Hey everyone. Welcome to the Jefferies Global Healthcare Conference. I'm Jordan Carey with the Jefferies Investment Banking team. Now introducing Neil Warma. Thanks, Jordan. Thanks, folks, for joining this morning at the conference to get an update of ProMIS Neurosciences' latest ongoings. My name's Neil Warma. I'm the CEO of ProMIS Neurosciences. I'll walk through a corporate presentation and certainly take some questions from the audience. Thanks to those who are listening on the webcast as well. Just to point out, which is not always evident, the name ProMIS is a double meaning, if you will. Certainly the promise of what we're trying to deliver to patients, also ProMIS represents really the focus of our technology platform. We are a company that's focused on protein misfolding, hence ProMIS. That's just an easy way to potentially remember the platform, the science, and the technology that comes from our platform. Just to remind everybody, we are a publicly traded company, we encourage everybody to review our SEC filings for a true corporate update as well. ProMIS Neurosciences, I mentioned public company ticker is PMN, traded on the Nasdaq Capital Market Exchange. We are a clinical stage company. I'll spend probably the lion's share of this update of this presentation on the clinical asset, on the clinical program. We're pleased to be where we are in the clinic. It's an important year for ProMIS, for our shareholders. We hope for the patients as well. We have a data readout later this year in our ongoing Alzheimer's study, and I'll update on the trial design and on the expectations around the data delivery. I'll speak a little bit about the platform and the technology, and really our differentiation comes from our ability to design antibodies that are uniquely selective for specific misfolded protein. Again, it's the targeting of these misfolded proteins that's really paramount to our clinical platform, but pipeline platform as well. The data release, I'll touch on this a little bit later. We have an interim analysis with respect to the Alzheimer's study coming up in early Q3, so a couple of months away. This will be a blinded, qualitative analysis around the Alzheimer's data. I'll come back to that in a minute. The ongoing Alzheimer's trial, which is running now, will be completed by the end of the year with expectations around top-line unblinded results early Q1 next year. A couple of really important data reads over the next really several months. We're excited about that. The market potential, I don't think I need to really speak too much about the potential of a potential best-in-class candidate in Alzheimer's disease. What is really evident beyond the market potential is the unmet medical need that still and currently exists in Alzheimer's disease. A couple of products on the market, but there's still a huge unmet medical need for these patients. The leadership team that joins me in these meetings is absolutely superb. We have a wonderful team of seasoned experts in the discovery of misfolded proteins, but also in the treatment of neurodegenerative diseases. Financing-wise, which is always an important question for biotech companies, our financial position is quite strong coming off the back of a capital raise I guess a few months ago now, early February, where we raised up to $175 million or $75 million upfront with a potential exercise of warrants for an additional $100 million upon revealing of the top-line data. What was very comforting and impressive to me at least, was the syndicate that came together for the financing. We had some of the top investors join. It was led by Ally Bridge and Janus Henderson. Participation from Wellington, Deep Track, Great Point Partners. Really a superb syndicate came together. As we said in our recent Q, we have cash through 2027, certainly well beyond data. We're excited to be in this relatively strong position financially and certainly with clinical data coming. Just to speak a couple of minutes around this technology platform. As I mentioned, it's the ability to be selective with the targeting of our antibodies. This EpiSelect platform, as we've trademarked it, proprietary platform to ProMIS, is designed differently than conventional approaches. The conventional approach tends to take a synthetic oligomer in a test tube and then screen antibodies to try to be selective to a given protein. What we do at ProMIS is really a computational modeling of predicting and identifying how specific proteins are going to misfold. This is really critical to the selectivity of the antibodies. We are able to predict, and we've been using AI at ProMIS for the past 20 years before it was even cool to say that. It really is an algorithmic approach to identify unstable regions of proteins and how they're going to misfold. It's not only a linear epitope, but it's also a three-dimensional conformation. It's a 3D epitope that is uniquely present on only the misfolded proteins of target. That really differentiates us from other antibodies that have a linear epitope, that due to the nature of that epitope, is conserved across multiple species of a specific protein. This 3D epitope binding region, epitope, for example, is present only on our misfolded form of amyloid beta, the toxic oligomers, and that is our target for Alzheimer's I'll come back to. It really is a unique approach to be able to design proteins differentiated from others, designing theirs with a conventional approach that gives us our differentiated ability potentially be best- in- class. With each misfolded protein is associated with a different neurodegenerative disease. As a result, we have a relatively healthy pipeline. The misfolded protein of choice for Alzheimer's is amyloid beta. When we look beyond that, we're targeting misfolded forms of TDP-43 for ALS, and misfolded forms of alpha-synuclein for Parkinson's disease, for Dementia with Lewy bodies. Again, we've got a healthy pipeline. We have a vaccine program where we're looking, and that's an interesting also set of candidates that's coming kind of behind the preclinical candidates. Really the focus is on Alzheimer's, and then behind that, ALS and Parkinson's as well. If we touch on the Alzheimer's program, and I'll talk a little bit about the importance of selectivity. There's been a lot of, I guess, change in thinking over the past 5 to 10 years. Previously, the singular focus was on targeting plaque and removing plaque from Alzheimer's patients. That was thought to be the factor that was driving disease progression. We now know that's not the case. Clearing plaque is not sufficient, and there are drugs that completely remove plaque, but patients continue to decline. As the field shifted over the past number of years, a lot of researchers and scientists were started to focus on the upstream low molecular weight oligomer species of amyloid beta protein. Now we appreciate that it's these oligomers that appear higher up in the cascade of the Alzheimer's disease progression pathway. It's the toxic oligomers that are really highly destructive, highly toxic to neurons, really specifically at the synaptic interface, and it's that destruction of the neurons and the synapses by the oligomers that is driving much of the cognitive decline in Alzheimer's patients. The field has shifted. We at ProMIS have been focused on the oligomer target for a long time. We were kind of beaten up a little bit when we said on purpose we were designing an antibody that did not bind plaque and certainly did not bind monomers, other species of amyloid beta. Now the field's shifted and the oligomer species is understood as one of the primary drivers of cognitive decline in Alzheimer's disease. The challenge is, okay, now if you look at this figure on the screen, the challenge is, well, all of these oligomers, plaque, and monomers are species of amyloid beta. It goes back to the selectivity. If you want to avoid monomers and plaque and only target the oligomers, how can you design an antibody that does not cross-react with all forms of Aβ protein? That's been the challenge kind of out there in existence, and that's what gives us at ProMIS our uniqueness. Again, we have the ability to design an antibody specifically targeting a three-dimensional epitope. This 3D conformation epitope only exists on the misfolded form of the oligomer species. It allows us to be highly selective for the oligomers. If we take a step back, looking at plaque, as we've said, the relevance in plaque of cognitive decline has now come under question. Not only that, we know that drugs that bind and clear plaque are also associated with a significant side effect issue. That side effect issue is kind of swelling and bleeding of the brain. This is ARIA, Amyloid-Related Imaging Abnormalities known as ARIA. There's ARIA- H, hemorrhaging of the brain, and ARIA- E, swelling of the brain. Not only is plaque not that relevant for clinical benefit, it also is associated with a pretty serious side effect issue, as you can imagine. Avoiding plaque becomes more of a heightened sense of urgency, if you will. That's where we're coming into the clinic with the ability to selectively target only the oligomers, avoiding plaque. We are in belief that by avoiding plaque, we will be able to lower the incidence of ARIA that we're seeing with the drugs on the market, which can be pretty significant in that kind of 20%- 25%- 30% range plus. That's one of our claims going into the clinic, the ability to have a much better safety profile. In addition, having a much better efficacy profile because all the drug that crosses the blood-brain barrier is able to bind our target, that being the toxic oligomers. When we look at kind of the evolution of the antibodies of the drug candidates coming the past decades to treat Alzheimer's disease, we look at the top of the list with solanezumab, for example. Solanezumab was designed to target the monomers. This was back when folks thought monomers was the appropriate species for Alzheimer's disease. The monomeric species of amyloid beta is actually beneficial and has a biological function. We now know that. We know that that's the wrong target for Alzheimer's. There's no clinical benefit observed with solanezumab. The next generation that came, gantenerumab, which is now the refashioned, repurposed, if you will, donanemab. Gantenerumab came along, and it binds everything. It cross-reacts with the monomers, with the oligomers, and with the plaque. Very little clinical benefit was shown with gantenerumab back in the day because it bound everything. As a result, most of the drug was soaked up by the monomers and soaked up by the plaque, and very little of the drug actually hit the real target, the oligomers. If you can remember the pyramid I showed a second ago, that was a little bit demonstrating the relative concentrations of each of those Aβ species. Monomers exist 1,000 higher concentration than the oligomers. If you've got drug in the CNS, if you've gotten drug across the blood-brain barrier, it gets sucked up by the monomers, it gets sucked up by the plaque before it ever hits the target. That was kind of the issue with gantenerumab. We'll see how donanemab fares on the efficacy side. Then we have the two drugs in the market, donanemab and lecanemab. Again, they cross-react unavoidably. They cross-react with all forms of amyloid beta. Lecanemab, interestingly, was designed to target upstream oligomers and protofibrils. When lecanemab was designed back in the day, they wanted an antibody. They understood the importance of these upstream oligomers and tried to design an antibody as best they could to really go upstream and target, similar to us, the low molecular weight oligomers. They're better at doing that, but again, they still cross-react with plaque. They still come associated with ARIA levels and muted efficacy because, again, the drug's getting soaked up by the off-target amyloid beta species. We have PMN310, the ProMIS drug, which we believe is in that sweet spot to selectively bind only these toxic oligomers, making us unique in our approach. When we looked at, because part of our goal to prove to ourselves and to prove to our investors and such, was really pressure testing whether we were true with our rationale and true with the design of the antibody that we truly did not bind plaque. It was really important to us to demonstrate this. We did multiple different assays and studies pre-clinically, and we did side-by-side tests with multiple different antibodies. The top row lights up green, showing the presence of plaque in Alzheimer's patients' brain sections, which is what this is. The purple shows which antibodies bind to plaque. We did the side-by-side with donanemab and lecanemab, a number of antibodies that were present to see were we differentiated at ProMIS, did we truly have something that was unique in avoiding plaque? Again, we did a number of studies, and this truly shows that we had PMN310, which is in the middle, was really the only antibody that really did not bind plaque. With that, I'll touch on the marketed products just for a second. We know that they're, and again, every step in this is, and I certainly don't mean to bring any disrespect to the companies developing these. A ton of work goes into any drug for any patient population. Certainly Alzheimer's is one of the most difficult. Bringing products to market is a step in the right direction regardless. I think what we're seeing because of the fact, as I said, because of the off-target, the soaking up of the antibody by the off-target amyloid beta species, we're seeing limited efficacy from the two products in the market. We're also seeing a relatively significant side effect issue with ARIA. The risk-benefit is modest with these products, but they still provide a valuable function to patients. They're still generating significant revenue. I think what this really tells us is that there still remains a significant unmet medical need for certain in the Alzheimer's population. The drugs that come to market with an improved safety and efficacy profile still have the ability to generate significant revenue and return for our shareholders. Armed with all this kind of knowledge and data from the pre-clinical side, we also did pre-clinical efficacy studies, which I'm not talking about here. On the pre-clinical efficacy models, our PMN310 did extraordinarily well in improving cognition and really returning the animal species back to normal function. The efficacy was really supportive pre-clinically. The safety and our potential for lack of serious ARIA was confirmed as well pre-clinically. We marched forward into the clinical program. Our first clinical study that we ran, this is a couple of years ago now, was a phase I-A study in healthy volunteers. Really the objective of this study was first and foremost, as with most, if not all I-A studies, safety and tolerability. We wanted to demonstrate or observe if the antibody that we had produced was safe and well-tolerated in humans. That we checked that box pretty substantially in the I-A study. We looked at five ascending doses in the I-A study, placebo-controlled, from 2.5 mg/kg up to 40 mg/kg in the dose escalation. All the way through, we had safe and well-tolerated product. We also observed from the PK studies that we did of the drug, that the half-life of the drug is approximately 27 days. That supported monthly dosing, which was important for us to note. Very importantly was to measure how much of the antibody actually crossed the blood-brain barrier. Were we getting sufficient antibody across the blood-brain barrier to engage our target? The target being these toxic oligomers. Interesting, as you can remember from my pyramid diagram, that the concentration of these oligomers is very low. In a way, fortunately for us, we don't need a ton of antibody across the blood-brain barrier just because the target is in such low concentration. What we observed from the phase I-A study is that we had more than enough drug across the blood-brain barrier, we believe even at the lowest doses, to maximally engage our target. That was an important finding for us, too. This comes to the whole discussion around brain shuttles and such, and we can talk about that a little bit. Our thinking was, well, is a brain shuttle required for PMN310? The two reasons that companies are using brain shuttles are primarily to reduce the incidence of ARIA. For us, we're not binding plaque. We don't think there's going to be a significant incidence of ARIA, so probably not. To get more drug across the blood-brain barrier to engage target. Since we're not having any off-target binding, all of our drug goes to the target. As we stated here, we have more than enough drug to maximally engage target. The rationale for the brain shuttle is not front and center. We're still exploring that and looking at ideas there, but the main driver of brain shuttle is not really front and center for PMN310, which is good. Taking these data then, next step in the development plan was to step into an Alzheimer's patient study. This decision was probably the best decision or most important decision we made as a company over the past year or two. We took a step back and we said we wanted to design a study that was going to give us a fairly definitive answer as to whether or not this antibody performed as we expect. There were other models out there of doing more of a shorter study with fewer patients just to look at biomarkers. For us, we did not want to end up in a space where interesting, but doesn't really tell us much. We have the advantage. Our chief medical officer, Dr. Larry Altstiel, not only is a practicing neurologist for the past 30- 40 years treating Alzheimer's patients, but he ran CNS at Pfizer for years. I went to Larry and I said, we need to design a study that's going to give us a definitive answer, which means we need enough patients, and we need to treat patients over enough length of time to be able to show some sort of clinical signal. Again, biomarkers are important, but again, you want to see if there's a clinical signal at the end of the day because that's how drugs are advanced and approved. We designed this study. Again, our 100 patients was our target. We wanted to have 100 completers in the study, and we wanted to dose for 12 months. At 12 months, we should start to see a clinical signal. This is the study we're running. We started it last year. It's a placebo-controlled, double-blind, randomized study. It's being run in the U.S. in 22 sites. We're looking at the three ascending doses of 5 mg, 10 mg, and 20 mg per kg. It is 3: 1 randomized, so three patients on drug for every one patient on placebo. 75% of the patients are getting drug, 25% are getting placebo. It's a really well-designed study. We have completed enrollment. We completed enrollment last December, a little bit ahead of schedule, which is always nice, but not very common. Interestingly, we were targeting enrollment of 128 patients in order to end up with 100 completers based on previous dropout rates. We ended up over-subscribing this trial. It was interesting when we went to the sites and said, we're getting to our 128 enrollment numbers. We need to wrap up enrollment. It was an interesting result from the PIs running the trial to encourage their patients to get into this study because I think there's a lot of support and enthusiasm for potentially the first time that we had an antibody that was not going to come with a significant ARIA liability. Because ARIA can be, obviously in addition to the patient, the bleeding and the swelling on the brain, it can be extraordinarily cumbersome to manage. You need the big treatment centers to do the MRIs and the constant vigilance and monitoring. For our sites and our PIs, it was like, wow, this might be the first time even if there's a moderate headache, we don't have to rush somebody to the neuro ICU. I think as a result of that, when we were shutting down enrollment, there was a surge of patients, if you will. We ended up with 144 instead of 128 subjects enrolled. Done end of the year, superb. Now they're dosed monthly for 12 months. We are looking at really three baskets of endpoints, biomarkers, which are relatively well understood for Alzheimer's disease. We've got a panel of biomarkers that we're looking at. We're looking at safety, including ARIA. Obviously, that's one of our key differentiators, so that's something that we are looking very closely at ARIA, and we are powered to show any incidents of ARIA. We're highly powered to show that. In addition, we want to have the clinical endpoints. These are the FDA approvable endpoints, the CDR sum of boxes. That's the course of the trial over the 12 months. Again, we submitted this to the FDA last year and got Fast Track designation. We're thrilled with that. Fully enrolled. We built into this an interim analysis, which I alluded to at the beginning of the talk. The interim analysis comes when all patients have been treated for six months instead of the 12 months. This was done just to keep the momentum and keep the news flow. Since the trial is not a three-month study, it is a 12-month study, so you need to maintain the enthusiasm of the investors, which is hard at the best of times. We built in an interim analysis just to remind people how things are going. That's coming up in early Q3, so really in the next couple of months for the company. We'll communicate the interim results. Then the final results, the last patients completed dosing at the end of the year. The final results, top line unblinded results will be early Q1 2027. From the interim analysis, we get a lot of questions about what exactly we're expecting and what exactly we're going to say around an interim analysis. We're being cautious. I think it's going to be an interesting signal. This is a blinded analysis. It's not a futility analysis at all. It's a qualitative assessment as to how the trial is going, to put it quite colloquially. We want to look at safety, including ARIA incidents. What are we seeing as far as the safety profile of the drug at the six-month time point on a blinded basis? Are we seeing ARIA levels that are within our expectations? Again, just to be clear, our expectations for ARIA is not zero. Some folks have said, oh, you're just going to eliminate ARIA altogether. It's like, no, because there is an underlying rate of ARIA, spontaneous rate of ARIA that exists in Alzheimer's patients without treatment. When you look at the placebo trials from the larger studies that have been done, the donanemab, lecanemab studies in hundreds of patients, that underlying rate of ARIA without treatment, the spontaneous rate, is in the range of 9%-14% of patients. For us, that's the placebo rate. We're not looking to take this to zero, obviously. We want to be somewhere around that 9%-14%, is what we're expecting, which is still a pretty high bar if we can lower it to placebo. We'll have a sense of how the ARIA, how the safety profile's looking. On the other side, we would like to show, hopefully to be able to show there is some directional movement in a couple of these biomarkers. If you have good safety, is there any sense of target engagement going on on the efficacy side? We'll look at a couple of these key biomarkers to be able to say, ideally, that there is target engagement. We do have the safety thing. Heads down, let's move forward to the end of the year, get everybody dosed, then we'll unblind all the data. We'll hopefully then be able to connect the biomarker, the target engagement, with a healthy safety profile, with a clinical signal from the clinical endpoints. Then with this, our thinking is, for us, we're obviously anticipating and preparing for the results coming out early Q1. Then even beyond that. This is really, for us, about the whole life cycle management for PMN310. What comes next? You plan for success, and we've designed a superb trial. The team has executed extraordinarily well. Then what comes next? Part of our thinking in designing such a comprehensive study was if this reads out well, we want to be able to step right into a single phase III registration study. That's our anticipation, and we've had thoughts around this. We've talked to strategics around this. I think if the safety profile holds up, the ability then to kind of step into a single registration study is certainly on the table. We've got the Fast Track designation, so we'll have those discussions with the agency. That's kind of the preparatory and the planning for that. Important in all this as well, as I mentioned, we're currently treating IV monthly dosing IV. The idea that we want to get this to market as a sub-Q formulation is high on our priority list. Ramping forward with sub-Q is something we might be informed by the interim analysis a little bit. That's in our sights, and that's in our plan, too. We want to get to market with a safer product for sure, a more efficacious product. Also one that's very patient compliant. Sub-Q formulation at launch is what we're gearing towards. That's really the Alzheimer's program. Kind of behind that, as we mentioned at the outset, the pipeline candidates are fascinating in the data they produced in their preclinical proof of concept. We are, as well, moving the ALS candidate and probably both the preclinical candidates closer towards the clinic. We want the company to be in a position where we read out the Alzheimer's study in early Q1. We've got proof of concept ideally for Alzheimer's disease and a potential best-in-class asset moving forward to an aggressive phase III plan. We also have proof of concept of the actual protein misfolding platform. When people look and they say, awesome on Alzheimer's, what else do you have? We'll have the two next candidates jockeying for the clinic in ALS and in Parkinson's disease or Lewy body dementia. That's another focus of the company. Certainly a second priority, kind of advancing those preclinical candidates along the path over the next number of months is important to us as well. We're also obviously engaging with a lot of the strategics. There's a lot of interest in the Alzheimer's space. There's been a lot of interest in what we're doing as well. The enthusiasm from the pharma companies is certainly there. Just on the last slide, just to sum it together, as I said, we've worked hard. The team is absolutely superb. For me as CEO, it's extremely important to have a differentiated asset. I think whatever industry or whatever company you're with, it's got to be differentiated in a good way, obviously. I think that's what we're pleased at and proud of at ProMIS. The platform differentiates us, and then the design of these selectively targeted antibodies differentiates us such that we do have the potential, we believe, to be best in class in the disease we're going after. That's a terrific place to be. Having near-term catalysts, obviously that's a good thing and being that they're clinical catalysts, that's a good thing for us as well. We're excited about that. The clinical profile as well, it's interesting. We've got the Fast Track approval. We're looking at how the future can take us rapidly to market if we succeed with our regulatory strategy. Again, importantly on the financial piece, which we all pay attention to very closely. Touch wood. We are now in strong position, able to importantly get well past data. We've got funding, as I said, through the end of next year. It gives us a position to really kind of position the company favorably upon successful data, whether we take this forward ourself or whether we take it forward with a strategic partner. We've got the runway to do that. We certainly have the team to accomplish that. That's really the kind of the update, the progress update from ProMIS. Thanks so much for listening and your attention. I don't know if we have a little bit of time on the clock. I don't know if we have questions from the audience. I'm happy to take a question or two if there's anything. Yeah, go ahead. You want to grab. It seems like the safety might have a little bit more meaning in the six-month readout given that a lot of the ARIA happens early on. Is that something you can comment on? Yeah, that's a good point. I don't know if you can hear, but the question was around the kind of the safety aspect, and it's a really important point with respect to ARIA. Safety from the interim analysis will be kind of a driving factor ideally if we get there and we can keep up to our expectations. Safety will be an important read, not only ARIA, but the whole side effect profile. The question specifically pointed to the fact that most ARIA exists or occurs in the first six months of treatment. We certainly saw that with most drugs that bind plaque and deliver ARIA. Donanemab, lecanemab, I think over 90% of ARIA cases came in the first six months of treatment. Very good point. That six months of treatment for our interim analysis, we're paying extra attention to that because we know that if there's going to be ARIA, most of it will have occurred in that first six months. That's going to be a bit more meaningful of a signal with respect to ARIA when we get there in a month or two, just to be able to say. Ideally, you never know what happens in the next six months. Again, if we see a healthy safety profile with respect to ARIA, knowing that, again, 90% + occurs in the first six months of treatment, that'll be more encouraging than not for sure. Good question. Thank you. Yeah, please. Dan. Yeah. Just a question on the spontaneous ARIA. Are you referring to all ARIA-E and ARIA- H or? Yes, Dan. Good question. All ARIA. Yeah. It's important, the ARIA- H and the ARIA-E. One could argue, it is true that ARIA-E tends to be the more serious ARIA that people focus on. The levels of ARIA-E are on the lower side. The ARIA- H, the hemorrhage, are on the higher side. The 9%-14% was all in E+ H. Thanks for pointing that out. Correct. I think the red light's flashing. I think that's time. Thanks very much, everybody. Appreciate it, and thanks for the questions