Good afternoon, everyone. Thank you for joining us for our next session at the H.C. Wainwright Global Investment Conference. My name is Joshua Corson, and I'm an equity research associate at H.C. Wainwright. For our next session, I would like to introduce our presenter, Neil Warma, who is the CEO of ProMIS Neurosciences. The floor is yours.
Thanks very much. I appreciate it. Thanks, everybody, for joining this afternoon as well, and thanks for all of you listening on the webcast. So I'll continue the Alzheimer's theme as our colleague introduced a few minutes ago to continue. So ProMIS Neurosciences, I'm the CEO. We are a publicly traded company. Ticker symbol is PMN. And just to remind everybody, as a public company, please review our SEC filings for a true kind of understanding of all of our corporate objectives. Just as a high level, and I'll break some of these points down over the next 19 minutes or so as we walk through them. But ProMIS Neurosciences, as the name may or may not indicate, ProMIS, we're focused on protein misfolding. That's the technology behind all of our antibody therapies.
We do have a platform. I'll touch on that in just a second, EpiSelect, which is the platform that allows us to generate these highly selective antibodies. We are in the clinic with our lead program. It is PMN 310 in an Alzheimer's study. We're currently treating Alzheimer's patients in a Phase Ib study. We also have an interesting pipeline of candidates I'll touch on as well based on this theme of targeting misfolded proteins. As far as, and I'll come back to these points as well, as far as having a differentiated, because Alzheimer's is an interesting space. It's an interesting field with a lot of activity going on in the past few years. Very important for, well, for me as a CEO, for us as a company, is to have a differentiated product.
I mean, regardless of the industry or the company, but for us, having a differentiated antibody for the treatment of Alzheimer's is absolutely critical. So we'll touch on this. We believe we'll have differentiation with respect to efficacy with our highly selective antibody. We certainly believe we'll have differentiation with respect to the side effect profile. I think many of us know, or those of you who know the field of Alzheimer's, the side effect issue around ARIA, brain swelling and bleeding is highly significant. So we believe we'll be able to offer a much better safety profile, and I'll come back to these points in a minute. Even with compliance, we're currently dosing monthly. We have the potential, we believe, depending on how the data come about, on delivering the product subcutaneously.
As far as where we are in our Phase Ib study, and again, I'll come back to this in just a minute, but the team, under the guidance of my colleague here, Dr. Larry Altstiel, our Chief Medical Officer, has been performing exceptionally well in the clinical study. We're enrolling probably a little bit ahead of schedule. We have 22 sites in the U.S. treating our target patient. Treatment is over 100 patients, and they're executing very, very well. We're kind of more than halfway through the study right now, and this is a placebo-controlled, randomized study, again, over 12 months of therapy, looking at endpoints related to biomarkers, safety, certainly ARIA, and clinical. We thought it was important to build in clinical endpoints over 12 months.
I'm happy to report that we just, not that long ago, publicly stated that we have fast track approval for PMN 310 by the FDA. We also, last week, announced that we have DSMB approval to go from our middle dose, cohort 2, up to our final dose, cohort 3. So we're doing well. We have an interim analysis coming just around the corner in Q2 of next year and final top line results targeted for Q4 next year. The team, an outstanding team. Again, our founding scientist, Dr. Neil Cashman, is one of the world leaders in protein misfolded diseases. And I'll acknowledge here as well, interesting, David Wishart is our Chief Physics Officer.
It's not a lot of companies that have a physics officer, biotech companies, but it's very relevant to our platform, this EpiSelect platform that we're developing based on Neil Cashman's kind of understanding and research in protein misfolding diseases. The chief physics officer is very relevant because this is very much kind of an algorithmic approach. What we do, in just a couple of words here, and we can follow up later if there's interest, is with this kind of computational approach, we're able to kind of predict the misfolding of certain proteins. With that, we can identify specific epitopes that only exist on these misfolded proteins, then we design an antibody that selectively targets this epitope. This is critical for all diseases, but certainly for Alzheimer's.
And as we know, proteins are manufactured by the cell, and they typically come out the other end in this three-dimensional kind of elegant shape and folded upon each other in order for them to kind of conduct their physiological role. But very often, the proteins come out, they're misfolded or not shaped properly, and these are kind of toxic proteins if they're misfolded. And typically, the immune system will clear them, but if the patient or the individual becomes older, immunocompromised, and the immune system can't clear these misfolded proteins, that's when trouble starts, and they go on to aggregate and form these large aggregates that cause numerous diseases. So our approach is to identify, predict when and how they'll misfold, design an antibody that selectively goes after only the harmful pathological misfolded form.
And with that, we've developed a really, really interesting pipeline of candidates, and each disease is associated with a different misfolded protein. So we'll come back to Alzheimer's in a minute, but the protein of choice is amyloid beta. That's the protein we're going after to try to prevent Alzheimer's. But then when we look at our next programs, PMN 267 targets misfolded forms of TDP-43, and we're investigating that in ALS, misfolded forms of alpha-synuclein, and we're investigating that in Parkinson's and MSA. And then we've got an interesting vaccine program, which we'll probably come back to later on, which is a similar approach to what we're doing with the therapeutic. So a healthy pipeline of candidates. So if we jump into kind of the lead program and look at the Alzheimer's program, it's interesting, just a little bit of science, if you will, around Alzheimer's disease.
As we know, amyloid beta has been a target for a long time for a number of different drugs, some successful, some not so. One of the challenges is how to selectively target kind of only the harmful form of amyloid beta, so there's multiple different species. As you can see here, we've got the monomeric form of A beta, the plaque, and the toxic oligomers. And the challenge has been how to develop an antibody that only goes after the toxic oligomers. We know that the monomers are not a target. They're actually useful. They have a physiological role, so you do not want to target monomers if you can avoid it. Plaque is an interesting one, another form of amyloid beta. We know plaque is not good.
It is inflammatory, but we do know now that clearing plaque doesn't necessarily result in clinical, meaningful clinical improvement. There are drugs that can completely eliminate plaque, and the patient continues to decline. What we also know with those drugs that bind and clear plaque is that they're associated with this side effect issue of ARIA, which is swelling and bleeding in the brain. If you can imagine the plaque, which is downstream from the oligomers go when they form this entangled mess of plaque, it gets embedded in the cerebral vasculature. If you kind of envision a little bit drugs that kind of bind and remove the plaque, you get this kind of rupturing of the blood vessels in the brain. This is kind of in 20%-30% of patients. These are the drugs that are on the market.
Donanemab and lecanemab are associated with relatively high levels of ARIA, as are other drugs in development. So again, the challenge is, well, how do you create an antibody that avoids these two and just goes after these toxic oligomers? Because most of them will cross-react with all species of amyloid beta. But that's the beauty in our platform, in our design, in our ability to kind of create and design an antibody that selectively targets the oligomers, and it does not bind to monomers, and it does not bind to plaque. And it's kind of a bold claim, because others have made it, that we don't believe we bind to plaque, and we've done a lot of tests to try to determine and give ourselves and others confidence that we don't. So kind of going into the pre-clinical program, our thesis and hypothesis, we've designed an antibody.
The epitope is not found on monomers, so we can't bind monomers. The epitope is buried in plaque, so we don't bind plaque. So all of our drug that's delivered should be focused and targeted to the toxic oligomers. And that's a really important point when it comes to how we plan to improve efficacy as well. And if you can see some of the generations of antibodies and developments in Alzheimer's disease, we started with solanezumab years ago, and that targeted these monomers. And again, we now know that is not the appropriate target, and it was not clinically relevant. Gantenerumab, crenezumab bound everything. Because again, if you can imagine, it's easier to develop a molecule that binds everything. It's like amyloid beta got a molecule that binds them all, which is, again, not a good thing, but it's tough to kind of be selective. So these two failed.
And then we've got Lecanemab. I mean, Aducanumab was pulled, but Donanemab and Lecanemab, the two on the market. So they're better. I mean, Lecanemab Biogen Eisai product was designed to selectively target the oligomers. But again, the challenge was how to make it exclusive and not cross-react. And they weren't able to achieve that because it's more selective, but it still targets and eliminates plaque, hence the association of ARIA and modest efficacy. And we believe the efficacy is coming because they do hit some of the oligomers. But again, keep in mind that if you're cross-reacting, you've got to get beyond this to get there. So you need a lot of drug into the CNS in order to kind of bind and bind and get here.
And that's why probably the efficacy is modest, because there's drugs getting soaked up by the plaque and getting soaked up by the monomers. So then we've got 310, and this is us coming again, ideally selectively targeting the oligomers. And we've done some assays and again, kind of testing to really proof test whether or not we are not binding plaque. And here we have brain sections from Alzheimer's patients. The green demonstrates there's plaque in the tissue. And then we applied the different antibodies. And again, we did side-by-side analysis of different antibodies to see which ones bound plaque. And the purple fluorescence shows they bind to plaque. And here's the control. So no binding to plaque because these are the controls. And this is PMN 310. So no binding to plaque here.
When we look at donanemab, this is Acumen ACU193, lecanemab, aducanumab, all of them bind to plaque, even though they weren't trying to. Again, here's just a way of quantifying, quantitating that analysis of how much fluorescence do we see. PMN 310, no binding to plaque. The others versus their control all bind plaque. That was a good test for us to say, I think we're on the right track. We did another, and I'll just touch on this, a mouse study. This is one of our formal tox programs where we dosed a number of mice for half a year, so 26 weeks, up to 800 milligrams per kilogram. We really dosed these animals to see whether or not we could see any signs of hemorrhage in the mice brain. These are mice with plaque.
So were we binding plaque and were we seeing any sort of hemorrhage at all? And we saw none. Squeaky clean brains, no evidence of hemorrhage in this tox study. So again, given that, we were really convinced we probably have a strong benefit here with respect to ARIA and side effect profile. And I won't go into this. I think we all know the challenges out there with the drugs on the market with respect to ARIA, not only the surveillance and the stratification, but also the infrastructure that's required to treat these patients. And again, it might be fine for the big New York hospitals, but if you're in the outlying regions, they do not have the infrastructure to manage ARIA, which is why we're seeing the uptake of some of these marketed drugs not very successful. So with that confidence, we went into the clinic.
We ran our Phase Ia study. This was done last year in healthy volunteers. Single ascending dose study, five doses, safe and well tolerated. So we've got a good, clean antibody. Importantly, we wanted to see whether or not we got drug into the CSF across the blood-brain barrier. These are antibodies. So how much of the drug was getting across the blood-brain barrier? We saw a nice dose response here. We looked at day three and day 29 in the CSF, a nice dose response. And importantly, what we determined in the phase Ia was we had more than sufficient quantity of drug to engage all of our targets. And keep in mind that our target is not this massive pyramid, but it's the tip of the pyramid. So we had over 100 molecules of drug to each oligomer.
We're kind of, again, sorry, confident that we have enough drug in the body to fully engage our target. With that, Dr. Altstiel and the team designed a really robust phase Ib study. Kind of coming out of the gate, I think we're getting kind of people surprised at how robust and how comprehensive a 1b study was. As I mentioned at the outset, it's 12 months of treatment because important to us was we wanted to have a clinical signal at the end of the day. We didn't want to do one of these quick and dirty biomarker studies, which others have done. We wanted a full, as much as possible, full study looking at 12 months of treatment, three different doses, 5, 10, and 20 milligrams per kilogram. Importantly, we're looking at endpoints. We're looking at a range of biomarkers.
Obviously, we're looking at safety with respect to ARIA, and we're looking at clinical endpoints. So the study's enrolling really well. As I mentioned, DSMB gave us approval to go up to that third dose. So we're currently in the top dose enrolling our final cohort of patients. Importantly, we reported this as well, we have not seen a single case of ARIA. Again, our claim is not to show no ARIA, but to show similar levels to placebo because we know there's an underlying presence of ARIA, even in placebo patients of about 1 to 2%. But to date, over half the patients have been enrolled. We have not seen a single case of ARIA. And importantly, when you look at the Biogen and the Lilly phase II studies, over 90% of their ARIA occurred in the first six months.
So again, we're kind of highly motivated and encouraged that thus far the safety profile looks superb. And knowing that, again, the drug is selectively only targeting the oligomers, because this is important, it can be safe and no ARIA, but is it working? But we expect the efficacy to be enhanced as well since we're only going after those toxic oligomers. So from our perspective, again, we've got a 12-month study. We built in an interim analysis because we wanted to keep enthusiasm moving as we enroll the study. The interim analysis will take place once all 100 patients have been treated for six months. Remember, it's a 12-month study. So when all patients have been treated for six months, we're going to look at the biomarker profiles, and we're going to look at efficacy. We're not going to look at clinical endpoints at six months in an interim.
We'll save that for the end. But the interim analysis will look at, and again, a very healthy panel of biomarkers. Dr. Altstiel can talk to you a little bit more specifically about why they're relevant, but they're very well understood and well known. So if in the interim analysis we see a nice directional separation in some of these biomarkers, and this will be on a blinded basis, that will be encouraging together with RA. So we built in a really healthy biomarker analysis. Interim analysis we expect in Q2 of next year, so kind of just around the corner. And then final top-line results will be in Q4. So again, the trial's running well. FDA fast track, DSMB green light to move forward. No cases of RA to date.
And it's interesting. We see that the 22 sites, and they're all enrolling well. The PIs at the sites are really kind of motivated, encouraged by the drug. And they're kind of, I think, probably promoting our study ahead of some of the others. I think for the first time, and they're telling us that we might have a drug here that doesn't come with a side effect issue. Whenever they have a patient presenting with a headache, do they have to worry about whether it goes kind of into the neuro ICU or anything? So they're very encouraged to get patients into the study to keep things rolling. So we're thrilled with that. As I said, Q2 of next year for the interim, Q4 for the final. I'm not going to touch on this just to point out that there's two products in the market that are.
The risk-benefit profile is challenging. The benefit is modest. The risk profile with ARIA is pretty significant. But what it does, but they're still doing reasonably well in pulling in $500 million a year. But what that does show us is that we have kind of regulatory validation. FDA wants products to treat Alzheimer's disease. There's a huge unmet medical need. It shows kind of commercial validation. They're generating significant revenue, even with a challenging risk-benefit. But it really kind of opens the door. And there remains a huge unmet medical need in Alzheimer's disease for patients for something to come that's safer and ideally more efficacious. And we believe we're kind of heading down the right path with our drug. So just to summarize, again, as I said, critical to have a differentiated product regardless of what industry and what company you're doing.
And we feel we have in a kind of highly competitive and complicated space such as Alzheimer's, we are kind of leading the race with a differentiated antibody that does not bind plaque, we believe, that does not bind monomers, goes after these highly toxic oligomers, which in theory kind of attack the synapses in the brain, which is what really drives Alzheimer's disease. We know there's significant unmet medical need despite having a couple of products on the market. And again, our clinical data is coming shortly in Q2 and Q4. So it's an interesting time for us to be out in front of you. And again, thank you for your support and attention. As I said, we'll continue to update as we progress with the trial and certainly as we get closer to the interim analysis and the final top-line results. So with that, I'll yeah, great.
We can open up and see if there's a question or two. Can open up the floor if anyone has any questions. So I saw for your phase IB, you're looking at earlier stage Alzheimer's. You plan to look at more moderate to more severe patients. Well, I mean, we'll judge by these data. Yeah, that's an important point. These are kind of mild Alzheimer's disease and kind of MCI patients that do have Alzheimer's. One important aspect of the 1B, as I mentioned, it's quite a robust design for a 1B study coming out of the gate, 100 patients, 12 months. I think what's important, and Dr.
Altstiel will kind of talk about this or can answer questions about this as well, is that we believe in designing a more robust study, the phase Ib study. We believe that if it's successful, if it reads out that shows it's safe, it's engaging its target, we have a defined dose, we believe quite strongly that there's the ability then to step into a pivotal phase III study. So we're kind of obviating the need for that middle phase II larger study by doing a more robust phase Ib. And we're kind of engaged with pharma discussions now about if successful, essentially, we would look at replicating this study instead of 100 patients, probably 1,000 patients in a phase III study. And then you save two years of work and $100-$200 million with the phase II middling program.
And then from this, we'll certainly look at, as we proceed, kind of expanding to later stage Alzheimer's patients as well. But now we're kind of earlier stage patients.
All right. Perfect. Yeah. So what's the mechanism of clearing the plaque once the antibody is attached to its epitope? Is it a macrophage activation?
It is. It is. It's an IgG1. So again, it's the kind of the effector profile comes into play when you get the binding, not to the plaque, to the oligomers. The antibody binds to the oligomers, and then we have the kind of the macrophage, the immune system comes and clears out. So it's kind of stabilizing the monomers, the oligomers, but also clearance from the macrophage. But it is IgG1.
The other who they bind to, they're all IgG1?
They are all IgG1. The one that's a little different is Acumen is IgG2.
But the others are IgG1 as well.