ProMIS Neurosciences Inc. (PMN) November 11, 2026 Conference Transcript

Hi, I'm Emily. I'm on performance assisting here at Steeple, and I'm really excited to announce, or to introduce Neil Warmer, CEO and President of Promise Neuroscience. So, yeah, do you want to maybe start with just like a kind of overview of what's going on?

Yeah, no, thanks. There's a lot going on. Thanks, Emily. And, yeah, terrific conference. As always, we're pleased to be invited. Thanks very much. And thanks for you attending in the audience as well. I'll excuse my voice at the outset in case I need to break for a sip of tea or water, but thanks very much. Appreciate it. Yeah, I'm happy to. I'm being represented here with Dr. Larry Alsteele, our Chief Medical Officer as well, who's responsible for a lot of the design and development of this program. So my name, Neil Warma, President and CEO of Promise Neurosciences. So I'll walk through a few slides with you today, and I'll give kind of a summary, Emily, if that's okay, just to walk through the slides, and I can interrupt, and you can interrupt me with questions as we go through. So just to remind everybody, we are a publicly listed company. PMN is the ticker, so please review all of our SEC documents that we file online. As Emily said, there's a lot going on in PROMIS currently. We are a company that's focused on neurodegenerative diseases, and we are right now in the throes of a really exciting clinical trial in Alzheimer's disease, which reads out in a matter of months. We've said publicly that the Alzheimer's study reads out in Q1 of next year, so we're on the verge of finishing up patient dosing and final visits to get our data out in Q1. So early catalysts coming up for sure. We are well-funded. We did a significant financing a number of months ago with some of the top investors coming into the financing with Ally Bridge, Janus, Wellington, DeepTrack. So we're funded well beyond data through to beyond the end of next year. The company promise. It's really based on our platform technology, protein misfolding. A little bit of a play on words, promise of novel drugs, but also the technology around misfolded proteins and their impact on a number of different diseases. And our ability, as we say here, EpiSelect is the platform, but our ability to selectively target misfolded forms of protein. So a very selective approach to design, a very exquisite approach at designing antibodies, which differentiates us from, I believe, certainly in Alzheimer's, all other kind of drugs currently on the market are in development, even those that claim to be selective to oligomers. Really, all of the others bind multiple different species of amyloid beta. We believe we're the only drug that selectively binds the toxic oligomers. Do you want me to continue through, or do you want to ask the questions back and forth? I'm happy just to run through the slides, and if that's easiest for you, Emily.

Yeah, I mean, maybe just since we've kind of paused right here, obviously, we recently got the data from Acumen that was a bit disappointing. So maybe if you could just talk to us, like, a little bit more about, you know, more in detail, like, what you think, why you're different, and, you know, and maybe point to any data that you can kind of show about, like, why you think you are really, like, selective for these oligomer species.

Of course, that's a good question. Yeah, and the data that came out a week or so ago from our colleagues at Acumen, disappointing certainly for, you know, first and foremost for the patients. But again, just to be front and center, we put out a bit of a communique last week as well. I mean, there are clear differentiations between our PMN310 antibody. And their antibody, and frankly, every other antibody as I mentioned out there, for one thing, ACU-193 Acumen's antibody is not purely selective to oligomers. Although that's been the thesis all along, and they're big believers in it's the toxic oligomers that are driving cognitive decline, as we believe, as the folks at ACI believe, with acanamab. It was designed to selectively target the oligomers. But at the end of the day, all the other antibodies, including AC193, bind a multiple assortment of amyloid beta species. Not one is selective to the oligomers. So the data that came out from Acumen doesn't really inform on the oligomer hypothesis because they bind multiple different species. And the other thing which is an important differentiator, if you look at the oligomer, because these are the toxic species of amyloid beta protein, it's important in our minds, and I think most people's, not only to go in there and bind the oligomers to prevent them from further destruction, but also clear them and remove them from circulation within the CSF. Because of that, we designed our antibody, which is actually similar to what lacanumab and donanumab did. We designed our antibody with an IgG1 background, not to get too immunological on you, but an IgG1 background provides for an immune response. So when the antibody binds to the oligomer, there's an immune response. It's a recruitment of microglia. The microglia come in. They bind the antibody-oligomer complex and remove oligomers from the CSF. So it's not only neutralization, it's clearance of those antibodies. And Acumen... So, I think acumen is more like the other group, the two out there and other folks rather than similar to us. So the differences are the drug does not bind selectively the oligomers, and it has a different kind of mechanism of action, if you will, in not being able to clear the oligomers. And the data really is important, Emily. When we look at the premise or the hypothesis supported by the data that we've communicated really for years now, that we believe it is the toxic oligomers, not plaque, and that's a whole other story, not plaque that's driving cognitive decline. And as a result, we've got this elegant platform because people say, well, If all the other people tried to design a selective antibody, and they end up binding all forms of amyloid beta, how is it that you at Promise can actually do this? And again, it comes to our EpiSelect platform. I can probably advance some of these slides just to kind of show people what I mean here. But the EpiSelect platform... Really is an elegant way of us being able to predict how proteins are going to misfold, and it's a conformational epitope, a three-dimensional epitope, to which we design an antibody against. So that epitope is only present on the misfolded form, the toxic oligomers. It's not present on monomers, and it's not present on plaque. So therefore, the design of the antibodies from the get-go, very different from the way other people design these antibodies. And that, and the data we've produced pre-clinically, we've tested. We've looked at multiple antibodies, including the acumen antibody and denanumab, lukanumab, side by side to say, what are the binding profiles of each of these? Are we differentiated with PMN310? Are we true to our belief that we're not binding plaque? And I'll come back to why that's really important, or not. And we did side-by-side testing, and this slide here shows that the green shows the presence of plaque in brain sections of Alzheimer's patients, and the purple shows which antibodies are actually binding to the plaque. And every antibody here, except for PMN310, shows binding to plaque. And with that, and we'll come back to this in a minute, with that binding of plaque, not only is it not that relevant for preventing further cognitive decline, but clearing plaque is also associated with a very serious side effect known as aria. And ARI essentially stands for Bleeding and Swelling on the Brain. So you've got kind of this double whammy that targeting plaque, you're not really getting a clinical benefit, but you're also getting the side effect issue with swelling and bleeding on the brain. So then the challenge becomes, well, then how do you design something? Because if you look at this picture... Which is kind of a bit of a representation of there's multiple different species of amyloid beta protein. And as I just said, and the field has really shifted away from plaque because there are drugs that can clear plaque totally, and the patient continues to decline. So therefore, okay, well, we've got this belief now, we understand it's the upstream, these oligomers, that as they travel downstream, trigger tau phosphorylation, they form into plaques. So our goal is to go upstream of all of this and hit the oligomers. But then, as I mentioned, the challenge is, well, how do you just hit the oligomers and avoid plaque and avoid monomers? And the other drugs cannot, and Acumen showed that they were not able to. But every step of the way, we have shown that we can, you know, bind oligomers, avoid plaque, avoid monomers. And I'll maybe touch on that in a minute, kind of the clinical data and how that's supported. But all the way along, all the data has supported our story, and we have not changed our story at all. And again, not to pick on acumen, but if you look at them, they were wanting to be that selective oligomer binding agent, but their data just told a different story for the past few years. Obviously, bind plaque in the 1B, they came with aria incidence. Now we see in the phase 2, double-digit aria incidence. So it's clearly a non-specific binding agent versus ours, which we believe is very specific to the toxic species.

And so, like, it's like our understanding that there's not necessarily, like, great assays, like, in humans for oligomers, you know, like, so kind of, like, could you maybe talk a little bit more about, like, the data you guys have shown thus far, and, like, why, again, like, you think, like, in patients you are, you know, binding to oligomers.

Yeah, it's a really good question, and to that point. And I'll come back to this, but up until now, there's never been an assay to enable us or people in the industry to look at and measure levels of oligomers. These are low molecular weight, very low concentration, soluble species, very challenging to actually measure with an assay, which is why no one's been able to show that until now. We've been, at Promise, we've been designing an assay to allow us to... Really, I guess, prove or elucidate our mechanism of action. And to do that, you have to show that here are these circulating oligomers, very low concentration, and here's what happens in the presence of the PMN310, our antibody, pre and post treatment. So that's an assay we've designed. We presented kind of validating data on that back in July at the Alzheimer's conference in London. So we're excited that for the first time, we're going to be able to take that assay and plug it into this clinical study. And the study we... This is it. The study... I think the most important decision we made as a company, and this is, you know, very much in part to, thanks to Dr. Alsteel, our CMO, and Larry was chief, was our chief medical officer, but he ran CNS at Pfizer for years. So when I joined the company as CEO, I said to Larry and the team, you know, we need to design a study that's going to give us, you know, a fairly definitive answer as to whether this works or not. And kind of coming on the back of our colleagues at Acumen, who had done a shorter three-month, 30-patient study, look at a few biomarkers, we said, well, that doesn't really tell us much. So, Dr. Alsteel, plan a study that's going to give us an answer. So Larry said we need to have, you know, we need to show some sign of clinical benefit here, because biomarkers only don't really tell a story. And we have to do it in enough patients to kind of give it some meaning. And again, it's a 1B first-in-human study, but we designed this so we need to treat at least 100 patients for 12 months, because 12 months should, could give us a signal of efficacy. So we designed this placebo-controlled double-blind randomized study, 12 months of IV administration. We look at three ascending doses. We were targeting 128 patients. We ended up oversubscribing. There's a lot of enthusiasm for the trial. We ended up with 144 subjects. This is being run across the U.S., and a lot of the physicians were... This is an interesting study. If this truly does not bind plaque and does not come with an ARIA liability, I want my patients in that study. So we kind of ran, we set the study up, and it was fully enrolled last year, again, ahead of target, more patients than we were thinking we'd get that we were targeting, which is a good thing. So we're now looking at winding up final patient visits over the next month and reporting on data in Q1. So again, it's a very comprehensively designed study. We're looking at multiple baskets of endpoints. Certainly, safety is key, and I'll come back to this in a minute, because safety is imperative in the two drugs on the market, and maybe I'll back up in a second, but the aria incidence, the 20%, 30% bleeding and swelling on the brain is, as you can imagine, significantly preventing uptake of the two drugs in the market. You know, it's a significant market. The two drugs on the market don't even have or have approximately 5% of the addressable patient population on Alzheimer's because of the challenges around safety. The efficacy is moderate. So we really come back to, we really emphasize this risk-benefit profile, and that's what the FDA looks at, that's what the physicians look at, that's what the patients look at. What is the risk versus benefit? And currently with the two drugs on the market, it's pretty poor. You know, the risks are really heavy on the aria. And not only is it swelling and bleeding on the brain, which is, you know, as serious as it sounds, but these patients require multiple MRIs. So I think it's six, Larry, six MRIs in the first year of treatment. You know, these are cognitively impaired elderly patients, and you got to get them to the, you know, the institution, got to get them inside an MRI. So that's a challenge unto itself. So that risk benefit is really poor. So our thinking was, you know, if we can solve or rebalance or materially change the risk benefit, that would be a huge achievement for an Alzheimer's drug. So this study is running well now, and as I said, we're presenting data across multiple endpoints, safety, biomarkers, efficacy, because we're looking at clinical efficacy. Again, it's a 12-month, 140-plus patient study, so we keep it in perspective. And then we're also looking at the oligomer mechanism of action measures as well. What we did in this study was we built an interim analysis. Since it was a longer study than, I think, than anybody's running a 1B study, certainly as an emerging company, we knew it was going to be a little bit longer to enroll for news flow for public companies. That's kind of critical. So we built an interim analysis to say, after six months, so when all patients have been treated for six months instead of 12, let's have a blinded look at what's going on with safety and what's going on with one or two of the biomarkers, just to give us a little bit of a sense as to, are we on the right track? And then the... This is a bit of the background of the trial. The trial is very representative of early Alzheimer's patients. So these are mild cognitive impairment due to Alzheimer's, so early AD patients. Very representative, very similar profile of the lakanumab, denanumab, big phase 3 studies, including the APOE4 heterohomozygotes, which is absolutely critical. They're at most risk for developing Alzheimer's and developing ARIA on top of it. So what we saw in the interim analysis, and this was reported on July 28th, I think, end of July, halfway through our study, was really encouraging. You know, we had high expectations on the safety side, and again, everybody had been claiming selectivity and lower ARIA. No one had achieved that. So we were kind of saying the same, selectivity and, you know, reducing ARIA liability. And what we saw at interim. It was, yeah, super safety. We were really, really impressed, if that's the right word, with our own drug. But as you can see, the two forms of ARIA, the edema, which is the more serious ARIA-E, and H for hemorrhage. So those are the two forms of ARIA. And we saw zero cases of ARIA-E in the first six months of therapy, which again, and I'll show you the slide in a second, which is really, really encouraging. We saw no cases of zero serious adverse events related to treatment, zero discontinuations related to treatment. So the overall kind of one infusion reaction, so the safety profile of PMN310 was absolutely superb. Again, a little bit better than our very high expectations. So safety, we're thinking this, and it's interesting. So you can see the next slide, I think, has our, you know, we kind of mapped this against the other drugs that had come before us, the nonamab, the canamab. How did they look with their ARIA cases at six months? We know what it was at 18 months, the length of their trial, and we looked at six months. And you can see by the current, this is just ARIA-E serious cases. And it's interesting because we know that if, when ARIA occurs, it typically comes in the first six months. So 95% of the ARIA cases in Donanumab and Canumab came in the first six months. So that six-month time point is extra special for that reason. So we hit zero while they were hitting. Double digits. So that was a really encouraging sign for us. And then. On the other side of it, it's like, you know, some of the people can say, well, that's great, Neil, it looks like it's safe, but is it actually doing anything? And again, this is a blinded analysis. We want to be careful that we're not unblinding because we're, you know, halfway through and things are going well. But let's look at a couple of the biomarkers that might give us a signal as to whether this is working. And we looked at two biomarkers, and these are measures of, excuse me, of of tau phosphorylation and disease progression. And there's really two. There's P-tau-217, which is a little bit upstream in the tau cascade, and there's MTBR. So we kind of bookmarked the two biomarkers. Excuse me, thanks. And normally, for both these biomarkers, we typically see, excuse me, we typically see an increase in, I'm getting choked up over the data.

It's just so, it's just water. I guess like maybe also a quick question. Will you guys be measuring? Are you guys measuring PET in this 1B study? Will that kind of be available by the time you guys release your top line?

Sorry for those listening in the back of the microphones. Yes, we are measuring PET. We have a PET image at the beginning for inclusion, then we have a PET scan at the end. We're not expecting much because we're not. We're not impacting plaque. So we're not expecting much, but we're certainly looking at PET to see if there are any changes. And then with the biomarkers, again, to see if there was some sort of target engagement, really impressive to see that both PTAL 217 and MTBR showed a decrease. In biomarkers from baseline to six months. And the typical progression is an increase in these biomarkers in untreated patients. So to be able to take these patients and bring them in a downward slope at six months with two key biomarkers, and interestingly, the graph on the right here is our randomization was three to one, three on active and one on placebo. And the tracking, if you will, of the patients that were less than zero versus greater than zero was pretty close to our 3-to-1 randomization. Sorry, I'm kind of choking up here. So that's kind of the, that's really the data that we've presented to date that kind of is supportive very much of our mechanism that gives us kind of enthusiasm going into the final top line data coming in, well, coming in Q1, coming in a few months. So the data has been supportive all the way along and quite encouraging. I'll let you ask when I take a break.

Okay, perfect. So I guess like, kind of like, you know, my next question here is just like, What do you expect as this data matures? And then, you know, like, as you come up to this, like, 12-month readout, you know.

May I interrupt? I have a lozenge. Is that going to help me? Hi. Nice to see you.

Yeah, I'm awesome. I haven't seen you for years, and all of a sudden you're nice. Thanks, my dear. I appreciate it.

Yeah, and so, you know, with the 12-month data, you know. What is maybe your base case scenario, and what do you maybe think you need to see to kind of move this product forward?

Really good question. We've thought about that a lot. I think it comes back to risk-benefit. We want to materially change the risk-benefit versus the drugs on the market. And again, that's risk is safety, benefit is efficacy. So when we look at our base case, You know, RE is certainly going to drive safety. Can we materially lower this rate of RE that's really crippling the patients and the drugs in the market? So if we can decrease that side of the balance significantly, even if we hit similar efficacy, that would be a significant win because that materially changes the risk-benefit ratio of the drug. So we're thinking going into this, and we're careful how we do this, because again, it's 12 months. You know, 140 patients. And I know the tendency is to compare to 18 months, 1,500 patients from the, you know, from the other drugs in the markets. We have to put this in perspective and context. But our thinking is, you know, a win for us base case, if you will, is taking the ARIA rate close to the placebo level. You know, as close as we can. I won't say hitting placebo, but that's where we want to go, dramatically reducing ARIA, certainly ARIA-E, down to placebo-ish or background rates. We know there's a level of ARIA that exists in Alzheimer's patients without treatment. So dropping down to that level would be... Outstanding, would be really impressive for a drug to get there. So that's kind of our, you know, I say base case, but that's pretty an aggressive case. Then the other side of the equation from efficacy, if we want to be, you know, at least as good as the drugs in the market from efficacy. And again, that tips the scales, whichever way it goes, that tips the scales significantly in a much improved risk-benefit profile. So if you look at... You know, what does the efficacy signal look like in a base case? If you look at the efficacy currently with the drugs on the market, you know, we saw after 18 months, again, longer study, 18 months in the range of 22%, 27% benefit. So we're trying to be careful with this, but if we say, if we kind of back that up to 12 months a little bit, if we see something in the range of, you know, 15% to 20%, and this is slowing of cognition. So if we see in that kind of range, and coupled with, you know, some relevant and important trends and biomarker movement on the efficacy side, I think that would be a significant win for us. And if it kind of goes above 20 percent. Separation versus placebo, that's all upside. So I think we're trying to balance this and put it in context with what we want to see. And I think if we get that separation on the efficacy side versus placebo, that's kind of the signal. And then the biomarkers at the end kind of tell us why we're seeing that. That's the biological mechanism as to why we're seeing efficacy separation where we are. And again, if we just hammer the aria down to manageable levels, if we take the MRIs, for example, that's the goal here is, you know, the goal is to get to that next study. And if we come with a safety profile like this and we reduce the MRIs from, you know, six per year down to one or two, again, that's a huge win as well. So this is kind of our base case, and I think if we deliver this with the data, again, 140 patient trials, we put it in perspective. We look holistically at what we're seeing here, the trends and the separations, but I think that'll be a, yeah, a huge win, Emily, Given the market potential and given the unmet medical need, pretty fantastic for us.

Could you remind me just, I know this is a smaller study, could you remind me what you're powered for in the study, or are you really just looking for like a clinical trial?

We're looking for, yeah, we're looking for, again, trends most certainly. We're powered, interestingly, and Larry likes to tell this story as well, we're powered kind of 97%, give or take. To detect a single case of ARIA, because important to us, I mean, this ARIA, which I keep hammering on, obviously is important. So we didn't want to be, you know, accused of, well, there was ARIA, you just didn't look hard enough. That's why you're not seeing any. So the trial's powered 95% plus to detect any case, a single case of ARIA. So that's been then for. With biomarkers, we want to see some key trends and key biomarkers, and same with efficacy. At 140 patients, we're not expecting a p-value 0.05 on the efficacy side at all. It's just too small a population. So favorable trends, clean safety is what we're shooting for.

Okay, that makes sense. And I know we only have a couple minutes left, but I was wondering, you know, if this study is successful, you know, what does next steps look like? And I know you guys are developing a sub-Q formulation, and could you maybe also talk about, like, whether or not a next study could incorporate that sub-Q dosing? Is that a separate development plan and, you know, kind of just like your plan on the path forward?

Yeah, exactly. It's important because we're not just sitting here, you know, waiting for the data to read out and then... Well, it's really good. Now what do we do? By any means, we've been thinking and planning, and part of the rationale for developing a study as comprehensive as this for 1B is to ideally, if we show we're safe, If we show we're engaging target with the biomarkers, if we show we've selected a dose and we've got clinical benefit, then those are the boxes that Larry likes to say give us the, you know, give us the preconditions and give us the support to go into a registration study, you know, subject to feedback from the FDA. So we'll sit down with the FDA next year with all the data. So designing that phase three registration study is what we've been doing. What we've been doing now, we just, we announced last month, we've just hired a chief commercial officer, Dr. Rubino, and Dr. Rubino was responsible for the global launch of Lacanumab at Biogen. So she was 11 years at Biogen. Prior to that, she did all the Alzheimer's research and CNS lead at Roche Basel. So she came in, outstanding individual, tons of expertise to lead the whole charge, you know, through phase three reimbursement pricing. Trial design with our team. So planning of the phase three trial design is ongoing. Sub-Q is, you're exactly right, is very important to us. We initiated the sub-Q development when we saw the interim results. We're pushing forward on that. The goal is to launch the product with a sub-Q formulation. So that's really important. We're full steam ahead on that. And interestingly, as well, the idea in a lot of the bigger trials, as you know, are going after this preclinical or asymptomatic patient population. These are patients that are... They kind of appear very healthy, but they have the underpinnings of Alzheimer's disease. They've got the formations of plaques and oligomer levels are elevated. So it's kind of going in and saying, well, we're detecting these. We can detect them earlier and earlier now. Then the thinking is, why don't we treat you earlier and really kind of hold you at that level forever kind of thing and prevent you from ever developing signs of Alzheimer's disease. And that premise is superb. But again, the challenge for the company is going after that now. Lily, Asai, and now Roche has gotten into it. They've got drugs that give you, you know, 20% chance of potential bleeding on your brain. So it's really a challenge, I think, for those patients, or those individuals, I mean patients, those individuals, to think about taking a drug with serious side effects. But for us, if we come with a clean safety profile like that, we'll kind of launch with the market with the MCI early AD patient population. But then, you know, kind of expanding into that preclinical or asymptomatic patient population is really attractive. But right now, it's first things first, get the data out the door in Q1, but also develop the sub-Q, you know, regulatory path, you know, registration path to be able to kind of, you know, step right into that next study as soon as the data, you know, hopefully are positive in a few months, you know, initiate that next clinical study as a phase three and get to market, you know. You know, speed to market is what it's all about for the patients, for the company, for the shareholders. So we're really focused on what comes next after hopefully a solid set of data in Q1.

Well, it looks like we're out of time, but thank you so much. This has been a really great discussion.

Well, thanks so much. I apologize for the loads. Thanks, Monica, for the lozenge, but thanks for your attention.