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 most commonly used measure the ADAS-Cog 11 and 13 skills, CT1812 treated participants showed a 39% slowing of cognitive decline after six months. With SHINE results into context, the recently approved monoclonal antibodies demonstrated 25% to 30% slowing in an early patient population over 18 months.

We were very encouraged by the 39% slowing in six months with a once-daily pill. Now furthermore, on the ADAS-Cog 11 and MMSE scale at day 98, the midpoint of the study, in the combined 100- and 300-milligram dose group, P-values of less than 0.05 were observed.

Putting the full SHINE data readouts in context in the completed trial, participants on placebo in the intent-to-treat analysis worsened by 2.7 points as measured by ADAS-Cog 11. In the pooled 100- and 300-milligram dose group, there was a reduction of 1.66 points or 39% lower loss of cognition and in the placebo group.

Said another way, CT1812 rescue, about 40% of the cognitive decline that participants could have experienced. In this trial, we used the functional measures of the ADCS-ADL or activities of daily living and the ADCS-CGIC, the Clinical Global Impression of Change. CT1812 demonstrated a slowing of loss of function towards the latter part of the trial.

With 150 people enrolled or approximately 50 people per arm, the SHINE trial did not achieve statistical significance on the ADAS-Cog 11 scale. However, this is the important part. The multiple measures we assessed show a consistency across time and dose that is positive.

It is this consistency that motivates us to look ahead to longer and larger trials. With regard to safety, CT1812 demonstrated a favorable safety and tolerability profile with most treatment adverse events being mild or moderate. The AEs were consistent with previous clinical experience. There was one case of asymptomatic ARIA-H and no cases of ARIA-E.

At the 300-milligram dose nine participants experienced treatment-emergent LFT increases greater than 3x the upper limit of normal. These resolved after cessation of drug without evidence of serious liver injuries. Importantly, there were no LFT elevations observed in the 100-milligram dose. This data is all publicly available on our website.

We are continuing to analyze the exploratory CSF biomarker program data. The study showed significant change in neurofilament light or NfL, and this is a marker of neurodegenerative disease. This occurred at the 300-milligram dose. We believe that this is evidence CT1812 acts as a synaptoprotective agent.

Other CSF biomarkers assessed, including neurogranin, synaptotagmin, SNAP-25, p-Tau, total Tau and g-Tau. We'll share more in the future as we continue analyzing biomarker data from this trial.

Taken in total, we believe these findings provide evidence that the amyloid oligomer antagonism, a new and distinct mechanism for therapeutic intervention may have a role as a monotherapy or a drug used in combination with approved drugs for the treatment of AD and other dementias.

We met our key objectives of assessing safety, tolerability, and cognitive and functional changes. We learned that the 100-milligram dose showed good efficacy and had no incidence of elevated liver enzymes or discontinuations due to AEs. There were no new safety signals in the SHINE trial.

We have a strong and consistent trend demonstrating potential efficacy as slowing cognitive decline in patients with mild to moderate disease. We believe the magnitude of effect is consistent with other drugs recently developed and approved. We believe the biomarker data supports the true slowing of neurodegeneration.

While in Philadelphia last week at the AAIC Conference, we had the opportunity to speak with multiple physicians and PIs from the SHINE trial. They were very supportive of the trial results and particularly the consistency of cognitive changes across the scale. They value the new safety information and profile of the 100-milligram dose group.

Consistent with feedback from various investors, RPIs are interested in the next steps in terms of the new trial, duration dose, patient population, endpoints, and trial size. We also know that pharma groups having winnowed CNS programs over the years are now looking to add to their portfolios, important CNS drugs.

For many, Alzheimer's disease is a top target. We continue to look -- we are looking forward to continuing our dialogue with these companies. Our next step is to convene a panel of leading neurologists to review our data best to finding and discuss their thinking on next steps in CT1812 drug development.

I would like now to turn to the SHIMMER study, which is our next data readout. This Phase 2 trial with CT1812 enrolled 130 people with mild to moderate dementia with Lewy bodies or DLB. As a reminder, there are an estimated 1.5 million people in the U.S. affected by DLB. And this disease is the second most common form of dementia.

These patients are characterized by dementia, mobility issues, visual and sensory hallucinations and significant GI issues. There are no currently approved treatment options. From a pathological perspective, more than half of the DLB patients are estimated to both have alpha-synuclein and Abeta oligomers in their brain.

We believe that CT1812 with its novel mechanism of action, protecting neurons from the pathogens from the toxicity of both pathogenic protein has the potential to treat DLB patients. This is a double-blind, randomized 3-arm study. Patients are randomized 1:1:1 with 100 or 300 milligrams of CT1812 or placebo.

This study is not powered to show significance. It is designed as a proof-of-concept study to determine the change in the MoCA that is the Montreal Cognitive Assessment scale, after six months of receiving CT1812 or placebo. This trial is supported by non-diluted funding from the NIH, and the trial is being led by Dr.

James Galvin from the University of Miami Miller School of Medicine. We have completed enrollment, and we expect to report top line results by year-end. We believe the SHIMMER trial results will add to the understanding of CT1812's potential for treating neurodegenerative disease.

As with AV patients in the SHINE trial, we look forward to providing patients and caregivers an effective, convenient options to slow the progress of DLB. Now a word about our other two trials. In brief, START trial is actively recruiting participants with early Alzheimer's disease.

Participants on stable background therapy with lecanemab and donanemab will be allowed to enroll in the trial. And we expect this will allow us to provide real world evidence of CT1812 potential as monotherapy and in combination with monoclonal antibody treatment. We're also actively enrolling participants in our MAGNIFY study.

This is a randomized placebo-controlled Phase 2 study of 240 participants, who have dry age-related macular degeneration and measurable geographic atrophy. Over the treatment period, change in lesion size and best corrected visual acuity will be assessed to determine, if CT1812 and slow vision loss.

Now during this past year, cognition scientists published multiple manuscripts and made at least nine presentations at medical and scientific converses. All the publications are available on our website.

Importantly, the scientific evidence generated by our team has continued to support our development efforts, providing insights into proteins and biological processes impacted by CT1812 in neurologic and dry and ophthalmology conditions.

In closing, in 2024, we have made significant progress advancing CT1812 and we believe this drug has the potential to be an important part of the developing paradigm for dementia treatments. With that, I turn the call over to John Doyle for a review of our results..

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..