ProMIS Neurosciences Inc. (PMN) September 2026 Conference Transcript

how you pronounce that. But yeah, thanks everybody for joining for the next few minutes. Neil Warma, CEO of Promise Neurosciences, and anybody who's sitting in the last presentation, this will be a little bit of a shift from data centers. This is all about potentially curing neurodegenerative disease, Alzheimer's, ALS, Parkinson's disease is our focus. So I'll walk you through. I won't get too heavy into the science, but it's a science-based company. So I'll walk you through some of the science. Just to remind everybody, we are a publicly traded companies so refer you to the SEC file documents on the on the SEC website as well. So with respect to PROMIS neuroscience in a way to maybe remember us a little bit better after today is the name PROMIS in addition to the promise of novel of safe and effective drugs to patients. Our technology is based on protein misfolding so the effects of misfolded proteins on a number of different disease, so PROMIS, protein misfolding. We are a publicly traded company, as I mentioned, the ticker is PMN, trading on the NASDAQ Capital Market Exchange. We've been public for a number of years. I've been CEO for about two and a half years. I've been on the board for longer than that. I have a neuroscience background, joined also by our chief medical officer in the audience, Dr. Larry Allsteel, who's a practicing neurologist and with vast amounts of development expertise as well. So we have a product in the clinic. We are a clinical stage company, and I'll speak a little bit about our, or fairly a lot about our clinical stage asset in Alzheimer's disease. The market in Alzheimer's disease is significant, huge on that medical need. From a financial perspective, we are financed quite well. We did a relatively large financing back in February of this year. A few months ago, we raised up to $175 million from some of the top long-term institutional investors in the biotech space. We were thrilled with that. Outstanding team managing the company. And again, we pride ourselves on our differentiation of our technology. And I won't speak too much about the technology, but I will come back to that in a minute. I'll spend a few minutes towards the middle part of the presentation talking about some of our clinical data. Obviously, the value in biotech pharma companies is generated by solid clinical data. We had an interim read back on July 28th. We are kind of well on our way through an Alzheimer's trial right now. We had an interim analysis we presented at the end of July, which is actually quite encouraging. It was blinded. It was a six-month analysis. I'll point to a few data slides in a minute. But again, what it showed us is the product appears to be very safe with a much better safety profile than the drugs in the market. And we showed what we believe to be some strong target engagement as well. So a really nice interim signal came a month or two ago en route to the final data package, which comes in about six months from now. So we've guided to top-line final results in our Alzheimer's study in Q1 of 2027. So a number of months from now, we should be able to unveil the top-line unblinded data and ideally speak about a really transformational product for the treatment of Alzheimer's disease. So our technology, just kind of briefly, again, around protein misfolding, and as you guys probably maybe remember from your biology classes a few ago, that proteins are manufactured by the cell and they typically come out of the cellular machinery in a very elegant three-dimensionally folded. They fold upon themselves and you've got this elegant shape of the protein which then goes off to perform its task. And continuously proteins come out the cellular machinery and they are misfolded or folded improperly. And these can be very harmful, but your immune system typically takes care of these, grabs hold of the misfolded proteins and clears them from circulation. Because if they're allowed to accumulate and build up the misfolded proteins, they can cause some serious, serious diseases as the ones listed here. So our technology, because sometimes when people get a little bit older, immune compromised, they can't clear these misfolded proteins and then they are allowed to aggregate and build up and cause all sorts of trouble. So our technology, we have the ability to predict how proteins are going to misfold and it's a really elegant process. It's kind of AI back in the days when AI wasn't even known or really cool to talk about. But we have a chief physics officer, and together we have a computational modeling that allows us to predict how proteins are going to misfold. And we design our antibody, our therapies, our monoclonal antibodies, and the antibodies specifically target these misfolded epitopes. And these misfolded epitopes, our binding domains, exist only on the misfolded form of the protein we're targeting. It makes us truly unique in the design of our antibodies, which is critical to our platform here. And different proteins are associated with different diseases. So for Alzheimer's disease we're looking at a second-generation antibody targeting beta amyloid. So A beta protein is a known target for Alzheimer's disease so that's our target, I'll come back to that in a minute, for the Alzheimer's program. And beyond Alzheimer's we're looking at misfolded form of TDP-43, which is known to cause ALS, that's our next potential clinical candidate. We're looking at misfolded forms of alpha-synuclein, which is responsible for a number of different diseases, including Parkinson's and Lewy body dementia. So different misfolded proteins are implicated in different diseases. We have a relatively healthy pipeline of a number of neurodegenerative diseases. So this slide is interesting because when we talk about Alzheimer's, we come back to the Alzheimer's indication, and we're focused on, as I mentioned, amyloid beta protein. That's the target that Lily's gone after with the nanomab. That's the target that ASI, Biogen have gone after with lakanomab. The challenge is there's different species or subspecies of amyloid beta protein, and some are beneficial. You've got the monomers, the monomeric species of amyloid beta is beneficial. It has a biological function, so you don't want to touch this if you can help it. The next is a plaque. We're all kind of aware of the plaque depositions in the brain caused by beta amyloid buildup in the brain. It was thought kind of years ago that that was the relevant target for Alzheimer's drugs. That if we can clear plaque, everything will be fine. We now know that, and there are drugs that completely remove plaque and the patients continue to decline. So it's like, hmm, so it's not plaque. There's something else there. And not only that, and this is important, the drugs that target and bind plaque and remove them are now associated with a very serious side effect, so swelling and bleeding on the brain. So not only is there not much cognitive benefit to the Alzheimer's patient by clearing plaque, you've also got this horrible side effect, bleeding and swelling on the brain. So now the field has come back to over the past number of years, these toxic oligomers, which are much lower concentration than the monomers in the plaque. Now we know that it's these upstream low molecular weight oligomers that if left alone they kind of go downstream and form plaque but their destructive properties come early on and they're highly destructive to neurons especially the synapses so that's the species that kind of everybody's trying to target now but the challenge has become well it's all amyloid beta protein so how can you pick and choose which ones you're gonna hit because it's the same epitope that's kind of consistent across everything but that's when it comes back to the beauty of our platform, we actually, again, predict and identify a binding domain, a binding epitope that only exists on the toxic oligomers. So our antibody only hits this, it avoids plaque, and it certainly avoids the monomers. So we're truly differentiated in the ability to go after these highly toxic species of beta amyloid. And that makes us unique. Others have tried and claimed that. Lakanumab, the drug on the market by Acybiogen, was designed to go after the oligomers. But again, because they don't have kind of our technology and the ability to be personalized or precise, they hit them all. So lakanamab binds everything. It also binds the oligomers, which gives it a little bit of efficacy, but it's associated with significant RA, the swelling and bleeding on the brain. So that's a little bit, and we, again, I won't go into this, we spend a lot of time looking at, are we differentiated? You know, do we bind plaque, or can we actually state and claim that we don't bind plaque, we believe we will not show a significant swelling, bleeding, aria, as it's known, side effect issue. So we did head-to-head with all the other antibodies saying, which ones bind plaque? And the green stains show that these are brain sections from Alzheimer's patients. The green shows there's plaque in the stains. The purple shows which antibodies bind the plaque. And all these guys do. So these are the ones on the market. Here's Acumen's product. And our product, PMN310, was the only one that did not bind plaque. And that's important because we went into the clinic saying, we don't believe we're going to have this serious side effect issue known as aria, and that's highly differentiated because aria is a significant issue. So we marched forward, a little bit of background on the two products in the market, you've got lakanamab, dananamab, and Lily as I mentioned earlier. Modest efficacy, again they kind of, part of the challenge is administering your drug, if you're binding all forms of amyloid beta, you know, 90% of it gets soaked up by the monomers and the plaque. You remember the pyramid, there's much more plaque and monomers than there are the target you're going after. So they show a little bit of efficacy, which is demonstrated here, but they have serious levels of swelling and bleeding on the brain, aria. They've got a black box warning from FDA, so the risk benefit of the drugs on the market is pretty poor, yet they're still projecting $3-4 billion in peak sales, but that's based more on the unmet need than the value those products are bringing to the market. So we designed, so going into the clinic with all that, we did a 1A trial and healthy volunteers, products safe and well tolerated. We designed probably one of the more comprehensive clinical trials for a first inpatient study, a 1B study, and with the help of Dr. Alstiel and the clinical team, we wanted to design a study that was robust enough to give us a definitive answer whether this drug actually worked in Alzheimer's disease. Others before us had done more of a quick and dirty kind of three-month 30-patient study. It was important for us to say, let's run a study that's going to give us a definitive answer. So that meant enough patients over enough time period to show a clinical signal. So he said, let's have at least 100 patients and let's go 12 months of treatment. So monthly doses for 12 months and that will give us the chance to show whether at the end of 12 months we have a clinical signal, which is critical, and then throughout the process we're also going to look at biomarkers, which are very well kind of understood in Alzheimer's disease and important to demonstrate target engagement and then obviously the safety piece is critical for us because we're going into this saying we believe we can significantly lower that swelling, bleeding, aria side effect issue which is plaguing the drugs in the market. So it's a very well-designed study we ended up enrollments completed as of last year 144 patients in the study running out for 12 months. We got fast-track designation by the FDA last year we applied for it they recognize that huge unmet medical need and this drug has the potential to do something quite impressive. So fast track from the FDA. So we're running this study. The one thing we built in is the interim data analysis. And we said a little bit because we're a public company and 12 months is a long time to wait for data. So we said, let's build in an interim analysis. We'll do a blinded analysis. Once everybody's been treated for six months instead of 12, we'll kind of look on a blinded basis to say how's the you know how's the data looking are we on the right track so we did that analysis July 20 yeah July 28th we presented those data and I'll touch on those just for the remaining few minutes and again it's important to remember these are blinded data so it's aggregated placebo and again I should have mentioned this is a placebo control double blind randomized study and it's randomized three to one. So three patients on active, one on placebo. So every four patients, three on active, one on placebo. So just as a little bit of background about the study, as I said, 144 patients were enrolled. The safety analysis included 136 of those patients. So very few dropouts in the study. Again we have three ascending doses, so low, medium, high dose, if you will. And just as a little bit of background, the average age was about 73 years, more females to males a little bit, which is pretty typical in the Alzheimer's population. Race was pretty mixed as well. Important, and I won't get into this, but the ApoE4 carriers, and these are individuals carrying at least one or two of the ApoE4 alleles that are more affected by Alzheimer's and certainly have a higher risk for aria, the side effects. So It's an important patient population to evaluate. So a fairly standard patient population, we're going after early Alzheimer's patients. So these are patients with mild cognitive impairment due to Alzheimer's disease. That's our kind of target. So a fairly well-designed trial. From a safety perspective, and this was critical, a lot of people were looking at safety saying, okay, we've got this whole area, we've got this black box with the two drugs in the market. How do you guys compare with that? Again, it's blinded, but it could be a pretty clear signal I think for us it was a pretty outstanding signal. And when we look at this case of aria, and there's two types of aria, as I say, swelling and bleeding. So aria edema, E, and the bleeding hemorrhage, H. Two types of aria. Aria E tends to be much more severe. So when we looked at six months, and it's also interesting to note that in the previous studies with the two drugs on the market, 90% of all this bleeding, swelling, aria came in the first six months. So that's an even more important signal for us that six months is more meaningful because you typically see aria, drug effect aria, in the first six months of dosing. So what we saw at six months was zero cases of aria-E. We saw no treatment-related serious adverse events. We saw no treatment-related dropouts. And the overall aria, which is this lesser but still important aria-H, tracked with placebo background rates, because every Alzheimer's patient will have this spontaneous hemorrhage aria. as they continue with Alzheimer's. So there is this background rate. I'll show you a chart in a minute that we tracked with. So very impressive on the ARIA signal or lack thereof. Overall safety beyond that, very well safe and well tolerated. So we were thrilled with the safety perspective. And if you look briefly on the ARIA charts, and these are the two drugs on the market, this is what they showed in their clinical trials moving over the past number of years before they got to market. So as I said, ARIA tends to occur in the first six months. And you can see with the Lilly product, 24% almost ARIA cases in six months. Lacanamab was at 12. We were at zero. So I think there's a lot of people that thought, and again, blinded placebo and active. But since there's no cases of ARIA, one assumes there's no cases in the active patient population. And when you look at the overall, kind of overall H plus E, you can see the numbers from the other two drugs. You know, that was an 18-month trial. But when you look at six months, significantly higher than where we were. and we were tracking with this background placebo rate. So really a terrific result from the ARIA safety signal coming out of that interim analysis. The APOE, the high-risk population, just to emphasize that again, you can see that the ARIA rates, ARIA-E with Acanamab, 30% were at zero. So from a safety perspective, we're tracking really, really well. On the other side of the equation, because people can say, well, it's very safe, that's awesome, you guys have a much safer profile, than the others on the market, but is it actually doing anything? Because you can be very safe and non-effective. So are you doing anything on the other side? So we actually looked at that to say, well, let's look at the biomarkers because we're not going to look at the clinical signal in six months. You know, we're waiting for 12 months to look at any clinical signal. So let's look at a couple of these key biomarkers. And if we can demonstrate something interesting there that the potential for the target engagement that our drug is hitting its target and there's a drug effect, that would be pretty interesting. So we looked at two biomarkers that are very relevant and two biomarkers that, in essence, should move early. So P-tau-217, not to get into the details, is a measure of disease progression. Very well understood biomarker. Everybody knows P-tau-217. It's used to identify Alzheimer's patients. It's predictable for clinical outcomes. So there's a lot of relevance in P-tau-217. We know that, over time, patients will increase their levels of this biomarker. P-tau-217 will go up in time without any treatment. So we know the slope of the line looks like that. And what we saw, which we thought was pretty encouraging, our slope started to come down. So we took an upward slope and we reversed it. So really, and again, this is combined placebo, three to one placebo and active patients. We were able to kind of pull this curve down with a 15% reduction in P-tau-217 in six months, which is pretty interesting to say the least. Also, we looked at, well, how many patients out of the 136 we evaluated, how many actually declined in PTAO-217 levels versus increased. And declined, you could say there's an improvement if they're declining and a worsening if they're increasing. And interestingly, it was about 68% declined to 31% increased. And that's roughly tracking our 3-to-1 randomization. Really neat signal. And then we also looked at another MTBR, microtubule binding region, Tau243. Another biomarker a little bit more downstream, it's kind of a nice bookend for 217, 243. We know that the trend will go up over time if untreated and what we saw very similar with MTBR243, downward trend and roughly a three to one tracking with our randomization code. So really interesting signal coming out of the interim analysis, terrific safety, you know potential really here for target engagement so it looks like something's going on on the other side again blinded six months you want to be careful how you position it but about as good as we were kind of you know going into the interim we were managing our expectations and we came out to the other end quite pleased so just the last couple of slides here is that you know from the interim analysis I think it it supports our differentiated mechanism we think we are avoiding plaque therefore should have lower aria which we demonstrated. We had that clean safety profile, we had our target engagement that we believe shows the efficacy signal potential coming out of the interim. The APOE for the high risk population which actually can't get the drugs on the market, they're not even approved in Europe for these patients they're so high risk, that patient population seems to be nicely addressed by PMN 310 and I won't get into this but there's a whole push now by the drug companies to look at treating Alzheimer's patients even earlier in diagnosis. So before they're symptomatic, again, which is a great thing to do if you can catch patients even earlier, just as they're developing the underlying pathology of Alzheimer's and keep them there, that would be wonderful. But again, if you've got 30% chance of bleeding and swelling in your brain, you're not doing that. So for us, coming with a clean product and sliding in there could be interesting. So last couple of slides here. So again, we're moving forward. As I said, we've got the top line results coming Q1 of next year, where we unblind all the data and we also look at the clinical signal, so that will be pretty interesting. We're also working on a subcutaneous formulation right now. We dose IV. Important to us will be to get to the market with a sub-Q formulation, so that process is going forward. We're getting ready for our next study. Again, one of the advantages of designing such a robust phase 1b study is that we believe we can then step right into a registration phase 3 study after this reads out hopefully very well. We'll go straight to a registration study. So we've cut our time to market significantly if this all works out as we expect. We've got two other candidates, the ALS candidate I mentioned at the beginning, the Parkinson's candidate. Those are both moving forward in preclinical development as well. So just as my time is running out, just to kind of reposition the company, truly differentiated platform allows us to create and design these highly selective antibodies. we've got one that's kind of demonstrating that differentiation now vis-a-vis the products in the market we've got a great clinical signal we've got some very near-term catalysts we're financially quite strong I think the disconnect before the disconnect between where we're trading today versus the potential of where this could get to and you know q1 q2 next year where the results is is quite significant so we're yeah we're confident in the ability of the team we're pleased with the interim analysis and how that looked and we're certainly excited about the potential in the next few months to unblind the data and ideally have a really truly transformative product for the treatment of Alzheimer's disease which we all