Okay, welcome to the 44th Annual Healthcare Conference. My name is Stacy Ku. I'm one of the biotech analysts here at TD Cowen. It's my pleasure to introduce Lisa Ricciardi of Cognition Therapeutics. Lisa, please take it away.
Thank you. Good afternoon, everybody. Thank you for joining, and, Stacy and Vish, thank you for including us in the conference today. I'm joined by two colleagues, Chief Medical Officer, Dr. Tony Caggiano, and John Doyle, our CFO, if you have other questions for them. Please take a look at our forward-looking statement. We completed our public offering in October of 2021. So over the next 15 or 20 minutes, I wanna take you through the value that's in our platform, focusing mostly on our clinical data, our recent clinical data. Cognition Therapeutics has a first-in-class asset that's been designed to restore impaired cellular response functions. We have a lot of data in neurodegenerative disease to show you that. This year, important catalyst for Cognition, 2 huge study, proof of concept studies reading out in multi-billion dollar categories. We punch above our weight.
We've been well-funded by grant sources from Michael J. Fox, the NIA, from the ADDF, and we have the team to execute. So our lead program, CT-1812, as it indicates here, is an orally delivered, first-in-class, highly brain-penetrant small molecule. It is, as I said, designed to restore cellular functions that are impaired in these conditions. We have trials running in all of these diseases. More specifically, this drug is a once-a-day pill with a high degree of CNS penetration, as I said. We believe our program is entirely focused on the right target. In Alzheimer's disease, the A beta oligomers, in dementia with Lewy bodies, the alpha-synuclein oligomers, and in the back of the eye, the retinal pigment outer segments. By going after these targets, we believe we're protecting the neurons, protecting the synapses and the neurons, and thus have potentially a disease-modifying drug.
It's interesting, when you talk to clinicians, they say, "I don't care what you call it, I just wanna know it works in my patients." I think that's important. Last, as we look towards manufacturing for phase III and commercialization, we have a pretty simple process, scaled from easily sourced materials and a very good IP estate. Let's talk about Alzheimer's disease. Okay, show of hands, who in here doesn't know anybody with Alzheimer's disease? Of course not, right? It's so prevalent. This condition is enormous, and one of the great things is that now we're seeing new drugs come forward, but there remain many, many challenges. Two approved drugs, lecanemab, aducanumab. We think donanemab is around the corner. Fantastic program. Pricing is unclear. Whatever price is chosen, it's gonna be a huge hit to Medicare, right? Because the population is so big.
We estimate, using Jeff Cummings' data and clinicaltrials.gov, some 140 trials running. Who knows how many drugs that will result in, but this landscape will clearly change. Now, part of the challenge is access. If you have to have this drug infused, there are not that many treatment centers. This is a survey of 100 infusion centers, and they all say, "We're capital constrained. We're fixed in terms of this physical space we have." And so it's very challenging after the great work of the immuno-oncology drugs to make room for this next set of infused products. MRI and PET scans, when you live on the coast, as some of us do, it's easy to access these things. It's not so easy in large parts of the country.
So we look at this and we say, "You know, to launch with a highly efficacious once-a-day oral drug that doesn't require surveillance, we think this will be a big advantage in the treatment paradigm of Alzheimer's disease." The data has to be borne out. Where does our drug work? Well, from left to right, you're probably familiar with this cascade from monomers to oligomers to protofibrils and plaques. If you go all the way to the right, you can see this is where both, Aduhelm and donanemab work. The monoclonal antibody, the plaques themselves are inert and insoluble, and yet you lower enough of it, and we have seen demonstrated, an improvement in or a slowing of cognitive decline. So that's inarguable as a target.
We also know from the literature that the oligomers are, in fact, the most toxic portion of the plaque, smallest in number, hard to visualize, and the most toxic, and that's why our program has been anchored on going after this target. As I said, the literature is replete with information that talks about the damage done by oligomers, and a number of other companies are going after this target. In brief, if I could visualize for you how the drug works, the yellow element is meant to indicate CT1812, our drug, binding to those two pink elements at the bottom, two proteins. In case you couldn't tell, those were two proteins, TMEM97 and PGRMC1, the sigma-2 receptor. So when our drug binds to that receptor, it causes the adjacent oligomer receptor, that's to the left in orange, to have a conformational shape.
The oligomers are displaced, and no new oligomers can bind. I love saying in about two sentences what took 10 years of work to find. We also have this video on our website, but this is how we prevent the binding of oligomers and the displacement of oligomers that are already in the brain. In our development program, like every good company, we started with target engagement. What's the target? Can we hit it? What happens when you do, right? From there, we went on to study early signals of efficacy, safety, dosing, and I'll take you through these points and show you the data that we've generated to date. So first, target engagement. We published a study last year. It was called the name of the trial was the SNAP Trial.
Now, what I've told you is we prevent oligomers from binding, we displace oligomers, right? We've seen this in vivo, in vitro, and in humans. On the left, you're seeing transgenic mice dosed with placebo in red. Green is 1 dose of drug every 10 minutes. A micro immunoelectrode assay is put into the mice, and we measured the displacement of the oligomers, and it looks much like on the right in humans, where patients were brought into an inpatient center, given a single dose of drug. After a run-in period, the green is drug, the red is placebo, and you see the same effect from the mouth across the blood-brain barrier, showing its effect, getting to the brain and displacing oligomers. And as I said, that paper was published last April. Now, why is this important?
Why do we care about that? Well, at the end of the day, we wanna see cognitive changes in Alzheimer's patients. So SHINE is the name of our trial that we'll read out this June. This is 153 patients, mild to moderate disease, three arms, two doses of drug and placebo. Primary endpoint is a combined look at the two doses of drug, and then 12 secondary endpoints. We also went outside the U.S., thinking ahead to phase III, so we have conducted trials in Australia, Czech Republic, Netherlands, Spain, to ensure it could be done on time. So what's the early look I'm talking about? When this trial was getting underway, the FDA engaged with Tony and indicated, "Look, your tox date is one month, your trial, six months. Let's look for safety." No issues with safety, no issues with tox.
I think we've studied five species. Once you unblind the data, you unblind the data. What we saw for efficacy is right here. In blue, those are two doses of drug. In orange, it's placebo, and at six months, you see that delta. That's a 3-point difference in cognitive measurement on the ADAS-Cog 11 score. Clinicians would say to us and do say to us, "Patients who achieve a 3-point difference in cognitive ability, cognitive decline, that's noticeable." You're gonna see that. As well from a regulatory perspective, we know that the acetylcholinesterase inhibitors, Aricept, et cetera, had as a target a 3-point difference for approvability. We're often asked by investors: "What do you wanna see at the end of June, July, whenever the data reads out?" Well, we'd certainly like to reprise these findings. That's a very significant result.
We'd love to see that with a larger dataset. We have a dozen secondary endpoints, and in the end, I think the real thing for cognition is to take a look at the data and say: Do we have the information that drives us into phase III? So that time is around the corner, and we are excited about it. Now, a year ago, we completed a trial called SPARK with our collaborators at Yale. Chris van Dyck, very well-known name in the field. One of the things we were looking at is SV2A, a synaptic protein. Again, if you're the company that protects synapses, there was a logic to engaging in this. What I'm showing you here is a part of the trial. On the left-hand side, this is volumetric MRI, 10,000 images collected from some 27 patients over six months. Orange is placebo.
The two blue lines are drug. Again, you see the delta, the mitigation of brain atrophy due to CT1812 being dosed over six months. Now, on the right, this was a P is 0.05 on the left, the aggregated data. But on the right, in regions of the brain associated with learning and memory, and in regions where the sigma-2 receptor is expressed, we saw significant differences. Here's another look at it. A picture is always worth a thousand words. Very exciting when you look at that. I think we all recognize it's hard to have a placebo effect on the size of your brain, and I'm sure you're all aware, as we age, our brains shrink. With disease and illness, they shrink considerably faster. And so this is an important finding in that trial.
One more study, I'll show you some data from this read out this past June. Name of this trial was our SEQUEL study, and what we were looking at here was real-time effects on the synapses of dosing with CT-1812. So we all know patients with Alzheimer's, they have had plaque in their brain for decades. And we showed in this trial, in four weeks, a positive impact is measured by looking at EEG patterns. So we're all sitting here, we're awake and cognitive, and this would be probably assessed by the global alpha power scale, right? We'd all check that box. With demented patients, the wave patterns change dramatically. I'll just take you through the middle column here, which is connectivity.
If you picture those stock photos of EEGs, where the electrodes are all over the head, the truth is, parts of your brain work with other parts of your brain. This is a function that's lost in neurodegenerative disease. So in this trial, patients were on drug for four weeks, 2-week wash out, four weeks of placebo. And in green, what you see is, in fact, in a 4-week period of time, those patients returning to normal EEG measurements, as opposed to when they were on placebo. So the idea here is you can quickly make an assessment, real time, of an impact on disease from using our drug. Now, those studies were all completed. They're all in mild to moderate patients. A study that's running right now with our collaborator is our START trial, and as you can see, this is in early disease.
So Leqembi and donanemab were both studied in patients in an early disease population. This is our study in that population. You can see 540 patients. This is an 18-month trial. You know, earlier patients need a longer trial. It simply takes longer to fail, right? That's what we're studying here. And in addition, I think one of the most important things, and I give Tony credit for this, is taking in patients on Leqembi. We all believe that Alzheimer's disease treatment is going to be a paradigm where there are multiple drugs used and at different points in time, triggered by different clinical milestones, much like HIV, AIDS, and oncology, right? We think that's going to be the way ahead when there are enough drugs, and we're fortunate enough to be able to study lecanemab in combination with our drug in this study.
Now, saving the best for last in this section, I will tell you the SHIMMER trial is looking at a slightly different population. Patients who have dementia with Lewy bodies. It is similar in some ways to Parkinson's disease, dementia, Alzheimer's disease, but indeed, its own clinical diagnosis, and there's just about nothing available for these patients. Six-month study, three arms, mild to moderate patients. We are pushing very hard on enrollment, and our goal is to be able to read out top-line data at the end of this year. And again, very excited to take forward something for this population. Now, I only mentioned in brief our work in geographic atrophy.
The question we most often get from investors is, "Why are you studying ophthalmology when you're a company with such deep expertise in neurodegeneration?" What I will tell you is there is a very long and deep scientific rationale for why Cognition has chosen to engage in this study. We know that there are patients who have a genetic mutation in the sigma-2 receptor, and what we've seen is a decreased risk of AMD. Independent scientific groups have published on this, on proteins, decreased levels of TMEM97, rescuing cell death. There is a great deal of literature, and there are all our own samples in an aged population, the biomarker samples that we have, that allowed us to look at GWAS studies and other factors.
So I'm not going to go into the history of it, only to say we convinced ourselves, then we convinced our board, and now we work with investors to ensure that this trial keeps running. The trial is a phase II trial. It is recruiting rapidly. PIs are very enthusiastic, not only because this is an oral drug and not another injection for them and for the patient, but also because this is possibly an orthogonal approach, right? There's a lot of complement drugs out there. This is a very different approach, so we're quite enthusiastic about this trial. Now, in brief, our third quarter financials were published last fall. $33 million in cash takes us to November of this year. We have received over $171 million.
The 171 is from the NIH, so that does not include multiple awards from the Michael J. Fox Foundation or from the ADDF. We have a balance there of $74 million. You do the work, you invoice the government, you get reimbursed with an overhead allocation. It supported this company, and that's the reason why a tiny group of 28 people can do four phase II studies in indications of this size. So let me close by looking ahead with all of you. 2 big catalysts for our company, mild to moderate Alzheimer's disease, reading out in the middle of this year. I've shown you what I hope is a preview of that data, the efficacy data, that I demonstrated earlier. The second trial is in pink here, mild to moderate SHIMMER. Again, another element of our neurodegeneration platform, targeted to read out at year-end.
Early-stage disease in Alzheimer's and dry AMD are on deck, actively recruiting both of those studies. As I said, all these other studies are completed, and the papers are published, or in the case of SEQUEL, about to come out. With that, I close my comments and would love to take your questions. Thank you.
Yeah. Thank you, Stacy.
So, for the first question, go back to the interim data that you've shown so far.
Well, have you talked about a dose-response that you've seen in your analysis? Are you seeing a dose-response? There any that you've been able to observe just.
I'm gonna let Tony address that question.
Yeah. We have shown in the past the two different doses. At this point, they're behaving very similarly, which given the numbers, the trial is not that surprising. The primary analysis is a grouped analysis with both doses versus placebo, so this is the primary efficacy outcome. Now, obviously, when it reads out, it needs to be positive and have a dose response that would be enough.
And then, could you talk about the different doses that you're carrying forward for SHINE versus START? Just talk about your rationale and-
Sure. I'm gonna let Tony take that as well.
Yeah. So the doses we've been using in the mild to moderate Alzheimer's and the ADA 100 and 300. At the higher dose levels, we had some level of discontinuations based on elevated liver enzymes reversible and very mild. And so in the other studies that are two years and 18 months, we wanted to use a dose level that we believe would be efficacious, but be a little more tolerable and have less discontinuation. So just a very practical approach. Yeah.
And then for the START trial, can you talk about potential timing for results, any type of guidance around that, or any potential for an interim look? Any understanding around that?
Yeah, no, it's a great question. It's a big trial and an important trial. You know, we haven't given guidance on any of our trials. We were asked repeatedly when it came to SHINE last November, we said, "The last patient has been recruited." Likewise, with this trial, we're not giving any guidance. It is continuing to recruit, and it's 540 patients. We may decide at the end of recruitment to say, "We've reached that milestone," but that is not where we are now. Your second question was timing.
Yeah, potential for interim.
Ah, interim. I think that's something that Tony and the other steering committee members are continuing to evaluate, and so right now there is no interim.
And then, last question is your thoughts around kind of the regulatory path forward. Obviously, you've had a lot of great funding from the NIH. But then, of course, there's some, let's say, framework around the, your ability to develop that fully. So just curious, what's your take on, let's say, you get positive studies, h ow are you going to move forward from there?
That's a great question, Stacy. The plan is that at the end of these studies, both this study as well as the SHIMMER study, Tony, with the team, will be looking at what do we have to do to be prepared for an end-of-phase II meeting with the FDA, and from there, determining what is the protocol for phase III. That can be a lengthy process. Do we anticipate, with really solid data, interest from strategics? Sure. I ran Pfizer's global licensing for a decade. Those companies are swarming every company in the space in important conditions like this. They're not only big markets, the large companies really do wanna make a huge difference. So we suspect with strong data, we'll have continued interest and dialogue. Does that mean we carry it in the U.S., someone takes it out of the U.S.?
I feel that as the CEO with Tony and John, the job is to create options. Come this year, when we understand human biology, if we've done our job well, the three of us, then we're gonna have a variety of options going to the capital markets, going to partners. The regulatory path, Tony is already very much on top of. So that stands alone, whether we're doing it or somebody else. Great, thank you. Yes?
Can you talk about the IP status for the model?
Yeah. We have a tremendous IP estate. I always joke with people, when I first started working with Tony, I would look at our legal bills and go, "What is this?" We have a very strong IP estate. I will tell you, in our lead program of a patent term, composition of matter, 2035, patent term extension, 2041, whole series of other patents as well as on follow-on compounds. So that's an area that we feel very confident about. You know, I came out of Pfizer, so I look at the world the way you know you're gonna get looked at, and I'm very pleased with how robust the effort is for our lead program and subsequent programs. And are we in every single market? We're in a lot of markets.
There are some where you say to yourself, "What is the cost of doing this in, you know, Burkina Faso?" I'm just joking about that. I simply wanna convey that you'll pick and choose the markets, as we go forward based on cost, but it is a strong part of our portfolio. Other questions? If not, thank you. Really appreciate it. Thank you.