ProMIS Neurosciences Inc. Common Shares (ON) H.C. Wainwright 28th Annual Global Investment Conference

Take it away. Thanks, Katie.

Appreciate it very much. That is loud. Thanks everybody for joining this morning and thanks for those attending on the webcast as well. Appreciate it, and appreciate the Wainwright folks for inviting us yet again to a superb conference. My name Neil Warma, President Chief Executive Officer of ProMIS Neurosciences. Just like to remind everybody first, please, we are a publicly traded company. Please review our SEC filings for a complete and accurate picture of our operations. Just to walk through our company a little bit, for those of you who might be introduced to us for a first time. Just as a bit of an important fact, I guess, the name ProMIS, in addition to the promise of novel therapies to help patients, it is also based on our technology which is focused on protein misfolding. So ProMIS. It might give you a way to remember us a little bit in the future.

We are a publicly traded company, as I mentioned. The ticker is PMN, traded on the Nasdaq Capital Market Exchange. We are based in Cambridge, Massachusetts. We had our foundings, if you will, out of Canada. Our chief scientific officer, one of the leaders in the field of protein misfolding, was and is a professor at University of British Columbia. So our discovery platform came out of University of British Columbia, and we have built on that over the past number of years. But now based in Cambridge and Boston, Massachusetts. Our lead candidate is currently in the clinic, and I will touch on that over the next few minutes. That is probably our most important milestone over the past number of months. We have top-line data coming in a matter of months, actually.

In Q1 2027 top-line results. I will touch on the interim results that we just put out there publicly with our Alzheimer's study. We are well-financed. We are coming off a few months ago now in February, we closed a significant financing up to $175 million. Importantly, with an absolutely superb syndicate of investors, co-led by Janus, Ally Bridge, participation by Wellington, Deep Track, Great Point Partners. We are funded, as we said publicly, through the end of 2027. So nicely funded. Superb leadership. Dr. Larry Altstiel is joining us today in the audience, and he is our chief medical officer. But beyond Larry, the team is superb in its ability to develop neurodegenerative drugs that we are developing. I am going to touch on. Actually, maybe I will back up a little bit. The protein misfolding aspect of our company is very important.

We are truly a differentiated company in that we are able to design highly selective antibodies that specifically target a specific misfolded protein responsible for the disease we're focused on. As many of you know, proteins are manufactured by cells, and as they come out of the cellular machinery, they're folded upon each other in an elegant three-dimensional shape, and they go on to carry out their function. But very often proteins come out of that cellular machinery and they are misfolded or folded improperly, and typically your immune system will grab hold of those misfolded proteins and remove them. But as you become older, immune-compromised, your immune system can't keep up with these misfolded proteins that are being generated. If they're allowed to aggregate and build up, that's when you get serious diseases that are forming.

Our technology allows us to design antibodies, and all our therapies are monoclonal antibodies designed to selectively target misfolded proteins and remove them from circulation, preventing them from aggregating and building up over time. I'm going to touch on the interim data, and I'm going to come back to this because this was a significant milestone for the company that we reported on July 28. It was an interim analysis based on six months of dosing with our PMN310 lead candidate in Alzheimer's patients. I'll come back to the design of that study. But just to put out a bit of a teaser now, the interim blinded six months analysis came back very positive. We were very pleased with the interim analysis on a blinded basis. It showed a clean safety profile, which is important to us. I'll come back to that in a minute.

Importantly, it showed target engagement, we believe, by the antibody on some key biomarkers. So some directional movement on biomarkers, and a clean safety profile on the interim result. I'll come back to that in a few minutes. The ability of our platform to allow us to design antibodies that target multiple different diseases. As I mentioned, different proteins are important for different diseases. Our target for Alzheimer's is beta-amyloid protein, specifically the oligomer species. But then beyond Alzheimer's, we have antibodies targeting misfolded TDP-43 for ALS and misfolded alpha-synuclein for Parkinson's disease and dementia with Lewy bodies. So a relatively healthy pipeline, again, with a strong patent position all around focused on neurodegenerative diseases.

One of the interesting aspects around the selectivity of these antibodies is to be able to design a drug candidate that identifies and selects and targets only the harmful species of the protein you're going after. If you look in this diagram here, this represents kind of multiple species of A-beta protein. Our target is A-beta as it is for donanemab, lecanemab currently on the market for Alzheimer's. The challenge becomes that there are multiple different species of A-beta protein. There's the monomers, there's the plaque, which we all know about, and there's the oligomers. It was previously thought that plaque was the driver of cognitive decline in Alzheimer's patients. So drugs were then designed to target plaque, remove plaque. We now know that removing plaque in individuals, has little impact on cognitive benefit or in preventing further cognitive decline.

This, we've learned over the decades, that plaque is not really a driver of cognitive decline. Not only that, drugs, and the two on the market are examples of that, drugs that bind and remove plaque are also associated with a very serious side effect, and this is swelling and bleeding on the brain, known as ARIA, A-R-I-A. Not only is targeting and removing plaque not that beneficial at preventing cognition, it also results in 20%, 30% of the patients getting swelling and bleeding on the brain. The challenge becomes, and now the field has really shifted to, well, if it's not plaque, because there are drugs that can totally clear plaque and the patient continues to decline. If it's not plaque that's driving the cognitive decline, what is it? That's where the field has come back to. It's upstream of plaque. There's these low molecular weight, soluble oligomer species of amyloid beta protein.

Now we know that these oligomers are highly toxic, especially to the neurons, more specifically to the synapses. These oligomers are destroying the synapses, destroying the neurons, and that is responsible for most of the cognitive decline in Alzheimer's patients. The challenge becomes, well, how do you design a drug, since this is all the same protein, that can avoid monomers, avoid plaque, and only get to the oligomers? That's been the challenge to the industry, which is where ProMIS comes with its very differentiated technology. Our ability to design antibodies comes from our ability to predict how proteins are going to misfold. It's not just the linear epitope we're targeting, but it's this three-dimensional conformational epitope. It's only ProMIS that has the ability.

We have a chief physics officer and very computationally driven approach to designing antibodies that says it's the linear epitope plus this three-dimensional confirmation. From that, we design an antibody that binds that three-dimensional epitope, which only exists on that misfolded protein, and that gives us our differentiation. We can design antibodies that avoid the monomers. That's a good species of beta-amyloid. You certainly do not want to target that. It avoids plaque. We know that it's not really that beneficial, and it has a side effect. We seem to be the only company that can selectively target only these toxic oligomers. I won't go into this, but we've pressure tested our antibody against multiple other antibodies to say, can we bind plaque? Do we bind plaque? Let's make sure our key differentiating factor is true.

Side by side with all the antibodies, it was clear PMN310 is the only antibody that we can see that does not bind plaque. Then we headed into the clinic with our. Just touching on the two drugs on the market, by Eli Lilly and Eisai. These drugs have modest efficacy. Every step is positive for the patient. They have modest efficacy, but they come with a black box warning because of this ARIA side effect. The risk-benefit profile of the drugs on the market is pretty poor. Yet they're still generating significant revenue. The opportunity exists, which we believe, for a company to come with a much safer and much more effective antibody and capture much of this market. The commercial validation is certainly there, but the risk-benefit for the drugs on the market is quite poor.

That gives us a whole opportunity to step into this market. Probably the best decision we made a couple of years ago, and certainly with the help and guidance of Dr. Altstiel, our Chief Medical Officer, was the design of the study we are running now, this phase I-B study. We wanted to run a study that would provide us with a fairly definitive answer as to whether the antibody worked. That meant having enough patients over enough period of time to be able to detect a clinical signal. Again, it is a phase I-B study, so it does not mean hundreds of patients. We have to keep that in moderation. Our study design, and it is a placebo-controlled, double-blind, randomized study in MCI, so mild cognitive impairments, early Alzheimer's patients.