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spk06: Good morning and welcome to the Cerevel Therapeutics First Quarter 2022 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 Mr. Matt Calistri, Vice President of Corporate Strategy and Investor Relations. Please go ahead.
spk11: Thank you. Good morning, everyone. We appreciate you joining us for our first quarter 2022 earnings call. On today's call, you'll be hearing from Dr. Tony Coles, our chairperson and chief executive officer, Dr. Ray Sanchez, our chief medical officer, Dr. John Renger, our chief scientific officer, and Mark Bodenrader, our interim chief financial officer. Abe Cisse, our president, will join us for Q&A. During our call today, please refer to our press release from this morning, detailing our Q1 2022 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 Dr. Tony Coles, Chairperson and CEO of Cerevel, to provide an overview of our achievements and outlook.
spk03: Thanks, Matt, and good morning, everyone. Thank you for joining us on our first quarter 2022 business results call. Cerevel aspires to become the premier neuroscience company, and I'm really proud of the progress we've made to date. We've got the pipeline, the people, and the capital we need to deliver innovative solutions for people living with some of the most vexing and difficult to treat neuroscience diseases. These diseases not only affect patients, but their families and society at large, and we all know that the unmet medical need is clear. We take a unique approach to addressing that unmet need. We begin with a deep understanding of neurocircuitry or how the brain is wired. We then focus on receptor and subtype selectivity and utilize our knowledge of differentiated pharmacology to develop novel therapies through which we seek to transform what's possible in neuroscience. And our results speak to the benefits of our approach. When I spoke to you last quarter, we had just announced positive anxiety data for DERIGABAT, our selective alpha-235 GABA positive allosteric modulator, or PAM. And less than a year ago, We announced positive phase 1B data in schizophrenia for imraculidine, our M4 selective PAM, and we're forging ahead. We're on track to initiate two parallel adequately powered phase 2 trials of imraculidine in schizophrenia by mid-year 2022, and we continue to execute on our broad diverse pipeline of neuroscience drug candidates, And finally, we're growing our talented and very experienced team, primarily in R&D with a deep passion for innovation in neuroscience. Looking specifically at our pipeline, we anticipate five data readouts in 2023. In the first half of next year, we expect to have data from our Trapadon Phase III trial in late-stage Parkinson's. We also expect data from our ongoing CVL871 Phase 2A trial in dementia-related apathy. In mid-year 2023, we expect data from our Derigabat Phase 2 proof-of-concept trial in focal epilepsy, as we announced this morning. And in the second half of 2023, we expect data from our two Tavapidon Phase 3 trials in early-stage Parkinson's, which would complete what we expect is needed for the registrational package for that drug. We expect to follow this important set of milestones with data from our two recently announced phase two trials of Imraclidine with data results in schizophrenia in the first half of 2024. Cerebral is also in a strong financial position and we're well capitalized to support operations into 2024. As of the close of the first quarter, we had $551 million in cash, cash equivalents and marketable securities to which we added $37.5 million funding in April from the second annual payment of the Devapodon risk-sharing arrangement we entered into in 2021. Cerebellum is embarking upon an exciting period of growth, and I'm really looking forward to updating you on our many milestones in the future. I'll now turn the call over to Dr. Ray Sanchez, our Chief Medical Officer, to provide some additional details about our lead programs and anticipated readout timings. Ray?
spk10: Thank you, Tony, and good morning to all of you. As Tony has outlined, Cerevel is well positioned to pave new paths in neuroscience. Our pipeline seeks to address some of the most challenging neuroscience diseases and brings forward a new treatment options with enhanced tolerability profiles. As a former clinician, I can attest to the challenges of treating people with schizophrenia, a disease that has rippling effects in all areas of the patient's personal, professional, and family life. The need for better treatment options is what drives us each day. Let's first turn to Imraclidine, our M4 positive allosteric modulator. Less than a year ago, we announced positive phase 1B data in schizophrenia, and the results were truly impressive. Both doses of Imraclidine demonstrated clinically meaningful and statistically significant antipsychotic effects with no meaningful differences in gastrointestinal side effects, extrapyramidal symptoms, or weight gain compared with placebo. We're very encouraged by those robust results, and we're now moving rapidly into our next phase of development. Importantly, as you can see on slide 15, we're on track to initiate two parallel adequately powered phase two trials by mid-year. Running these two trials in parallel enables us to fully explore the therapeutic dose range of umbraclidine, while minimizing the number of treatment arms with the hope of reducing the variability observed in clinical trials, as well as placebo response. We designed these trials to potentially meet the criteria necessary to serve as pivotal, based on what we expect the FDA will evaluate in a registrational package. Beyond schizophrenia, we also plan to evaluate this mechanism and other indications in populations, including psychosis associated with dementia. Turning now to DERIGABAT, as Tony mentioned, we have updated the timeline for REALIZE, our phase two proof of concept trial in focal epilepsy, which we now expect will read out in mid-year 2023, rather than the second half of this year. This outcome is based on the use of excluded concomitant medications in the target population, as well as COVID-19 disruptions at clinical trial sites. Consequently, In order to augment slower than anticipated enrollment, we have added three additional countries to participate in the trial. But unfortunately, one of these countries was Ukraine. In the time it took to activate these new sites, the war in Ukraine broke out, and we no longer expect the Ukrainian sites to contribute to enrollment in this trial. In the coming months, we do expect enrollment to initiate in the two remaining new countries, Poland and Serbia, which enables us to anticipate data in mid-year 2023. Last quarter, we were able to share our very encouraging positive top-line data from our DERIGABAT Phase I Healthy Volunteer Trial in Acute Anxiety. These results provide strong evidence of DERIGABAT's potential as a differentiated daily maintenance treatment for anxiety-related disorders while minimizing tolerability concerns in contrast to benzodiazepines. Based on the robustness of our Phase I data, we're exploring various indication opportunities for DERIGABAT with the first likely to be panic disorder. Turning next to tevapidon, our D1, D5 partial agonist, that we're developing for Parkinson's disease is both a monotherapy and adjunctive treatment to levodopa for symptomatic motor control. We continue to dose in all of our phase three trials, known collectively as the TEMPO trials, and all remain on track with our expected timelines. We expect data from TEMPO3, the adjunctive trial in late-stage Parkinson's, to read out in the first half of 2023, and data from TEMPO1 and TEMPO2 trials in early-stage Parkinson's to read out in the second half of 2023. Turning to CVL871, our second D1D5 partial agonist, which we are currently evaluating in a Phase II exploratory trial in dementia-related apathy. We expect data in the first half of 2023. In June of last year, we received fast-track designation for CVL871 in this indication, which enables early and more frequent interactions with the FDA as well as the potential for rolling NDA submission and priority review. We are looking forward to interacting closely with the agency in determining the best path forward for developing a treatment in this novel and much-needed indications since there are no currently approved therapies. With that, Dr. John Renger, our Chief Scientific Officer, will speak about our early stage portfolio and our presentations at medical conferences. John?
spk13: Thank you, Ray. Good morning, everyone. I'd like to first provide an overview of our earlier stage clinical and preclinical programs. First, we have an active program to identify an N4-selective full agonist molecule as part of our goal of creating an industry-leading N4 franchise. We believe this novel asset will provide for additional therapeutic indication optionality as we consider the clinical utility of this mechanism of action and its demonstrated potential in treating psychosis. Second, I'd like to highlight our Kappa Opioid Receptor Antagonist Program, which continues to progress in our planned phase one single and multiple ascending dose studies. We believe this mechanism of action has the potential to address major depressive disorder and substance use disorder, based upon both clinical and preclinical data generated with compounds that target the Kappa opioid receptor. We are also progressing a PDE4B antagonist program, a clinically approved mechanism of action that has seen previous drug approvals in both inflammatory diseases and dermatologic and respiratory indications. This mechanism of action has also demonstrated early clinical activity in the treatment of depressive symptoms in prior proof-of-concept studies. Our program within Cerevel is directed at creating a CNS-active PDE4B selective inhibitor for potential use in major depressive disorder and in CNS-inflammatory neurodegenerative therapeutic indications, while aiming to avoid the tolerability limitations of GI distress that were associated with prior CNS-active non-selective PDE4 inhibitors and limit their clinical utility. Finally, we made a decision to discontinue further investment in CVL936, our dopamine D3 preferring D2D3 receptor subtype selective antagonist for the treatment of substance use disorder. This decision was based on the results of a multiple dose non-clinical EEG study. We continue to build a robust drug discovery engine at our research labs in Cambridge Crossing with additional ongoing discovery stage and pre-IND programs. We are leveraging our differentiated understanding of disease-based neurocircuitry and world-class chemistry to develop and explore the therapeutic potential of small molecules to address major unmet patient needs. We believe our research engine will fuel future innovation for years to come, and we look forward to keeping you updated on our progress on these earlier stage efforts as appropriate. Finally, I also want to emphasize how proud I am of our team's recent presence at medical meetings. which is an important aspect of our journey to becoming the premier neuroscience company. Our teams presented at the American Academy of Neurology, highlighting our progress on our duragabat and tavapidon programs. Subsequently, we also presented our hemorrhagic gene data at the Schizophrenia International Research Society Congress. These presentations underscore our belief that we are well-positioned as a scientific and clinical development leader across several neuroscience diseases associated with significant unmet patient needs. I'd like to publicly extend my congratulations to our teams for their ongoing commitment to our company and also the patients who are relying on us. I'd now like to hand it over to Cerevel's Interim Chief Financial Officer, Mark Bodenreiter, to review our financial performance for the first quarter. Mark?
spk09: Thank you, John, and good morning, everyone. I'm pleased to provide an overview of Cerevel's strong financial position in our first quarter 2022 financial results. please refer to this morning's press release for the full details of our financial update. For the first quarter, total operating expenses were approximately $73 million, which includes R&D expense of $55 million and G&A expense of $18 million. As expected, total operating expenses for the first quarter grew over prior quarters, driven by the continued progression of our clinical trials and increased personnel costs to support the advancement of our pipeline. Relative to the first quarter of last year, R&D expenses increased by approximately $18 million. This increase is primarily due to the continued advancement of Ceravel's clinical programs for Tevapidon, Imraclidine, and Deringabat, investment in our preclinical and discovery efforts, and an increase in personnel and other infrastructure costs as we expand capabilities to advance our pipeline. We expect our quarterly R&D expense to continue to increase as we plan to initiate the two phase two clinical trials for imraculidine in schizophrenia by mid-year. G&A expense for the first quarter increased by approximately $3.5 million over last year. We also continue to expect our G&A expense to increase as we support the growth of the company, including the progression of our R&D programs and the initiation of commercial planning activities. As of March 31st, 2022, our cash and cash equivalents and marketable securities total $551 million. This cash position does not include the additional $37.5 million received in April under our Tavapadon risk sharing arrangement that Tony mentioned earlier. In closing, we remain well capitalized. We expect our cash resources to fund our current operations into 2024. We look forward to multiple value-creating data readouts over the next couple years, and we continue to think creatively, and opportunistically about further strengthening our balance sheet to support our extensive pipeline while pursuing earlier stage clinical programs in drug discovery initiatives. With that, I'll hand the call back to Tony for closing remarks.
spk03: Thanks, Mark. As you can see, we continue to advance our broad and diverse pipeline and building what we hope will become the premier neuroscience company. Cerevel is at the forefront of the next great frontier in medicine, and it is our daily privilege to work with the aim of delivering new solutions to patients who are in great need. Thank you for joining us this morning. I want to thank our teams, whose dedication and commitment make this possible. And in particular, let me extend my deepest gratitude and appreciation to the clinical trial participants and the investigators who contribute to the development of these important therapies. With that operator, we can now open the call for questions.
spk06: Thank you. And as a reminder, to ask a question, please press star 1 on your telephone keypad. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your first question comes from Corey Casimo from JP Morgan. Your line is open.
spk02: Hey, good morning, guys. Thank you for taking the questions. I've got two for you, one on Dorigabat and one on Imrakladine. So for Dorigabat and the epilepsy trial, can you comment on how much you're hoping to enroll, how many patients you're hoping to enroll in Poland and Serbia, and your confidence in generating high-quality data in those regions? And then for Imrakladine, with the pending phase two of possibly pivotal efficacy studies being 10 weeks in duration, and then, of course, having that open label extension safety study for 52 weeks, do you have a sense as to how much safety data and duration you may need in the event the efficacy studies do enable a filing, as that seems to clearly be the future rate limiting step? Thanks a lot.
spk03: Okay, good morning, Corey, and thanks for the questions. Ray, I think I'll actually ask you to get us started here with Corey's first question about Derigabat, the enrollment numbers, and the quality of data from Poland and Serbia.
spk10: Terrific. Good morning, Corey, and thanks for that question. So we are looking at we've activated six sites in Poland and five sites in Serbia. We're still determining the number of patients that those two countries can enroll. But what I can tell you is that the reason that they were chosen is because they generally historically have actually provided very good quality data. And so we're hoping that the same will be true in the data that they generate moving forward. But in terms of the number of patients that they will enroll, we're still working with the sites on that. And they'll start in the next few weeks enrolling patients into the trial.
spk03: And, Ray, the second question was about Imraclidine and the 10-week duration. So can we just – let's just – maybe we just review the general design for the two studies for Imraclidine. I think Corey's question was would we have adequate safety data that would support a patient package.
spk10: Yes. So, Corey, as you know, that we are conducting, starting very soon, two six-week pivotal trials in patients with acute schizophrenia. But we also need for registration, as you're outlining correctly, long-term safety data. And per ICH guideline, we would need a minimum of 300 at six months and 100 exposed at one year. Our hope is that we can exceed, of course, those numbers. but that is what it would be needed in addition to the two positive Phase II trials that really characterize the dose range for registration.
spk03: Okay, very helpful. Thank you. Thank you. Thank you very much. Operator, we will take the next question.
spk06: Thank you. Your next question comes from Michael Yee from Jefferies. Your line is open. Thank you.
spk07: Hey, good morning. Thank you, Tony, for the update, and thanks for the question. With respect to emiraclidine, can you shed some light on the registration-enabling studies, for example, the blood pressure monitoring study, which I think is ongoing? I know there's been various questions about how to put that study into context, so I was wondering if you could right-size our expectations for what you would expect that study to show, the relevance of that study, and even such details as is there a placebo arm and is that important to have a placebo arm or it doesn't really matter? Maybe just talk a little bit about that study. Thank you.
spk03: Okay. I'm going to ask Ray to make a few specific comments, but let me offer a couple of points by context. This is a standard clinical pharmacology trial that the agency will require for registration purposes. So we are working to comply with the agency's outline for what they'll be looking for. And the primary purpose, as you certainly know and will remind everyone else, is to assess a sustained effect on blood pressure. We did see transient increases in blood pressure in the Phase 1B study, but those increases were not sustained. And this is, of course, to give the agency assurance that we won't have a significant effect going forward. The trial is going quite well. And, Ray, maybe you'd offer some additional specific comments. But, Mike, I just wanted to set the context for the ordinary course of practice for this particular trial. We're working to have everything ready for registration if these data are supportive of that. Ray, what else would you add?
spk10: Sure. Thank you, Tony. I think you answered that well. But Michael, just to give you some relevance, this is an eight-week trial that has 150 patients that are participating in it, looking at doses of 10 milligrams and 30 milligrams, so the low dose and the high dose, with the objective of assessing a sustained, as Tony mentioned, effect on systolic blood pressure over the eight weeks. and it's 90% powered to rule out a 3-millimeter of mercury or above change from baseline. So we're encouraged as the enrollment is going very well. We do expect the results to read out in the fourth quarter of this year. But I think importantly, as Tony mentioned, that – This is a phase one trial like other phase one trials that is required for FDA guidance for registration and labeling, most importantly. So we will disclose those results at the appropriate time when they're available.
spk07: But let me emphasize something I think you've alluded to before. Even if there was a small signal or not, your point has been that that may or may not be totally relevant for patients, and it's more of a clinician labeling thing. Is that correct?
spk10: That's correct. So as you know, this is a trial that is not gating to our being able to pursue the larger trials that we're starting soon. And again, like, you know, drug-drug interaction studies, like food effect studies, this is really a study that will inform labeling for practitioners to understand the sustained effect on blood pressure if there is any.
spk07: Thank you.
spk10: Thank you, Michael.
spk03: Operator, we'll take the next question.
spk06: Sure. Your next question comes from Paul Middles from Stifel Alliance.
spk04: Hey, thanks so much for taking the questions. On the ambulatory blood pressure monitoring study, I feel like one important detail that hasn't been talked about much is that some of the data you presented so far has been close to CMAX, whereas I think that study is doing 24-hour monitoring So can you put into context, if we're looking at blood pressure changes over 24 hours, how much more modest are they on average versus the data that we've seen so far? I guess am I right in assuming that they're more modest? And any numbers you could put to that I think would be interesting. And then just on the kappa opioid target, I was wondering how you view the totality of the data we have so far for major depressive disorder. I know there's been a couple studies. One was a publicly funded study that looked all right. One more recent data point from J&J. Just curious how you would sort of contextualize that in your confidence in moving forward. Thank you. Okay.
spk03: I think, Ray, if you would start on the question about blood pressure observations from the Phase 1B trial. And I think we'll have J.R. continue with that, particularly on the CMAX point that Paul's raising about And then, J.R., if you'd lateral right into the core point, that would be great. I appreciate the question, Paul, because we do want to feature the early stage pipeline, and we're excited about the core opportunity along with all the later stage stuff we're doing. So, Ray, if you'd start and then toss it to J.R.
spk10: Good morning, Paul. So if you recall that during the six-week trial, the Phase 1b trial, that at six weeks, placebo that the average systolic, diastolic blood pressure and heart rates were all very similar to placebo with really no concerns raised there. And really what the agency, and rightly so, is interested in is not so much the transient changes that you see around CMAX, but really the long-term sustained effects on systolic blood pressure, which really have the most cardiovascular impact. So consequently, the trial is designed, as you mentioned correctly, to look at a 24-hour monitoring of blood pressure over the eight weeks at certain times. So we'll do it at baseline. We'll do it at weeks four and weeks eight. The change from baseline at week eight is the primary endpoint. But again, the core objective being the sustained systolic blood pressure. It's eight weeks. We're encouraged by that because it's six weeks. As I said before, we saw minimal effects. And so, it's really around the average sustained effect versus what we see around CMAX at any given time and moment. Paul, does that answer your question?
spk04: It does. Thank you.
spk10: Thank you.
spk03: JR, would you add anything to that? And if you could pick up on the CORA question as well. and our thoughts on the totality of data in major depressive disorders.
spk13: Sure, Tony, thanks. Yeah, I'll just add one other note, and I think, Paul, part of your question may have been the transient, not over multiple days of dosing, but the transientness that we've seen even within a 24-hour period. So if you think back to the study design, we had done a BID dosing at 20 megs and a once-a-day dosing at 30 megs. And subsequently to capture the C-max, we had to collect blood pressures twice a day, C-max to be covered at both the BID doses. So, you know, we didn't see that it was maintaining a transient effect with a single dose data. So I'll just add that we can confirm what we've seen previously in a clinical setting and in the preclinical studies from that. I'll transition over now to the question you had about our confidence in CORA and the previous study that was done in depression and the recent J&J study where the results were posted in the EMA version of the clinicaltrials.gov. So, yeah, I think that those two studies that you mentioned, particularly the J&J study, are very... you know, kind of guiding for us and how we're thinking about taking the program forward. As you know, there was also a publication from J&J. It was a very well-done paper where they actually talked about how they picked their doses and the receptor occupancies and how they approached the translational piece of understanding receptor occupancy and actually publishing that data prior to the results that they'd seen in the depression study. Obviously, this is guidance for us. We won't necessarily follow exactly what they did, but we're really confident about how they picked their doses to go forward, and we were really kind of excited to see the data that they got in the depression study. So I think we're excited about it, but I think we will also have our own spin on how we proceed based on what we think we understand about the circuitry involved here and the patient needs.
spk04: Very good. Thank you.
spk03: Yep. Thank you, Paul. Thanks, JR and Ray. Okay, operator, we will take the next question.
spk06: Thank you. Your next question comes from Douglas Chow from HC Wainwright.
spk01: Hi. Good morning. Thanks for taking the questions. And maybe just sticking to the early stage pipeline, I was just hoping maybe you could talk a little bit more about the M4 program, and just given what we've seen with the miraclidine, what you're trying to accomplish with those molecules, and what does that potentially, you know, sort of open you up to accomplish clinically?
spk03: Yep. I'm going to ask JR to address that, but let me make a couple of comments, Doug. You know, from all of my years at least as a marketer and as a commercial guy, it's always been advantageous to have more than one entrant with the same mechanism, particularly if the mechanism is effective. So I think this gives us an opportunity, assuming we can generate positive clinical data with the M4 agonist, gives us the opportunity to cover an even greater number of potential indications in the neuroscience space. I think about this as a complement to what we're doing with Imraclidine, certainly in schizophrenia and potentially even the dementia-related psychosis, which is very much of interest to us. And if we can add a third and potentially a fourth indication by advancing an M4 agonist that might have the potential to work in other related disorders, that would be really attractive. JR can talk specifically about the mechanisms, but I just wanted to offer that higher level kind of strategic franchise vision that we have for advancing multiple entrants with multiple related mechanisms. JR, please add some details to that.
spk13: Sure. Thank you, Tony, and thanks for the question. I think that a couple of things are relevant here in kind of the background. So First of all, you know, with the ability to have a really exceptional group, both in our in vivo biology group as well as our med kin group, what we've done is made a wide range of different molecules that are in force selective and have various types of pharmacology. Also, you know, working very closely with the clinical group, what we've really carefully considered is the fact that when you look at potential for a new mechanism in treating psychosis and you look at the current treatments, that are used, you know, and you start to think about various indications you can pursue. I think that there's some indications that are very obvious for a PAM. So what we've seen is the kind of results that are outstanding for looking at psychosis in schizophrenia patients. We know previously that there was a very strong rationale for believing that psychosis associated with dementia in the Alzheimer's population is another one that we're very interested in. But, you know, if you think about clinical practice, what you actually see is that there are certain types of psychosis where even with the classic typical and atypicals, the clinical practice is to actually start at very high doses of the initial treatment to offset, for instance, a manic break in patients that have, you know, a certain severity of disease. And so when you think about the potential of this mechanism being one that hasn't required titration to date with imraculidine, and thinking about clinical practice and even how typicals and atypicals are used at higher doses in certain populations. And knowing what we've characterized preclinically in our models, we believe that there's a real opportunity to expand on indications with a full agonist. It would really, from the get-go, really hit as hard as possible the M4 receptor to provide clinical benefits. So we think that with a full agonist, what we can do is actually pursue some of those optional indications that weren't kind of the first layer indications that we're going after with imraculamine, but to help us really build a franchise around what we've learned on this mechanism, its tolerability, and when you have enforced selectivity, how important that is that you can start at a starting dose without titration, particularly in the most severe types of patients with psychosis. So We see a real opportunity here, and because we have that opportunity to make new molecules and characterize them and show how they differentiate frequently based on the research labs that we have here at Cambridge Crossing, we think we have a real opportunity to build upon a science that we've been leading in with the enforced selectivity and create new opportunities to actually build a franchise here, not just a single asset, as Tony was saying. Thank you.
spk03: Okay, great. Thanks, Doug. Yep, thanks, Doug, for the question. Operator, we'll take the next question.
spk06: Sure. Your next question comes from Madhu Kumar from Goldman Sachs.
spk12: Hi, this is Omari on Madhu. We have a couple questions. So can you provide any color on the target population you're looking to pursue for the regabat anxiety? And then second question is, on the epilepsy trial pushback. Just to clarify, there's nothing about trial design that's changing, so just like total patient numbers.
spk03: Yes, thanks. What we said in the prepared remarks for dirigibet anxiety is we are looking very closely at panic disorder. That seems to be one of the anxiety subtypes where there could be a potential role for dirigibet, so our teams are studying that very carefully. And no, there are no clinical trial changes for the epilepsy study. This is just a matter of getting all the patients into the trial, getting them processed, and analyzing the data. So no new update in trial design.
spk12: All right, thank you.
spk03: Okay, thank you. Operator, we'll take the next question.
spk06: Sure. Your next question comes from Matthew Harrison from Morgan Stanley.
spk08: Hi, thank you for taking our question. I'm Wen Zhang online for Matthew. So we have two questions. One is about amiraclidine. So is there any other non-clinical work still needs to be completed which could have any impact on phase 2 or even relative phase 3 preparation? The second question is about 871. So how robust are you expecting the signal could be So that could be just a trend you could envision or you expect a clearer picture of efficacy.
spk03: Okay, good. JR, would you address the amount of non-clinical work that's remaining on imraculidine? And, Ray, I'll get you to talk about 871.
spk13: Sure. Thank you, Tony, and thanks for the question. Yeah, so... There is additional work that is ongoing. So we've actually started studies. As you know, CARSO studies that are two years in duration are part of a required registration package. And those are typically the longest studies that have to be completed. So we actually pre-invested in getting those earlier to take them off of the critical path. Obviously, when we complete these next two studies that we talked about starting in a very short time period, one of the things we'll do is go back to the agency with our package, and one of the things that we will do is determine whether or not they feel that the preclinical package will support registration, and we can get any additional feedback at that time if they think that there's additional studies. But we do have a very experienced preclinical talks group And we've done a lot of pre-investment in this program to make sure that we can move as rapidly as possible. So, you know, thinking kind of what is standard fare has been addressed. There may always be additional questions that the agency might have, but we'll be able to answer those in time that we can get those studies done. to make sure they're not on critical paths. So I would say that we have it well in hand and the plan is in place, but there's always an opportunity for the agency to give feedback and we'll respond accordingly.
spk03: Thanks, JR. Thank you, JR. Ray, if you can, let's just talk, I think the second question has to do with efficacy outcomes from the 871 trial and the clinical tool we're using to measure efficacy there.
spk10: Right, right. Good morning. So, as you know, apathy is the leading neuropsychiatric symptom associated with dementia, and it's one of the strongest symptomatic predictors of disease progression. So, we see great utility in this D15 partial agonist that operates in areas of the brain that operate under lower dopaminergic tones. So, our goal really is, one, to to conduct, which we're doing now, a phase 2A trial that we're working very closely with the agency on to better understand the utility of this therapy in this population. And so we're conducting this 12-week trial with 75 patients looking at doses of 1 milligram and 3 milligrams, which achieve 50 and 80 percent receptor occupancies, and looking at a variety of actually endpoints and scales. And so there's no primary endpoint per se, but it's really truly an experimental trial to give us an understanding using a variety of scales that have been historically used to understand apathy, but also have been used in the ADMET trials with methylphenidate in the past. And so when these data will read out in the first half of 2023, We'll look at these data. We'll work with the agency to look at what kind of validation work will need to be done in order to then progress to the later stages of development. The good news is that, as I mentioned earlier, we received fast-track designation from the FDA, which allows us to work very closely with them in order to assess which endpoints would be viable and what the path forward would be since there are no approved therapies.
spk03: Okay, thank you.
spk10: Okay.
spk03: Very, very good. Okay, operator, we will take the next question.
spk06: Thank you. Your next question comes from Esther Hong from Barenburg.
spk05: Hi, thanks for taking my question. So on Darigabat, I was wondering if the FDA has provided any guidance regarding the study design. Have you spoken with them about the anxiety disorder? And then I was wondering when we could expect patient enrollment in the phase two trial for anxiety. Thanks.
spk03: Okay. Thank you for the question. Ray, can you talk about our planning work and how we're thinking about the next steps for drug about anxiety?
spk10: Right. So as I mentioned earlier, that our first likely pursuit will be in panic disorder, which is the second highest anxiety disorder after generalized anxiety disorder. obviously stemming from the phase one proof of principle trial. We do plan on meeting with the agencies since, of course, you know, they change their thought process over time. These trials historically have been fairly prescriptive, 10 to 12 weeks in duration, looking at panic attack frequency and so forth. But we just want to make sure that the agency's views are still aligned and So, yes, the process that we'll be following will be to look at the historical precedents, meet with the agency to ensure that the path forward is clear. And we'll, of course, disclose that when we internally have that clarity as well.
spk05: Great. Thank you.
spk03: Thanks, Ray. Operator, we'll take the next question.
spk06: Again, to ask a question, please press star 1 on your telephone keypad. There's no further question this time. I would like to turn the call over back to Mr. Tony Coles for closing remarks.
spk03: Very good. Thank you. Well, thank you guys for joining us. As you can see, there is, as always, a lot going on here at Cerebral. Really good progress that we're making in the later stage pipeline. A lot of very exciting data readouts that we're expecting in the months to come. And as you well see, both for CORA, as well as for the M4 agonist, some very interesting early-stage work that will complement what we are advancing rapidly towards the clinic and towards registration. So the team is very focused on creating value. We've got the capital to do that, and we really appreciate you guys listening today and look forward to our next update with you. Thanks for joining the call, and everyone enjoy a great day.
spk06: Thank you. And this concludes today's conference call. Thank you all for joining. You may now disconnect.
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