Good morning, everyone. Welcome to Day four of the Needham Healthcare Conference. I'm Ami Fadia, biotech analyst here at Needham. It's my pleasure to be kicking off the day with Cognition. I have with me Lisa Ricciardi, who is the President and CEO of the company. Thank you, Lisa, for taking the time to take us through the story this morning. I wanted to give our listeners a quick reminder that you can send over questions to me through the dashboard so I can ask those questions to Lisa. With that, let me turn it over to Lisa to take us through the presentation. Ami, thank you very much. Thank you to the Needham team for including us, and thank you to the listeners this morning. I'm Lisa Ricciardi, President and CEO of Cognition, and I'm joined today by my Chief Financial Officer, John Doyle. He's not on screen, but he is here with us. Let me begin by taking you through the forward-looking statement. Please note the information discussed today is covered by the Safe Harbor Provisions of the Private Securities Litigation Reform Act. We caution you that during this presentation I may be making forward-looking statements. Please see our K and our previous filings for any information about risks in the company's business. In brief, Cognition Therapeutics has a number of leading attributes. The first is our first-in-class asset. Our drug is referred to as CT1812, and it has been designed to restore damaged cellular response function. We're in multiple trials now, phase 2 trials, so we have an advanced pipeline in several indications, and these are multi-billion-dollar opportunities: Alzheimer's disease, dementia with Lewy bodies, and geographic atrophy. As for financial discipline, we have been well supported by non-dilutive grants for many years from the NIA, from the Michael J. Fox Association, from the ADDF, the Alzheimer's Drug Discovery Foundation, and we have the management team to execute on our ambitious program. Now let's establish the groundwork by talking briefly about the actual drug we're working with. CT1812 is an orally delivered drug. It is first-in-class, and it is a highly blood-brain barrier crossing drug or high-brain penetrating drug. As I said, we are working with this drug in three different indications. Some brief background: as I said, it is an oral once a day. It is a small molecule ligand of the Sigma-2 receptor. We believe that we are targeting one of the most crucial aspects of Alzheimer's disease, and that is the toxic oligomers, both A beta oligomers and alpha-synuclein oligomers. That is the focus of this drug. By removing these toxins from synapses, our drug protects neurons and restores cellular function. We have the right target, we believe. We believe that we have and will continue to demonstrate neuroprotection. With regard to manufacturing, as we look ahead to phase 3 and then commercialization, we know that we have a highly scalable development process from readily sourced materials as well as a very strong patent portfolio. Let's turn to something that everybody is familiar with: Alzheimer's disease. There have been tremendous advances. In the last several years, we have finally seen breakthroughs: drugs that work, drugs that got across the finish line. I think we're all waiting with great expectation for Lilly's drug and how that reads out this summer. So real progress in the clinic. Along with that is the reality of how these drugs are delivered and what it takes to get these drugs to patients. So one of the great advances in recent therapeutic history are all the immune drugs for cancer. That means those patients are in these infusion centers, making it challenging to schedule. In addition, MRIs and PET scans required for diagnosis and surveillance. All of this means that for those patients with Alzheimer's disease, the good news comes with some real complexity. We believe that having a drug, an oral drug, a once-a-day drug easily taken by patients or administered by caregivers would be a great addition to the portfolio of drugs available for treating Alzheimer's and other conditions. I would like to tell our listeners where we fit in this continuum. What you see here are an array of drugs from an array of drugs as well as the process, the Alzheimer's disease cascade, if you will. Monomers aggregate to become oligomers, multiple oligomers aggregate to become fibrils and protofibrils, and eventually what you have is inert and insoluble plaques. Many of you are probably aware that this process works both ways. From From the plaques, seeded are these other elements, and the monomers, of course, continue to develop into plaques. Where our drug works is right here at the oligomer stage of the process. We displace A beta oligomers, and we prevent their ability to bind, thereby protecting the synapses. A visual representation of what I said is here, and I would also tell you that this is available as a short video on our website. Here is CT1812, this yellow figure, binding to its receptor, the Sigma-2 receptor. These are two proteins. And next to it is the oligomer receptor. Upon binding to its docking station, if you will, the oligomer receptor changes shape, and the oligomers are displaced. I think I've just given you about 20 years of science in two minutes, but that's the upshot of how the drug works. We just published a paper. That is to say, our collaborator just published a fantastic paper, Dr. Tara Spires-Jones, excuse me, and her team at the U.K. Dementia Research Institute recently did work imaging the location of these proteins, giving visible evidence to our belief about how our drug works in this process. Fantastic work by our collaborator. Let me turn to trials. I said to you in the beginning we're in multiple late-stage trials, and we got there by doing a lot of early work. We learned from these trials and have brought that information forward. I'd like to cover that with you. The first problem always in drug development is target engagement. What is it you have to hit? Can you get there with your drug? We've done that. I'll show you that information. In addition, we have early indications of efficacy in our SHINE trial. I said earlier that we have two data catalysts reading out. This is the first, the SHINE study. We'll have this full study in several months, but we had an early look at data a while ago. In addition, we've done a study looking at the anatomical effect of CT1812. That is its ability to mitigate brain atrophy. And last, our most recently completed study was the SEQUEL study, where we were looking in real time at the ability to impact synapses, returning them towards normal health. So let's look at these studies in brief. The first study, as I said, is target engagement. We referred to this trial as the SNAP trial. On the left, you see animal data; on the right, human data. And in each case, with a single dose of drug, what you see is, in green, oligomers displaced into the CSF. Vehicle, in both cases, is in red. So the animal model data, the transgenic mice data, is replicated here in humans. This study was completed. It was published last year in the Journal of Translational Neurodegeneration. And what I can tell you is we have done this work in multiple species. We have demonstrated that the drug can go from the mouth, across the blood-brain barrier to the brain, and displace oligomers, ultimately hitting the target that we are looking for. We've done this in vitro, in vivo, in human studies, and so we are very confident in this work that was done as the groundbreaking part of our clinical work. I'd like to turn to our SHINE study. This data is what will be released in several months, as I said. Let me cover what the trial is first. We're talking about mild to moderate Alzheimer's disease patients. There are 153 patients. We studied patients in the U.S., Australia, the Czech Republic, Netherlands, and Spain. Fantastic collaboration partner on this trial. Patients were given two doses of drug or placebo over a six-month period of time, and the primary efficacy endpoint is the ADAS-Cog11 scale. In addition, we have a great deal of secondary measures. Consistent with our prior work, we have done a great investment in biomarker and proteomic work, and we anticipate reading some of that information out shortly as well. Now, I said that we had a previous look at this data. When the trial started, the FDA said, "This is the longest study you've run. Let's look at the first tranche of patients," which happened to be 24 patients. A 3-point difference was shown on the ADAS-Cog11 score at the end of six months. Our endpoint is actually the combined drug groups, which are reflected here, and this is the 3-point difference we're talking about. Clinicians would say and have said, "That's a meaningful difference. If you show a 3-point difference in the ADAS-Cog score, you're going to see that in the behavior of the patients." We also know that from a regulatory perspective, a 3-point difference from placebo was the basis of approval for the acetylcholinesterase inhibitors. So we were very enthusiastic to see this data. Now, I suspect anybody listening to the Cognition call this morning has one question: "Well, what is going to be success when you read out the full study? What do you think is going to happen?" Here's how we think about it. First, as an objective measure, we look at the results from the most recently approved drug, lecanemab, a monoclonal antibody intravenous infusion. What we learned from that study is that participants had a 1.4 point difference over an 18-month period of time. Now, we exceeded that in our preliminary analysis of these first 24 patients, where we saw a 3-point difference at six months. So if you ask us, we would say success looks like having a 3-point difference or results, rather, that replicate what we're seeing here in the early study. To be clear, there are multiple secondary endpoints: cognitive and functional scores, the neuropsych test, the ADCS activities of daily living. There are many, many ways that we can show the impact of our drug on patients. But we believe that what we know about our drug and looking at this data sets us up well for the full readout in the coming months. I mentioned earlier that we had another trial that looked at structural parameters. That is, reduction in brain atrophy. We refer to this trial as our SPARK trial. This was done in collaboration with our partners at Yale's Alzheimer's Disease Research Unit. What you're looking at on the left is a function of 27 patients who were treated for six months. Orange is placebo. Blue are two doses of drug. And this is a composite of volumetric MRI. So what you're seeing here is a trend, a visually apparent trend. This was a 0.06 p-value in the reduction of brain atrophy. We started this study looking at a synaptic protein, SV2A. When we saw this result, we looked further at regions of the brain where the Sigma-2 receptors express: the hippocampus, the prefrontal, and prefrontal cortex. These numbers that are shown in red look like this when you graph them. I feel this makes a compelling visual statement of the ability of our drug to impact atrophy in these regions of the brain. This paper was also published in the fall. I'll take you now to our most recent clinical data. We completed a trial called the SEQUEL trial. In this study, we were looking to assess how quickly we would impact synaptic function. The quickest way to measure change was through quantitative EEG. So this trial was conducted with our partners in Europe in Amsterdam as a single-site study. We had 16 patients in the trial in crossover design. Patients were on drug for four weeks, had a washout, and then turned to placebo or the alternate for another four weeks. A short but impactful study. Now, one of the things you see here, I'll take this as an example. In each case, green means going in the direction of normalization, whereas blue is when patients were on placebo consistently showing increased neurodegeneration. Let's talk about this for a moment. This measure, AECC, reflects connectivity, which means parts of your brain working together synchronously. As we age and with disease, this function is significantly reduced. And yet here we saw a significant increase in the difference between patients treated and those on placebo. Across all three parameters, we saw this: theta waves, if you're familiar with it, are associated with aging and are clearly much more significant in patients with disease. These are slower waveforms. This last measure, global alpha power, think of that as executive functioning. So all the parameters turned in the direction of normal functioning. Why is this important to us? Well, if you have Alzheimer's disease and you've had plaques in your brain for possibly decades, the fact that we can show a measurable impact in a matter of weeks, we felt was very, very compelling. So this paper is being written up, and we hope to have a publication soon. Everything I've been saying pertains to a mild to moderate Alzheimer's population, but we have expanded into an early-stage population in our whoops, in our START trial. Let me get to the right slide. Apologies for that. This trial is enrolling 540 patients, early patients. There'll be three arms to the study: two doses of drug and placebo. And patients will be followed for 18 months. The reason, of course, is early-stage patients need a longer period of time to show the decline in function and thus to measure the difference from placebo to active. We're conducting this study with our partners, the Alzheimer's Clinical Trials Consortium, led by Paul Aisen. We're actively enrolling in this study. We were given a grant of over $80 million to complete this work, one of the largest grants that I'm aware of. We are delighted to be engaged in this work. Now, the most important thing about this study, from my perspective and our perspective, is the fact that we are collecting data on combination use of CT1812 with standard of care. In the time since the study was conceived, lecanemab has come to the market. So the steering committee made the decision that for patients who are stable on lecanemab, they can enroll in this study, giving us a chance at looking real-time at how combination therapy works. We think that's critical because, like everybody who follows this disease area, there is an expectation that multiple drugs will be involved. And this gives us a chance to assess how we impact efficacy, safety, all the other parameters early on. What I'd like to do now is turn to our second catalyst for 2024, the SHIMMER trial. This is a study in patients who have DLB or dementia with Lewy bodies. Our PI always reminds us, "This is the most common dementia you've never heard of." I suspect everyone listening could say, "Yep, there are six million Alzheimer's patients in the U.S." And some people probably know there's about one million patients with Parkinson's disease, and there are many drugs for Parkinson's disease. DLB is 1.5 million patients, frequently misdiagnosed. Few clinical trials are being conducted. It is a highly underserved area and one that we are so enthusiastic about bringing a solution to, bringing a treatment option. One of the things that led us to study DLB is the fact that our drug not only blocks or displaces A beta oligomers, but our drug also impacts alpha-synuclein oligomers, preventing those oligomers from binding. Now, the truth is, this patient population, 50%-80%, I know that's a broad range. Those are the estimates. These patients have toxic oligomers of both pathologies. We potentially have a solution to that to help these patients. Again, these are mild to moderate patients. This trial will read out at the end of this year. The second important catalyst for Cognition Therapeutics. With that, I'd like to turn in brief to another phase 2 trial that is running, and this is our study of geographic atrophy secondary to dry AMD. We had, when we embarked on this study, a very strong scientific rationale. We are seeing tremendous enthusiasm from our PIs on enrolling patients. Why? It's a new modality, that is to say, an oral drug that could get to the back of the eye, and it's a new mechanism. If you follow this space, you know there are many drugs, some approved recently, which is terrific, many more in development addressing the complement pathway. We are targeting the retinal pigment epithelial cells. And so you have a potentially complementary approach in an oral drug. I'm not going to cover this, but I will tell you we have not only evidence from genetic studies. There's evidence in the literature. We had samples from our patient population. There were a number of things that led us to believe it made sense to pursue CT1812 in this patient population. This is the trial design. This is a two-year trial. Patients are on one dose of drug or on placebo. We are measuring, as it says over here, change in lesion size. We're effectively following the same regulatory pathway that you saw with Apellis and Iveric. In addition, we have included measures of visual acuity, not just change in lesion size. This trial is actively recruiting at the moment. And as I said, it is met with great enthusiasm by PIs because of the additional elements it brings: ease of convenience for patients as well as for the doctors, and a new approach to treating this disease. In closing, let me talk about our financials. As of December of last year, we had $30 million of cash. We raised last month $11.9 million net through a capital raise, $10.4 million plus the shoe that closed. Importantly, it brings our runway to June of 2025, through June of 2025. For us, that's critical because, as I said, we have these important catalysts in the middle of this year and our SHINE data at the end of the year. We want to be in a very solid position to do all the analytic and supporting work we need and then make our plans for phase 3. With regard to funding, I told you we received $170 million just from the NIA. Some of that money has been used. It's used as the studies are executed. Our remaining balance is $67 million to deploy against our continuing studies. In closing, let me say this: 2024 is a very significant year for Cognition with these catalysts. First, our SHINE study reading out in several months. Second, our START trial, which is continuing to enroll in an early patient population. Our second catalyst reading out at the end of the year is SHIMMER. And of course, we have our ongoing work in the MAGNIFY trial. With that, I would like to thank you for your interest and attention in Cognition Therapeutics. And I'll turn it back to Ami. Thanks, Lisa, for that presentation. I have a few questions here for you. With regard to the SHINE study, can you talk about the enrollment criteria and the baseline characteristics of the patients there and how that might have compared with the study for lecanemab? We haven't said much about it. I can tell you it's a mild to moderate patient population, amyloid measured on imaging as a criteria for enrollment. We will cover all of those demographics shortly. This is squarely mild to moderate patients. There will be, in the 153 patients, those patients that are less advanced, if you will, that have higher MMSE scores. And perhaps there will be some similarities between that portion of our enrolled patients and that of lecanemab. So that is to be seen. But the goal here was to target a more advanced population than what we saw with LEQEMBI. What would be the best sort of way to think about the apples-to-apples comparison in terms of the change in ADAS-Cog in the context of perhaps sort of the baseline characteristics of these patients? I think what you're asking me, Ami, is in an early-stage population is a 1.4-point change reasonable relative to an advanced population where you see a 3-point change. I think that, in all honesty, Ami, I feel like we need more successful trials out there to be able to make those comparisons. We have loads of failed studies in the industry. The trial done by ACTC was excellent, beautifully executed. There are no faults with that trial. I'm sure they chose all of their 5 significant endpoints with care. So all I can say is I would anticipate that with a more advanced population, we have the ability to show a greater impact. The reason being, it's not about our companies or anything else. It's about more advanced patients are declining more quickly. And so in a study, you're able to capture those differences, whereas they had to wait, as we are in our START trial, for those earlier patients to show decline. Okay. Can you talk about some of the safety data you saw from the 24 patients, and especially with regards to adverse events related to ARIA? What are your expectations there? And maybe under that sort of same topic, given that your drug is taken orally, are there other aspects of safety that one should be thinking about? So let me start with ARIA, Ami. We don't believe, based on the mechanism of our drug, that we will see ARIA. We are not removing plaque from vessel walls or anything of that sort. Now, the truth is, our Chief Medical Officer, Tony Caggiano, always says, "When you have a drug that's in thousands and thousands and thousands of patients, you're going to learn more about it." In clinical trials, what we've seen are very benign mild side effects: headache, nausea, the kinds of things that you would see in this age population. The one thing that we look at are elevated liver function tests. What we know is there's no upper quadrant pain. There is nothing indicative of concern or damage. And what we also know is when patients come off the drug, the liver function levels return to normal. That's the one thing that we do look at. ARIA is really not on the landscape. That would be a surprising finding. We believe that we have a well-tolerated, I don't want to use this word too strongly, somewhat benign drug. We'll see. When we conduct our clinical trials, we'll have a full picture of the drug. That's what we've seen to date: a well-tolerated oral drug. Okay. With regards to the trial for CT1812 in the early-to-mild patients, what would success of that trial look like? Maybe if you could sort of discuss that in the context of the endpoints. Of course, safety is an important piece of it. From an efficacy perspective, what would you like to see? I guess the best answer to that, Ami, lies with the drug that's already on the market, LEQEMBI. And coming is the drug donanumab, right? Different modalities, similar patient population. Those will serve as benchmarks for us. What we can say is in a more advanced population, we showed a more meaningful result in protecting cognition, if you will, in a much shorter period of time. But apples to apples, as you said, what we will look at are those drugs. So I don't have any other insight as to how the drug will perform in that population. As I said previously, when we open up the SHINE data in 10 weeks or whatever it is, we will have the ability to stratify by MMSE and perhaps gain insights to your question based on that data, looking at patients who are at the less advanced end of the spectrum. Got it. Okay. In the DLB SHIMMER trial, you're evaluating CT1812 on top of lecanemab. Is that right? No, let me clarify. In the early AD trial, which we refer to as START, we are looking at patients who have lecanemab being allowed to enroll in the study. Because they're out there and they're not doing as well as they want, clinicians may say, "Take a look at adding CT1812." Those are Alzheimer's disease patients. The SHIMMER trial, which we'll read out by the end of this year, is a trial for patients that have dementia with Lewy bodies. So it's a very specific pathology. You're looking mostly at alpha-synuclein as well as A beta oligomers in this population. They have cognitive deficits. They have issues with gait and falling, hallucinations, so many parameters which make them different from Parkinson's and Alzheimer's disease. And we believe our drug squarely targets those patients based on the pathology of their condition. Got it. That's very helpful. That's very helpful. So in the Alzheimer's disease sort of trial where you are studying it on top of lecanemab, what type of synergistic effect do you anticipate of combining these two mechanisms? It's a great question, Ami. We're so excited about being able to assess that. This will be the first time we get a look at the data, which will answer your question. I would like to believe, now, this is Lisa talking, that we have an additive effect. It makes sense in combination. It's a different approach. We're going after the oligomers. We're not pulling off the plaques, right? So there are different mechanisms. I don't think there is a person in the world working in this space that would say anything other than, "We know there are multiple factors." If there was a single silver bullet, it would have been found a long time ago. There's inflammation. There's astrocytes going awry. There's microglial impacts of this disease. We believe, Ami, we're working at the front end of disease where the oligomers are damaging synapses, killing off the ability of the neurons to function. We believe by starting earlier on, we have an additive effect to those drugs that are peeling out plaques on the back end. What's been shown recently in the industry is you remove enough plaque, as LEQEMBI did, you will see a change, a period of time when the patients function better. You put those things together and you say, "Wow, could we really enhance the ability of those patients to stay more well at an earlier stage of disease for a longer period of time?" I would say that today, it's conjecture until you study the patients. That's why we're so excited in the START program to look at combination therapy. Would you say that sort of where do you see kind of the biggest utility from a mechanistic perspective of your drug? Is it at an earlier stage of the disease or in more advanced patients? Well, I think that the common wisdom is if you're able to work in a more advanced patient population, likely you will have a positive impact on patients at an earlier stage of disease. Because what we're doing, getting rid of the oligomers and preventing new toxins from sitting there in the brain, is preserving function. And so logically, one would think if you get to patients earlier, there's simply more to protect. And hopefully, that means a longer period of time. Nobody has figured out how to stop this disease. But if we could make a significant impact on the slowing of disease and start earlier when patients are more independent, have greater function, we think that would be a big impact. Now, our trials are in mild to moderate disease. So that's the first thing we'll learn. But I do believe that we will see an impact in this other earlier population as well. That will be a function of running long enough trials to measure those differences. Sure. Okay. I think those are kind of the main questions that I had. I think that maybe if you could just close by talking about kind of the key readouts and what the next steps are likely to be following those data readouts, that'll be helpful. Terrific question. Thank you, Ami. So the first readout is the SHINE results, 153 patients. As I said, an international patient population. We'll be looking at efficacy, safety, efficacy, functional readouts, as well as all of the biomarker work that has been well prepared for analysis in advance. So that's the first thing that will happen. Following that, we will be looking at our SHINE data. We believe that positive data in the SHINE study will read well on the SHIMMER data. Of course, we have to wait for the studies to read out. But it's our belief that by affecting oligomers in this patient population, we will show benefits, whether it's on the MoCA scale or on the ADAS-Cog scale. As for our work, when the study reads out over the summer, there are a series of things we need to do to prepare for our FDA meeting and a phase 2 meeting, in addition to preparing the phase 3 protocol. During that time, we will give consideration to what capital needs do we have. Likely, with positive data, we will continue to engage with strategics as well. So upon the release of data, I feel that there are many, many things that we need to be doing, and bright days are ahead. The option to bring an oral drug to this patient population is really, it's a privilege to be able to do this work. So we look forward to a well-done trial, an excellent discussion with the FDA, and very thoughtful preparations for the next stage of development. Okay. I think that's a lot of exciting work that you guys are doing. We'll obviously be watching with a lot of interest. Thank you for taking the time to take us through the story. Thanks to all our listeners as well. Thank you for inviting us, Ami. Appreciate your questions. Have a great conference. Thank you.