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spk16: important indication with a substantial unmet need. Turning now to Tabapadon, our D1, D5 partial agonist in Parkinson's disease. Our phase three trials, known collectively as the TEMPO trials, are ongoing along with the corresponding open label extension, in which we are encouraged by a greater than 90% rollover rate. We expect data for TEMPO3 in the first half of 2024, with data for TEMPOS1 and 2 coming in the second half of 2024. We look forward to walking you through the scientific rationale and prior data for Tabapadon, as well as its clinical potential during our investor event in December. With Turigabat, or a selective GABA-A pan, we believe there is potential for both anti-epileptic and anxiolytic activity comparable to benzodiazepines with an improved side effect profile. Unlike benzodiazepines, which are only used for acute episodes due to tolerability, abuse potential, and other debilitating side effects, DERIGABAT's novel mechanism of action and anticipated favorable tolerability profile provide the potential for chronic dosing. We expect results from our Phase II realized trial in focal epilepsy in mid-year 2024, and we are encouraged by a continued high rollover rate into the realized open-label extension. Beyond focal epilepsy, our ADAPT Phase II trial in panic disorder is currently underway. A new drug has not been approved in panic disorder in nearly 20 years, and we are excited about the potential of providing DERIGABAT as a daily chronic therapy to patients in need. Cerevel's mid- to late-stage pipeline has the potential to bring forward numerous treatments to address some of the most devastating neuroscience diseases, and I am so proud of the team that is working diligently to make this potential a reality. With that, let me turn it over to Dr. John Renger, our Chief Scientific Officer, to provide an update on our early stage portfolio. John.
spk20: Thank you, Ray, and good morning, everyone. I'm very pleased with the progress we've made in discovery research and early clinical development here at CeraVal. Today, I'd like to focus on our Kappa Opioid Receptor Antagonist, or CORA program, also known as CDL354. We have completed both our single and multiple ascending dose trials, in which CDL354 has been generally well-tolerated. We currently believe we will be able to interrogate a range of receptor occupancies in both the kappa and mu opioid receptors. We believe and anticipate we'll be able to explore multiple indications of interest such as major depressive disorder and substance use disorder. Our ongoing phase one pet receptor occupancy trial will clarify both kappa and mu receptor pet tracer displacement to further characterize selectivity across the compound exposures. We encourage by the potential impact of this asset We look forward to providing more updates in our plans in the near future. Beyond CORA, we have a growing number of programs, some initiated within our labs and exclusively developed here at Cereval, which we continue to progress, including our M4 selective agonist, a PDE4D sparing antagonist, and a selective TMAM175 potentiator program. We will provide further updates and plans for these specific programs as appropriate. With that, I'm going to turn it over to our Chief Financial Officer, Dr. Susan Altshuler, to review our financial performance for the third quarter. Susan?
spk23: Thank you, John. Turning to our financials, in October, we opportunistically bolstered our balance sheet with a $499 million capital raise, providing strong validation of Cerevel's potential from both new and existing high-quality investors. This additional capital, along with the roughly $758 million in cash, cash equivalents, and marketable securities we ended the third quarter with, will support our operations into 2026. Turning to the third quarter of 2023, operating expenses were approximately $111 million, comprised of $85 million of research and development expenses and $26 million of general and administrative expenses. Looking forward, our financial strength enables us to focus on execution and provides optionality to maximize the value of our pipeline. That said, we will take a disciplined approach to resource allocation as we further build our pipeline, advance our lead assets, and prepare for two potential NDA filings in parallel. With that, I will hand the call back over to Ron for his concluding remarks.
spk18: Thank you, Susan. At Cerevo, we believe we have an unparalleled pipeline in neuroscience. With multiple mid and late stage readouts across three different assets expected next year, and the balance sheet that provides us with cash runway into 2026, we are focused and aligned on executing our trials, delivering high quality data next year, and as Susan mentioned, preparing for two potential NDA filings. These are exciting times at Cerego, and I'm so proud to be leading this organization. I want to offer my sincere appreciation to all of our employees who work tirelessly every day to deliver on Sarah Bell's mission. And I also want to thank our investigators and participants in our clinical trials, without whom none of what we seek to achieve would be possible. With that, let's open the call for questions.
spk21: Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster.
spk26: One moment for our first question. And our first question comes from Michael Yee of Jefferies.
spk30: Hey, guys, good morning, and thanks for the question, and thanks for the update, Ron. I know everyone's focused on execution. Two questions, first on Emraklanine. Obviously since last quarter there was some concern about some of the timeline changes. Can you maybe just describe what initiatives give you the confidence that things are progressing on time and specifically maybe for the team what the right patients are, the right site selections are that give you the confidence on executing on that enrollment? And the second question is on epilepsy. There's actually a bunch of competitor readouts happening, and maybe you could help us understand about the placebo arms and what things you're integrating into your study that might help us give us confidence there because that has historically been an issue, and I know that's a concern for others as well. Thank you.
spk18: Yeah, sure. So let me take the first part of your first question, and I'll let Ray address the second part in terms of site selection from racletin and then the placebo work on our epilepsy studies. So, look, you know, as we mentioned last quarter, you know, we're focused on trying to address the challenges that we saw with some of the enrollment issues that we had. And, look, we're doing that with boots on the ground. You know, I've spent time at sites with Ray and the team and the leader of our clinical development groups and really working with the sites to see what's going on. And I think we're quite pleased with the progress that we've seen so far, and that's why we can stand by the guidance that we've given here in the quarter. That all said, our focus will always remain on ensuring the quality of the data, and I think that gets to the second part of the question. We're gonna maintain, continue to maintain rigorous site selection, and focus on our placebo variability reduction strategies. But I'll let Ray address, you know, how we think about the sites and how we think about, you know, all of those things as we continue to make progress here and also talk about our placebo group in the epilepsy studies.
spk16: Thank you, Michael, and good morning to you. So as you know, Michael, as I historically define, you know, what does a good site look like? And it's really the access to the right patients and having good, solid raters. And that really determines, for the most part, the success of the trial. So that's what we have been achieving and are continuing to try to achieve. But if you look at when we started the Embracadine trials, they started quite robustly for the first year, and then the momentum slowed down in the spring of this year. What we've learned is how to manage the competitive landscape a bit more effectively. And to that end, we're seeing increased momentum in our enrollment without, as Ron mentioned, diluting the data quality in any way. So again, having very close communication with the sites, ensuring that the radar recertifications occur frequently, and continuing that communication ensures us that we have the greatest likelihood of success moving forward. In terms of epilepsy and the placebo response, as you know, that we are seeing placebo response in indications like spinal cerebellar ataxia and epilepsy, and that would surprise as many. But we are also taking the same aggressive approach and dedicated approach to mitigating the placebo response in our focal hunts and epilepsy trial by having placebo mitigation protocols at each site. but also it's about patient selection, making sure that the right patient profile is included in these trials, and really monitoring the data, the blinded data, to ensure the quality is there. So all taken together, the approach we're taking to help epilepsy to reduce placebo response is really the same approach we've taken to all our trials to reduce placebo response, and we're confident that we're positioning these trials for the greatest likelihood of success.
spk25: Thank you, guys.
spk26: Thank you. One moment for our next question. And our next question comes from Paul Matise of Stifel.
spk32: Great. Thanks so much, and congrats on the progress.
spk31: I honestly wanted to ask a really similar question on Imraqudine. And that is related to this recent tar one setback and the implications of that. I guess when you look at that, that data and the huge placebo response they saw and anything else when that within those results, what sort of metrics are you tracking specifically on a blinded basis, uh, in the American within studies beyond the obvious, like just changing pans, um, that I guess today give you confidence that you're getting the patient and site quality, um, that you intended or hope to. And then on the CAPA program, I wanted to ask a quick question for John. Just Novacoprant and Aticoprant both cite really high selectivity for CAPA over MU. What's behind your thesis that MU might actually contribute to efficacy in some of the conditions that you plan on pursuing?
spk17: Thanks so much. It's all that retakes the first part.
spk16: So, Paul, good morning. Good question. So, you know, we review the data on a monthly basis and sometimes more frequently, but it's blinded. So really, in terms of data quality, we want to ensure that all of the parameters that we're assessing are correct and that they're not conflicting. And so if that occurs, we obviously intervene at the site level to make sure that the raters are doing what they need to do or they need to have a refresher. And that validation, of course, occurs frequently with the raters. In terms of having the confidence that we're mitigating that placebo response. It's really around other measures that I mentioned earlier in Michael's question in terms of looking at the right patients and how do we do that. We have an independent committee that really looks at the patient qualifications to ensure that they meet the criteria for the profile that needs to occur for them to be enrolled in the trials. And then we have a placebo protocol at each site allows us to standardize the way we actually approach each patient at every site to increase the likelihood of success and mitigate that placebo response. So really, we've taken the learnings from so many years, as well as the advice from key advisors who understand placebo response and have infused them into our program. So we're confident that we're taking all measures to ensure that that placebo response is mitigated. We're also limiting the number of countries, limiting the number of sites, all which contribute to placebo response. If you look at the trials that you've mentioned, the recent trial that, you know, over six countries, over 35 sites in those trials, and so all of that contributes to variability. Everything that we're trying to minimize to ensure the greatest likelihood of success.
spk20: Good morning, Paul, and thanks for the question on the camp opioid receptor antagonist. So, yeah, to your question about what does Mu provide in terms of potential therapeutic benefit and indications. And so, as an example, what I would do is point to opioid withdrawal syndrome patients. And so, if you think about what it is you want to achieve potentially with our profile, What we can do is we can go through a receptor occupancy range at Kappa, where we can have selectivity to Kappa, but if we continue to go up the receptor occupancy curve and exposure curves, we can bring in Bu. And so why does that provide something to us that seems exciting? It's because what you can get is a therapeutic benefit from Kappa, and what we believe the potential there is is to reduce things like the Q-induced reinstatement data that you see in the preclinical models where you can remove some of the things that would cause relapse in patients that are undergoing withdrawal or undergoing abstinence from use of opioids. But if you think about what you're actually trying to achieve in the long term, it's also reducing the potential for exposure to new agonists. And so if you think about how you could approach that population, you could actually begin with a lower dose range gain the benefit of the kappa without having any kind of mu antagonism that might induce withdrawal symptoms. And then as the patient progresses, you can actually increase the dose, so you actually bring in the mu antagonism potential. What that does is it has the ability to block the opioid activation if there is an exposure to an opioid in the future with that patient. So let's say they have a relapse, they take an opioid agonist at that point, having an antagonist could benefit that patient population, both as a safety measure in terms of blocking activation with an opioid so you can prevent the potential for harm, but you can also potentially, depending on what exposure they get to what opioid, you can actually prevent the rewarding benefit. And so you can imagine where you would start a patient going through the phase of withdrawal, starting with more of a kappa selectivity dose range, And what you could do is build up that dose range over time so that if there is an exposure, you have the protection of having a mu antagonism benefit on board in that same patient.
spk22: So that's how we're thinking about it.
spk24: Thanks a lot. Thanks, Paul.
spk26: Thank you. One moment for our next question. And our next question comes from Mohit Pansal of Wells Fargo.
spk04: Great. Thank you for taking my question, and thank you for having an uneventful quarter. I really appreciate it, and congrats on the financing. I have two questions. One is on terapidon. In our checks, doctors are suggesting that the dopamine agonists are a little bit out of fashion. They're not used as much, so could you talk a little bit about how you're thinking about the bar for success clinically, not just static benefit, what it should be? And then on the second one, can you remind me, Derigabeth, about what was the reason for slow enrollment and how you are mitigating that?
spk25: Thank you.
spk16: So, Mohit, thanks for that question to wrap it on. If you think about the novel mechanism of tovapidon being a D15 partial agonist that selectively targets those receptors of the direct nigrostriatal pathway, it really gives us a confidence that it's going to be a transformative therapy in symptomatically treating Parkinson's disease. Clinically, we've designed a program to show the benefits as both a monotherapy and as an adjunctive therapy, and the monotherapy 27-week trials looking at the UPDRS, you know, Parts 2, which looks at the daily functioning, and Part 3 that looks at the motor symptoms. And that's the primary endpoint, and change from baseline is the primary endpoint on that. So to show really the benefits on not only motor symptoms, but the quality of life as impacted by motor symptoms. For the adjunctive trial, which is our first trial to read out in the first half of next year, we're looking at the benefit of tavapidon as the best adjunctive treatment with levodopa to decrease the off-time, but importantly, increase the on-time without troublesome dyskinesis, which is the primary endpoint and really what's clinically relevant. So that's how we are thinking about that program. And really, we're thinking of it as really backbone therapy, meaning that when the patient is first diagnosed, as being the best therapy to initiate patients on, and then when levodopa needs to be introduced as the best adjunctive treatment. So we're hoping that if the results read out as we expect that they will next year, that we will then proceed to file that NDA and give patients a transformative therapy for symptomatic treatment of Parkinson's. No, during that question, not at all. So can you repeat that question?
spk04: Yeah, I mean, so the question was, can you remind me what was the reason for slow enrollment in the beginning and how are you trying to mitigate that? I think it was more to do with the fact that you were taking patients off the background medication, right? I mean, what was the issue there?
spk15: No, so there are a couple of reasons for the enrollment issues with the epilepsy program.
spk16: Remember, these are patients who are drug resistant. There are at least one and no more than three anti-epileptics. They continue on those therapies at a static dose, so that's not changed. One of the challenges that that program has had is the fact that the concomitant medications, concomitant anti-epileptics are 3A4 inducers. In fact, they are all 3A4 inducers, and we, as you know, cannot allow patients who are on drugs that are 3A4 inducers because it impacts the pharmacokinetic profile of the therapy and it will impact the outcome of the trial. So the challenge there has been to find the right patient profile, but there are not concomitant medications like carbamazepine, oxcarbazepine, and other therapies that are 3A4 inducers. So we've been challenged by that. The good news is that John and his team have conducted a drug-drug interaction trial that will allow us to then overcome that obstacle in phase three. But we really had to know that the actual dose data based on those individuals that are not on those concomitant medications that would impact the pharmacokinetic profile. So what we've done is we've heightened the number of sites, the number of countries that we know well to increase the enrollment. We're seeing great momentum. And so the good news is that we are planning to read out in mid-year next year. And if the results are what they are, then we can proceed with a robust phase three program.
spk18: The other thing I might add here, I know there's going to be more questions on Tevapidon Mohit. And as I mentioned in my prepared comments, we're going to host an investor webcast focused on Tevapidon on December 11th at 10 a.m. So if Tune into that, and I think if you have additional questions, that'll be a good forum to get some clarity.
spk24: Thank you very much. Congress for the Progress.
spk26: Thank you. One moment for our next question. And our next question comes from Joseph Thorne of TD Cowan. Joseph Thorne, your line is open. Please check your mute. One moment for our next question. And our next question comes from Jeff Hung of Morgan Stanley.
spk08: Thanks for taking my questions. For CVL871, can you talk about the challenges clinical sites are facing on patient identification for dementia-related apathy? And then for the DERIGABAC real-life study in focal epilepsy, what do you need to see next year to consider the proof of concept of success? You know, is there a particular bar for reduction in seizure frequency? Thanks.
spk16: Hi, Jeff. Good morning. So the apathy program, as you know, the 871 program is a phase 2A trial that's really experimental in nature. As you know, it's the leading neuropsychiatric syndrome that you see in patients with dementia, and we're conducting in all of the dementias experimentally as a first step. It's also a predictor of disease progression. There's three components, and it's really decreased goal-directed behavior, decreased emotional responsiveness and lack of motivation. The challenge with that is that the landscape is really still trying to understand what that patient profile looks like. Remember, these are patients that are not agitated. They're not really a problem clinically, but it does impact their quality of life. It does impact the longevity of their disease. So one of the challenges is really identifying the right patient profile. So to that end, that's one of the challenges that we've encountered. But we believe that the therapy has a great potential of being a novel therapy that will work in that population. But again, I think the landscape is trying to catch up and really clinically understand what that profile looks like. So that's been a limiting step for that program. But we're continuing to move it along. We're continuing to identify the sites that have access to the the right patients, because that's really critical to get the signal detection that we need for success. So, that's where we are with that program now.
spk19: And then, Ray, the other question was, for the realized study, what are you looking for for success?
spk16: Right, right, right. So, for epilepsy, for DERIGABAT, so remember, it's 80% power to detect at least a 30% placebo-adjusted difference in reduction of seizure frequency. So, If we achieve it, that's terrific. As you know, we've got the Xenon product. We've got Sinovimate that have had very compelling outcomes, which fall into the mid-30s. Capra falls around 28%. So if we achieve our 30% threshold and above, that would be really a successful outcome for us. So we'll stay tuned for that. And based on that data, It'll allow us to then tailor our phase three program accordingly. But based on the mechanism of action and selectivity of the SCABA APAM compound, we are very hopeful that this will introduce a novel therapy that will benefit patients with epilepsy.
spk12: Great. Thank you.
spk26: Thank you, Jeff. Thank you. One moment for our next question. And our next question comes from Greg Sivanovich of Mizuho.
spk25: Hi.
spk09: This is for Greg Sivanovich. Good morning, and thank you for taking my question. Congrats to the team for the recent capital raise and just two quick questions from us. What is needed from nonclinical and clinical pharmacology studies in order to support a potential registrational package in schizophrenia? And two, what drove the decision to proactively raise equity capital ahead of your multiple clinical data events in 2024? Thank you.
spk22: Sure, thanks for the question.
spk20: Yeah, so we have been looking forward to getting the package ready to submit to the NDA. To summarize briefly, we've done almost all the work that we need to do, actually, to prepare the preclinical section of the NDA already. So we have a few things to finish up, but there is nothing that's going to be on the critical path from that area at all.
spk18: So I hope that addresses your question. Yeah, and then, you know, I think on the capital rates, you know, I'll let Susan add to this as well, but, you know, I think largely This was, you know, one thing that, you know, we had been talking to a number of investors about over the last few months, and there was a significant amount of interest in, you know, doing the raise from outside investors, and so we thought it was a good time to do that so that we could really be focused on execution in 2024. As we mentioned, you know, we're going to be working on two NDAs in parallel, and so to be able to, you know, have the balance sheet shored up and really have a line of sight and focus on execution on those lead programs was really the primary driver behind that. I'm not sure if there's anything to add to that, Susan.
spk23: You know, we'll continue to be judicious with our spending. I mean, ultimately, what the capital raise enabled us to do, as Ron said, was focus on execution. The runway gets us into 2026, so we can turn over the data cards next year. and not have any overhang limiting our upside potential.
spk26: Great. Thank you. Thank you. One moment for our next question.
spk21: And our next question comes from Charles Duncan of Cantor Fitzgerald.
spk14: Good morning, Ron and team. Thanks for taking the question. Congrats on the progress. Had a quick question on Imraclidine and one follow-up on Darigabat. On Imraclidine, the ADP study, I'm wondering if you could give us a little more color on timing of data and really the kind of rate-limiting step for enrollment of that study, and what's the key parameter that you're looking for or looking at to decide whether or not to move forward in ADP?
spk18: Yeah, Charles, so as we've talked about in the past, this is more or less a first-of-its-kind type of study, and right now we're in Healthy Elderly Volunteers, And so we haven't, you know, to that end, we haven't given any guidance on when we expect to enroll that study in terms of, you know, I'll let Ray address, you know, how we're thinking about the indication itself. But just stay tuned on that. That's something that, you know, we will continue to move ahead and we're looking forward to. But we're not going to provide any guidance on enrollment on that program at this time.
spk16: And to follow up with that, Charles, for ADP, currently we're doing, as Ron mentioned, multiple ascending dose trial and healthy volunteers. There's other work that needs to be done subsequent to that that will allow us to understand the dosing in that population, which is important because it's a very different manifestation of symptomatically, but also population in terms of the psychotic symptoms that that they experience, mostly hallucinations and delusions. The good news is we got fast track from the FDA, which will allow us to work closely with them in terms of what does that development program look like. So stay tuned for that.
spk14: Okay.
spk18: And then, Charles, I think you had a follow-up on Durgabat.
spk14: Yep, yep. Quickly, just I think Ray mentioned that he's encouraged with high rollover rate. Probably not a surprise in focal onset epilepsy. if there is perceived efficacy. So I'm just wondering what a high rollover rate means. And more importantly, what do you see in terms of persistence in that open label part of that study? Thanks.
spk16: Yeah. So Charles, you know, obviously we're always encouraged by, you know, patients rolling over into the open label extension, meaning that, you know, they are tolerating the therapy well. In terms of efficacy, it's really hard to really understand that because the data is blinded and it's in the patient's purview to roll over if they feel that there's benefit or they want to continue with the therapy. We can comment on the open label extension data. That'll be disclosed when we lock that database and that data becomes available mid-year next year. So, while we review the data for data quality, we don't review it in terms of patterns of anything other than that at this juncture. So, we'll stay tuned for that data readout in mid-2024. Thank you.
spk13: Look forward to the progress. Thank you, Charles.
spk26: Thank you. One moment for our next question. And our next question comes from David Anselm of Piper Sandler.
spk06: Hey, thanks. So just a couple of quick ones. Looking more broadly at imraclidine, how important is it to develop it and explore clinical work as an adjunct to D2 blockers? How do you think about that? commercially? And then secondly, as you look at the CAPA, can you talk about what you think makes sense in MDD vis-a-vis monotherapy or adjunctive therapy and how you're thinking about it based on the body of data for your competitors and what you've seen to date? Thank you.
spk16: Okay. So, hi, David. So, in terms of adjunctive treatment, so, you know, we are very encouraged that we do believe that imraculidine will be a best-in-class muscarinic agent with once-a-day dosing, no need for titration, and a very benign tolerability profile. No doubt that adjunctive treatment plays a role in the clinical landscape and probably has utility. The first step is for us to really understand the dose range in the trials that we'll read out in the second half of next year. Following that, then we will pursue other programs in schizophrenia. Adjunctive treatment may potentially be one of them, so we're not going to comment on that just yet because we really want to understand the profile of imraculamine and schizophrenia first before we consider it as an adjunctive treatment. In terms of core of MDD monotherapy versus adjunctive therapy, as you know, there are two companies that have done, one has done a monotherapy, a second one has done adjunctive therapy. If you look at the outcomes of those trials that really are very similar, the monotherapy to what standard of care has shown and the adjunctive treatment is very similar to what the standard of care as adjunctive treatment basically the neuroleptics have shown. So, if you think about the value proposition of CORA in as adjunctive treatment to displace the neuroleptics because of a better tolerability profile based on the neuroleptic tolerability profile, that seems like a very exciting approach and also has great commercial and also potential, but also in the best interest of the patient. So, We think that that's probably the best approach, but we're evaluating all that. We're continuing to understand our core compound internally, which we believe has the potential to be another best-in-class therapy. So we'll stay tuned for all that moving forward. Okay.
spk05: That's helpful. Thank you.
spk26: Thank you. One moment for our next question. And our next question comes from Joseph Tomei of TD Cohen.
spk10: Hi there. Good morning. Are you able to hear me?
spk21: We can hear you.
spk10: Yep.
spk11: Perfect. Thank you. Great. Just a quick question on the Devapidon filing strategy. I think it was mentioned earlier that it was going to be a 2025 submission. So would early and late Parkinson's be filed together? And is there anything else aside from the open label that is kind of gating to that submission. And then maybe a second on the panic disorder study for DERIGABAT. I know there's a minimum number of panic attacks that patients need to have, but is there a maximum number that patients could have given that the primary endpoint is panic attack freedom? Thank you.
spk16: This is Joseph. Thank you for the question. So for Tavapidon, yes, we plan to file in 20 to 25. As you know, those studies we'll read out next year, nothing is gating. In fact, the open label extension has progressed well, and those exposures have been met. So we're excited about that potential in the Parkinson's arena. In terms of the panic program, you are correct that they have to have at least eight panic attacks in the month prior to screening and then four panic attacks in the two weeks of screening in order to qualify for the trial. So we don't have a floor effect. We actually can show that there is potential to reduce panic attack symptoms, but there is no maximum. So it's really around meeting that minimum threshold. And then from there, you can have as many panic attacks as the patient's experiencing. We're really wanting to ensure, though, that we get the right patient profile that really drives success, and that's why that criteria is set that way, and there's precedent for that. So we are continuing to enroll in that program and excited about the potential of DERIVABAT really being an innovative therapy and a needed therapy in the anxiety disorder space. So we'll stay tuned for that data in the future.
spk19: Part of Joe's question about filing for Tabapadon was, is it early and or late? Could you just give a little more detail on how you think about the filing for Tabapadon?
spk16: Right. So when we filed the Tabapadon NDA, we will file all three trials and the open label extension. So we will get a label like others have received for the treatment of Parkinson's disease. So The NDA will consist of the TEMPO3 trial, which we'll read out in the first half of next year, which is the adjunctive to levodopa trial, the two monotherapy trials that we'll read out in the second half of next year, as well as the TEMPO4, which is actually the open-label extension trial.
spk07: Perfect. Thank you very much.
spk25: Thank you, Joseph.
spk21: Thank you. I'm showing no further questions at this time. I would like to turn it back to Ron Renaud for closing remarks.
spk18: So I'd like to thank everybody for joining us this morning. And keep in mind, again, I just remind folks about our Tavapodon Investor Event on December 11th. Thanks, and we'll talk soon.
spk21: This concludes today's conference call.
spk26: Thank you for participating, and you may now disconnect. Hello. Thank you. Thank you. Thank you.
spk21: Good morning, and welcome to the Sarah Bell Therapeutics Third Quarter Financial Results Conference call. At this time, all participants are in listen-only mode. Later, you will have the opportunity to ask questions during the Q&A portion of the call. Please note that this call may be recorded. I will now hand the call over to Matt Calistri, Vice President of Investor Relations.
spk19: Thank you. Good morning, everyone. We appreciate you joining us for our third quarter 2023 earnings call. On today's call, you'll be hearing from Rod Renaud, our President and Chief Executive Officer, Dr. Ray Sanchez, our Chief Medical Officer, Dr. John Renger, our Chief Scientific Officer, and Dr. Susan Altshuler, our Chief Financial Officer. During our call today, please refer to our press release from this morning, detailing our third quarter 2023 financial performance, as well as our updated corporate presentation, both of which are available on our website. I would like to remind you that we will be making forward-looking statements that reflect our current views related to, among other things, the potential attributes and benefits of our product candidates, and the format and timing of our product development activities and clinical trials. We strongly encourage you to review the information that we file with the SEC regarding specific risks and uncertainties. I will now hand the call over to Ron Renaud, President and CEO of Ceravel, to provide an overview of our achievements and outlook.
spk18: Thanks, Matt, and good morning, everyone, and thank you for joining us for our third quarter 2023 business results call. I'm pleased to be with all of you today to review our third quarter results and to discuss how we're preparing for what we expect will be an exciting 2024. Let me start with some high-level thoughts on how the management team is thinking about and planning for the future of Ceravel. To begin, we believe this organization has one of the most robust neuroscience pipelines in the industry, and next year will be a pivotal one for Ceravel, as we look forward to multiple mid- and late-stage readouts across three different assets and three different indications. Our recent capital raise significantly bolstered the balance sheet, extending our runway into 2026, well over 12 months beyond all of our expected data readouts next year. As an organization, we are laser-focused on execution and maximizing the value creation opportunities for each of our lead assets. Our ongoing clinical trials are progressing well, and we expect to deliver data for Tavapidon, Therigabat, and Imracidine on the timelines we laid out last quarter. We are planning for success in proactively preparing to potentially file two NDAs in 2025 for Tabapadon and Imracladine if data are positive. Furthermore, we are diligently exploring lifecycle opportunities for our lead programs and other indications. Let me now provide an overview of our lead programs. Imracladine, our M4 selective positive allosteric modulator, or PAM, is currently in development for schizophrenia and Alzheimer's disease psychosis. as a once daily medicine without the need for titration. Imraclidine is a potential next generation antipsychotic with a novel mechanism of action that targets the M4 pathway. By selectively targeting M4, we believe Imraclidine may reduce psychotic symptoms without challenging side effects of current antipsychotics. Our two potentially registrational trials, MPOWER1 and MPOWER2, are enrolling well. and we expect data to read out in the second half of 2024. We are excited about the potential of Imraclidine and the benefit it may bring to patients with schizophrenia who have not seen innovation in decades. Moving to Tavapidon, the first D1-D5 partial agonist in development for the treatment of Parkinson's disease, we expect our TEMPO3 adjunctive trial to be our first data readout in the first half of 2024, with the TEMPO1 and TEMPO2 monotherapy readouts coming in the second half of the year. Building on our excitement for this program, we are pleased to announce that we will host a Tavapadon investor webcast on December 11th, during which we will explore this novel mechanism and its potential to address patient needs in greater depth. We believe there is a significant opportunity in Parkinson's disease to deliver sustained motor control with a favorable side effect profile. And finally, let me turn to Derigabat, our selective alpha-235 GABA-A PAM currently in development for both focal epilepsy and panic disorder. As we recognize Epilepsy Awareness Month in November and the 3.4 million people living with epilepsy in the United States, we are hopeful that we can bring forward a new treatment option for people living with this difficult disease. Our phase two realized trial in focal epilepsy to be our second readout of 2024 coming mid-year. We've also initiated our ADAPT trial, a phase two proof of concept trial in panic disorder. Behind our mid- to late-stage pipeline is an innovative discovery engine that is focused on bringing forward additional novel mechanisms to address neuroscience diseases. And we look forward to providing greater detail on those programs, including our Kappa opioid receptor antagonist, as we make further progress. I'm quite excited about all that we're doing here at Cerebell. And all that is to come for our pipeline and the potential benefits we hope to bring to patients. We are well positioned as we go into 2024 to truly transform what is possible in neuroscience. With that, I'll now turn the call over to Dr. Ray Sanchez, our Chief Medical Officer, to provide some added color about our lead programs. Ray?
spk16: Thank you, Ron, and good morning, everyone. I want to echo Ron's sentiments about the excitement around our pipeline. As a former clinician, I can tell you that I am energized by the potential we have here at Cerevel to make a meaningful difference in the lives of patients with neuroscience diseases. Beginning with Imrakladine, our EMPOWER program is advancing, and data are expected in the second half of 2024. Preserving data quality while mitigating placebo response risk remains the utmost priority for these trials, and we are pleased with our recent efforts to reinvigorate enrollment. As a reminder, EMPOWER 1 and EMPOWER 2 are two adequately powered three-armed trials that include adults living with schizophrenia and experiencing an acute exacerbation of psychotic symptoms. We designed these trials to potentially meet the criteria necessary to serve as pivotal trials based on what we expect the FDA will evaluate in a registrational package. We're also enrolling our 52-week open-label safety extension trial in Power 3 and prioritizing the completion of non-clinical and clinical pharmacology studies to accelerate a potential registrational package for imoraclidine in schizophrenia. We believe imoraclidine has tremendous potential in other disease areas plans for further development are underway. In Alzheimer's disease psychosis, or ADP, our phase one healthy elderly volunteer trial is ongoing, and the results of this trial will guide our clinical development plan as we advance this important indication with a substantial unmet need. Turning now to Tabapadon, our D1, D5 partial agonist in Parkinson's disease. Our phase three trials, known collectively as the TEMPO trials, are ongoing along with the corresponding open-label extension, in which we are encouraged by a greater than 90% rollover rate. We expect data for Tempo 3 in the first half of 2024, with data for Tempos 1 and 2 coming in the second half of 2024. We look forward to walking you through the scientific rationale and prior data for Tababadon, as well as its clinical potential during our investor event in December. With Turigabat, our selective GABA-A PAN, We believe there is potential for both anti-epileptic and anxiolytic activity comparable to benzodiazepines with an improved side effect profile. Unlike benzodiazepines, which are only used for acute episodes due to tolerability, abuse potential and other debilitating side effects, DERIGABAP's novel mechanism of action and anticipated favorable tolerability profile provide the potential for chronic dosing. We expect results from our Phase II realized trial in focal epilepsy in mid-year 2024. and we are encouraged by a continued high rollover rate into the realized open-label extension. Beyond focal epilepsy, our ADAPT Phase II trial in panic disorder is currently underway. A new drug has not been approved in panic disorder in nearly 20 years, and we are excited about the potential of providing DERIGABAT as a daily chronic therapy to patients in need. Cerevel's mid- to late-stage pipeline has the potential to bring forward numerous treatments to address some of the most devastating neuroscience diseases, and I am so proud of the team that is working diligently to make this potential a reality. With that, let me turn it over to Dr. John Renger, our Chief Scientific Officer, to provide an update on our early-stage portfolio. John.
spk20: Thank you, Ray. Good morning, everyone. I'm very pleased with the progress we've made in discovery research and early clinical development here at Cereval. Today I'd like to focus on our Kappa Opioid Receptor Antagonist, or CORA program, also known as CDL354. We have completed both our single and multiple ascending dose trials in which CDL354 has been generally well tolerated. Further, we currently believe we will be able to interrogate a range of receptor occupancies in both the Kappa and Mu opioid receptors. We believe and anticipate we'll be able to explore multiple indications of interest, such as major depressive disorder and substance use disorder. Our ongoing phase one pet receptor augmentation trial will clarify both kappa and mu receptor pet tracer displacement to further characterize selectivity across the compound exposures. We are encouraged by the potential impact of this asset and look forward to providing more updates in our plans in the near future. Beyond CORA, we have a growing number of programs Some initiated within our labs and exclusively developed here at Cereval, which we continue to progress, including our M4 selective agonist, a PDE4D sparing antagonist, and a selective TMAM175 potentiator program. We will provide further updates and plans for these specific programs as appropriate. With that, I'm going to turn it over to our Chief Financial Officer, Dr. Susan Altshuler, to review our financial performance for the third quarter. Susan?
spk23: Thank you, John. Turning to our financials, in October, we opportunistically bolstered our balance sheet with a $499 million capital raise, providing strong validation of Ceravel's potential from both new and existing high-quality investors. This additional capital, along with the roughly $758 million in cash, cash equivalents, and marketable securities we ended the third quarter with, will support our operations into 2026. Turning to the third quarter of 2023, Operating expenses were approximately $111 million, comprised of $85 million of research and development expenses and $26 million of general and administrative expenses. Looking forward, our financial strength enables us to focus on execution and provides optionality to maximize the value of our pipeline. That said, we will take a disciplined approach to resource allocation as we further build our pipeline, advance our lead assets, and prepare for two potential NDA filings in parallel. With that, I will hand the call back over to Ron for his concluding remarks.
spk18: Thank you, Susan. At Cerevo, we believe we have an unparalleled pipeline in neuroscience. With multiple mid- and late-stage readouts across three different assets expected next year, and the balance sheet that provides us with cash runway into 2026, we are focused and aligned on executing our trials, delivering high-quality data next year, and as Susan mentioned, preparing for two potential NDA filings. These are exciting times at Cerebell, and I'm so proud to be leading this organization. I want to offer my sincere appreciation to all of our employees who work tirelessly every day to deliver on Cerebell's mission. And I also want to thank our investigators and participants in our clinical trials, without whom none of what we seek to achieve would be possible. With that, let's open the call for questions.
spk21: Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster.
spk26: One moment for our first question. And our first question comes from Michael Yee of Jefferies.
spk30: Hey, guys, good morning and thanks for the question. And thanks for the updates, Ron. I know everyone's focused on execution. Two questions. First on, obviously, since last quarter, there was some concern about some of the timeline changes. Can you maybe just describe what initiatives give you the confidence that things are progressing on time and specifically, maybe for the team, what the right patients are, the right site selections are? that give you the confidence on executing on that enrollment. And the second question is on epilepsy. There's actually a bunch of competitor readouts happening, and maybe you could help us understand about the placebo arms and what things you're integrating into your study that might help us give us confidence there, because that has historically been an issue, and I know that's a concern for others as well. Thank you.
spk18: Yeah, sure. So let me take the first part of your first question, and I'll let Ray, you know, address the second part in terms of site selection from racletine and then the placebo work on our epilepsy studies. So look, you know, as we mentioned last quarter, you know, we were focused on trying to address the challenges that we saw with some of the enrollment issues that we had. And look, we're doing that with boots on the ground. You know, I've spent time at sites with Ray and the team, and the leader of our clinops and clinical development groups and really working with the sites to see what's going on. And I think we're quite pleased with the progress that we've seen so far. And that's why we can stand by the guidance that we've given here in the quarter. That all said, our focus will always remain on ensuring the quality of the data. And I think that gets to the second part of the question. We're going to maintain, continue to maintain rigorous site selection. and focus on our placebo variability reduction strategies. But I'll let Ray address, you know, how we think about the sites and how we think about, you know, all of those things as we continue to make progress here and also talk about our placebo group in the epilepsy studies.
spk16: Thank you, Michael, and good morning to you. So as you know, Michael, as I historically defined, you know, what does a good site look like? And it's really the access to the right patients and having good solid raters. And that really determines, for the most part, the success of the trial. So that's what we have been achieving and are continuing to try to achieve. But if you look at when we started the embracolating trials, they started quite robustly for the first year, and then the momentum slowed down in the spring of this year. What we've learned is how to manage the competitive landscape a bit more effectively. And to that end, we're seeing increased momentum in our enrollment without, as Ron mentioned, diluting the data quality in any way. So again, having very close communication with the sites, ensuring that the radar recertifications occur frequently, and continuing that communication ensures us that we have the greatest likelihood of success moving forward. In terms of epilepsy and the placebo response, as you know, that we are seeing placebo response in indications like spinal cerebellar ataxia and epilepsy, and that surprises many. But we are also taking the same aggressive approach and dedicated approach to mitigating the placebo response in our focal hunts and epilepsy trial by having placebo mitigation protocols at each site. but also it's about patient selection, making sure that the right patient profile is included in these trials, and really monitoring the data, the blinded data, to ensure the quality is there. So all taken together, the approach we're taking to help epilepsy to reduce placebo response is really the same approach we've taken to all our trials to reduce placebo response, and we're confident that we're positioning these trials for the greatest likelihood of success.
spk25: Thank you, guys.
spk21: Thank you. One moment for our next question. And our next question comes from Paul Matice of Stiefel.
spk32: Great. Thanks so much, and congrats on the progress.
spk31: I honestly wanted to ask a really similar question on Imraqudine, and that is related to this recent TAR-1 setback and the implications of that. I guess when you look at that that data and the huge placebo response they saw and anything else within those results, what sort of metrics are you tracking specifically on a blinded basis in the Emrak within studies beyond the obvious, like just changing pans that I guess today give you confidence that you're getting the patient and site quality that you intended or hope to. And then on the CAPA program, I wanted to ask a quick question for John, just Navacaprint and Atikaprint both cite really high selectivity for Kappa over Mu. What's behind your thesis that Mu might actually contribute to efficacy in some of the conditions that you plan on pursuing? Thanks so much.
spk17: I'll let Ray take the first part.
spk16: So, Paul, good morning. Good question. So, you know, we review the data on a monthly basis and sometimes more frequently, but it's blinded. So really, in terms of data quality, we want to ensure that all of the parameters that we're assessing are correct and that they're not conflicting. And so if that occurs, we obviously intervene at the site level to make sure that the raters are doing what they need to do or they need to have a refresher. And that validation, of course, occurs frequently with the raters. In terms of having the confidence that we're mitigating that placebo response. It's really around the measures that I mentioned earlier in Michael's question in terms of looking at the right patients and how do we do that. We have an independent committee that really looks at the patient qualifications to ensure that they meet the criteria for the profile that needs to occur for them to be enrolled in the trials. And then we have a placebo protocol at each site that allows us to standardize the way we actually approach each patient at every site to increase the likelihood of success and mitigate that placebo response. So really, we've taken the learnings from so many years, as well as the advice from key advisors who understand placebo response and have infused them into our program. So we're confident that we're taking all measures to ensure that that placebo response is mitigated. We're also limiting the number of countries, limiting the number of sites, all which contribute to placebo response. If you look at the trials that you've mentioned, the recent trial that, you know, over six countries, over 35 sites in those trials, and so all of that contributes to variability. Everything that we're trying to minimize to ensure the greatest likelihood of success.
spk20: Good morning, Paul, and thanks for the question on the CAP opioid receptor antagonist. So, yeah, to your question about what does Mu provide in terms of potential therapeutic benefit and indications. And so, as an example, what I would do is point to opioid withdrawal syndrome patients. And so, if you think about what it is you want to achieve potentially with our profile, What we can do is we can go through a receptor occupancy range at Kappa where we can have selectivity to Kappa, but if we continue to go up the receptor occupancy curve and exposure curves, we can bring in Bu. And so why does that provide something to us that seems exciting? It's because what you can get is a therapeutic benefit from Kappa, and what we believe the potential there is is to reduce things like the Q-induced reinstatement data that you see in the preclinical models where you can remove some of the things that would cause relapse in patients that are undergoing withdrawal or undergoing abstinence from use of opioids. But if you think about what you're actually trying to achieve in the long term, it's also reducing the potential for exposure to new agonists. And so if you think about how you could approach that population, you could actually begin with a lower dose range gain the benefit of the kappa without having any kind of mu antagonism that might induce withdrawal symptoms. And then as the patient progresses, you can actually increase the dose, so you actually bring in the mu antagonism potential. What that does is it has the ability to block the opioid activation if there is an exposure to an opioid in the future with that patient. So let's say they have a relapse, they take an opioid agonist at that point, having an antagonist could benefit that patient population, both as a safety measure in terms of blocking activation with an opioid so you could prevent the potential for harm, but you can also potentially, depending on what exposure they get to what opioid, you could actually prevent the rewarding benefit. And so you could imagine where you would start a patient going through the phase of withdrawal, starting with more of a kappa selectivity dose range, And what you could do is build up that dose range over time so that if there is an exposure, you have the protection of having a muon antagonism benefit on board in that same patient.
spk22: So that's how we're thinking about it.
spk24: Thanks a lot. Thanks, Paul.
spk21: Thank you. One moment for our next question. And our next question comes from Mohit Pensal of Wells Fargo.
spk04: Great. Thank you for taking my question. Thank you for having an uneventful quarter. I really appreciate it, and congrats on the financing. I have two questions. One is on Tevapidon. In our checks, doctors are suggesting that the dopamine agonists are a little bit out of fashion. They're not used as much. So could you talk a little bit about how you're thinking about the bar for success clinically, not just static benefit, what it should be, And then on the second one, can you remind me, Derigabed, about, Derigabed, what was the reason for slow enrollment and how you are mitigating that?
spk25: Thank you.
spk16: So, Mohit, thanks for that question on tabapadon. So, if you think about the novel mechanism of tabapadon being a D15 partial agonist that selectively targets those receptors of the direct nicostriatal pathway, it really gives us a confidence that it's going to be a transformative therapy in symptomatically treating Parkinson's disease. Clinically, we've designed a program to show the benefits as both a monotherapy and as an adjunctive therapy. In the monotherapy, 27-week trials looking at the UPDRS parts two, which looks at the daily functioning, and part three that looks at the motor symptoms and that's the primary endpoint, and change from baseline is the primary endpoint on that. So to show really the benefits on not only motor symptoms, but the quality of life as impacted by motor symptoms. For the adjunctive trial, which is our first trial to read out in the first half of next year, we're looking at the benefit of tavapidon as the best adjunctive treatment with levodopa to decrease the off-time, but importantly, increase be on time without troublesome dyskinesis, which is the primary endpoint and really what's clinically relevant. So that's how we are thinking about that program. And really we're thinking of it as really backbone therapy, meaning that when the patient is first diagnosed as being the best therapy to initiate patients on and then when levodopa needs to be introduced as the best adjunctive treatment. So we're hoping that if the results read out as we expect that they will next year, that we will then proceed to file that NDA and give patients a transformative therapy for symptomatic treatment of Parkinson's? No, during that question, not enrollment. So can you repeat that question?
spk04: Yeah, I mean, so the question was, can you remind me what was the reason for slow enrollment in the beginning, and how are you trying to mitigate that? I think it was more to do with with the fact that you were taking patients off the background medication, right? I mean, what was the issue there?
spk15: No, so there are a couple of reasons for the enrollment issues with the epilepsy program.
spk16: Remember, these are patients who are drug-resistant. There are at least one and no more than three anti-epileptics. They continue on those therapies at a static dose, so that's not changed. One of the challenges that that program has had is the fact that the concomitant medications, concomitant antiepileptics are 3A4 inducers. In fact, they are all 3A4 inducers. And we, as you know, cannot allow patients who are on drugs that are 3A4 inducers because it impacts the pharmacokinetic profile of the therapy and it will impact the outcome of the trial. So the challenge there has been to find the right patient profile. but there are not concomitant medications like carbamazepine, oxcarbazepine, and other therapies that are 3A and 4A inducers. So we've been challenged by that. The good news is that John and his team have conducted a drug-drug interaction trial that will allow us to then overcome that obstacle in phase 3, but we really had to know that the actual dose data based on those individuals that are not on those concomitant medications that would impact the pharmacokinetic profile. So what we've done is we've heightened the number of sites, the number of countries that we know well to increase the enrollment. We're seeing great momentum. And so the good news is that we are planning to read out in mid-year next year. And if the results are what they are, then we can proceed with a robust phase three program.
spk18: The other thing I might add here, I know there's going to be more questions on Tevapidon and Lohit. And as I mentioned in my prepared comments, we're going to host an investor webcast focused on Tevapidon on December 11th at 10 a.m. So tune into that. And I think if you have additional questions, that'll be a good forum to get some clarity.
spk04: Thank you very much. Congressional progress.
spk21: Thank you. One moment for our next question. And our next question comes from Joseph Thorne of TD Cowan.
spk26: Joseph Thorne, your line is open. Please check your mute. One moment for our next question.
spk21: And our next question comes from Jeff Hung of Morgan Stanley.
spk08: Thanks for taking my questions. For CDL871, can you talk about the challenges clinical sites are facing on patient identification for dementia-related apathy? And then for the DERIGABAC real-life study in focal epilepsy, what do you need to see next year to consider the proof of concept of success? You know, is there a particular bar for reduction in seizure frequency? Thanks.
spk16: Hi, Jeff. Good morning. So the apathy program, as you know, the 871 program is a phase 2A trial that's really experimental in nature. As you know, it's the leading neuropsychiatric syndrome that you see in patients with dementia, and we're conducting in all of the dementias experimentally as a first step. It's also a predictor of disease progression. There's three components and it's really decreased goal-directed behavior, decreased emotional responsiveness, and lack of motivation. The challenge with that is that the landscape is really still trying to understand what that patient profile looks like. Remember, these are patients that are not agitated. They're not really a problem clinically, but it does impact their quality of life. It does impact the longevity of their disease. So one of the challenges is really identifying the right patient profile. So to that end, that's one of the challenges that we've encountered But we believe that the therapy has a great potential of being a novel therapy that will work in that population. But again, I think the landscape is trying to catch up and really clinically understand what that profile looks like. So that's been a limiting step for that program. But we're continuing to move it along. We're continuing to identify the sites that have access to the right patients because that's really critical to get the signal detection that we need for success. So that's where we are with that program now.
spk19: And the other question was for the realized study, what are you looking for for success?
spk16: Right, right, right. So for epilepsy, for DERIGABAT, so remember, it's 80% power to detect at least a 30% placebo-adjusted difference in reduction of seizure frequency. So if we achieve that, that's terrific. As you know, we've got the Xenon product, we've got that have had very compelling outcomes, which fall into the mid-30s. CAPRA falls around 28%. So if we achieve our 30% threshold and above, that would be really a successful outcome for us. So we'll stay tuned for that. And based on that data, it'll allow us to then tailor our Phase 3 program accordingly. Based on the mechanism of action and selectivity of the SCABA-APAM compound, we are very hopeful that this will introduce a novel therapy that will benefit patients with epilepsy.
spk12: Great. Thank you.
spk25: Thank you, Jeff.
spk21: Thank you. One moment for our next question. And our next question comes from Greg Sivanovesh of Missouho.
spk09: Hi. This is for Greg Sivanovesh. Good morning and thank you for taking my question. Congrats to the team for the recent capital raise and just two quick questions from us. For MRACody, what is needed from non-clinical and clinical pharmacology studies in order to support a potential registrational package in schizophrenia and to what drove the decision to proactively raise equity capital ahead of your multiple clinical data events in 2024? Thank you.
spk22: Sure, thanks for the question.
spk20: Yeah, so we have been looking forward to getting the package ready to submit to the NDA. So to summarize briefly, we've done almost all the work that we need to do actually to prepare the preclinical section of the NDA already. So we have a few things to finish up, but there is nothing that's going to be on the critical path from that area at all.
spk18: So I hope that addresses your question. Yeah. And then, you know, I think on the capital raise, you know, I'll let Susan add to this as well, but I, you know, I think largely this was, you know, one thing that, you know, we had been talking to a number of investors about over the last few months and there was a significant amount of interest in, you know, doing the raise from outside investors. And so we thought it was a good time to do that so that we could really be focused on execution in 2024. As we mentioned, is we're going to be working on two NDAs in parallel. And so to be able to have the balance sheet shored up and really have a line of sight and focus on execution on those lead programs was really the primary driver behind that. I'm not sure if there's anything to add to that, Susan.
spk23: You know, we'll continue to be judicious with our spending. I mean, ultimately, what the capital raise enabled us to do, as Ron said, was focus on execution, The runway gets us into 2026, so we can turn over the data cards next year and not have any overhang limiting our upside potential.
spk25: Great.
spk26: Thank you. Thank you. One moment for our next question.
spk21: And our next question comes from Charles Duncan of Cantor Fitzgerald.
spk14: Good morning, Ron and team. Thanks for taking the question. Congrats on the progress. Had a quick question on Imraclidine and one follow-up on Darigabat. On Imraclidine, the ADP study, I'm wondering if you could give us a little more color on timing of data and really the kind of rate-limiting step for enrollment of that study, and what's the key parameter that you're looking for or looking at to decide whether or not to move forward in ADP?
spk18: Yeah, Charles, so as we've talked about in the past, this is more or less a first-of-its-kind type of study, and right now we're in healthy elderly volunteers, And so we haven't, you know, to that end, we haven't given any guidance on when we expect to enroll that study in terms of, you know, I'll let Ray address, you know, how we're thinking about the indication itself. But just stay tuned on that. That's something that, you know, we will continue to move ahead and we're looking forward to. But we're not going to provide any guidance on enrollment on that program at this time.
spk16: And to follow up with that, Charles, for ADP, currently we're doing, as Ron mentioned, multiple ascending dose trial and healthy volunteers. There's other work that needs to be done subsequent to that that will allow us to understand the dosing in that population, which is important because it's a very different manifestation of symptomatically, but also population in terms of the psychotic symptoms that that they experience, mostly hallucinations and delusions. The good news is we got fast track from the FDA, which will allow us to work closely with them in terms of what does that development program look like. So stay tuned for that.
spk14: Okay.
spk18: And then, Charles, I think you had a follow-up on Dergabat.
spk14: Yep, yep. Quickly, just I think Ray mentioned that he's encouraged with high rollover rate. Probably not a surprise in focal onset epilepsy. if there is perceived efficacy. So I'm just wondering what a high rollover rate means, and more importantly, what do you see in terms of persistence in that open-label part of that study? Thanks.
spk16: Yeah, so Charles, you know, obviously we're always encouraged by, you know, patients rolling over into the open-label extension, meaning that, you know, they are tolerating be the therapy. Well, in terms of efficacy, it's really hard to really understand that because the data is blinded and it's in the patient's purview to roll over if they feel that there's benefit or they want to continue with the therapy. We can comment on the open label extension data. That'll be disclosed when we lock that database and that data becomes available mid-year next year. So, while we review the data for data quality, we don't review it in terms of patterns of anything other than that at this juncture. So, we'll stay tuned for that data readout in mid-2024. Thank you.
spk13: Look forward to the progress. Thank you, Charles.
spk21: Thank you. One moment for our next question. And our next question comes from David Anselm of Piper Sandler.
spk06: Hey, thanks. So just a couple of quick ones. Looking more broadly at Imraclidine, how important is it to develop it and explore clinical work as an adjunct to D2 blockers? How do you think about that commercially? And then secondly, as you look at the kappa, Can you talk about what you think makes sense in MDD vis-a-vis monotherapy or adjunctive therapy and how you're thinking about it based on the body of data for your competitors and what you've seen to date? Thank you.
spk16: Okay. So, hi, David. So, in terms of adjunctive treatment, so, you know, we are very encouraged to that we do believe that Imraclidine will be a best-in-class muscarinic agent with once-a-day dosing, no need for titration, and a very benign tolerability profile. No doubt that adjunctive treatment plays a role in the clinical landscape and probably has utility. The first step is for us to really understand the dose range in the trials that we'll read out in the second half of next year. Following that, then we will pursue other programs in schizophrenia. Adjunctive treatment may potentially be one of them. So, we're not going to comment on that just yet because we really want to understand the profile of imraculidine in schizophrenia first before we consider it as an adjunctive treatment. In terms of core of MDD monotherapy versus adjunctive therapy, as you know, there are two companies that have done, one has done a monotherapy A second one has done adjunctive therapy. If you look at the outcomes of those trials that really are very similar, the model therapy to what standard of care has shown and the adjunctive treatment is very similar to what the standard of care as adjunctive treatment, basically the neuroleptics have shown. So if you think about the value proposition of CORA, in as adjunctive treatment to displace the neuroleptics because of a better tolerability profile based on the neuroleptic tolerability profile. That seems like a very exciting approach and also has great commercial and also potential, but also in the best interest of the patient. So we think that that's probably the best approach, but we're evaluating all that. We're continuing to understand our core compound internally, which we believe has the potential to be another best-in-class therapy. So we'll stay tuned for all that moving forward. Okay.
spk05: That's helpful. Thank you.
spk21: Thank you. One moment for our next question. And our next question comes from Joseph Tomei of TD Cohen.
spk10: Hi there. Good morning. Are you able to hear me? We hear you.
spk11: Yep, perfect. Thank you. Great. Just a quick question on the Devapodon filing strategy. I think it was mentioned earlier that it was going to be a 2025 submission. So would early and late Parkinson's be filed together? And is there anything else aside from the open label that is kind of gating to that submission? And then maybe a second on the panic disorder study for DERIGABAT. I know there's a minimum number of panic attacks that patients need to have, but is there a maximum number that patients could have given that the primary endpoint is panic attack freedom? Thank you.
spk16: This is Joseph. Thank you for the question. So for Tevapidon, yes, we plan to file in 20 to 25. As you know, those studies we'll read out next year. Nothing is gating. In fact, you know, the open label extension has progressed well. And, you know, those exposures have been met. So, we're excited about that potential in the Parkinson's arena. In terms of the panic program, you are correct that they have to have at least eight panic attacks in the month prior to screening and then four panic attacks in the two weeks of screening in order to qualify for the trial. So we don't have a floor effect. We actually can show that there is potential to reduce panic attack symptoms, but there is no maximum. So it's really around meeting that minimum threshold. And then from there, you can have as many panic attacks as the patient's experiencing. We're really wanting to ensure, though, that we get the right patient profile that really drives success. And that's why that criteria is set that way. And there's precedent for that. So we are continuing to enroll in that program and excited about the potential derivative of that really being an innovative therapy and a needed therapy in the anxiety disorder space. So we'll stay tuned for that data in the future.
spk19: Part of Joe's question about filing for Tabapadon was, is it early and or late? Could you just give a little more detail on how you think about the filing for Tabapadon?
spk16: Right. So when we filed the Tabapadon NDA, we will file all three trials. So, and the open label extension. So, you know, we will get a label like others have received for the treatment of Parkinson's disease. So, the NDA will consist of the TEMPO3 trial, which we'll read out in the first half of next year, which is the adjunctive to levodopa trial, the two monotherapy trials that we'll read out in the second half of next year, as well as the TEMPO3, which is actually the, excuse me, the TEMPO4, which is actually the open label extension trial.
spk07: Perfect. Thank you very much.
spk25: Thank you, Joseph.
spk21: Thank you. I'm showing no further questions at this time. I would like to turn it back to Ron Renaud for closing remarks.
spk18: So I'd like to thank everybody for joining us this morning. And keep in mind, again, I just remind folks about our Tabapadon Investor Event on December 11th. Thanks, and we'll talk soon.
spk21: This concludes today's conference call. Thank you for participating and you may now disconnect.
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