be a really important signal for the.
You mentioned at the beginning lecanemab was sort of maybe designed to at least partially target these oligomers as well. There's another company, Acumen, who says they also are doing that. Is there anything we can learn from those biomarker data that sort of benchmarks what we should expect to see in terms of the percent reduction for some of these biomarkers that you're looking at at six months?
Sure. I think because they've got the numbers out there. I mean, it's important too when we talk about this targeting of these oligomers. And again, for years, we were, you know, a little bit beaten up because we were going after the oligomers. And people were saying, let me get this straight. On purpose, you're avoiding plaque. And we're like, yeah, we believe that it's the oligomers driving the toxicity, not plaque. So people kind of, you know, people kind of pick on you a little bit. But now the whole field has come on to it is these oligomers. And it's important that, you know, we're not the only group out there saying this. I mean, lecanemab, you know, Lars Lannfelt, these guys and, you know, Biogen and Eisai are now saying that their efficacy, they believe, comes from the targeting of the oligomers.
Acumen, as another company, as you point out, was claiming that they had a selective that their target, you know, was the oligomers. So there's a lot of folks looking to get to these oligomers. Again, the challenge has been that they do, you know, designing an antibody that does not cross-react. And we know that the other antibodies do cross-react, you know, lecanemab, Acumen, cross-react with other amyloid beta species. But they are, you know, they are more selective there. They're kind of, I think the efficacy is being driven by their ability to, certainly in lecanemab, to bind the upstream oligomers and protofibrils. And then what we've seen from their, you know, reduction, Lilly and donanemab, lecanemab reduction in biomarkers, we'll certainly look at that at the end of the study, Eddie.
We're not going to, you know, we're not going to break the blind or we're not going to be able to look at specific % reductions on an interim basis. But certainly at the end of the study, at the 12-month time when we unblind the data, we will look at kind of our rate of decrease on some of these biomarkers versus others that have gone before us. And what we're expecting, given our, because that's kind of the efficacy, are we engaging target?
That's where the efficacy comes from. And given our selectivity to the oligomers, I mean, all of our drugs going to the oligomers. And we believe we have more drug in the CNS than target. We're expecting to see, you know, kind of at least as good, but hopefully better decrease in some of these biomarkers, better efficacy that translates into better efficacy for PMN310 than what others have shown.
Yeah. Neil, a few clarification questions. So this analysis is on a blinded basis. But would you be able to do, will you be doing the analysis on all the cohort or it's just a blend of all the cohort versus placebo?
What we're kind of saying now, Yatin, is, you know, to look at a kind of a collective group of biomarkers to see a downward trend. There may be, we may pull it out by cohort. But I think, you know, looking at kind of collectively the data to see a, you know, ideally a downward trend in the biomarkers at the interim. And then at the unblinded, at the end of the study, certainly breaking it all apart and looking at the individual cohorts as well.
Got it. So for ARIA, I think it's straightforward, right? I think you have articulated the range 9% to 14%. Even if you look at on a blinded basis, if you are in that range, you're fine. But are there similar numbers for these four or five biomarkers that you've identified at this sort of six-month time point?
But again, yeah, six, they've, you know, they've published on six months and 12 months. We're not going to look at specific quantitative results at our six months. But then again, when we unblind at 12 months, we'll certainly look at kind of our six-month data versus, you know, and 12-month data versus them. And there are, yeah, they've published on some of the, I think, I can't remember specifically the numbers, but in the range of a 20% decline in some of the p-tau217. So that's kind of our benchmark. And again, we would expect to be, you know, at least as good, if not better than what others have shown.
Thank you. Back to you, Eddie.
Yeah. So just in our last minute here, if you wanted to just talk a little bit about the pipeline and any other things we should get excited about moving forward.
Sure. I mean, the pipeline, again, we're excited about the pipeline. As I mentioned, you know, once and if, but once we show proof of concept with the Alzheimer's program, it does open up the whole potential for the platform. We've had some superb conversations. Again, we've, you know, we've been obviously discussing with pharma companies. Importantly, they could be a partner going forward. There's a lot of enthusiasm for that.
The one thing I might actually mention just that we didn't touch on was our thinking around the design of the 1b was that if, you know, when we are successful in showing this, we believe that we will then be able to step into a pivotal phase 3 study, you know, kind of bypassing, if you will, the phase 2, you know, 2 to 3-year program, $200 million going from our 1b straight to a pivotal phase 3. And I think if we get all the answers to target engagement, dose, you know, efficacy, clinical signal, that will enable us to step into that phase 3 pivotal study. And that's what we're talking about with pharma companies around the ability to move straight to a phase 3. The interest in the ALS program, in the alpha-synuclein program for sure is there with pharma companies.
We're excited to be, you know, to have a truly differentiated and proprietary platform across multiple dementias, if you will, neurodegenerative diseases with data coming, you know, with data coming months away in a trial that's been, I mean, the clinical team has been superb in its execution, you know, oversubscribed on the enrollment, you know, financing that was oversubscribed by some of the top funds out there, data a few months away.
And I think it's going to be a watershed year for Alzheimer's patients. I mean, we're in it for the patients, most certainly. I think it'll be a watershed transformational year for ProMIS as well. Again, it's nice to be after years of research. That's such a key unmet medical area to have a, you know, a truly differentiated product that could really transform the treatment of Alzheimer's disease, which would be outstanding for patients and shareholders alike.
Well, thank you for being here and good luck. We're looking forward to data coming soon.
Yeah. Thanks very much, guys.
Thank you. Thank you, Neil.
Thank you.