Good morning, ladies and gentlemen, and welcome to Cognition Therapeutics SEQUEL Study Clinical Update conference call and webcast. My name is Sarah, and I will be your conference operator today. This call is being recorded. I would like to turn the presentation over now to your host for today's call, sorry, Mr. Daniel Kontoh-Boateng, Investor Relations for Cognition Therapeutics. Please proceed, Mr. Kontoh-Boateng.
Good morning. Thank you for participating in Cognition Therapeutics conference call and webcast today. With me today are Lisa Ricciardi, President and Chief Executive Officer of Cognition; Anthony Caggiano, Chief Medical Officer and Head of R&D of Cognition; and Willem de Haan, neurologist and senior researcher of Amsterdam University Medical Centers. A press release of the company's phase II SEQUEL study results are available on the investor section of the company's investor website. In addition, this conference call is being webcast through the company's website and will be archived for 90 days. Please note that certain information discussed on the call today is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. We caution listeners that during this call, management will be making forward-looking statements.
Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in Cognition's press releases and SEC filings, including its annual report on Form 10-K and previous filings. This conference call contains time-sensitive information that is accurate only as of this date of the live broadcast. Cognition undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. With that, I would now like to hand the call over to Lisa Ricciardi. Lisa?
Thank you, Daniel Kontoh-Boateng. Good morning, everyone. Thank you for joining our discussion on the positive and compelling top-line results from our SEQUEL study in patients with mild-to-moderate disease. Against the backdrop of Alzheimer's & Brain Awareness Month, we are pleased to report out the findings of this trial. Please see our forward-looking statement as we begin our discussion. With generous funding from the NIA, Cognition colleagues and advisors designed this exploratory study to further understand the potential of CT1812 to protect synaptic function as measured by brainwave activity in EEG patterns. In this trial, we met our primary endpoint of confirming safety and tolerability and showed strong positive trends in our primary EEG endpoints. In total, we believe the data support the role of CT1812 in normalizing synaptic function.
CT1812 targets sigma-2 receptors, protecting neurons from toxic amyloid beta oligomers that disrupt signals between cells and ultimately lead to cell death. By protecting and maintaining neurons and their synapses, we hypothesized that the neuroprotective effect of CT1812 would be detectable through meaningful changes in quantitative EEG patterns, and the data support this hypothesis. Our trial used a novel approach to incorporate quantitative EEG, measuring multiple parameters with an emphasis on theta waves, a type of brain activity associated with processing information and memory formation. In addition, improvements were seen in brain connectivity during the CT1812 treatment period. Chief Medical Officer and Head of R&D, Dr. Anthony Caggiano, will now take you through our top-line results. Tony?
Thanks, Lisa. As most of you know, current belief in the field is that the Aβ oligomers are the most toxic species of amyloid-beta and bind to synapses and disrupt neuronal activity. We believe that our drug, CT1812, which is a ligand for the sigma-2 receptor, interacts with the oligomer receptor, displaces Aβ oligomers, and thereby protects neurons from their toxicities. In this study, we're testing the hypothesis that displacement of those oligomers could have a relatively rapid effect on synapse activity, which could be measured by quantitative EEG.
This study, which was conducted at a single site in Amsterdam, is a 16-patient study, double-blind, placebo-controlled in a crossover design, where individuals with mild to moderate Alzheimer's disease, as confirmed by positive CSF, amyloid beta screening and a score of MMSE between 18 and 26, were enrolled and were treated with either CT1812 or placebo for 4 weeks. Before and after this treatment period, we assessed their EEGs. There was a washout period and each subject then crossed to the other treatment and received either placebo or CT1812 for another 4 weeks. Again, their EEGs were assessed before and during those treatment periods.
This study was run under the guidance of our principal investigator, Jort Vijverberg, again at Amsterdam UMC, and then with the guidance of neurophysiologist and neurologist Willem de Haan, who we have here to answer questions, should they come up. Going into a little more detail around the study design, again, we had 16 individuals with mild-to-moderate Alzheimer's disease. The primary objectives of this study, as Lisa had mentioned, were to demonstrate consistent safety and tolerability, pharmacokinetics of CT1812 throughout the treatment period. Also as a primary objective, we're looking at whether CT1812 could alter EEG patterns. Primarily the global relative theta power, global alpha AEC, global relative alpha power, and then there were several other secondary measures behind that. Exploratory measures which were collected, or cognitive measures, including ADAS-Cog-14, the CJC, and in the activities of daily living.
We also collected cerebrospinal fluid and plasma for biomarkers. These biomarker data are still pending and will be reported out at a future time. Going through the data very quickly. First, we'll go through the disposition of the patients, the safety and tolerability data, and then the top-line EEG data. We screened 34 individuals. 16 were randomized as planned. 15 individuals completed the study. We had no discontinuations due to adverse events. One subject did discontinue because of a death in this individual's family, and they chose not to continue in the study. One individual did not attend one of their EEG visits, in the end, we have 14 individuals with data in the placebo period, and we have 16 individuals with data during their CT1812 treatment period.
Looking at the demographics of the individuals who participated in this study, the mean age was 66.5 years. We had an even split of male and female patients. They were all white, non-Hispanic. We see here that the entering cognitive function, the MMSE of 21, the ADAS-Cog of 30, and activities of daily living of 52.6. When looking at the distribution of APOE, we saw that about a 3rd did not express APOE4, approximately a 4rd were heterozygous, and about approximately four were homozygous with an E4. Most of our patients were approximately one year or 1.14 years, from the time of diagnosis. These characteristics are similar to what we have seen in our previous studies. Taking a look at the safety and tolerability data.
As we've seen in previous studies, CT1812 was generally well-tolerated and safe. All of our AEs in this study were mild or moderate. There were no severe AEs, there were no serious SAEs, and no AEs led to death or discontinuation. When we look in more detail at the treatment-emergent AEs, there are 11 participants who had treatment-emergent AEs in the CT1812 period, and six participants had treatment-emergent AEs during their placebo treatment period. We had six treatment-emergent AEs, which were categorized as related to study drug, and those were evenly split between people receiving CT1812 and receiving placebo. The most common AEs that we saw, again, consistent with previous studies, were GI related, specifically nausea, diarrhea.
As is typical in patients of this age, there were injuries such as falls, procedural complications, which largely in this study meant headaches following lumbar punctures. Consistent with previous studies, we had one individual who had mild elevated liver enzymes with no further complications. Taking a little bit of a deeper look here at the biomarker, at the EEG. We now have several ways of looking at biomarkers in Alzheimer's disease, right? We can look at amyloid burden by PET. We can measure amyloid and other canonical biomarkers in serum and cerebrospinal fluid. We have anatomical measures such as volume, and we have ways to assess cognition with tools such as the ADAS-Cog. Here, quantitative EEG is really a biomarker for us to look at the active neurophysiology of the brain.
Here, we're looking at global activity, we're looking at regional activity, and also we're able to look at the connectivity of brain regions in real time. What we're showing here is an example of what the EEG patterns look like. The EEG is simply a measure of the difference of electrical potential between two different leads that are placed on the scalp. Fast waves, like the alpha and beta waves, are typically dominant in healthy individuals and indicative of awake and alert state. Individuals with dementias, particularly Alzheimer's disease, have a greater preponderance for the slower waves, particularly theta and delta waves. And here, throughout the rest of the presentation, you'll see the phrase relative power. What that means is the portion of the total EEG, which is made up of that particular band, either theta or alpha or beta.
As we mentioned, we met the primary outcome of demonstrating consistent safety and tolerability, and now we'll turn to the EEG data. As we mentioned before, we're looking at several measures of EEG, and these were analyzed in a ranked and ordered for manner. First, was the global relative theta power. After that, was the global alpha AEC, then the global relative alpha power. Then, as we mentioned before, there were many other secondary outcomes and exploratory outcomes, which will be discussed in the future. Turning now to the data, which we're showing on the screen now, on the left side, what you can see is the change in global relative theta power. What you'll observe here is that, as a reminder, the increased theta power is typical of worsening disease in Alzheimer's disease.
What you'll see here, shown in green, is that during the treatment period when folks are on CT1812, there is a decrease or a normalization in their relative theta power, in contrast to the general increase that you see in placebo. Now, this difference was not significant. The p-value was 0.123, but this is a strong trend, and Willem can give us more detail on this as we go forward. Also, what we observed was a nominally significant increase in the global alpha AEC, or the connectivity, meaning how the different regions of the brain were acting in synchrony. What you'll see here is that in general, in the disease state, there's a reduction in the alpha AEC. W hereas here, during the CT1812 period, there's an increase in the alpha AEC power.
In the individuals who are taking placebo, there's a decrease in that alpha AEC power. Finally, when we look at the global relative alpha power, again, in the disease state, you tend to see a decrease in the relative alpha power. Here in this study, what you'll see is individuals taking CT1812 had an increase in alpha power or a normalization of that signal. I n contrast to these same individuals who had continued decrease during their placebo period. We'll take a little bit deeper look into each of these measures. Again, remembering that the global relative theta power was our first outcome measure, and that data is shown here. We showed a nice trend for reduction in, with that theta power, which would be in a treatment direction.
The theta power, the global theta power, is made up of several different regions, and here we're showing all the regions that comprise the global theta power, so the frontal, the temporal, the posterior, and the central. What you see is that throughout the brain is the same consistent trend, or a reduction in global relative theta power or relative theta power in each region when individuals are receiving CT1812, in contrast to a general increase during the same time while they are receiving placebo. In the central region, this difference was nominally significant. As we look at the global alpha AEC, again, this is a measure of connectivity. This outcome looks at the synchrony of the peaks and troughs of the of the EEG patterns, between two different regions of the brain, and it suggests the ability of the brain to communicate and exchange information efficiently.
Again, in individuals with Alzheimer's disease, this connectivity measure tends to decrease. What you can see here is that in individuals, in this study, an increase in the global alpha AEC, while on CT1812 in comparison to a general decrease while on placebo. These findings are both directionally and nominally significant. Finally, looking at the global relative alpha power. Again, the alpha power tends to decrease in individuals with Alzheimer's disease. Alpha power is thought to be a general background rhythm of the healthy brain.
What you can see here in this data is that in individuals in this study, there was an increase in global relative alpha power during their CT1812 treatment period in comparison with during their placebo period, where there was a general decrease in global relative alpha power. Again, this finding was not significant, with a p-value of 0.149, however, directionally favorable. In conclusion, what we were able to show in the SEQUEL study was that CT1812 was safe and well-tolerated and that the safety and tolerability findings were consistent with our previous studies. We have strong trends on our prespecified quantitative EEG measures. All of the EEG measures were consistent and directionally favorable.
Finally, we'd like to point out that CT1812, these data really demonstrate that CT1812 has an impact on brain activity in these individuals with mild to moderate Alzheimer's disease. Obviously, we've completed several other studies up to this point, and in summary, these studies have demonstrated target engagement. This was demonstrated in our SNAP study, which we recently published. We have anatomical effects of CT1812 and volume, slow reduction of brain volume, which was shown in our SPARC study. We have preliminary data on improved cognitive function from the 1st part of our SHINE study. Finally, now, we have trends for improved neurophysiology in this SEQUEL study. We've shown in all of our studies supportive biomarker evidence that we can impact Alzheimer's disease biology.
Finally, we'll point out that we have three ongoing, fully funded proof-of-concept studies, one in early Alzheimer's disease, one in mild to moderate Alzheimer's disease, and one in dementia with Lewy bodies. These studies, we plan to complete enrollment for the SHINE study and for the SHIMMER study towards the end of this year, and then be able to read out data towards the middle of next year. At this point, I'll pass it on to Lisa.
Great. Thank you, Tony. Operator, over to you for questions.
Thank you. We will now conduct the question and answer session. If you would like to ask a question, please press star one on your telephone keypad.
Your first question comes from the line of Charles Duncan with Cantor Fitzgerald. P lease go ahead.
Hi, this is Elaine on for Charles Duncan at Cantor Fitzgerald. Congratulations on the data. Just wanted to ask, in consideration of the normalization of the data waves and the AEC analysis showing greater connectivity of the brain regions, have you seen a correlation with the CSF and plasma biomarkers that suggest the removal of the beta oligomers? Thank you.
The plasma and the CSF biomarkers are still pending. They're being processed right now, and will be read out in the near future.
Okay. Thank you.
Your next question comes from the line of Mayank Mamtani with B. Riley Securities. Please go ahead.
Good morning, team. Thanks for taking our questions and very interesting data. I was just curious in terms of protocol, were the researchers blinded to sort of how the EEG information was collected throughout the protocol? I have a quick follow-up.
This was a double-blind, placebo-controlled trial. You see in the crossover design, the subjects and the investigators, and us obviously, had no idea whether they were receiving active or placebo. Obviously, the investigators knew they were collecting EEG, and they knew the subjects were in the study, but they did not know which period the participants were in.
Understood. Then the in terms of the you looked at a number of different waves, I understand the focus is on the theta wave and the understanding on cross connectivity. Could you just talk about, sort of, your observations on the overall other additional waves that you looked at? How should we think about as you know, prepare to present on, some of the additional CSF biomarkers, the correlation to kind of exist? If you could clarify what medical conferences you may target in the fall, for full data disclosure, that would be helpful.
Sure. Why don't we start with the second question? Obviously, we don't know yet what meeting this will be disclosed at. We'll be, you know, applying and submitting abstracts now, and we'll make an announcement once it's accepted. Maybe we can ask Willem to comment briefly on, you know, what additional measures and data we might be able to examine in this robust data set.
Yes, thank you, Tony, and thanks for the question. Yeah, as Tony pointed out, I think the- what we see so far, the effects seem to be quite consistent, eh? It's more fast activity and less slowing, and there's seems to be a better functional connectivity. Yeah, these are the main things that we would be interested in. I think it's important to emphasize that we see this now in a relatively short time span of four weeks. Yeah, that is something we have not really seen before.
Yeah, besides this, we can look at a large list of exploratory outcomes where we have, for example, the AEC, so the connectivity measure, we can also look at that in a regional session, so see how this differs between regions. That's something I would expect, actually. There are other also exploratory variables not mentioned now, that we will have looked to also have a better understanding of what we see here, for example, why the central theta is showing this strong difference. That's will be subject of further exploration.
Great. Thank you.
Sounds great. Thanks for taking our questions.
Once again, ladies and gentlemen, if you would like to ask a question, it is star one on your telephone keypad. Your next question comes from the line of Jay Olson with Oppenheimer. Please go ahead.
Oh, h ey. C ongrats on these results and t hanks for taking the questions. Can you talk about the correlation of quantitative EEG with clinical outcomes and the predictability of clinical outcomes? Would Quantitative EEG be considered reasonably predictive of clinical benefits, such that it could be used for accelerated approval? I had a couple of other follow-up questions.
I don't know necessarily whether it could be used for accelerated approval. Certainly, if we continue to collect data and it's strong, we could address that in the future with FDA. maybe again, we can ask Willem to comment. His group has done a lot of work looking at how EEGs correlate with advancement of disease. Willem, you want to comment on that?
Yes, sure, if I may add. So I think by now, if you look at the EEG literature, you can say that these measures, especially the robust, relatively robust theta power and connectivity, they show clear correlation with cognitive performance during the disease course. We see deterioration in cognition and relevant domains like episodic memory and executive function, and with these quantitative measures. There is less data how they behave as treatment monitoring. Now with these new results and also with some other recent trials, we do see correlations. This is also something that we have to investigate more, looking at the neuropsychological results for the study as well.
Okay, great. Thank you. Can you talk about whether it's more important to look at the change in alpha waves in the global brain, or is it more important in certain regions of the brain? And also, if you could talk about how you plan to leverage these findings in your other studies. For example, are there any implications for quantitative EEG in Lewy body dementia?
Great.
Yeah.
Great question.
Great question. In general, what I could say is that what we expect is that the posterior part of the brain, so the parieto-occipital region, and in the bar diagrams here, labeled as posterior, that is where we see most of the pathological slowing. You can see it in other regions, but the dominant changes are in the back. Those regions have our special interest. That's also because this alpha rhythm, what Tony talked about earlier, the healthy rhythm that adults have, that is slowing down, and that's also found mainly in the posterior part. Further regional analysis will be interesting. I hope that answers your question.
Yeah, also just how you plan to leverage these findings in your other studies. For example, do you expect quantitative EEG to have applicability in Lewy body dementia?
Yeah. Right now, we don't have any specific plans to alter the trials that we are executing right now. However, this is encouraging that, and given the relatively non-invasive and manner in which EEG is collected, it is something that we could incorporate in the future.
Okay, great. Thanks for providing the update. Thank you again for taking the questions.
Sure.
Thank you. I will now turn the call to Lisa Ricciardi for closing remarks.
Thank you, Sarah. Cognition is laser-focused on taking innovative science and through the course of drug development, bringing new medicines to the market. Our lead candidate, CT1812, is a neuroprotective compound targeting the sigma-2 receptor, and in this SEQUEL data, we saw, again, new evidence for the neuroprotective effect of our drug in Alzheimer's disease. As Tony indicated, readouts from our development program build on target engagement demonstrated in our SNAP trial. This was published last month. The paper can be found on our website. Our SPARC trial demonstrated anatomic impact on CT1812 on brain volume, and our SHINE study demonstrated early proof of cognitive changes in mild to moderate patients. With SEQUEL, we have now added neurophysiology evidence for neuroprotection to our understanding of CT1812. As noted earlier, we're grateful to the NIA for their continued financial support of our trials.
With their funding and our disciplined fiscal practices, we have cash to fund our work to the 2nd half of 2024. This management team and our R&D organization are focused on achieving our targets and milestones over the next 24 months. In closing, I'd like to thank the NIA, researchers, patients, and their caregivers who participated in this study. They are essential in advancing medical care to battle disease. As we commemorate Alzheimer's and Brain Awareness Month, we recognize the considerable progress this year, with new treatment approvals offering a new sense of hope and optimism in the field of neurodegeneration. The science is truly progressing, and we're pleased to play a role in these advances. In closing, at Cognition, we have an important mission to take on Alzheimer's disease, dementia with Lewy bodies, and dry age-related macular degeneration.
All of these conditions impact people as they age, eroding their quality of life and independence, and a struggle for them as well as their loved ones. We look forward to sharing our future progress with patients, caregivers, clinicians, investors, and the scientific community. Thank you again.
This concludes today's conference call. Thank you for joining. You may now disconnect your lines.