Q1 2022 Cerevel Therapeutics Holdings Inc Earnings Call

Yeah.

Good morning, and welcome to the <unk> Therapeutics first quarter 2022 financial results conference call.

Operator: Good morning, and welcome to the Cerevel Therapeutics First Quarter 2022 Financial Results Conference Call. At this time, all participants are in a listen-only mode.

Operator: 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.

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. Matt <unk>, Vice President of corporate strategy and Investor Relations. Please go ahead.

Thank you good morning, everyone. We appreciate you joining us for first quarter 2022 earnings call.

Matt Calistri: 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 Cissé, our president, will join us for Q&A.

On today's call you'll be hearing from Dr. Tony Coles, our chairperson and Chief Executive Officer, Dr raised Sanchez, our Chief Medical Officer.

Dr. John <unk>, our Chief Scientific Officer, and Mark <unk>, our interim Chief Financial Officer.

<unk>, our president will join us for Q&A.

Matt Calistri: 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.

During our call today, please refer to our press release from this morning, Dean Karen 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 form and timing of our product development activities and clinical trials.

Matt Calistri: 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 outreach. Thanks, Matt.

We strongly encourage you to review the information that we filed with the SEC regarding specific risks and uncertainties.

I will now hand, the call over to Dr. Tony Coles Chairperson and CEO , Sarah Bell to provide an overview of our cheapest and outlook.

Thanks, Matt and good morning, everyone. Thank you for joining us on our first quarter 2020 to business results call. Several 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 <unk>.

Tony Coles: 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 affect not only 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.

People living with some of the most vexing and difficult to treat neuroscience diseases. These diseases not only affect patients 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.

Begin with a deep understanding of neuro circuitry or how the brain is wired. We then focus on receptor 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.

Tony Coles: We then focus on receptor 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 Darigabat, 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 emraclidine, our M4-selective PAM, and we're forging ahead.

When I spoke to you last quarter, we had just announced positive anxiety data for <unk>, our selective alpha <unk>, Gaba positive allosteric modulator or Pam.

And less than a year ago, we announced positive phase <unk> data in schizophrenia, <unk>, our imports selected Pam.

And we're forging ahead.

Tony Coles: We're on track to initiate two parallel, adequately powered phase 2 trials of emraclidine 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.

On track to initiate two parallel adequately powered phase II trials of <unk> in schizophrenia by mid year 2022 and.

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 and neuroscience.

Looking specifically at our pipeline, we anticipate five data readouts in 2023.

Tony Coles: In the first half of next year, we expect to have data from our Trafadon Phase III trial in late-stage Parkinson's. We also expect data from our ongoing CBL 871 Phase 2a trial in dementia-related apathy. In mid-year 2023, we expect data from our Dorigabat Phase 2 Proof of Concept trial in focal epilepsy, as we announced this morning.

In the first half of next year, we expect to have data from our <unk> phase III trial in late stage Parkinson's.

We also expect data from our ongoing CBL 87, one phase two <unk> trial in dementia related apathy.

In mid year 2023, we expect data from our <unk> phase II proof of concept trial in focal epilepsy, as we announced this morning and in the second half of 2023, we expect data from our <unk>.

Tony Coles: And in the second half of 2023, we expect data from our two Tavapidon Phase 3 trials in early-stage Parkinson's disease, 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 recently announced Phase 2 trials of amraclidine, with results in schizophrenia in the first half of 2024. Cerevel is also in a strong financial position, and we're well capitalized to support operations into 2024.

Rapid on phase III 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 III trials that were more equity.

With data results in schizophrenia in the first half of 2024.

Several was also in a strong financial position and we're well capitalized to support operations into 2024.

Tony Coles: 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 in funding in April from the second annual payment of the Davapidon risk-sharing arrangement we entered into in 2021.

As of the close of the first quarter, we had $551 million in cash cash equivalents in marketable securities to which we added 37 and a half million dollars funding in April from the second annual payment of the rapid on risk sharing arrangement, we entered into in 2021.

Several of US embarking upon an exciting period of growth and I'm really looking forward to updating you on our many milestones in the future.

Tony Coles: Cerevel is embarking upon an exciting period of growth, and I'm really looking forward to updating you on our mini milestone. I'll now turn the call over to Dr. Ray Sanchez, our Chief Medical Officer, to provide some additional detail about our lead programs and anticipated readout timings.

Now I'll turn the call over to Dr. Rey Sanchez, our chief Medical officer to provide some additional detail about our lead programs and anticipated readout timings right.

Thank you Tony and good morning to all of you as.

Ray Sanchez: 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 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.

As Tony has outlined terrible 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 are.

A disease that has rippling effects in all areas of the patients personal professional and family life.

Ray Sanchez: The need for better treatment options is what drives us each day. So, let's first turn to emraclidine, 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 anti-psychotic effects with no meaningful differences in gastrointestinal side effects, extrapyramide symptoms, or weight gain compared with placebo.

<unk> for better treatment options is what drives us each day.

Let's first turn to <unk>, our M for positive allosteric modulator.

Less than a year ago, we announced positive phase <unk> data in schizophrenia, and the results were truly impressive.

Both doses of <unk> demonstrated clinically meaningful and statistically significant antipsychotic effects with no meaningful differences in gastrointestinal side effects extra pyramidal symptoms or weight gain compared with placebo.

Ray Sanchez: 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 remraclidine while minimizing the number of treatment arms with the hope of reducing the variability observed in clinical trials as well as placebo response.

We're very encouraged by those.

Robust results and we are now moving rapidly into our next phase of development.

Importantly, as you can see on slide 15, we are on track to initiate two parallel adequately powered phase II trials by mid year.

Running these two trials in parallel enables us to fully explore the therapeutic dose range of <unk>, 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.

Ray Sanchez: 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 Darigabat, as Tony mentioned, we have updated the timeline for REALIZE, our Phase 2 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.

And while we expect the FDA will evaluate in Registrational package.

Beyond schizophrenia, we also plan to evaluate this mechanism in other indications in populations, including psychosis associated with dementia.

Turning now to rig about as Tony mentioned, we have updated the timeline for realize our phase II proof of concept trial in focal epilepsy, which we now expect will readout in mid year 2023, rather than the second half of this year.

Ray Sanchez: 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. Unfortunately, one of these countries was Ukraine.

This outcome is based on the use of exclude concomitant medications in the target population as well as COVID-19 disruptions at clinical trial sites.

Consequently in.

In order to augment slower than anticipated enrollment we've added three additional countries to participate in the trial, but unfortunately, one of these countries was Ukraine.

Ray Sanchez: 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 start in the two remaining new countries, Poland and Serbia, which enables us to anticipate data in mid-year 2020. Last quarter, we were able to share our very encouraging positive top-line data from our Dirigibat Phase 1 Healthy Volunteer Trial in acute anxiety.

And 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 into two remaining new countries, Poland in 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 drug about phase one healthy volunteer trial in acute anxiety.

Ray Sanchez: These results provide strong evidence of Darigabat'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 one data, we're exploring various indication opportunities for Darigabat, with the first likely to be panic disorder. Turning next to Tavapidon, our D1, D5 partial agonist that we're developing for Parkinson's disease, which is both a monotherapy and adjunctive treatment to levodopa for symptomatic motor control.

These results provide strong evidence of drug about potential burst as a differentiated daily maintenance treatment for anxiety related disorders, while minimizing tolerability concerns in contrast to benzodiazepines.

On the robustness of our phase one data, we're exploring various indication opportunities for <unk> with the first likely to be panic disorder.

Turning next to vapid on R. D. One Steve five partial agonist weird that we're developing for Parkinson's disease as both a monotherapy and adjunctive treatment to levodopa for symptomatic motor control.

Ray Sanchez: 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 time. 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 Tempos I and II trials in early-stage Parkinson's to read out in the second half of 2022. Turning to CFEL 871, our second D1, D5 partial agonist, which we are currently evaluating in a phase two exploratory trial in dementia-related apathy. We expect data in the first half of 2020.

We continue to dose in all of our phase III trials known collectively as the tempo trials and all remain on track with our expected timelines.

We expect data from temple three the adjunctive trial in late stage Parkinson's to readout in the first half of 2023 and data from temple's one and two trials in early stage parkinsons to readout in the second half of 2023.

Turning to <unk> 871, our second D. One D. Five partial agonist, which we are currently evaluating in a phase two 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 CBL 871 in this indication, which enables early and more frequent interaction with the FDA as well as the potential for rolling NDA submission and priority review.

John Renger: In June of last year, we received FASTRAC 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 indication 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.

We're looking forward to interacting closely with the agency and 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 <unk>, our Chief Scientific officer will speak about our early stage portfolio and our presentations at medical conferences John .

Thank you Ray good morning, everyone I'd like to first provide an overview of our earlier stage clinical and preclinical programs.

John Renger: Thank you, Ray. Good morning, everyone. First, we have an active program to identify an M4-selective full agonist molecule as part of our goal of creating an industry-leading M4 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.

First we have an active program to identify and enforce selective full agonist molecule as part of our goal of creating an industry leading <unk> franchise.

We believe this novel asset will provide for additional therapeutic indication optionality as we can sensitive considered the clinical utility of this mechanism of action and its demonstrated potential in treating psychosis.

John Renger: 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 study. 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.

I would like to highlight our Kappa opioid receptor antagonist program, which continues to progress and 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 the PD four b antagonist program clinically proven mechanism of action that has been has seen previous drug approvals in both inflammatory diseases in dermatology and respiratory indications. This.

John Renger: 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 applications. 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 PD-4B 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 limited their clinical utility.

This mechanism of action has also demonstrated early clinical activity in the treatment of depressive symptoms in prior proof of concept studies.

Our program with and serve all its directed at creating a CNS active PD or be selective inhibitor for potential use in major depressive disorder, and CNS inflammatory neurodegenerative therapeutic indications, while aiming to avoid the tolerability limitations of Gi distress there were associated with prior CNS active nonselective.

<unk> four inhibitors and limit there.

Clinical utility.

John Renger: Finally, we made a decision to discontinue further investment in CVL-936, our dopamine D3-preferring, D2-D3 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.

Finally, we made a decision to discontinue further investment in CBL $93, six or dopamine D. Three preferring <unk> receptor subtype selective <unk> agonist 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 out our robust drug discovery engine and our research labs in Cambridge crossing with additional ongoing discovery stage and pre IND programs. We're on.

Leveraging our differentiated understanding of disease base, neuro circuitry and world class Chemistries to develop and explore the therapeutic potential small molecules to address major unmet patient needs.

John Renger: 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 durogavet and tavapidon programs. Subsequently, we also presented our maracodine data at the Schizophrenia International Research Society Congress.

I 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 wanted 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 <unk>.

Our teams presented at the American Academy of Neurology, highlighting our progress on our journey into rapid on programs. Subsequently, we also presented <unk> data at the schizophrenia International Research Society Congress.

Mark Bodenrader: 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 to 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?

These presentations underscore our belief that we are well positioned in the scientific and clinical development leader across several neuroscience diseases associated with significant unmet patient need.

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 would now like to turn it over to serve as interim Chief Financial Officer, Mark Bowden writer to review our financial performance for the first quarter Mark.

Thank you John and good morning, everyone. I am pleased to provide an overview of several strong financial position and our first quarter 2022 financial results.

Mark Bodenrader: Thank you, John, and good morning, everyone. I'm pleased to provide an overview of Cerevel's strong financial position in our first quarter of 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.

Please refer to this mornings 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 in G&A expense of $18 million.

Mark Bodenrader: 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 Cerevel's clinical programs for Tavapidon, Imraclidine, and Dorigabat, investment in our preclinical and discovery efforts, and an increase in personnel and other infrastructure costs as we expand capabilities to advance our pipeline.

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 was primarily due to the continued advancement of service clinical programs for <unk> <unk> enduring about investment in our preclinical and discovery efforts and an increase in personnel and other infrastructure costs as we explore.

<unk> capabilities to advance our pipeline.

We expect our quarterly R&D expense to continue to increase as we plan to initiate the two phase III clinical trials for <unk> in schizophrenia by mid year.

Mark Bodenrader: We expect our quarterly R&D expense to continue to increase as we plan to initiate the two phase two clinical trials for amraclidine in schizophrenia by mid-year. G&A expense for the first quarter increased by approximately $3.5 million over last year.

G&A expense for the first quarter increased by approximately three and a half million dollars over last year.

Mark Bodenrader: 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 31, 2022, our cash and cash equivalents, and marketable securities totaled $551 million. This cash position does not include the additional $37.5 million received in April under our Tevapanon risk-sharing arrangement that Tony mentioned earlier. In closing, we remain well-

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 31, 2022, our cash and cash equivalents in marketable securities totaled $551 million. This cash position does not include the additional 37 and a half million received in April under active app and on risk sharing arrangement that Tony mentioned earlier.

In closing, we remain well capitalized we expect our cash resources to fund our current operations into 'twenty 'twenty four we look forward to multiple value, creating data readouts over the next couple of years and we continue to think creatively and opportunistically about further strengthening our balance sheet to support our extensive pipeline.

Mark Bodenrader: 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 of 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.

While pursuing earlier stage clinical programs in drug discovery initiatives.

With that I'll hand, the call back to Tony for closing remarks.

Thanks, Mark as you can see we continued to advance our broad and diverse pipeline and building what we hope will become the Premier Neuroscience company serve outlets 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 <unk>.

Tony Coles: Thanks, Mark. As you can see, we continue to advance our broad and diverse pipeline and build 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 made this possible.

<unk>, 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.

Tony Coles: And in particular, let me extend my deepest gratitude and appreciation to the clinical trial participants and the investigators who contributed to the development of these important therapies. With that operator, we can now open the call for questions. 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.

The call for questions.

Thank you.

As a reminder to ask a question. Please press star one on your telephone keypad to enjoy a question press the pound key.

Operator: Please stand by while we compile the Kuhn-Ross Rankings. Your first question comes from Corey Catimo from JPMorgan Airlines. Good morning guys. Thank you for taking the questions. I've got two for you, one on Drigabat and one on Emraquadine. So for Drigabat 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.

Please standby ela level, we compile the Q&A roster.

Your first question comes from Cory <unk> from JP Morgan Your line is open.

Hey, good morning, guys. Thank you for taking the questions I've got two for you want them to rig about and one on <unk>. So for <unk> and the epilepsy trial can you comment just on how much you're hoping to enroll how many patients hoping to enroll in Poland in Serbia and your confidence in generating high quality data in those regions.

Operator: And then for Emraquadine, you know, with the pending phase two or 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 in duration you may need in the event the efficacy studies do enable a filing of that, which seems to clearly be the future rate limiting step? Thanks a

And then for <unk>, you know with the with the pending phase two or 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 in duration you may need in the event the efficacy.

Studies do enable the filing is that seems to clearly be the future great limiting step thanks a lot.

Okay. Good morning, and thanks for the questions.

Ray Sanchez: Okay, good morning, Corey, and thanks for the question. Ray, I think I'll actually ask you to get us started here with Corey's first question about Dorigobad, the enrollment numbers, and the quality of data from Poland and Serbia. Terrific. Good morning, Ray.

I think I'll ask actually ask you to get us started here.

With Korea's first question about <unk>, the enrollment numbers and the quality of data from Poland in Serbia.

Terrific. Good morning converted Corey and thanks for that question. So we are looking at.

Ray Sanchez: 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, 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.

We've activated six sites in Poland in five sites in Serbia, where.

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.

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 enrol, we're still working with the sites on that and they'll start in the next few weeks enrolling patients into the trial.

Ray Sanchez: 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 enrolling patients into the trial in the next few weeks. And Ray, the second question was about emraclidin and the 10-week duration. So can we just, let's just, maybe we just review the general design for the two-phase, two studies for emraclidin? I think Corey's question was, would we have adequate safety data that would support patients... Yep.

And then the second question was about <unk>.

<unk>.

The 10 weeks duration. So can we just let's just make we just review the general design for the two phase two studies for <unk>, but I think <unk> question was would we have adequate safety data that would support.

Package.

Ray Sanchez: So, Corey, as you know, we are conducting, starting very soon, two six-week pivotal trials in patients with acute schizophrenia, but we also need, as you're outlining correctly, long-term safety data, and per ICH guidelines, 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 would be needed in addition to the two positive phase two trials that really characterize the dose range for registration. Okay, very helpful.

So Cory as you know that we are conducting a starting very soon.

Two six week pivotal trials in patients with acute schizophrenia.

But we also need for registration as you're outlining correctly, a long term safety data and per ICA ICH guideline, we would need a minimum of 306 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 paused.

<unk> phase II trials that really characterize the dose range for registration.

Okay.

Okay very helpful. Thank you.

Ray Sanchez: Thank you. Thank you. Thank you very much.

Thank you.

Operator, we will take the next question.

Thank you. Your next question comes from Michael <unk> from Jefferies. Your line is open.

Operator: Operator, we will take the next question. Thank you. Your next question comes from Michael Yee from Jefferies. Hey, good morning.

Hey, good morning, Thank you Tony.

Operator: Thank you, Tony, for the update, and thanks for the question. With respect to emaraclidine, 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 your expectations for what you would expect that study to show, the relevance of that study, and even such details as whether there is a placebo arm, and is that important to have a placebo arm, or it doesn't really matter?

And thanks for the question.

Operator: Maybe I could just talk a little bit about that study. Thank you. Okay, I'm going to ask Ray to make a few specific comments, but let me offer a couple of points in 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.

With respect to <unk> can you.

Shed some light on the.

Registration, enabling studies for example, the blood pressure monitoring study, which I think is ongoing I know theres been various questions about how to put that study into context. So I was wondering if you could right size your expectations for what you would expect that study to show the.

The relevance of that study and <unk>.

Such details as or a placebo arm and is that an important to have a placebo arm or it doesn't really matter, maybe just talk a little bit about that study. Thank you.

Tony Coles: 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?

I'm going to ask Ray to make a few specific comments, but let me offer a couple of points by context.

Ray Sanchez: 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 percent powered to rule out any three millimeters of mercury or above change from baseline.

This is a standard clinical pharmacology trial that the agency will required for registration purposes. So we are working to comply with the agencies outline for what they'll be looking for in the primary purpose as you certainly know and we'll remind everyone else is to assess a sustained effect on blood.

Pressure, we did see transient increases in blood pressure in the phase <unk> 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.

It is growing quite well and Ray maybe you can 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 are working to have everything ready for registration. If these data are supportive of that Ray what else would you add.

Thank you Tony I think you you answered that well, but as Michael just to give you some some relevance.

This is an eight week trial that has a 150 patients.

That will are participating in it looking at doses of 10 milligrams and 30 milligrams with a low dose and a high dose.

With the objective of assessing a sustained as Tony mentioned effect on systolic blood pressure over the eight weeks.

Ray Sanchez: So, we're encouraged, as enrollment is going very well, and 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 I trial, like other Phase I 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. But, 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?

And its 90% powered to.

To rule out.

Three millimeter of mercury or above.

Change from baseline.

So so.

So were encouraged as the enrollment is going very well, we do expect the.

Results should readout 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 a per FDA guidance for registration and and labeling most importantly.

So we will do.

Disclose those results at the appropriate time when they're available.

But let me let me emphasize something I think you've alluded to before even if there was a small signal or not to 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.

That's correct. So as you know this is a trial that is not gating to our being able to pursue the larger trials or we're starting soon.

Ray Sanchez: 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 drug-drug interaction studies, like food effects studies, this is really a study that will inform labeling for practitioners to understand the sustained effect on blood pressure if there is any. Thank you. Operator, we'll take the next question. Sure.

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.

Thank you.

Okay Michael.

Operator, we'll take the next question.

Sure.

Operator: Your next question comes from Paul Middles from Stifel Online. 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?

Your next question comes from Paul <unk> from Stifel. Your line is open.

Operator: I guess I'm right in assuming that they're more modest than any numbers you could put on that, which I think would be interesting, and then just on the cap of opioid target, I was wondering how you view the totality of the data we have so far for major depressive disorder. I know there have been a couple studies, one was a publicly funded study that looked alright, and one more recent data point from J&J. Just curious how you Okay, I think, Ray, if you could start on the question about blood pressure observations from the Phase 1b trial, and I think we'll have JR continue with that, particularly on the C-max point that Paul's raising.

Hey, Thanks, so much for taking my questions I mean ambulatory blood pressure monitoring study I feel like one important detail that hasnt been talked about much is that some of the data you presented so far has been close to C. Max 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 are 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 theres been a couple of studies one was a publicly funded study that look all right. One more recent data point from J&J. Just curious how you would sort of contextualize that and your confidence in moving forward. Thank you.

Okay.

Got a few board.

Ill start on the question about blood pressure observations from the phase one B trial, and then I think we'll have Jr. Continue with that particularly on the <unk> point that Paul's raising and then Jr. If you'd lateral right into the core point that would be great. I. Appreciate the question Paul because we do want to feature their early stage pipe.

And we're excited about the car opportunity.

Along with all the latest stage stuff, we're doing so ray if you'd start and then toss it to Jr.

Operator: And then, JR, if you'd allow me to write into the CORA point, that would be great. I appreciate the question, Paul, because we do want to feature their early-stage pipeline, and we're excited about CORA, along with all the later stage stuff we're doing. So Ray, if you'd start and then toss it to JR. Good morning, Paul.

Good morning, Paul So if you recall that during the six week trial the phase one b trial that at six weeks.

Ray Sanchez: So if you recall that during the six-week trial, the Phase 1b trial, at six weeks versus placebo, 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 C-Max but really the long-term sustained effects on systolic blood pressure, which really has the most cardiovascular impact.

Versus placebo that the the average systolic diastolic blood pressure and heart rates were all very similar to placebo with really no no no concerns raised there and really what the agency.

And rightly so as not as interested in that is set so much the transient changes that you see around C. Max but really the long term sustained effects on systolic blood pressure, which really had the most cardiovascular impact. So consequently, the trial is designed as you as you mentioned correctly to look at.

Ray Sanchez: So consequently, the trial is designed, as you mentioned correctly, to look at 24-hour monitoring of blood pressure over eight weeks at certain times. So we'll do it at baseline, we'll do it at weeks four and week eight. The change from baseline at week eight is the primary endpoint. But again, the core objective being sustained systolic blood pressure for eight weeks.

24 hour monitoring of blood pressure over the.

Weeks at certain times, so we will do it at baseline we'll do it at weeks four weeks eight the change from baseline at week eight as the primary endpoint, but again the.

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 C. Max at any given time.

Ray Sanchez: 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 C-max at any given time in most.

In a moment.

Paul does that answer your question.

Ray Sanchez: Paul, does that answer your question? Doug, thank you. Thank you. J.R., 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? Sure, Tony, thanks. Yeah, I'll just add one other note. I think, Paul, part of your question may have been transient, not over multiple days of dosing with the transientness that we've seen, even within a 24-hour period.

Got it thank you.

Thank you.

Jr. Would you add anything to that and if you could pick up on the core question as well and our thoughts on the totality of data in major depressive disorder.

Sure Toni Thanks, Yeah, I'll just I'll just add one other note I think Paul part of your question May have been the transient.

Not over multiple days of dosing with the trans weakness that we've seen even within the within a 24 hour period. So.

Ray Sanchez: So if you think back to the study design, we had done a BID dose of 20 megs and a once-a-day dose of 30. 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 we didn't see that it was maintaining a transient effect with single-dose data.

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.

Subsequently to capture the same actually had to collect blood pressures twice a day.

Max to be covered at both.

I'd doses. So we didn't see that it was maintained at a training effect of the single single dose data. So I'll just I'll just add that we can turn and what we've seen previously in the clinical setting and in the preclinical studies from that.

John Renger: 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. Now, I'll transition over now to the question you had about our confidence in CORE and the previous study that was done in depression and the recent J&J study where the results were posted on the EMA version of 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 in how we're thinking about taking the program forward.

I'll transition over now to the question you had about our confidence in core in the recent.

The previous study that was done in depression and the recent J&J study that was.

The results were.

Posted in the EMEA.

You know version of the clinical trials that go so.

Yes, I think.

Those two studies that you mentioned, particularly the J&J study.

Our very.

You know kind of guidance guiding force in how we're thinking about taking the program forward. As you know there was also a publication from J&J.

John Renger: As you know, there was also a publication from J&J that was a very well-done paper where they actually talked about how they picked their doses and their 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.

Very well done paper, where they actually talked about how they pick their doses and the receptor occupancy and then how they approach the transition the translational piece of understanding receptor occupancy and actually publishing that data prior to the results that they've seen in the in the depression study.

John Renger: So 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, you know, 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. Very good Thank you. Yep. Thank you, Paul.

Obviously this is guidance for us we wont necessarily follow exactly what they did but we're really confident about how they pick their doses to go forward and we were really.

Kind of excited to see the data that they've got in depression study so.

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 need.

Very good thank you.

John Renger: Thanks, Jaron. Okay operator, we will take the next question. Thank you. Your next question comes from Douglas Chow from H.C. Wainwright. Hi, good morning.

Thank you Paul Thanks, J Aron right. Okay, operator, we will take the next question.

Thinking your next question comes from Douglas Tsao from H C. Wainwright.

Hi, good morning, Thanks for taking the questions and maybe just sticking to the early stage pipeline I was hoping maybe you could talk a little bit more about the M. Four program and just given what we've seen with <unk> and what you're trying to accomplish with those molecules and what does that potentially sort of open you up to accomplish.

Operator: 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 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? I'm going to ask J.R. 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.

<unk>.

Yes, let me I'm going to ask Jr. Too to address that but let me make a couple of comments Doug.

From all of my years.

As a market as a commercial guy that's always been advantageous to have more than one entrant with the same mechanism, particularly if it's if the mechanism.

Is effective so I think this gives us an opportunity assuming we can generate positive clinical data with the <unk> agonist gives us the opportunity to cover an even greater number of potential indications in the neuroscience space.

Tony Coles: 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 mRaclidin, certainly in schizophrenia and potentially even 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. J.R. can talk specifically about the mechanism, but I just wanted to offer that higher-level kind of strategic franchise vision that we have for advancing multiple entrants and multiple, with multiple related mechanisms.

I think about this as a complement to what we're doing with <unk>.

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 M. Four agonist that might have the potential to work in other related disorders that would be really attractive.

<unk> can talk specifically about the mechanism, but I just wanted to offer that higher level kind of strategic franchise vision that we have.

We're advancing multiple entrants and multiple multiple related mechanisms Jr. Please add some detail to that.

Sure. Thank you Tony and thanks for the question.

Tony Coles: J.R., please add some details. Sure, thank you, Tony, and thanks for the question. Yeah, I think that a couple of things are relevant here in the background.

I think that a couple of things <unk>.

Irrelevant here and kind of the background so.

John Renger: 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 Medkin 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 the 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 PAM, so what we've seen is the kind of results that are outstanding for looking at psychosis in schizophrenia patients.

First of all.

With the ability to have a really exceptional group.

Both in our in vivo biology group as well as our made kin group. What we've done is made it a wide range of different molecules that are important selective and have various types of pharmacology.

Also working very closely with our clinical group what we have.

Really carefully considered as the fact that when you look at the potential for a new mechanism of treating psychosis and you look at the current treatments that are used and you start to think about various indications you can pursue I think that there is some indications that are very obvious for a P.

John Renger: 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, the manic break in certain patients that have, you know, a certain severity of disease, and so when you think about the potential of this mechanism being one that doesn't, hasn't required titration to date with emraclodine 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 pre-clinically in our models, we believe that there's a real opportunity to expand on indications with a full agonist that would really from the get-go really hit as hard as possible the M4 receptor to provide clinical benefit, 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 emraclodine, but to help us really build a franchise around what we've learned on this mechanism, its tolerability, and when you have M4 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 pre-clinically based on the research labs that we have here at Cambridge Crossing, we think we have a real opportunity to build upon the science that we've been leading in with M4 selectivity and create new opportunities to actually build a franchise here, not just a single asset, as Tony was saying. Thank you. Okay. Great. Thank you. That's very helpful. Thanks, Doug. Yep.

So what we've seen is the kind of results.

Standing for looking at psychosis and schizophrenia patients. We know previously that there was a very strong rationale or believing that psychosis associated with dementia and Alzheimer's population is another one that we're very interested in but 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 atypical with.

With clinical practices to actually started at very high doses of the initial treatment to offset for instance, Atlantic break.

And in certain in patients that have certain severity of disease and so when you think about the potential this mechanism being one that doesn't hasn't required titration to date with <unk>.

And you're thinking about clinical practice and even how typical is an atypical as were used at higher doses and certain populations.

And knowing what we've characterized pre clinically in our models, we believe that theres, a real opportunity to expand on indications.

With a full agonist would really from the get go really.

As hard as possible.

The <unk> receptor to provide clinical benefit so we think that with a full agonist. What we can do is actually pursue some of those optional indications that werent ended the first way are indications that we're going after with <unk>, but to help us really build a franchise around what we've learned on this mechanism its tolerability and when.

Do 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.

Patients with psychosis, so we see a real opportunity here and because we have that opportunity to make new molecules and characterize them in <unk>.

So how they differentiate pre clinically.

Based on that.

The research labs, we have here at Cambridge crossing we think we have a real opportunity to build upon our science that we've been leading in with the enforcement activity and create new opportunities to actually build a franchise here not just a single asset as Tony was saying.

Thank you.

John Renger: Thanks, Doug, for the question. Operator, we'll take the next question. Your next question comes from Madhu Kumar from Goldman Sachs. Hi, this is Omari.

Okay, great. Thanks, Dara. Thanks, that's very helpful. Thanks, Doug Yep. Thanks, Doug for the question operator, we'll take the next question.

Okay.

Your next question comes from Matthew Kumar from Goldman Sachs.

Hi, This is omar on the module, we have a couple of questions. So can you provide any color on that target population, you're looking to pursue particularly with the rig.

Operator: We have a couple questions. So can you provide any color on the target population you're looking to pursue for Dorigabat anxiety? And then, second question, on the Epilepsy Trial Perspective. Yes, thanks. What we said in the prepared remarks for Doricabet anxiety is that 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 Doricabet.

And the second question.

On the epilepsy trial with respect just to clarify there's nothing about trial design is changing so I'd just like total patient numbers.

Yes. Thanks.

What we said in the prepared remarks for a generic of Red anxiety is we are looking very closely at panic disorder.

It seems to be one of those sub anxiety subtypes, where there could be a potential role for director bets. So our teams are studying that very carefully and no. There are no clinical trials changes for the epilepsy study. This is just a matter of getting all the patients into the trial getting them.

Tony Coles: 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. All right, thank you. Okay, thank you. Operator, we'll take the next question.

First in analyzing the data so no new update on trial designs.

Alright, thank you.

Okay. Thank you.

Operator, we'll take the next question.

Sure.

Your next question comes from Matthew Harrison from Morgan Stanley .

Operator: Your next question comes from Matthew Harrison from Morgan Stanley. Hi, thank you for taking our question. I'm Wenjiang online for Matthew.

Hi, Thank you for taking my question won Jong online for Matthew So I have two questions. One is about Iraq lifting.

Operator: So we have two questions. One is about accuracy. So is there any other non-clinical work still needs to be completed which could have any impact on phase two or even relative phase three preparation? The second question is about 871. So how robust are you expecting the signal to be?

So is there any other noncritical work still needs to be completed.

Which could have an impact on our fish to our event related to phase III preparation.

The second question is about a seven one so how robust are you expecting the signal could be so that could be just a trend you could envision are you excited a clearer picture of efficacy.

Operator: So that could be just a trend you could anticipate, or you expect a clearer picture of efficacy. Okay, good. JR, would you address the amount of non-clinical work that's remaining on emraclidane? And Ray, I'll get you to talk about H7-1.

Okay. Good Jr would you address that.

Amount of non clinical work, that's remaining on them rack Levine and Ray I'll get you to talk about <unk> 71.

Sure. Thank you Tony and thanks for the question Yeah. So.

John Renger: 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.

There is additional work that is ongoing so we've actually started studies as you know <unk> studies that are two years in duration are part of the required registration package.

And those are typically long the longest studies that have to be completed so we would actually pre invested in getting those earlier to take them off the critical path.

John Renger: 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 are additional studies. But we do have a very experienced preclinical research group, and we've done a lot of pre-investment in this program to make sure that we can move as rapidly as possible.

Obviously.

When we complete these next two studies that we talked about starting.

Any short time period, one of the things we will do is go back to the agency.

Our package and one of the things that we will do is the.

Chairman, 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 is additional studies, but we do have a very experienced preclinical tox group.

We've done a lot of pre investment in this program to make sure that we can move as rapidly as possible. So.

John Renger: So, you know, thinking kind of what 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 so we can get those studies done to make sure they're not on the critical path. 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.

Thinking kind of.

Standard fare has been addressed.

<unk> be additional questions that the agency might head, but we'll be able to answer those in time that we can get those studies done.

To make sure they are not on critical path. So I would say that we are a well well in hand.

The plant is in place, but there's always an opportunity for the agency to give feedback and we'll respond accordingly.

Thanks, Sean.

John Renger: 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 H7-1 trial and the clinical tool we're using to measure efficacy there. 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.

Thank you Jr. Greg why don't if you can let's just talk I think the second question has to do with.

Efficacy outcomes from need seven one trial and the clinical tool we are using to measure efficacy there.

Right.

Good morning, So as you know apathy is the leading neuropsychiatry symptom associated with dementia and it's one of the strongest symptomatic predictors of disease progression. So we.

Ray Sanchez: So, we see great utility in this V15 partial agonist that operates in areas of the brain that operate under lower dopaminergic tone. So, our goal really is to conduct, what 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 achieved 50 and 80 percent receptor occupancy, and looking at a variety of, actually, endpoints and scales.

We see great utility in the C. One five partial agonist.

That operates in areas of the brain that operate under lower dopaminergic tone. So our goal really is one to two conduct which we're doing now a phase Iia 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 one milligram and three milligrams, which achieved 50 and 80% receptor occupancies.

And looking at a variety of actually endpoint and scales and so there is no primary endpoint per se, but it's really truly an experimental trial.

Ray Sanchez: 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.

To give us an understanding using a variety of scales that have been historically used to understand apathy, but also it had been used in the.

Admit trials with methylphenidate ER in the past and so when these data will read out in the first half of 2023, we'll look at these data will work with the agency to look at what kind of validation work does need to be done in order to then progressed to the later stages of development. The good news is that as I.

Ray Sanchez: And so, when these data read out in the first half of 2023, we'll look at these data, and 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 treatments. Okay, thank you. Bye.

And 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.

Okay. Thank you.

Okay very very good okay. Operator, we will take the next question.

Ray Sanchez: Okay, very, very good. Okay, operator, we will take the next question. Thank you. Your next question comes from Esther Hall from Baron. Hi, thanks for taking my question. So on the subject of that, 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?

Thank you. Your next question comes from Esther Hong from Marin.

Hi, Thanks for taking my questions. So on <unk> I was wondering if the FDA has provided any guidance regarding the study design have you spoken with them about the anxiety disorder.

Disorder and then.

Was wondering when we could expect and patient enrollment.

Operator: I was wondering when we could expect patient enrollment in the phase two trial for anxiety. Thanks. 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-event anxiety? Right. So, as I mentioned earlier, our first likely pursuit will be in panic disorder, which is the second most common anxiety disorder after generalized anxiety disorder, obviously stemming from the phase one proof of principle trial.

Moment in the phase two trial for anxiety. Thanks.

Thank you for the question.

Can you talk about our planning work and how we're thinking about the next steps for drink about anxiety.

Right. So as I mentioned earlier that our first likely pursuit will be in panic disorder, which is the second highest.

Yeah.

<unk> disorder after generalized anxiety disorder.

Obviously stemming from the phase one proof of principle trial.

We do plan on meeting with the agency since of course, they change their thought process over time.

Operator: We do plan on meeting with the agency 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.

These trials historically had been fairly prescriptive 10 to 12 weeks in duration looking at looking at.

Ray Sanchez: But we just want to make sure that the agency's views are still aligned. So, yes, the process that we'll be following will be to look at the historical precedents, and 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. Thank you. Okay, thanks Ray. Again, to ask a question, please press star 1 on your telephone keypad. There are no further questions at this time. I would like to turn the call over back to Mr. Tony Coles for closing remarks.

Panic attack frequency and so forth, but we just wanted to make sure that the agencies views is still are still aligned so yes. The process that we'll be following will be to look.

Look at the historical precedence meet with the agency to ensure that the path forward is clear and we will of course disclose that when we internally have that clarity as well.

Great. Thank you.

Thanks, Ray operator, we'll take the next question.

Again to ask a question. Please press star one on your California Keybanc.

There is no further question at this time I would like to turn the call over back to Mr. Tony calls for closing remarks.

Very good. Thank you well. Thank you guys for joining us as you can see there is as always a lot going on here. It's terrible 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 core as well as for the <unk>.

Tony Coles: 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 Cerevel. We're making really good progress on the later stage pipeline. A lot of very exciting data readouts that we're expecting in the months to come. And as you can see, both for CORA as well as for the M4AG, there's 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.

Some very interesting early stage work that will complement what we are advancing rapidly towards 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.

Tony Coles: 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 have a great day. Thank you. And this concludes today's conference call. Thank you all for joining. [music]

And look forward to our next update with you. Thanks for joining the call and everyone enjoy a great day.

Thank you and this concludes today's conference call. Thank you all for joining you may now disconnect.

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