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spk06: Good morning. Welcome to the Servil Therapeutics Second Quarter 2021 Financial Results Conference Call. At this time, all participants are in a 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. Matthew Calistri, Vice President of Corporate Strategy and Investor Relations.
spk03: Thank you. Good morning, everyone. We appreciate you joining us for our second quarter 2021 results 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 Kathy Yee, our chief financial officer. Please refer to our press release from this morning detailing our Q2 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 our financial performance, future events, and industry and market conditions, as well as forward-looking statements including 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 it over to Dr. Tony Coles, Chairperson and CEO of Cerebellum, to provide an overview of our achievements and outlook.
spk11: Thanks, Matt, and good morning, everyone. Thank you for joining us. This quarter has been a pivotal one for Cerevel as we begin to deliver on our aspiration to become the premier neuroscience company. We were pleased to announce positive phase 1B top-line data for CBL231, our M4-selected PAM in schizophrenia, earlier in the quarter. The results were robust and very encouraging, and we believe this compound has the potential to truly transform schizophrenia therapy and improve quality the lives of millions of patients and their caregivers. In a moment, our Chief Medical Officer, Dr. Ray Sanchez, will review the trial results in more detail. Following our positive data readout for CVL231, we're proud to have completed a $350 million follow-on offering with approximately $328 million in net proceeds. With our continued focus on creative capital formation, including our Tevapidon risk sharing deal and redemption of our public warrants, we have now raised a total of more than $800 million as a public company. The proceeds of this most recent raise will be used to fund a comprehensive phase two program for CBL 231 and to advance several of our earlier stage programs. Together with proceeds from the redemption of our outstanding public warrants, we have strengthened our balance sheet and have the resources we need to advance our pipeline through multiple data readouts over the next three years. Specifically, we anticipate two data readouts for DERIGABAT in 2022, with data from our Phase I acute anxiety trial expected in the first half of the year and the readout from our Phase II focal epilepsy trial in the second half. Also in the second half of 2022, we expect a Phase II readout of CVL871 in dementia-related apathy, an asset for which we recently received fast-track designation from the FDA. And in 2023, we expect data from our Phase III program for tevapidon in early and late-stage Parkinson's. Finally, as I mentioned, we'll be advancing CVL231 into a comprehensive Phase II program, and we'll provide additional details on timing and design in the months ahead. So, as you can see, we have a rich late-stage pipeline that is poised to deliver a number of potential catalysts in 2022 and 2023, and we look forward to sharing those results with you as they become available. We're also showing great progress in our earlier-stage pipelines. During the second quarter, we submitted an IND for CBL354, our Kappa opioid antagonist, and we anticipate another IND submission for CBL047, our selective PDE4 inhibitor, in the fourth quarter of this year. As we enhance our discovery capabilities, we continue to leverage enabling technologies such as gene editing and artificial intelligence at our new Cambridge Crossing facility, to identify the most impactful drug targets for neuroscience diseases. I'd now like to ask Dr. Ray Sanchez, our Chief Medical Officer, to provide the latest updates on our clinical development efforts. Ray?
spk07: Thank you, Tony, and good morning to all of you. I'd like to start by spending a few minutes reviewing the recent Phase 1b data for CVL231, our M4-selective positive allosteric modulator, or PAM, in schizophrenia. CVL231 is designed as a once-daily oral medication that is highly selective for M4 over other muscarinic receptors. We believe this selective targeting enables CVL231 to drive antipsychotic effect while avoiding serious GI, extrapyramidal, akathisia, and metabolic side effects that are commonly observed with non-selective muscarinic agents and or approved antipsychotic agents. As a reminder, the Phase 1B trial was designed in two parts. Part A was designed to evaluate the safety and tolerability of multiple ascending doses up to 20 milligrams twice daily. The results of Part A informed the dose selection for Part B, which was a placebo-controlled double-blind pharmacodynamic assessment to detect trends in the antipsychotic potential of the compound over six weeks of treatment, in addition to evaluating the pharmacokinetic safety, and tolerability profiles of two doses. Both doses of CVL231 demonstrated clinically meaningful and statistically significant antipsychotic effects with no meaningful differences in gastrointestinal side effects, extrapyramidal symptoms, or weight gain compared with placebo. The antipsychotic effect observed after six weeks of treatment was truly remarkable given that Part B of the trial was only 59% powered to show a seven-point difference from placebo on the PANS total score. The 30 mg once daily group demonstrated an absolute improvement versus baseline of 19.5 points, while the 20 mg twice daily cohort showed an improvement of 17.9 points on the PANS total score. And relative to placebo, both treatment groups had statistically significant reductions of 12.7 and 11.1 points, respectively. These results are further supported by statistically significant and clinically meaningful improvements in the PANS negative subscale for both doses. The 30 mg once daily group resulted in a 3.1 point improvement over placebo with a p-value of 0.009, and the 20 mg twice daily group showed a 3.7 point improvement over placebo with a p-value of 0.002. We also observed clinically meaningful improvements on the PANS positive subscale for both doses with 30 milligram once daily group demonstrating a statistically significant reduction of 4.3 points versus placebo. While there were no clinically meaningful differences on the brief assessment of cognition schizophrenia symbol coding test, changes in the CGIS were consistent with other metrics with the 30 milligram Q-day dose showing a clinically meaningful and statistically significant improvement of 0.9 versus placebo at week 6 and 20 milligrams twice daily cohort, also achieving a clinically meaningful outcome. With respect to safety and tolerability, CVL231 was overall well tolerated in the trial. Treatment emergent adverse events were similar across all three arms and very low rates of gastrointestinal AEs were observed. Importantly, CVL231 was not associated with extrapyramidal side effects akathisia, or weight gain. Cardiovascular AEs were observed in only a few patients, and the details can be found on page 55 of today's accompanying presentation. These six subjects had asymptomatic cardiovascular changes reaching the pre-specified thresholds, including three in the placebo group and three in the active treatment groups. No events were clinically significant or associated with other reported AEs. As expected, we did see modest elevations in heart rate and blood pressure with CVL231 compared with placebo, which are described on page 56. These increases attenuated over the six-week course of treatment. At week six, the average systolic blood pressure increase relative to placebo was 1.2 and 0.9 millimeters of mercury, with the 30 milligram once-daily dose and the 20 milligram twice-daily dose, respectively, as measured two hours post-morning dose. There were no meaningful differences in diastolic blood pressure at week six. Heart rate increases at week six relative to placebo were 4.4 and 5.3 beats per minute for the 30 milligram once daily and 20 milligram twice daily doses, respectively, also as measured two hours post-morning dose. All cardiovascular effects were asymptomatic, and the increases were not clinically significant. We are highly encouraged by the safety and tolerability profile for CVL231. Given the very strong antipsychotic activity observed, we're eager to advance CVL231 into phase two development for the treatment of schizophrenia. We also plan to evaluate the potential of the M4 mechanism in other populations, such as dementia-related psychosis. This is an important step in the execution of our pipeline, and as Tony mentioned, we believe CVL231 has the potential to be a transformative treatment for psychosis. We're taking a deliberate and thoughtful approach regarding next steps in the development of CVL231, and we're exploring every avenue to bring this therapy to market as rapidly as possible. Our next expected data readout will be for DERIGABAT, our alpha-235 selective GABA-A receptor PAM in acute anxiety. Derigabat is currently being studied in a Phase I randomized, positive, and placebo-controlled proof-of-principle trial in Healthy Volunteers. This trial utilizes a well-established hypercapnia or carbon dioxide inhalation model to evaluate the potential of Derigabat in acute anxiety. Acute inhalation of 35% carbon dioxide can reliably trigger a transient acute emotional response and symptoms that resemble a naturally occurring panic attack in both panic disorder patients and healthy volunteers. This model has been shown to be sensitive to pharmacological treatments by a range of drugs used to treat anxiety disorder, including benzodiazepines and SSRIs, as well as emerging new treatments with novel mechanisms of action. Recently, it was used as a proof of principle study by Johnson and Johnson with the orexin-1 receptor antagonist to support advancement of the molecule into clinical development for major depression with anxious distress. Our ongoing hypercapnia trial is carefully designed to assess the anxiolytic activity of two doses of DERIGABAT administered over eight days. The trial is a two-period, two-sequence crossover design with three cohorts comparing DERIGABAT at high doses of 25 mg BID, a low dose of 7.5 milligrams VID, and a positive control treatment alprazolam extended release 1 milligram VID versus placebo. Importantly, only individuals who are found to be sensitive to the anxiogenic effects of CO2 inhalation at screening will be eligible for randomization. Participants in each cohort will be randomly assigned to one of two sequences and exposed to both an active arm and placebo. The primary endpoint for the trial is a change in the panic symptoms checklist score. This trial is being conducted at the Center for Human Drug Research, or CHDR, which is a single specialized site in the Netherlands and is therefore uniquely affected by national Dutch regulations related to the ongoing COVID-19 pandemic. In July, Dutch government authorities reimposed restrictions due to rising Delta variant cases in young unvaccinated adults, which have impacted the recruitment timelines for this trial. While the trial remains ongoing and actively recruiting, we now expect data in the first half of 2022 and will continue to closely monitor the evolving COVID-19 guidance from the Dutch authorities. The results from this acute anxiety trial will inform how we advance this compound in one or more anxiety-related indications. We're also dosing DERIGABAT in our Phase II Global Proof of Concept Trial in Focal Epilepsy, now known as the REALIZE trial, as well as its corresponding open-label extension trial. Data in focal epilepsy continues to be expected to root out in the second half of 2022. Meanwhile, our Phase III global TEMPO program for Tavapodon and Parkinson's disease is ongoing. We continue to dose in all three of the Phase III trials, TEMPO III in late-stage Parkinson's and TEMPO I and II in early-stage Parkinson's. In addition, we're also dosing both rollover and de novo patients in TEMPO IV, our 58-week open-label extension trial. We expect data from TEMPO III in the first half of 2023 and data from TEMPOS I and II in the second half of 2023. Now that I've reviewed the updates to our three lead clinical programs, Dr. John Renger, our Chief Science Officer, will provide updates on the rest of our pipeline. John?
spk05: Thank you, Ray. Good morning, everyone. Let's begin by updating everyone on a CBL871, which is our D1, D5 partial agonist in Phase II development for the treatment of dementia-related apathy. As you will recall, apathy is among the most common neuropsychiatric comorbidities associated with dementia and remains a devastating condition without a currently approved treatment option. Given the seriousness of the condition and the significant unmet patient need, the FDA has expressed strong interest in the development of a treatment for apathy in dementia patients. In June of this year, we announced that we were granted fast-track designation for CBL871 for the treatment of dementia-related apathy. This designation by the agency has the potential to enable early and more frequent interactions with the FDA, as well as the potential option for rolling and priority review of our NDA. This is a particularly exciting opportunity for us to work more closely with the agency as we have begun screening in our exploratory phase 2A trial for dementia-related apathy. We anticipate clinical trials to be available in this novel indication in the second half of next year, 2022. Based on the results of this trial, we are looking forward to interacting closely with the FDA in determining the best clinical development strategy for bringing forward a treatment in this novel but impactful indication. As announced today, we'll be hosting an R&D event on October 7th to discuss the scientific background of our CVL871 program in greater detail, along with updates on CVL231 and schizophrenia and other programs. I hope you will all be able to join us. Now, moving beyond 871, we're also advancing CBL936. This molecule is our D3-preferring dopamine receptor antagonist for the treatment of opioid use disorder. As we can all acknowledge, this is an incredibly challenging area of unmet patient need, and Cerebell is excited to be progressing on potential treatment in this important area where there's been a concerning expansion of overdose and overdose-related deaths due to opioid misuse. We plan to initiate a non-clinical safety pharmacology study in support of continuing a phase one single and multiple sending dose trial with CBL936 to evaluate this compound's safety and tolerability profile. As we guided previously in the second quarter of this year, we submitted an IND for CBL354, our selective cap opioid receptor antagonist, also known as a CORA lead molecule, which has the potential to be a novel mechanism of action and a much needed differentiated treatment option in potentially addressing major depressive disorder, or MDD. We intend to initiate our Phase I First-in-Human Single and Multiple Ascending Dose Trial in Healthy Volunteers for CVL354 in the third quarter of this year. Furthermore, in the fourth quarter of this year, we continue to plan to submit an IND for CVL047. This compound is a phosphoesterase subtype-selected PDE4B inhibitor. We're particularly excited about this clinically validated anti-inflammatory mechanism of action where clinical development of brain penetrant molecules has been hindered by dose-limiting side effects, which we believe are related to non-selective action of prior compounds that acted equally across all PDE4 subtypes. By selectively sparing inhibition of the PDE4D subtype, we believe CVL47 has the potential to address symptoms of both MDD and schizophrenia. At Ceravel, we are in the midst of building a robust world-class drug discovery engine. In our newly opened research labs at Cambridge Crossing, we are leveraging our differentiated understanding of neurocircuitry and world-class chemistry to develop and explore the potential of highly sophisticated small molecules. Currently, we are positioned to be a scientific leader in identifying and progressing selective muscarinic compounds, and as such, we are actively working through a range of additionally highly potent and enforced selective agonists and modulators to potentially advance into the clinical setting alongside CVL231 to expand on the clinical utility that we have demonstrated with that lead molecule. Complementing our medicinal chemistry molecule optimization approaches, our cutting-edge combination of neuroscience research enabling technologies including comp chemistry, gene modification approaches, AI-based compound screening, and DNA-encoded library screening activities are all designed to enable us to rapidly and efficiently validate some of the most promising new drug targets and lead us to identify candidates to address the underlying processes in debilitating neuroscience disease. We believe the discovery engine we are creating will allow us to maintain a regenerative pipeline of novel therapeutics that will continue to fuel Cerevel's goal of becoming the premier neuroscience company. We're looking forward to updating you on the ongoing progress of our extensive early and late stage pipeline in the months to come. However, I'd like to now turn it over to Kathy Yee, our CFO, to review our financial performance for this quarter. Kathy?
spk01: Thank you, John. Good morning, everyone, and thank you for joining today's call. We issued a press release earlier today that included a financial update, which I will briefly summarize. Our total operating expenses were $50.5 million for the second quarter of 2021, which includes R&D expense of $37.3 million and G&A expense of $13.2 million. Relative to the second quarter last year, R&D expense increased by $15.1 million, and the second quarter results included $2.1 million of equity-based compensation. The increase was primarily driven by the advancement of our late stage and early stage programs, as well as increased infrastructure costs to support the progress of our pipeline. We expect R&D expenses to continue to increase as we advance our 11 clinical and preclinical assets. General and administrative expenses for the second quarter of this year were $13.2 million relative to $13.0 million for the same period last year. G&A for the second quarter included equity-based compensation of $3.1 million. To date, we have maintained a slower growth in G&A expenses relative to R&D, but we do expect a modest G&A increase over the coming quarters as we support the expansion of our programs and general infrastructure of the company. Moving to our cash position, as of June 30th, our cash and cash equivalents were $327.1 million. This cash position does not include the approximately $328 million of net proceeds from our recent follow-on offering in July. In addition, we recently announced the redemption of our outstanding public warrants, which could provide up to approximately $57 million of additional capital, assuming full exercise. With our current balance sheet, we're well-positioned to advance our lead programs, including mid- to late-stage clinical trials in Parkinson's, epilepsy, dementia-related apathy, and schizophrenia, as well as pursue other earlier stage programs such as Derrick Abad in Anxiety, CORA, and PD4. Overall, we have multiple opportunities for value creation milestones for the next few years, and CeraVal is in a very strong financial position to fund these programs to their next inflection points. Finally, we expect our current balance sheet to fund our operations into 2024. I have to now hand the call back over to Tony to conclude.
spk11: Thanks, Kathy. As you can see, we've made tremendous progress here at Cerevo in just a few short months. As you've heard this morning, we're advancing our extensive pipeline in order to bring novel therapies to patients facing some of the most challenging neuroscience diseases. We believe that neuroscience is the last great frontier in medicine, and we're at the point of that frontier. Over the next three years, we anticipate important data readouts across a range of vexing neuroscience diseases, including anxiety, focal epilepsy, dementia-related apathy, and Parkinson's. And we will move successful programs ahead with speed and determination, as we're going to do with our phase two program for CVL231 in schizophrenia. And through a robust early discovery program, we expect to bring forward additional novel compounds in other disease areas as we continue on our mission to unravel the mysteries of the brain. Thank you for being on this journey with us, and I hope you'll be able to join us for our October 7th R&D event, where we will focus on CVL871 in dementia-related apathy, along with updates on CVL231 in schizophrenia and other programs. In addition, as I always do, I want to thank our employees who are dedicated to our mission to improve the lives of millions of patients suffering from neuroscience diseases. And of course, I want to give my heartfelt appreciation to the participants and investigators in our clinical trials for their continued courageous contribution to the development of our therapies. We could not do this without you. With that operator, we can now open the floor for questions.
spk06: At this time, if you would like to ask a question, press star then the number one on your telephone keypad. Again, it's star one on your telephone keypad. We'll pause for just a moment to compile the Q&A roster. Your first question comes from the line of Paul Maris from SIFO. Your line is open. Please ask your question.
spk02: Hey, thanks so much for taking my questions. I appreciate it. Good morning. Thank you. Good morning, Tony. Thank you. On the CVL231 development path, I was wondering if you could expound a little bit upon the press release talking about a comprehensive Phase II development program. Since the 1B results were pretty robust, I guess my question would really be why not go right into Phase III off that? And then on the safety data that you shared, thank you for giving more color there. I just wanted to clarify if the heart rate data is too fine and whether or not that even matters in your view to kind of interpretation. Thanks so much.
spk11: Okay, sure. So I think, Paul, I'm going to ask Ray to address both of those questions. John Ringo may have some additional comments. But, Ray, why don't you start, and we'll go from there.
spk07: Sure. Sure. Hi, Paul. Good morning. Two good questions. So the first one, in terms of our comprehensive approach, as you can imagine, we're quite excited about the data that's been generated to date, and we're looking at all possibilities of trying to accelerate and getting this medication to the patients as quickly as possible. We're in the process of developing that program now and plan to initiate it sometime next year. Our comprehensive approach not only addresses the clinical aspects, but also the non-clinical aspects of the full program that we are also looking at accelerating so that we can get the medications to patients as soon as possible. So in the months to come, we will provide more clarity and more detail on what that path looks like. But for now, we are working on understanding the data and putting together that program along with the rest of the team. And, Paul, can you please clarify your second question again, please?
spk02: Yeah, thank you, Ray. I appreciate it. Yeah, look, and again, thanks for the additional color on heart rate and blood pressure. It's very helpful. I just was wondering if the heart rate data are standing or supine, and if that at all matters to kind of the interpretation of it. I think we've seen it presented both ways, so we were more curious.
spk07: Yeah, no, it's supine. And it was done one time in the morning and one time in the evening. But as you can see, we're quite encouraged by what we've observed really over the long term is really what's clinically meaningful. And the changes that we've seen over the long term, meaning over the six weeks, as you can see, are quite encouraging. So we'll continue, of course, to monitor that as we move forward in development.
spk02: Yep, makes sense. Thanks, Rick.
spk11: Thank you, Paul. Thanks, Paul. Operator, we'll take the next question.
spk06: Your next question comes from the line of Michael Yee from Jefferies. Your line is open. Please ask your question.
spk09: Hi, good morning. Great to hear your voice, Tony.
spk08: Hey, good morning.
spk09: We had a couple nuanced questions on 231, and then I had a broader question on the development of your pipeline technology. On 231, can you just talk about the, I guess, disclosure and timing of the PET data? How important is that data into your development plan? And would you consider both doses being taken forward? How do you think about that? Because you look at the 20 mg and the 30 mg, they're quite close. On one hand, one's more convenient and maybe a little more efficacious, but maybe there's some slightly different cardiovascular data.
spk10: So maybe just talk about that a bit in terms of your decisions for doses going forward. And then on the other question, it's around the update around the anxiety data timing and COVID. Can you speak to whether other studies are enrolling in areas that need to be watched? How do you think about that? And how are you just managing COVID and the geographies that you're involved in? Thank you.
spk11: Yeah, okay. I'm going to ask J.R. to take the questions regarding the PET receptor occupancy data and the dosing as well, and then Ray will come back on the anxiety study and the update on COVID impact. So, J.R., if you'd start with the receptor occupancy data, timing, and importance, and then the dosing.
spk05: Sure. Thank you, Tony, and thank you, Michael, for the question. Yeah, so the PET receptor occupancy studies are ongoing. They are important for us in comparing the efficacy data that we've achieved and reported upon and relating that to the PK exposures and what we understand between the BID and the once-a-day dosing. And so what we have to pull together is the receptor occupancy data, the PK data, the efficacy data, and all of our safety and tolerability data and really help us firm up what the decision will be around the doses going forward. And so that data is rolling out. We will be increasing our understanding of where we're at with that through the next couple of months as we put together the plans for our next set of studies. But we'll have all of the information that we need to make an informed decision about the doses to take forward into late development by the end of this year. Does that help?
spk09: Yeah. You think the R&D day is a reasonable timing?
spk11: So we have a number of studies. I think, you know, we may indeed have some of the RO data by that time, Mike, but I think what we want to do is study it as we always do, comprehensively. And if we've got clear direction and a compelling set of answers, we'll be able to provide that. But, you know, look, this is one of the top priorities. to get both the dosing right and then the design for the next stage of development for 231. So as quickly as we complete our thinking and finalize our plans, we'll let you know. But we do expect to provide some updates at the R&D Day event later this year. So stand by and stay tuned, but it will all depend upon when those studies are completed.
spk10: Perfect. And then on COVID and other impacts. Thank you.
spk11: Yeah, sure. Ray, if you could take that one, that would be great.
spk07: Yes. Michael, good morning. How are you? So, yes, we are monitoring the COVID situation quite closely. As you know, because the anxiety trial, as I mentioned, is being conducted at this one site, the Center for Human Drug Research in the Netherlands, that that's one site that has the capabilities to do that type of trial, that because of the Dutch regulations, that that trial was impacted accordingly. To date, we've not seen any other impacts to any of our other programs. As you know from other calls, that we do have contingency plans that are built into the protocols to address some of those challenges if those were to occur. We're monitoring it closely, but no changes to our enrollment, fortunately, at this juncture beyond the anxiety trial. Got it. Thank you. Okay.
spk11: Thanks, Mike. Okay, operator, we'll take the next question.
spk06: Your next question comes from the line of Matthew Harrison from Morgan Stanley. Your line is open. Please ask your question.
spk08: Good morning, everyone. This is for Matthew. One question about dementia-related psychosis. Can you talk a little bit about your view of the landscape here, and how are you thinking about the clinical development in this population? Thank you.
spk11: Okay. Ray, if you would take that question, that would be great. Obviously, you know, we're very excited about CBL231, not just in schizophrenia, but possible other indications. dementia-related psychosis is one of those potential opportunities for us. But, Ray, if you could expand on the clinical relevance and significance of that syndrome, I'd appreciate it.
spk07: Sure, Tony. Good morning, Matt, and thank you for that question. I mean, as you know, there is quite a need for treating dementia-related psychosis. Over a decade ago, a lot of the antipsychotics are currently available, attempted trials in that population, and FDA did a meta-analysis that resulted in a black box warning for cardiovascular CV stroke effects and death, and so there is a great need. There's a drug called primavanserin that you may be familiar with, which is used for psychosis related to Parkinson's disease, but there's really nothing really available beyond the current antipsychotics to treat patients and, of course, with those associated risks. So the need remains to have therapies that can effectively treat psychosis in the population. We are going to be pursuing that population, but we will be going to the FDA with a pre-IND meeting to get clarity in terms of the what the regulators believe is the path forward to seeking an indication in that population. So stay tuned for that.
spk11: Thank you. Thank you for the question. Operator, we'll take the next question.
spk06: Your next question comes from the line of Greg Zwanowicz from Goldman Sachs. Your line is open. Please ask your question.
spk04: Hey, good morning. It's Greg Sivanovic. Thanks so much for taking my questions. Thanks for the update. Can I just maybe focus on the DeRigabat Phase 1 results that you're expecting now in the first half of 22? And as I'm looking at Slide 27 and the trial design, realizing that it's a small study, maybe could you walk us through what the expectations should be? And I'm just trying to get a sense of realizing that it's just a phase one study, but as it relates to, I guess, the primary endpoint being the panic symptom list, could you just walk us through kind of how we should think about the data when it comes out, what would look good, and also in terms of the trial, even though it's well established, as you alluded to in your prepared comments, what are the, perhaps, the features around the trial that we should watch out for in case there are certain pressure points within the study or trial design that might impact the outcome of the data.
spk11: Okay. Ray, would you respond to that one? In your preamble, just talk a little bit about the currently available therapies for anxiety and where we think doing the back could play a role if it shows.
spk07: Sure. Thank you, Tony. Good morning. Good morning. So, you know, available therapies now to treat anxiety are really somewhat limited in terms of opportunity, but also in terms of efficacy. The SSRIs and 1-SNRI are approved for generalized anxiety disorder as well as panic disorder. Not all of them, but some of them are. And, of course, the benzodiazepines, because of their issue with tolerance and addiction and so forth and all the side effects that are really driven by Alpha-1s, really limit their chronic use. So our hope is that we have this novel compound that has selectivities at alpha-2, 3, 5, but importantly at alpha-2, 3, that what we believe drives anxiolysis. And you can still have patients who are sedated or somnolent, but who are still anxious. And we see that clinically frequently. So our hope is that we have this compound that can actually help become an effective therapy for treating anxiolytic events, not just acutely but also chronically and potentially even preventively over the course of our indication-seeking development program. So our first step is really to understand if there's a signal in terms of dirigibat's potential to actually be an effective anxiolytic therapy. And if you look at this design that is a two-period, two-sequence crossover design looking at the two doses of DERIG, about 25 BID, which is about 80% receptor occupancies. And we've learned preclinically that you need higher receptor occupancies to achieve anxiolysis. We also are reviewing a lower dose of 15 milligrams or 7.5 milligrams BID to understand a minimum effective dose. That's about 50% to 60% receptor occupancy. But also importantly, the alprazolam extended release one milligram BAD was included as an active comparator because that's what was used in the J&J study with the erection one inhibitor to allow them to make a decision to prosecute their compound based on seeing differences from placebo in both of those doses in that compound. So what we've done is we've are working with a group of advisors who understand this model well, understand the anxiety landscape well. And while we don't have any predetermined thresholds or assumptions in terms of what the data should read like, in other words, it's not statistically powered. It's designed to give us an understanding of the extent of a signal of derigabat in this healthy volunteer population that we've induced panic symptoms, the experts, as well as having this active character juxtaposed with not only the J&J data, but also the data that's been generated by other compounds, it'll allow us to make a collective decision in terms of the next step forward and the signal that we'll detect with derigabat in this But there's no specific predetermined specification of what that data should look like.
spk11: Okay. Okay. Thank you. Great. Very good. Thank you, Ray, for that. Operator, we will take the next question.
spk06: There are no further questions at this time. You may continue.
spk11: Okay. Okay. Well, I think this brings us to the end of the call. Thank you guys for joining us this morning. It really was a terrific quarter, and even in the days ensuing with the capital raise and some of the other things that we've been able to achieve. So we are focused on advancing the pipeline, very focused on CDL231 as a priority, but importantly on the rest of the pipeline where we're making really significant progress. We'll look forward to speaking with everyone on October 7th for our R&D update, and we'll bring you additional information on dementia-related apathy and why that's so important and what we plan to do with CBL 871. So thank you guys for joining this morning. Enjoy the rest of the summer. Happy Labor Day, and we will see you in the fall. Thank you.
spk06: This concludes today's conference call. Thank you for participating. You may now disconnect.
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