Hello, and thank you for standing by. At this time, I would like to welcome you to the Cognition Therapeutics Second Quarter 2024 Earnings Call. All lines has been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. [Operator Instructions]. I would now like to turn the conference over to Tom Johnson. Please go ahead.

Thank you, operator, and good morning, everyone. Welcome to the Cognition Therapeutics second quarter 2024 results conference call. With me today are Lisa Ricciardi, President and Chief Executive Officer; John Doyle, Chief Financial Officer; and Tony Caggiano, Chief Medical Officer. This morning, the company issued a press release detailing its financial results for the second quarter and first half of the 2024 fiscal year. We encourage everyone to read this morning's press release as well as Cognition's' quarterly report on Form 10-Q, annual report on Form 10-K and periodic reports on Form 8-K, which are now filed with the SEC and available on our website. In addition, this conference call is being webcast through the company's website and will be archived for 30 days. Please note that certain information discussed on the call today is covered by 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 cautionary statements contained in the Cognition press release and SEC filings, including its quarterly report on Form 10-Q and previous filings. This conference call contains time sensitive information, which is accurate only of the date of this 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 like to hand the call over to Lisa Ricciardi. Lisa?

Thank you, Tom, and good morning, everyone. We appreciate your participation in Cognition Therapeutics' financial results conference call. Today, our CFO, John Doyle, and I will share prepared remarks on the company's progress and financial performance over the first half of the year, after which, we'll take your questions. For Q&A, we will be joined by our Chief Medical Officer and Head of R&D, Dr. Tony Caggiano. At Cognition Therapeutics, our focus is on the development of innovative, orally available drug candidates targeting age-related degenerative conditions of the CNS and retina. Our clinical programs include multiple Phase 2 trials for both early and mild to moderate Alzheimer's disease. We are also studying CT1812 in dementia with Lewy bodies and geographic atrophy, secondary to dry AMD. Now during today's call, my formal remarks will be on the completed SHINE trial, and then on our next study to read out the SHIMMER trial. Let's begin with SHINE. Our SHINE study was a Phase 2 clinical trial, proof-of-concept study of CT1812 in mild to moderate Alzheimer's disease. This was our first proof-of-concept study. The trial enrolled a total of 153 adults with mild to moderate Alzheimer's disease. Participants for randomized to receive either placebo or oral doses of 100 or 300 milligrams of CT1812 and there were 51 participants in each arm of the study. Our primary purpose was to assess safety and tolerability after 6 months of daily dosing. We also evaluated multiple cognitive endpoints, including the ADAS-Cog 11, ADAS-Cog 13, cognitive composite and the MMSE, functional improvement scales were included as were biomarker analysis. In this study, participants were treated with CT1812 for six months showed a consistent trend in slowing cognitive decline compared to placebo across all cognitive measures, the ADAS-Cog 11 and 13 cognitive composite at MMSE. On the…

Thank you, Lisa. For the first half of 2024, we continue to execute with financial stewardship by efficiently managing our resources and leveraging NIA grant funding to support our clinical programs. As of June 30, 2024, our cash and cash equivalents were approximately $28.5 million and total grant funds remaining from the NIA were $57.3 million. The company estimates that it has sufficient cash to fund operations and capital expenditures into the second quarter of 2025. Research and development expenses were $11.6 million for the second quarter ended June 30, 2024, compared to $8.5 million for the comparable period in 2023. This increase was primarily related to higher costs associated with advancing our clinical programs, including Phase 2 trial activities, with contract research organizations and personnel costs. General and administrative expenses were $3.1 million for the second quarter ended June 30, 2024, compared to $3.3 million for the comparable period in 2023. The decrease was primarily related to lower professional services. The company reported a net loss of $7 million or $0.18 per basic and diluted share for the second quarter ended June 30, 2024, compared to a net loss of $4.7 million or $0.16 per basic and diluted share for the same period in 2023. I'll now turn the call back over to the operator, who can open the call to questions. Operator?

Floor is now open for your questions. [Operator Instructions]. First question comes from Charles Duncan from Cantor Fitzgerald.

Hi, this is Elaine Kim on for Charles Duncan. Thank you for taking our questions. So in the SHINE trial, the 100 mg dose did not meaningfully alter the AB 40 and 42 levels, while the 300 mg did. But with the changes with the 100 mg dose, perhaps being more pronounced after a year of dosing versus the six months? And I have a follow-up.

Tony, do you want to address that? Thank you, Elaine.

Yes. Elaine, you're right. The 100-milligram dose did not significantly alter the A-beta monomers in the same way that the 300-milligram dose had. I think a more relevant biomarker here is the NfL, which is a marker of general neurodegeneration where we saw a really robust change, both to the 300 mg and the 100 mg. The monomers, we believe, is part of the basic mechanism of our receptor, rather than a key part of the disease modifying process that you see here. To further answer your question around longer trials, we do expect that with longer trials, such as 12- or 18-month trials, we would then begin to see more of the downstream biomarkers moving as well.

Got it. Okay. That makes sense. Thank you. And for the follow-up, your cash runway is into the second quarter of 2025. How do you plan on lengthening that runway and support later-stage trials? And then maybe jumping the guns, but maybe up to Phase 3, how do you plan on doing that?

Yes. Thank you, Elaine. I mean there's a lot of things that we need to evaluate. There will be a lot of options available to us. So as we look to extend our runway, we'll certainly take all of those into consideration and move forward as we design the next stage of those trials.

Got it. Thank you for taking our questions.

Our next question comes from Ram Selvaraju from H.C. Wainwright.

Thanks very much for taking my questions. First of all, somewhat intellectually provocative one, if I may. There was some discussion at AAIC in Philadelphia last month about the potential applicability of GLP-1 receptor agonism to the treatment of Alzheimer's disease. Do you think there could be any synergistic activity of CT1812 with GLP-1 receptor agonist specifically in the context of Alzheimer's?

That's a very interesting question, Ram. Tony, any thoughts on that?

Sure. Yes, interesting. I think, obviously, the world is very interested to see how the GLP-1s behaves in Alzheimer's disease. Given the mechanism of our drug is a very basic upstream interaction within the basic pathophysiology of Alzheimer's disease. We think CT1812 has the potential as a monotherapy as well as in conjunction with other therapies. We're certainly interested in seeing it with approved -- current approved to therapies, and if GLP-1 were to be approved for Alzheimer's disease, it would be very interesting to see how it acts together. So perhaps in the future, we'll see that data.

Great. And then just a quick follow-up on the dosage. I was wondering if there were doses intermediate between the 100 and the 300 that you would consider assessing further in clinical development? Or if at this juncture, you've ruled that out. And if you were to study intermediate doses, which ones do you think are likely to be most appropriate?

Yes. So we do have intermediate doses being studied right now. In our START trial, which is the 540 participant study in early Alzheimer's disease, we have a 200-milligram dose. And in our MAGNIFY trial, which is the study in dry AMD, we also have the 200-milligram dose. And indeed, we introduced those doses a few years back for this very reason, believing that it might be a very nice, sweet spot, where we see really good efficacy, but fewer adverse events. So those doses are already in the clinic, and it's likely that we'll see them again in the future.

Thank you.

Our next question comes from Mayank Mamtani from B. Riley.

Can you hear me?

Yes, Mayank. Good morning.

This is Kevin Kuo [ph] for Mayank. Thanks for taking our question.

Great. Hi, Kevin.

Hi, so now that we saw the detail from the SHINE trial, just wondering if you can talk about your expectation for your SHIMMER trial later this year and specifically, maybe your expectation for new [Technical Difficulty] or other biomarkers that such as GFAP that may not be as relevant in different disease groups like Alzheimer, but maybe you have a different actions in like DLB disease. And maybe if you can point to whether you still expect 300-milligram to have some liver insight signal? Thanks.

So I think there were three questions. Kevin, you broke up in the middle. One is overall expectations for SHIMMER. Second, you were looking for a read on a number of the biomarkers. And the last thing you mentioned was the 300-milligram dose.

Yes.

What might be the profile of that dose. I'll turn those three questions over to Tony.

Sure. Thank you. Right. So the SHIMMER study is designed very much like the SHINE study was, enrolling a similar number of individuals as the first proof-of-concept study where we're really looking again for safety and tolerability, and then for a clear and consistent trend that we can slow progression of the disease across multiple outcome measures. As we've announced previously, we're looking for a readout towards the end of this year. As far as the biomarkers go, I think as you've implied, the biomarker profile and changes within DLB are not nearly as well studied or predictable as they are currently in Alzheim's disease. Having said that, we have a pretty robust program, where we're looking at changes in biomarkers from both CSF and blood, looking at canonical biomarkers as well as, as you've seen in our previous publications, proteomics and phosphoproteomics looking at changes there. So we look forward to seeing those changes. As far as the liver signal goes, we would expect the same thing in these individuals. The -- these are folks who are nearly the same age, there's no reason we would expect to see anything different. So obviously, when that data reports out, will know that then.

Okay. Thank you.

Our next question comes from Daniil Gataulin from Chardan.

Hey, good morning guys. Thank you for taking the question. Yes. I have a couple.

Good morning Daniil.

Yes, good morning. Yes. First, on the SHINE, having had a bit of time to look through the data and now thinking about the next steps. What do you think are the key learnings from SHINE that you'll look to incorporate into the next trial outside of -- being a larger and the longer trial?

Great question, Tony?

Sure. Well, I think the key learnings, again, that we saw a very consistent and clear trend across all of the cognitive outcome measures that we can slow disease progression. More specifically, we see the magnitude of effect here as well as the variance. So this study now allows us to power future studies. Again, having seen nearly 40% decrease in progression as per the ADAS-Cog scales. We can now look to the next round of studies, which I anticipate will both be quite larger and longer. So that we can see these changes. We've also nicely identified a dose range, right, where we see effect without troublesome adverse events. Indeed, as Lisa mentioned, there are no discontinuations due to AEs in the 100-milligram dose and no changes in liver enzymes. So we have a very nice place to operate here for future studies.

Excellent. Got it. And another question, with the recent approvals in Alzheimer's, how did that affect the enrollment rate for your CT1812 trials? And related to that, what fraction of participants in the START trial, do you expect to be on concurrent approved Alzheimer's disease medications?

Tony?

Yes. So the inclusion criteria or the patient population for the monoclonal antibodies, and for our SHINE participants, we're somewhat different, a little bit overlapping, but generally different. So I'm not sure it really impacted recruitment. I think overall, the -- having -- the general population is now very away and interested that there are drugs available for Alzheimer's disease has been a great asset and people are coming into clinics and interested in acquiring. So overall, I'd say it was a boost. But again, it's a somewhat different population. As far as how many individuals will be randomized or will be on approved monoclonal antibodies within our START trial, that's still a little unknown. Obviously, one of the antibodies launched not long ago and we'll see how it penetrates the market. The other antibody just recently received approval and is just now launching, right? So we'll see. And within that study, we are stratifying all individuals, so that we'll have an even number of people on monoclonal antibodies across the different treatment groups. So we'll have a very good look at safety and tolerability of combined and depending on how many people were able to randomize, also potentially see if there are additive effects.

Okay. Got it. Thank you.

There are no further questions at this time. So I'll turn the call back over to Lisa Ricciardi, CEO.

All right. Thank you. To conclude, we are focused on advancing our work to find a treatment to improve the lives of those afflicted with neurodegenerative diseases. The science is sound, we are compelled to move forward, and we continue to build evidence about what CT1812 can do for patients. Thank you for joining us today.

Conference has now concluded. You may now disconnect.