Q3 2023 Cerevel Therapeutics Holdings Inc Earnings Call

Speaker 1: Post.

Okay.

Good morning, and welcome to the bank.

Speaker 2: Sarah Valthera Pugix, third quarter financial results conference call. At this time, all participants are in listen only mode. Later, you will have the opportunity to ask questions during the Q&A portion of the call.

Tariff L Therapeutics third quarter financial results conference call.

At this time, all participants are in listen only mode.

Later, you will have the opportunity to ask questions during the Q&A portion of the call.

Speaker 2: Please note that this call may be recorded. I will now hand the call over to Matt Callisteri Vice President of Investor Relations.

Please note that this call may be recorded I will now hand, the call over to Matt <unk>, Vice President of Investor Relations.

Speaker 3: Thank you. Good morning, everyone. We appreciate you joining us for a third quarter of 2023 earnings call. On today's call, you'll be hearing from Roderna O, our president and chief executive officer, Dr. Ray Sanchez, our chief medical officer, Dr. John Ranger, our chief scientific officer, and Dr. Susan Oleshuler, our chief financial officer.

Thank you good morning, everyone. We appreciate you joining us for third quarter 2023 earnings call.

On today's call you'll be hearing from Ron Renaud, our President and Chief Executive Officer, Dr. Rey Sanchez, our Chief Medical Officer, Dr. John <unk>, Our Chief Scientific Officer and Dr. Susan All Schuller, our Chief Financial Officer.

Speaker 3: During our call today, please refer to our press release from this morning, D-Tong, our 3rd quarter 2023 financial before.

During our call today, please refer to our press release from this morning detailing our third quarter 2023 financial performance as well as our updated corporate presentation, both of which are available on our website I would like to remind you that we will be making forward looking statements that reflect our current views related to among other things the percent.

Speaker 3: as well as our updated corporate presentation, both of which are available on our website.

Speaker 3: I would like to remind you that we will be making for looking statements that reflect our current views related to among other things. The potential attributes and benefits of our product canvass and the format and timing of our product development activities and clinical trials.

Attribute the benefits of our product candidates and a format and timing of our product development activities and clinical trials. We strongly encourage you to review the information that we filed with the SEC regarding specific risks and uncertainties.

Speaker 3: We strongly encourage you to leave the information that we follow the SEC regarding specific risks and uncertain.

Speaker 3: I will now hand the call over to Ron Renaud, President and CEO of Cerevelle to provide an overview of our achievements and outlook. Thanks Matt, and good morning everyone, and thank you for joining us for our third quarter of 2023 business results call. I am pleased to be with all of you today to review our third quarter results, and to discuss how we're preparing for what we expect will be an exciting 2024.

I will now hand, the call over to Ron Renaud, President and CEO, Sarah Bell to provide an overview of our achievements and outlook.

Matt and good morning, everyone and thank you for joining us for our third quarter 2023 business result call.

We used to be with all of you today to review, our third quarter results and to discuss how we're preparing for what we expect will be an exciting 2024.

Speaker 3: Let me start with some high-level thoughts on how the management team is thinking about and planning for the future of Saravelle.

Let me start with some high level thoughts on how the management team is thinking about and planning for the future I'm sorry Bill.

Speaker 3: To begin, we believe this organization has one of the most robust neuroscience pipelines in the industry. And next year will be a pivotal one for Sarabelle. As we look forward to multiple mid- and late-stage readouts across three different assets and three different indications.

To begin we believe this organization has one of the most robust neuroscience pipelines in the industry and next year will be a pivotal one for sure though as we look forward to multiple mid and late stage readouts across three different assets in three different indications.

Speaker 3: Our recent capital raise significantly bolstered the balance sheet, extending our runway into 2026.

Our recent capital raise significantly bolstered the balance sheet, extending our runway into 2026.

Speaker 3: Well, over 12 months beyond all of our expected data readouts next year.

Well over 12 months beyond all of our expected data Readouts next year.

Speaker 3: As an organization, we have leads are focused on execution and maximizing the value creation opportunities for each of our lead aspects.

As an organization, we are laser focused on execution and maximizing the value creation opportunities for each of our lead assets are.

Speaker 3: Our ongoing clinical trials are progressing well, and we expect to deliver data for two vapodons, the Rigubat and Imracidine on the timelines we laid out last quarter.

Our ongoing clinical trials are progressing well and we expect to deliver data put you back on.

The rig at about <unk> on the timeline, we laid out last quarter.

Speaker 3: We are planning for success and proactively preparing to potentially file two NDAs in 2025 to tapaton and emracorine if data are positive.

We are planning for success and proactively preparing to potentially buy out two NDA in 2025.

But on <unk> if data are positive.

Speaker 3: Furthermore, you're diligently exploring life cycle opportunities for our lead programs and other indications. Let me now provide...

Furthermore, we are diligently exploring lifecycle opportunities for our lead programs in other indications.

Let me now provide an overview of our lead programs.

Speaker 3: And MACLADIN, our M4 selective positive ulceric modulator, OPAM, is currently in development for schizophrenia and Alzheimer's disease, likeosis, as they once daily medicine without the need for titration.

<unk>, our <unk> selective positive allosteric modulator or Pam is currently in development for schizophrenia, and Alzheimers disease psychosis as a once daily medicine without the need for titration.

Speaker 3: And bracketing a potential next generation effect the caudic with a novel mechanism of action that targets BM4 pathway.

<unk> as a potential next generation anti psychotic with a novel mechanism of action that targets the M four pathway.

Speaker 3: By selectively targeting M4, we believe in reckoning may reduce the conduct symptoms without challenging side effects of current anti-psychotics.

By selectively targeting them for we believe <unk> may reduce psychotic symptoms without challenging side effects.

Current anti Psychotics.

Speaker 3: Our two potentially registrational trials and Power One and then Power Two are enrolling well. And we expect data to read out in the second half of 2024. We are excited about the potential of our Mrakodyn and the benefit it may bring to patients with schizophrenia who have not seen innovation in decades.

Our two potentially registrational trials in power, one and empower two are enrolling well.

And we expect data to read out in the second half of 2024.

We are excited about the potential of <unk> and the benefit it may bring to patients with schizophrenia, who have not seen innovation in decades.

Speaker 3: Moving to Tavapidon, the first D1, D5 partial agonist in development for the treatment of Parkinson's disease.

Moving to tobacco on the price <unk> partial agonist in development for the treatment of Parkinson's disease.

Speaker 3: We expect our Tempo 3 adjunctive trial to be our first data readout in the first half of 2024, with the Tempo 1 and Tempo 2 monotherapy readouts coming in the second half of the year.

We expect our temple III adjunctive trial to be our first data readout in the first half of 2024 with a temporal one in Tampa two monotherapy readouts coming in the second half of the year.

Speaker 3: Building on our excitement for this program, we are pleased to announce that we will host the Tivapidon Investor Webcast on December 11th, during which we will explore this novel mechanism and its potential to address patient needs in greater depth.

Building on our excitement for this program. We are pleased to announce that we were closer to that but an investor webcast on December 11, during which we will explore this novel mechanism and its potential to address patient needs in greater depth.

Speaker 3: We believe there is a significant opportunity in Parkinson's disease to deliver sustained motor control with a favorable side effect profile.

We believe there is a significant opportunity in Parkinson's disease to deliver sustained motor control with a favorable side effect profile.

Speaker 3: And finally, let me turn to Dorigabat, our selective alpha-235 GABA-A-PAM currently in development for both focal epilepsy and panic disorder.

And finally, let me turn to worry about our selective Alpha 235, Gaba Pam currently in development for both focal epilepsy in panic disorder.

Speaker 3: As we recognize Epilepsy Awareness Month in November and the 3.4 million people living with epilepsy in the United States, we are hopeful that we can bring forward a new treatment option for people living with this difficult disease.

As we recognize epilepsy awareness month in November and the $3 4 million people living with epilepsy in the United States. We are hopeful that we can bring forward a new treatment option for people living with this difficult disease.

Speaker 3: Our phase 2 realized trial in focal epilepsy to be our second readout of 2024 coming mid-year. We've also initiated our ADAPT trial, a phase 2 proof of concept trial in panic disorder.

Our phase II realized trial in focal epilepsy to be our second read out of 2024 coming mid year.

We have also initiated our adapt trial a phase II proof of concept trial in panic disorder.

Speaker 3: Behind our mid to late stage pipeline is an innovative discovery engine that is focused on bringing forward additional novel mechanisms to address neuroscience diseases.

Behind our mid to late stage pipeline is an innovative discovery engine that is focused on bringing forward additional novel mechanisms to address neuroscience diseases.

Speaker 3: And we look forward to providing greater detail on those programs, including our capital opioid receptor antagonist as we make further progress.

And we look forward to providing greater detail on those programs, including our Kappa opioid receptor antagonist.

Make further progress.

Speaker 3: I'm quite excited about all that we're doing here at Sarah Bell and all that is to come for our pipeline and the potential benefits. We hope to bring the patients. We are well positioned as we go into 2024 to truly transform what is possible in neuroscience. With that, I'll now turn the call over to Dr. Ray Sanchez, our chief medical officer to provide some added color about our lead programs. Right? Thank you, Ron. And good morning. Everyone.

I am quite excited about all that we're doing here at <unk> and all of that has to come from our pipeline and the potential benefits, we hope to bring to patients.

We're well positioned as we go into 2024 to truly transform what is possible in neuroscience with.

I'll now turn the call over to Dr. Rey Sanchez, our Chief Medical officer to provide some added color about our lead programs right. Thank you Ron and good morning, everyone.

Speaker 4: I want to echo Ron's sentiments about the excitement around our pipeline.

I want to Echo Ron's sentiments about the excitement around our pipeline as a former clinician I can tell you that I am energized by the potential we have here at <unk> to make a meaningful difference in the lives of patients with neuroscience diseases.

Speaker 4: As a former clinician, I can tell you that I am energized by the potential we have here at Cerebel to make a meaningful difference in the lives of patients with neuroscience disease.

Speaker 4: Beginning with Embraclavine, our EMPOWER program is advancing and data are expected in the second half of 2024.

Beginning with Iraq Levine, our empower program is advancing and data are expected in the second half of 2024.

Speaker 4: Preserving data quality while mitigating placebo response risk remains the utmost priority for these trials, and we are pleased with our recent efforts to reinvigorate enrollment.

Reserving data quality, while mitigating placebo response risks remains the utmost priority for these trials and we are pleased with our recent efforts to reinvigorate enrollment.

Speaker 4: As a reminder, EMPOWER-1 and EMPOWER-2 are two adequately powered three-armed trials that include adults living with schizophrenia and experiencing an acute exacerbation of psychotic symptoms.

As a reminder, in power, one and power to our two adequately powered.

Trials that include adults living with schizophrenia, and experiencing an acute exacerbation of psychotic symptoms.

Speaker 4: We designed these trials to potentially meet the criteria necessary to serve as pivotal trials based on what we expect the FDA will evaluate in a registrational package.

We designed these trials, who potentially meet the criteria necessary to serve as pivotal trials based on what we expect the FDA will evaluate in.

In our Registrational package.

Speaker 4: We're also enrolling our 52-week Open Label Safety Extension trial in Power 3 and prioritizing the completion of non-clinical and clinical pharmacology.

We're also enrolling our 52 week open label safety extension trial and power three and prioritizing the completion of non clinical and clinical pharmacology studies to accelerate a potential registrational package from rack with schizophrenia. We believe <unk> has tremendous potential in other disease areas and plans for further development.

Speaker 4: to accelerate a potential registrational package for a miracle unit schizophrenia.

Speaker 4: We believe in raclidin has tremendous potential in other disease areas and plans for further development are underway.

Speaker 4: In Alzheimer's disease, psychosis, or ADP, our phase one healthy elderly volunteer trial is ongoing, and the results of this trial will guide our clinical development plan as we advance this important indication with a substantial unmet need.

They are underway.

Alzheimer's disease psychosis, or ADP, our phase one healthy elderly volunteer trial is ongoing and the results of this trial.

Guide, our clinical development plan as we advance orphan indication with a substantial unmet need.

Speaker 4: Turning now to tabapiton, our D1, D5 partial agonists in Parkinson's.

Turning now to <unk> <unk> five partial agonist in Parkinson's disease.

Speaker 4: Our phase three trials, known collectively as the TEMPO trials, are ongoing along with the corresponding open label extension in which we are encouraged by a greater than 90% rollover rate.

Our phase III trials known collectively as the capital trials are ongoing along with the corresponding open label extension and which we are encouraged by a greater than 90% rollover rate.

Speaker 4: We expect data for Tempo 3 in the first half of 2024, with data for Tempos 1 and 2 coming in the second half of 2024.

We expect data for $10 three in the first half of 2024 with data for chemicals wanting to coming in the second half 2024.

Speaker 4: We look forward to walking you through the scientific rationale and prior data for tabapiton, as well as its clinical potential during our investor event in December .

We look forward to walking you through the scientific rationale and prior data for tobacco as well as its clinical potential during our investor event in December.

Speaker 4: With jirigamat or selective GABA-A pan, we believe there is potential for both anti-epileptic and angiolytic activity comparable to benzodiazepines with an improved side effect profile.

With your rig or that are selective Gaba a pan we believe there is potential for both anti epileptic and enjoyed activity comparable to end demand and agents with an improved side effect profile.

Speaker 4: Unlike benzodiazepines, which are only used for acute episodes due to tolerability, abuse potential and other debilitating side effects, Dorigabat's novel mechanism of action and anticipated favorable tolerability profile provide the potential for chronic dose.

Unlike benzodiazepines, which are only used for acute episodes beauty tolerability abuse potential and other debilitating side effects to rig about novel mechanism of action and anticipated favorable tolerability profile provide the potential for chronic dosing.

Speaker 4: We expect results from our Phase 2 realized trial in focal epilepsy in mid-year 2024, and we are encouraged by a continued high rollover rate into the realized open label extension.

We expect results for our phase III realized trailing vogel outlets at midyear 2024, and we are encouraged by continued high rollover rate into the realized open label extension.

Speaker 4: Beyond focal epilepsy, our ADAPT Phase 2 trial in panic disorder is currently underway. A new drug has not been approved in panic disorder in nearly 20 years, and we are excited about the potential of providing Darigabat as a daily chronic therapy to patients in need.

Beyond focal epilepsy, our adapt phase II trial in panic disorder is currently underway a new drug has not been approved panic disorder in nearly 20 years and we're excited about the potential of providing rigor bad as a daily chronic therapy to patients in need.

Speaker 4: Cerebell's mid- to late-stage pipeline has the potential to bring forward numerous treatments to address some of the most devastating neuroscience diseases, and I am so proud of the team that is working diligently to make this potential a reality.

Sir about mid to late stage pipeline has the potential to bring forward numerous treatments to address some of the most devastating neuroscience diseases and I am so proud of the team that is working diligently to meet the potential this potential a reality.

Speaker 4: With that, let me turn it over to Dr. John Renger, our Chief Scientific Officer, to provide an update on our early-stage portfolio. John . Thank you, Ray.

With that let me turn it over to Dr. John <unk>, our Chief Scientific officer to provide an update on our early stage portfolio John.

Thank you Ray good morning, everyone.

Speaker 3: I'm very pleased with the progress we've made in discovery research and early clinical development here at Cerebel.

I'm very pleased with progress we've made a discovery research and early clinical development well.

Speaker 3: Today, I'd like to focus on our CAP-Opioid Receptor Antagonist, or CORA program, also known as CDL-354.

Today I'd like to focus on our Kappa opioid receptor antagonist or <unk> program also known as CVR 354.

Speaker 3: We have completed both our single and multiple ascending dose trials in which CDL354 has been generally well-tolerated. Further, we currently believe we will be able to interrogate a range of receptor occupancies in both the Kappa and Mu opioid receptors.

Completed both our single and multiple ascending dose trials in which <unk> 354.

And generally well tolerated further.

Currently believe we will be able to deteriorate range of receptor occupancy is in both of the cabin and Mu opioid receptors.

Speaker 3: We believe and anticipate we'll be able to explore multiple indications of interest, such as major depressive disorder and substance use disorder. Our ongoing phase one PET receptor occupancy trial will clarify both kappa and mu receptor PET tracer displacement to further characterize selectivity across the compound exposure.

We believe anticipate we'll be able to explore multiple indications of interest such as major depressive disorder and substance use disorder.

Going phase one receptor occupancy trial will clarify both Tampa <unk> receptor penetration displacement.

Would you characterize productivity across the countdown exposures.

Speaker 3: We are encouraged by the potential impact of this asset and look forward to providing more updates in our plans in the near future.

We are encouraged by the potential impact of this asset we reported through any more updates on our plans in the near future.

Speaker 3: Beyond CORA, we have a growing number of programs, some initiated within our labs and exclusively developed here at Cerewell, which we continue to progress, including our M4 selective agonist.

The encore, we have a growing number of programs some issue within our labs and exclusively developed here to serve all which we continue to progress, including our enforce selective agonist of <unk>.

Speaker 3: PDE-4D Sparing Antagonist, and a Selective T-MIM-175 Potentiator Program.

PD Board deep spearing antagonist, and a selective team in 175 potentiate or program.

Speaker 3: We will provide further updates and plans for these specific programs as approved.

We will provide further updates on plans for these specific programs as appropriate.

Speaker 5: With that, I'm going to turn it over to our Chief Financial Officer, Dr. Susan Altshuler, to review our financial performance for the third quarter. Susan? Thank you, John . Turning to our financials, in October , we opportunistically bolstered our balance sheet with a $499 million capital raise, providing strong validation of CeraVel's potential from both new and existing high-quality investments.

With that I'm going to turn it over to our Chief Financial Officer, Susan offshore to review, our financial performance for the third quarter.

Susan.

Thank you John turning to our financial in October, we Opportunistically bolstered our balance sheet with $499 million capital rates.

Adding certain validation of fair enough potential from both new and existing high quality investors.

Speaker 5: This additional capital, along with the roughly $758 million in cash, cash equivalents and marketable securities we ended the third quarter with, will support our operations into 2026.

This additional capital along with the roughly $758 million in cash cash equivalents and marketable securities. We ended the third quarter with the partner.

<unk> into 2026.

Speaker 5: Turning to the third quarter of 2023. Operating expenses were approximately $111 million, comprised of $85 million of research and development expenses and $26 million of general and administrative expenses.

Turning to the third quarter of 2023.

Operating expenses were approximately $111 million.

Price of $85 million of research and development expenses and $26 million of general and administrative expenses.

Speaker 5: Looking forward for financial strength, enables us to focus on execution and provides optionality to maximize the value of our pipeline. That said, we will take a disciplined approach to resource allocation as we further build our pipeline, advance our lead assets, and prepare for two potential NDA filings in parallel. With that, I will hand the call back over to Ron for his concluding remarks. Thank you, Susan.

Looking forward, our financial strength enables us to focus on execution and provides optionality to maximize the value of our pipeline that said, we will take a disciplined approach to resource allocation and the further build our pipeline advance our lead assets and prepare for potential NDA filings in parallel with that I will hand, the call back over to Randy for his group.

Many of our remarks, thank you Susan.

Speaker 6: At Turbo, we believe we have an unparalleled pipeline and a nervous fire.

We believe we have an unparalleled pipeline in neuroscience.

Speaker 6: with multiple mid and late stage readouts across three different assets expected next year. And the balance sheet that provides us with cash runway into 2026.

With multiple mid and late stage readouts across three different assets expected next year and the balance sheet that provides us with cash runway into 2026.

Speaker 6: We're focused and aligned on executing our trials, delivering high quality data next year. And as Susan mentioned, prepare for two potential NDA filing.

Our focused and aligned on executing our trials delivering high quality data next year.

And as Susan mentioned preparing for two potential NDA filings.

Operator: Good morning and welcome to the Cerevel Therapeutics third quarter financial results conference call. At this time, all participants are in listen only mode. Later, you will have the opportunity to ask questions during the Q&A portion of the call. Please note that this call may be recorded.

Speaker 6: These are exciting times at Sarago and I'm so proud to be leading this organization. I want to offer my sincere appreciation for all of our employees who work tirelessly every day to deliver on Sarago's mission.

These are exciting times at Ceragon and I'm, so proud to be leading this organization.

I want to offer my sincere appreciation to all of our employees, who work tirelessly everyday to deliver on serve <unk> mission.

Speaker 6: And I also want to thank our investigators and participants in our clinical trials, those who none of this would none of what we seek to achieve would be possible. With that, let's open the call for questions.

I also want to thank our investigators and participants in our clinical trials without whom none of this.

Matthew Calistri: I will now hand the call over to Matt Calistri, vice president of investor relations. Thank you. Good morning, everyone.

None of what we seek to achieve would be possible with that let's open the call for questions.

Speaker 2: Thank you, as a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster.

Thank you as a reminder to ask a question. Please press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one one again please.

Matthew Calistri: We appreciate you joining us for a third quarter 2023 earnings call.

Matthew Calistri: On today's call, you'll be hearing from Ronald Renaud, our president and chief executive officer, Dr. Ray Sanchez, our chief medical officer, Dr. John Renger, our chief scientific officer, and Dr. Susan Altschuller, our chief financial officer. During our call today, please refer to our press release from this morning, each on our third quarter 2023 financial performance, as well as our updated corporate presentation, both of which are available on our website. I would like to remind you that we will be making for-looking statements that reflect our current views related to, among other things, the potential attributes and benefits of our product candidates and the format and timing of our product development activities and clinical trials. We strongly encourage you to review the information that we file at the SEC regarding specific risks and uncertainties.

Please standby, while we compile the Q&A roster.

One moment for our first question.

Speaker 2: And our first question comes from Michael Yee of Jeffrey.

And our first question comes from Michael <unk> of Jefferies.

Speaker 7: you guys good morning and thanks for the question and thanks for the update Ron I know everyone's focused on execution. Two questions.

Hey, guys. Good morning, and thanks for the question and thanks for the updates Ron I know everyone's focused on execution.

Speaker 7: First on emrackling, obviously since last quarter, there were some concern about some of the timeline changes. Can you maybe just describe what initiatives give you the confidence that things are progressing on time and specifically maybe for the team, what the right patients are, the right site selections are?

Two questions first on <unk>, obviously since last quarter. There was some concern about some of the.

Timeline changes can you maybe just describe what.

What initiatives.

Gives you the confidence that things are progressing on time and specifically maybe for the team what the right patients are the right sites.

Ronald Renaud: I will now hand the call over to Ron Renaud, president and CEO of Servel to provide an overview of our achievements and outlook. Thanks, Matt, and good morning, everyone, and thank you for joining us for our third quarter 2023 business results call. I am pleased to be with all of you today to review our third quarter results, and to discuss how we're preparing for what we expect will be an exciting 2024.

Speaker 7: confidence on executing on that enrollment. And the second question is on epilepsy. There's actually a bunch of competitor readouts happening, and maybe you could help us understand about the placebo arms and what things you're integrating into your study that might help us give us confidence there because that has historically been an issue. And I know that's a concern for others as well. Thanks.

Elections are.

I'll give you the confidence on executing on that.

Enrollment in.

The second question is on epilepsy.

There is actually a bunch of competitor readout happening and maybe you could help us understand about the placebo arms and what things you're integrating into your study that might help us give us confidence there because that's historically been an issue and I know thats a concern.

Ronald Renaud: Let me start with some high-level thoughts on how the management team is thinking about and planning for the future of Servel. To begin, we believe this organization has one of the most robust neuroscience pipelines in the industry. And next year will be a pivotal one for Servel, as we look forward to multiple mid and late-stage readouts across three different assets and three different indications. Our recent capital raise significantly bolstered the balance sheet, extending our runway into 2026.

For others as well thank you.

Speaker 6: Yeah, sure. So let me take the first part of your first question and I'll let Ray, you know, address the second part in terms of study selection from racketing and then, and then the placebo work on our epilepsy studies.

Yeah sure. So let me take the first part of your first question and then I'll, let ray.

Address the second part in terms of site selection from rack waiting and then and then the placebo work on our epilepsy studies. So look you know as we mentioned last quarter. We're focused on trying to address the challenges that we saw with some of the the enrollment issues that we had and look we.

Speaker 6: So look, as we mentioned last quarter, we're focused on trying to address the challenges that we saw with some of the enrollment issues that we had.

Ronald Renaud: Well over 12 months beyond all of our expected data readouts next year. As an organization, we have leaves are focused on execution and maximizing the value creation opportunities for each of our lead assets. Our ongoing clinical trials are progressing well, and we expect the delivered data for to Vapodon, the Rigubat and Imracodine on the timelines we laid out last quarter. We are planning for success and proactively preparing to potentially file two NDAs in 2025 for to Vapodon and Imracodine if data are positive. Furthermore, we are diligently exploring life cycle opportunities for our lead programs and other indications.

We're doing that with boots on the ground I've spent time at sites with Ray and the team and the leader of our <unk> in clinical development groups and really working with the sites to to see what's going on and I think we're quite pleased with the progress that we've seen so far and that's why we can we can stand by the guidance that we've given.

Speaker 6: and really working with the sites to see what's going on. And I think we're quite pleased with the progress that we've seen so far. And that's why we can stand by the guidance that we've given here in the quarter. That all said, I'll always remain on ensuring the quality of the data. And I think that gets to the second part of the question. We're going to continue to maintain rigorous fight selection and focus on our placebo variability reduction strategies. But I'll let Ray address how we think about the sites and how we think about all of those things that we continue to make progress here. And also talk about our...

Here in the quarter that all said our focus.

Always remain on ensuring the quality of the data and I think that gets to the second part of the question. We're going to maintain continue to maintain rigorous site selection and focus on our placebo variability reduction strategies.

Speaker 6: But I'll let Ray address how we think about the sites and how we think about all of those things that we continue to do to make progress here and also talk about our placebo group in the epilepsy studies.

I'll, let ray address how we think about the sites and how we think about all of those things as we continue to make progress here and also talk about our placebo group in the epilepsy studies.

Ronald Renaud: Let me now provide an overview of our lead programs. Imracodine, our M4 selective positive ulceric modulator of PAM, is currently in development for schizophrenia and Alzheimer's disease psychosis as they once daily medicine without the need for titration. Imracodine is a potential next generation anti-psychotic with a non-miconymsum of action that targets the M4 pathway, by selectively targeting M4, we believe in raccordine may reduce psychotic symptoms with both challenging side effects of current anti-psychotics.

Speaker 4: Thank you, Michael, and good morning to you. So, as you know, Michael, as I historically define, you know, what does a good site look like? And it's really the access to the right patients and having good solid raters. And that really determines.

Thank you Michael and good morning to you. So as you know Michael I would say historically defined.

What does a good site looked like and it's really the access to the right patients and having good solid readers and that really determines in front of them.

Speaker 4: for the most part the success of the trial. So that's where we have been achieving and are continuing to try to achieve.

Most part the success of the trials. So that's where we have been achieving and are continuing to try to achieve but if you look at when we started the <unk> trials, starting quite robustly for the first year and then the momentum slowed down in the spring of this year.

Speaker 4: But if you look at when we started the emiraculating trials, they started quite robustly for the first year, and then the momentum slowed down in the spring of this year.

Ronald Renaud: Our two potentially registrational trials, Empower 1 and Empower 2, are enrolling well, and we expect data to read out in the second half of 2024. We are excited about the potential of a raccordine and the benefit it may bring to patients with schizophrenia who have not seen innovation in decades.

Speaker 4: Well, we've learned is how to manage the competitive landscape a bit more effectively. And to that end, we're seeing increased momentum in our enrollment without, as Ron mentioned, diluting the data quality in any way. So again, having very close communication with the sites, ensuring that the rate of recertifications occur frequently and continuing that communication ensures us that we have the greatest likelihood of success.

We've learned is how to manage the competitive landscape a bit more effectively and to that end, we're seeing increased momentum in our enrollment without as Ron mentioned diluting the data quality.

Ronald Renaud: Moving to Tvapodon, the first D1D5 partial agonist in development for the treatment of Parkinson's disease, we expect our Temple 3 adjunctive trial to be our first day to read out in the first half of 2024, with the Temple 1 and Temple 2 monotherapy readouts coming in the second half of the year.

In any way, so again, having very close communication with the sites ensuring that.

Later us re certifications occur frequently.

And continuing that communication ensures us that we have the greatest likelihood of success moving forward.

Speaker 4: In terms of epilepsy and the placebo response, as you know, that we are seeing placebo response in indications like spinal servile or attacks, you know, an epilepsy and that would surprise us.

Ronald Renaud: Building on our excitement for this program, we are pleased to announce that we will host the Tvapodon Investor webcast on December 11th during which we will explore this novel mechanism and its potential to address patient needs in greater depth. We believe there is a significant opportunity in Parkinson's disease to deliver sustained motor control with a favorable side effect profile.

In terms of epilepsy in the placebo responses.

Know that we are seeing placebo response.

Indications like spinal cerebellar ataxia in epilepsy in that.

Speaker 4: But we are also taking the same aggressive approach and dedicated approach to mitigating the placebo response in our vocal honds and epilepsy trial.

Prizes many.

We are also taking the same aggressive approach in dedicated approach to mitigating the placebo response.

Ronald Renaud: And finally, let me turn to Derrick Abat, our selective alpha 235 GABA PAM currently in development for both focal epilepsy and panic disorder.

Speaker 4: by having placebo mitigation protocols that each site.

Okay onset epilepsy trial by having placebo mitigation protocols at each site.

Speaker 4: but also it's about patient selection, making sure that the right patient profile is included in these trials, and really monitoring the data, the blinded data to ensure the quality is there. So all taken together, the approach we're taking to help epilepsy to reduce placebo responses, really the same approach we've taken to all our trials to reduce placebo response, and we're confident that we're positioning these trials for the greatest likelihood of success. So all taken together, the approach we've taken to all our trials to reduce placebo response, and we're confident that we're positioning these trials for the greatest likelihood of success.

Ronald Renaud: As we recognize epilepsy awareness month in November and the 3.4 million people living with epilepsy in the United States, we are hopeful that we can bring forward a new treatment option for people living with this difficult disease. Our phase 2 realized trial and focal epilepsy to be our second readout of 2024 coming mid-year. We've also initiated our adapt trial, a phase 2 proof of concept trial in panic disorder. Behind our mental late stage pipeline is an innovative discovery engine that is focused on bringing forward additional novel mechanisms to address neuroscience diseases.

But also it's about patient selection, making sure that the right patient profile.

As included in these trials.

And really monitoring the data and the blinded data to ensure the quality is there. So all taken together they are really the approach we're taking to help epilepsy to reduce placebo response is really the same approach we've taken to all our trials to reduce placebo response, and we're confident that we're positioning these trials for the greatest likelihood.

Success.

Thank you guys.

Thank you one moment for our next question.

Ronald Renaud: And we look forward to providing greater detail in those programs, including our Kappa opioid receptor antagonist, as we make further progress. I'm quite excited about all that we're doing here at Sarah Bell and all that is to come for our pipeline and the potential benefits we hope to bring to patients. We are well positioned as we go into 2024 to truly transform what is possible in neuroscience.

Okay.

Speaker 2: And our next question comes from Paul Matthijs of Stiefel.

And our next question comes from Paul Matteis of Stifel.

Speaker 8: Great, thanks so much and congrats on the progress. I honestly wanted to ask a really similar question on immracidine and that is related to this recent Tar 1 setback and the implications of that. I guess when you look at that data and the huge placebo response they saw on anything else when that within those results.

Great. Thanks, so much and congrats on the progress I don't honestly wanted to ask a really similar question on <unk> and that is related to this recent tier one setback and the implications of that I guess when you look at that that data and the huge placebo response rates saw him anything else within that within those results.

Ray Sanchez: With that, I'll now turn the call over to Dr. Ray Sanchez, a chief medical officer, to provide some added color about our lead programs. Right? Thank you, Ron, and good morning everyone. I want to echo Ron's sentiments about the excitement around our pipeline.

Speaker 8: What sort of metrics are you tracking specifically on a blinded basis in the MRAC with the in studies? Beyond the obvious, like just change in pants.

What sort of metrics are you tracking specifically on a blinded basis and the <unk> studies beyond the obvious like just change in patterns.

Ray Sanchez: As a former clinician, I can tell you that I am energized by the potential we have here at Sarah Bell to make a meaningful difference in the lives of patients with neuroscience diseases. Beginning with the reckoning, our empower program is advancing and data are expected in the second half of 2024. Preserving data quality while mitigating placebo response risk remains the utmost priority for these trials and we are pleased with our recent efforts to reinvigorate enrollment.

Speaker 8: But I guess today give you confidence that you're getting the patient and site quality that you intended or hope to. And then on the capitol, I want to ask a quick question for John , just the back of print and a ticker print both site really high selectivity for capo over mu. What's behind your thesis that mu might actually contribute to efficacy in some of the conditions that you plan up for sewing? Thanks so much.

But I guess today give you confidence that youre getting the patient and site quality that you attended or hope to and then on the Capex as I wanted to ask a quick question for John just in the back of <unk> and a ticket print both site really high selectivity for Capa overview.

What's behind your thesis that new might actually contribute to efficacy in some of the conditions that you plan on pursuing thanks, so much.

Ray Sanchez: As a reminder, empower one and empower two are two adequately powered three-arm trials that include adults living with schizophrenia and experiencing an acute exacerbation of psychotic symptoms. We design these trials to potentially meet the criteria necessary to serve as pivotal trials based on what we expect the FDA will evaluate in a registration pack. We're also enrolling our 52-week open-label safety extension trial in Power 3, and prioritizing the completion of non-clinical and clinical pharmacology studies to accelerate a potential registration package for an wrackled unit schizophrenia.

Speaker 4: We'll let Ray take the first part. So, Paul, good morning. Good question. So, you know, we review the data on a monthly basis and sometimes more frequently, but it's blinded.

Yes, I'll, let ray take the first part so Paul good morning, Good question. So.

We review the data on a monthly basis, and sometimes more frequently but its blinded. So really in terms of data quality, we want to ensure that all of the parameters that we're assessing our are correct and that they are not conflicting and so if that occurs we obviously being at the site level to make sure that the raters are dual.

Speaker 4: So really in terms of data quality, we want to ensure that all of the parameters that we're assessing are correct and that they're not conflicting. And so if that occurs, we obviously intervene at the site level to make sure that the Raiders are doing what they need to do or they need to have a refresher and that validation of course occurs frequently with the Raiders.

What they need to do or they need to have a refresher and net validation of course occurs frequently.

Speaker 4: In terms of having the confidence that we're mitigating that placebo response, it's really around other measures that I mentioned earlier, and Michael's question, in terms of looking at the right patients and how do we do that? We have an independent committee that really looks at the patient qualifications to ensure that they meet the criteria for the profile that needs to occur for them to be enrolled in the trial.

The Raiders.

In terms of.

Ray Sanchez: We believe in wrackled unit has tremendous potential in other disease areas and plans for further development or underway. In Alzheimer's disease psychosis or ADP, our phase one healthy, elderly volunteer trial is ongoing, and the result of this trial will guide our clinical development plan as we advance its important indication with a substantial unmet need. Turning now to Tavapidon, our D1-D5 partial agonism Parkinson's disease, our phase three trials known collectively as the temple trials are ongoing along with the corresponding open-label extension in which we are encouraged by a greater than 90% role of a rate.

Having the confidence that we're mitigating that placebo response, it's really around other measures that I mentioned earlier Michael's question in terms of looking at the right patients and how do we do that we have an independent committee that really looks at the patient qualifications to ensure that.

The criteria for the profile of that needs to occur.

Occur for them to be enrolled in the trials. So and then we have a placebo protocol at each site that allows us to standardize the way we actually approach each patient at every site to increase the likelihood of success and mitigate that placebo response, so really we've taken.

Speaker 4: So, and then we have a placebo protocol at each site that allows us to standardize the way we actually approach each patient at every site to increase the likelihood of success and mitigate that placebo response. So, really we've taken the learnings from so many years, as well as the advice from key advisors who understand placebo response that have infused them into our programs. So, we're confident that we're taking all measures and a

Ray Sanchez: We expect data for temple three in the first half of 2024, with data for temples one and two coming in the second half of 2024. We look forward to walking you through the scientific rationale and prior data for Tavapidon, as well as its clinical potential during our investor event in December. With Joriga that, for a selective GABA PAN, we believe there is potential for both anti-epileptic and angelic activity comparable to benzodiazepines with an improved side effect profile.

Earnings from so many years.

As well as the advice from key advisers, who understand placebo response and infuse them into our program. So we're confident that we're taking all measures to give to ensure that that placebo response is mitigated.

Speaker 4: to ensure that that placebo response is mitigated. We're also limiting the number of countries, limiting the number of sites, all which contribute to placebo response. If you look at the trials that you've mentioned, the recent trial that you know.

So limiting the number of countries limiting the number of sites all of which contribute to.

CEVA response, if you look at the trials that you've mentioned.

Ray Sanchez: Unlike benzodiazepines, which are only used for acute episodes due to tolerability, abuse potential of the debilitating side effects to rig a vast novel mechanism of action and anticipated favorable tolerability profile provide the potential for chronic dosage. We expect results from our phase two realized trial and focal epilepsy in mid-year 2024, and we are encouraged by a continued high role of a rate into the realized open-label extension. Beyond focal epilepsy, our adapt phase two trial and panic disorder is currently underway. A new drug has not been approved in panic disorder in nearly 20 years, and we are excited about the potential of providing to rig a vast as a daily chronic therapy to patients in need.

The recent trial that.

Speaker 4: over six countries, over 35 sites in those trials. And so all of that contributes to variability, everything that we're trying to minimize to ensure the greatest likelihood of success.

Over six countries over 35 sites.

And those trials and so all of that contributes to variability everything that we're trying to minimize to ensure the greatest likelihood of success.

Speaker 3: Morning, Paul. Thanks for the question. I the camp will be a reception tag. And so

Good morning, Paul and thanks for the question.

Okay.

Speaker 3: Yeah, to your question about what does new provide in terms of potential therapeutic benefit in indications. And so as an example, what I would do is point it to opioid withdrawal syndrome patients. And so if you think about what it is, you want to achieve potentially with our compound, with our profile. What we can do is we can go through a receptor occupancy range, the capa, where we can have selectivity to capa. And we can go through a receptor occupancy range, the capa, where we can have selectivity to capa.

So.

Yes.

Question about what does you provide in terms of potential therapeutic benefit.

Indications and so.

As an example, what I would do is pointed to opioid withdrawal syndrome patients and so if you think about what it is you want to achieve potentially with our.

Compound with our profile what we can do is we can go through a receptor occupancy range in Tampa, where we can have selectivity to capa, but if we continue.

Ray Sanchez: Cereval's mid-to-late stage pipeline has the potential to bring forward numerous treatments to address some of the most devastating neuroscience diseases, and I am so proud of the team that is working diligently to make the potential of this potential a reality.

Speaker 3: continue to go up the receptor accuracy curve and exposure curves, we can bring in view. And so why does that provide something to us that seems exciting?

Continue to go up the receptor occupancy urban exposure curves, we can bring in view and so why does that provide something that to us it seems exciting.

John Renger: With that, let me turn it over to Dr. John Ringer, our chief scientific officer, to provide an update on our early stage portfolios, John. Thank you, Ray. Good morning, everyone. I'm very pleased that the progress has made in discovery research and early clinical development here at Cereval. Today, I'd like to focus on our CAF opioid receptor antagonist recording program, also known as CDL-354. We have completed both our stingle and multiple sending dose trials, in which CDL-354 has been generally well-tolerated.

Speaker 3: because what you can get is a therapeutic benefit from CAPA and what we believe the potential there is is to reduce.

Just because you can get as a therapeutic benefit from Cabo and while we believe the potential there is to reduce.

Speaker 3: things like the Q and Ducy restatement data that you see in preclinical models where you can remove some of the things that would cause relapse of patients that are undergoing withdrawal, undergoing abstinence from use of opioids.

Things like the cue induced reinstatement data that you see in the preclinical models, where you can remove some of the things that would cause relapse in patients that are undergoing.

Undergoing withdrawal.

Undergoing abstinence from use of opioids.

Speaker 3: But if you think about what you're actually trying to achieve in the long term, it's also reducing the potential for exposure to new agonists. And so if you think about how you could approach that population, you could actually begin with a lower dose range.

Right.

If you think about what youre actually trying to achieve the long term is also reducing the potential for exposure to new agonists and so if you think about how you can approach that population you can actually begin with the lower dose range gain the benefit of the cat, but without having any kind of new antagonism that might reduce withdrawal symptoms and then as the patient.

John Renger: Further, we currently believe we will be able to interrogate a range of receptor occupancies in both the CAF and new opioid receptors. We believe, and anticipate, we'll be able to explore multiple indications of interest, such as major depressive disorder and substance use disorder. Our ongoing phase one receptor agency trial will clarify both CAF and new receptor penetration displacement, preferring carry-droid selectivity across the compound exposure. We recruit the potential impact of this asset.

Speaker 3: gain the benefit of the CAPA without having any kind of new antagonism that might induce withdrawal symptoms.

Speaker 3: And then as the patient progresses, you can actually increase the dose. So you actually bring in the mu antagonism potential. What that does is it has an ability to block the opioid.

Progresses, you can actually increase the dose that you're actually bringing the <unk> antagonism potential and what that does is it has the ability to block the opioid.

Speaker 3: activation if there is an exposure to an opioid in the future of that patient. So let's say they have a relapse they they take take an opioid agnist at that point having an antagonist could benefit that patient population Both as a safety measures in terms of blocking activation with an opioid so you could prevent the potential for harm But you can also you know

Activation, if there is an exposure to an opioid in the future of that patient. So I would say they have a relapse.

John Renger: We'll report a variety of more updates than our plans in the near future. Beyond Cora, we have a growing number of programs, something issued within our labs and exclusively developed here at Cerevel, which we continue to progress, including our him for selective agonist, a PDE for deep sparing antagonists, and a selective team in 175 potential year program.

<unk> taken opioid agonist at that point, having an antagonist could benefit that patient population both of the safety measures in terms of blocking activation with an opioid. So you can prevent the potential for harm, but you can also.

Speaker 3: potentially depending on what exposure they get to what opioid, you can actually prevent the rewarding benefit. And so you can imagine where you would start a patient going through the phase of withdrawal, starting with more of a.

Potentially depending on what exposure they get to what opioid you can actually prevent the rewarding benefit and so you can imagine where you would start a patient going through the phases of withdrawal starting with more of a kappa.

John Renger: We'll provide further updates and plans for these specific programs as a program.

Susan Altschuller: With that, I'm going to turn it over to our Chief Financial Officer, Dr. Susan Altschuller, to review our financial performance for the third quarter. Susan? Thank you, John. Turning to our financial, in October, we opportunistically bolstered our balance sheet with a $499 million capital rate, providing strong validation of Cerevel's potential from both new and existing high quality investors. This additional capital, along with the roughly $758 million in cash, cash equivalents, and marketable securities, the end of the third quarter with, will support our operations into 2026.

Speaker 9: selectivity, dose range, and what you can do is build up that dose range over time, so that if there is an exposure, you have the protection of having a new antagonism benefit on board in that same patient. So, that's how we're thinking about it. Thanks.

Activity dose range and we can do is build up that dose range over time. So that if there is an exposure you have the protection of having a new antagonism benefit onboard and that same patient. So that's how we're thinking about.

Thanks, a lot.

Thanks, Paul.

Thank you one moment for our next question.

Yes.

Speaker 2: And our next question comes from Mohit Pansal of Wells Fargo.

And our next question comes from Mohit Bansal of Wells Fargo.

Susan Altschuller: Turning to the third quarter of 2023, operating expenses were approximately $111 million, comprised of 85 million of research and development expenses, and 26 million of general and administrative expenses. Looking forward, our financial strength enables us to focus on execution and provide optionality to maximize the value of our pipeline. That said, we will take a disciplined approach to resource allocation as we further build our pipeline, advance our lead assets, and prepare for two potential NDA filings in parallel.

Speaker 10: Great, thank you for taking my question and thank you for having an

Great. Thank you for taking my question.

Thank you for having us on the bank for the quarter.

Really appreciate it and congrats.

Speaker 10: I have two questions. One is on Tibetan. In our checks, doctors are suggesting that

Nancy.

Two questions one is on <unk>.

Don.

Jack's doctors ask suggesting that.

The P P dopamine.

Speaker 10: and agonists are a little bit out of fashion. They're not used as much. So could you talk a little bit about how you're thinking about the bar for success clinically, not just.

I can just talk a little bit out of fashion.

Yes.

Could you talk a little bit about how youre thinking about the bar for success clinically.

Ronald Renaud: With that, I will hand the call back over to Ron for his concluding remarks.

Toxic benefit.

Speaker 10: And then on second one, can you remind me about what was the...

Ronald Renaud: Thank you, Susan. At Cerevel, we believe we have an unparalleled pipeline in neuroscience. With multiple mid and late stage readouts across three different assets expected next year, and a balance sheet that provides us with cash runway into 2026, we are focused and aligned on executing our trials, delivering high quality data next year, and as Susan mentioned, preparing for two potential NDA filings. These are exciting times at Cerevel, and I'm so proud to be leading this organization.

It should be and then the second one can you remind me do you go back about when you go back to <unk>.

First of all enrollment and how you got to piggyback. Thank you.

Speaker 4: So, Mohite, thanks for that question. That's a tabapid on. So, if you think about the humble mechanism of tabapid on being a D15 partial agonist that selectively targets those receptors of the direct nagostrade or pathway, really gives us a confidence that it's gonna be a transformative therapy and symptomatically treating Parkinson's disease.

So mohit thanks for that question <unk>. So if you think about that.

Novel mechanism to wrap it up being a D. One five partial agonist that selectively targets those receptors of the direct nigrostriatal pathway really gives us the confidence that it's going to be a transformative therapy in symptomatically treating.

Ronald Renaud: I want to offer my sincere appreciation for all of our employees who work tirelessly every day to deliver on Cerevel's mission. And I also want to thank our investigators and participants in our clinical trials, without knowing what we seek to achieve would be possible.

Speaker 4: You know, clinically we've designed the program to show the benefits of both the model therapy and as an adjunct of therapy and the model therapy, 27 with trials looking at the UPDRS.

Parkinson's disease.

Clinically we have designed a program to show the benefits as both a monotherapy and adjunctive therapy in the mono therapy 27 with trials looking at <unk>.

Operator: Let's open the call for questions. Thank you, as a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. One moment for our first question.

Speaker 4: Part two, which looks at the daily functioning in parts three that looks at the motor symptoms, and that's the primary endpoint in change from baseline is the primary endpoint on that. So to show really the benefits and not only motor symptoms, but the quality of life as impacted by motor symptoms.

Part, two which looks at.

The daily functioning in part through either looks at the motor symptoms and that's the primary endpoint in change from baseline is the primary end point on that so to show really the benefits not only motor symptoms, but the quality of life as impacted by motor symptoms for the adjunctive trial, which is our first trial to readout in the first half of next year.

Speaker 4: For the Adjunctum trial, which is a first trial to read out in the first half of next year, we're looking at the benefit of the tababadon as the best adjunctum treatment with levadova to decrease.

Michael Yee: And our first question comes from Michael Yee of Jeffries. Hey guys, good morning, and thanks for the question. And thanks for the updates, Ron. I know everyone's focused on execution.

Here, we're looking at the benefit of <unk> on ads.

The best Adjunctive treatment with levodopa to decrease.

Speaker 4: the off time, but importantly, increase the on time without troublesome disconnections, which is the primary endpoint, and really what's clinically relevant.

The off time, but importantly increase the on time without troublesome dyskinesia, which is the primary endpoint and really what's clinically relevant. So thats. How we are thinking about that program and really we're thinking of it as really backbone therapy, meaning that when the patient is first diagnosed as being the best.

Ronald Renaud: Two questions. First on emrackling. Obviously, since last quarter, there was some concern about some of the timeline changes. Can you maybe just describe what initiatives give you the confidence that things are progressing on time, and specifically, maybe for the team, what the right patients or the right site selections are? that give you the confidence on executing on that enrollment.

Speaker 4: how we are thinking about that program. And really we're thinking of it as really fact phone therapy, meaning that when the patient's first diagnosed as being the best therapy to initiate patients on and then when leave a dope, I need to be introduced as the best adjunctive treatment. So we're hoping that.

Therapy to initiate patients on and then when levodopa needs to be introduced as the best adjunctive treatment. So we're hoping that.

Speaker 4: If the results read out as we expect that they will next year, that we will then proceed to file an NDA and give patients a transformative therapy for symptomatic treatment of Parkinson's.

If the results readout is we expect that they will next year.

Ray Sanchez: The second question is on epilepsy. There's actually a bunch of competitor readouts happening, and maybe you could help us understand about the placebo arms and what things you're integrating into your study that might help us give us confidence here because that has historically been an issue and I know that's a concern for others as well. Thank you. Yeah, sure. So let me take the first part of your first question and I'll let Ray, you know, address the second part in terms of site selection from racqueting and then and then the placebo work on our epilepsy studies.

<unk> been perceived to file that NDA in patients a transformative therapy for symptomatic treatment of Parkinson's.

The majority of that question Matt.

Speaker 11: So can, and Mohit, can you repeat that question?

So Ken.

Can you repeat that question.

Speaker 10: Yeah, I mean, so the question was, can you remind me what was the reason for slow enrollment in the book?

Yes. So the question was can you remind me what was the reason for.

Slow enrollment in the beginning and how long do you trying to mitigate that I think it was more to deal with.

The fact that you were taking patients off the background medication right I mean, what's the issue there.

Speaker 4: You know, so there are a couple of reasons for the enrollment issues with the epilepsy program. Remember, these are patients who are drug-resistant. They're at least one and no more than three anti-apholastics. They continue on those therapies at the static dose, so those that's not changed.

Ray Sanchez: So look, you know, as we mentioned last quarter, you know, we were focused on trying to address the challenges that we saw with some of the enrollment issues that we had. And look, we're doing that with boots on the ground. You know, I've spent time at sites with Ray and the team and the leader of our clinics and clinical development groups and really working with the sites to see what's going on.

So so there are a couple of a couple of reasons for the enrollment.

<unk> with the.

<unk> epilepsy program remember these are patients who are drug resistant there are at least one and no more than three.

Anti epileptics they continue on those.

And those therapies.

At a static dose that has not changed one of the challenges that that program has had is the fact that the concomitant medications concomitant anti epileptics are 384 inducers. In fact, they are all three eight per induces and we as you know and not allow patients who are on drug.

Speaker 4: One of the challenges that that that program has had is the fact that

Ray Sanchez: And I think we're quite pleased with the progress that we've seen so far and that's why we can stand by the guidance that we've given here in the quarter. That all said, you know, I focus always remain on ensuring the quality of the data and I think that gets to the second part of the question. We're going to maintain, you know, continue to maintain rigorous fight selection and focus on our placebo variability reduction strategies.

Speaker 4: The concomitant medications, concomitant anti-epileptics are 3A4 inducers. In fact, they are all 3A4 inducers. And we, as you know, cannot allow patients who are on drugs that are 3A4 inducers because it impacts the pharmacokinetic profile of the therapy and it will impact the outcome of the trial.

There are 384 induces because it impacts the pharmacokinetic profile of the therapy and it will impact the outcome of the trial. So the challenge there has been to find the right patient profile.

Speaker 4: So the challenge there has been to find the right patient profile, but there are not uncommon medications like carbamazepine, oxcarbazepine and other therapies.

Ray Sanchez: But I'll let Ray address, you know, how we think about the sites and how we think about, you know, all of those things as we continue to make progress here and also talk about our placebo group and epilepsy studies.

There are not on concomitant medications like carbamazepine oxcart <unk> and other therapies that are three aimed for inducers. So.

Speaker 4: that are three and four inducers. So we've been challenged by that. The good news is that John and his team have conducted a drug-drug interaction trial that will allow us to then overcome that.

Ray Sanchez: Thank you, Michael.

Ray Sanchez: Good morning to you. So as you know, Michael, I was historically defined, you know, what does a good site look like? And it's really the access to the right patients and having good solid Raiders and that really determines for the most part the success of the trial. So that's where we have been achieving and are continuing to try to achieve.

We've been challenged by that the good news is that John and his team.

We have conducted a drug drug interaction trial that will allow us to then overcome that that obstacle in phase III, but we really had to know the.

Speaker 4: that obstacle in phase three, but we really had

Speaker 4: to know the actual dose data based on those individuals that are not on those concomitant medications that would impact the pharmacokinetic profile. So what we've done is we've heightened the number of sites, the number of countries.

Actual dose data based on those individuals that are not on those concomitant medications that we did.

Ray Sanchez: But if you look at when we started the immorality trials, he started quite robustly for the first year and then the momentum slowed down in the spring of this year. What we've learned is how to manage the competitive landscape a bit more effectively. And to that end, we're seeing increased momentum in our enrollment without, as Ron mentioned, diluting the data quality in any way. So again, having very close communication with the sites, ensuring that the Raider recertifications occur frequently and continuing that communication ensures us that we have the greatest likelihood of success moving forward.

Pat.

Pharmacokinetic profile. So what we've done is we've heightened the number of sites. The number of countries that we know well to increase the enrollment we are seeing great momentum and so the good news is that we are.

Speaker 4: that we know well to increase the enrollment. We've seen great momentum. And so the good news is that we are planning to read out in mid-year next year. And if the results are what they are, then we can proceed with a robust phase three program.

Our planning to readout in mid year next year and if the results are what they are then we can proceed with a robust phase III program.

Speaker 10: The other thing I might add here, I know there's going to be more questions on Tevapadon, Mohit, and as I mentioned in my prepared comments, we're going to host an investor webcast focused on Tevapadon on December 11th at 10 a.m. So tune into that, and I think if you have additional questions, that'll be a good forum to get some clarity. Thank you very much.

The other thing I might add I know, there's going to be more questions on <unk> and as I mentioned in my prepared comments, we're going to host an investor webcast focused on <unk> on December 11th at <unk>.

Ray Sanchez: In terms of epilepsy and the placebo response is, you know, as you know, that we are seeing placebo response in indications like spinal cerebellar attacks and epilepsy. And that would surprise as many. But we are also taking the same aggressive approach and and dedicated approach to mitigating the placebo response in our in our vocal Hansen epilepsy trial. By having placebo mitigation protocols that each site, but also it's about patient selection, making sure that the right patient profile is included in these trials and really monitoring the data, the blinded data to ensure the quality is there.

So tune into that and then I think if you have additional questions that'll be a good forum to two <unk>.

Get some clarity.

Thank you very much and congrats on the progress.

Thank you one moment for our next question.

Speaker 12: And our next question comes from Joseph Thorn of TD Cowan.

And our next question comes from Joseph Thorn of TD Cowen.

Joseph Thorne your line is open.

Please check your mute.

Ray Sanchez: So all taken together, there would really be a approach we're taking to help epilepsy to reduce placebo responses, really the same approach we've taken to all our trials to reduce placebo response. And we're confident that we're positioning these trials for the greatest likelihood of success, for your success.

Okay.

One moment for our next question.

Michael Yee: Thank you, guys. Thank you, one moment for our next question.

Speaker 2: And our next question comes from Jeff Hung of Morgan Stanley .

And our next question comes from Jeff Hung of Morgan Stanley.

Speaker 13: Thanks for taking my questions. For CDL-871, can you talk about the challenges clinical sites are facing on patient identification for dementia related apathy? And then for the Deriga back, Realized Study and Focal epilepsy, what do you need to see next year to consider the proof of concept of success? Is there a particular bar for reduction in seizure frequency? Thanks.

Thanks for taking my questions for CBL 871 can you talk about the challenges clinical sites are facing on patient identification for dementia related apathy and then for the <unk> realized study until quite Biloxi, what do you need to see next year to consider the proof of concept of success is there particular bar for reduction in seizure frequency.

Paul Matteis: And our next question comes from Paul Matisse of Defal. Great. Thanks so much and congrats on the progress.

Paul Matteis: I honestly wanted to ask a really similar question on immracidine and that is related to this recent tar one setback and the implications of that. I guess when you look at that data and the huge placebo response they saw and anything else when that within those results. What sort of metrics are you tracking specifically on a blinded basis in the immracidine studies? Beyond the obvious, like just change in pans that I guess today give you confidence that you're getting the patient and site quality that you intended or hoped to.

Speaker 4: Hi Jeff, good morning. So the apathy program, the AIDS-711 program is a phase 2A trial that's really experimental in nature. As you know, it's the leading neuropsychiatric syndrome that you see in patients with dementia. And we're conducting in all of the dementia experimentally as a first step. It's also a predictor of disease.

Okay.

Hi, Jeff Good morning, So the apathy program as you know the <unk> program is a phase Iia trial Thats really experimental in nature.

It's the leading neuroscience theatrics syndrome that you see in patients with dementia.

And we are conducting an all of the dimensions.

Mentally as a first step.

Or a predictor of disease progression there's three.

Speaker 4: There's three components and really decreased goal-directed behavior, decreased emotional responsiveness, and lack of motivation.

Ponant sense really.

John Renger: And then on the capitals, I wanted to ask a quick question for John, just the back of print and a take a print both site really high selectivity for capo over mu.

Decreased goal directed behavior decreased emotional responsiveness and lack of motivation the challenge with that is that the landscape is really still trying to understand what that patient profile looks like remember. These are patients that are not agitated theyre not really a problem clinically.

Speaker 4: The challenge with that is that the landscape is really still trying to understand what that patient profile looks like. Remember, these are patients that are not agitated, they're not really a problem clinically, but it does impact their quality of life. It does impact the longevity of their disease. So one of the challenges is really identifying the right patient profile.

Paul Matteis: What's behind your thesis that mu might actually contribute to efficacy in some of the conditions that you plan on pursuing? Thanks so much. It's not everything the first part. So Paul, good morning. Good question. So, you know, we review the data on a monthly basis and sometimes more frequently but it's blinded. So really in terms of data quality, we want to ensure that all of the parameters that we're assessing are correct and that they're not conflicting.

But it does impact their quality of life it does impact the longevity of their.

Our disease so.

One of the challenges is really identifying the right patient profile, so to that and that's one of the challenges that we've encountered but we believe that the therapy has a great potential of being a novel therapy that won't work in that population, but again I think the landscape is trying to catch up and really that.

Speaker 4: So to that end, that's one of the challenges that we've encountered, but we believe that the therapy has a great potential of being a novel therapy that will work in that population. But again, I think the landscape is trying to catch up and really that...

Paul Matteis: And so if with that occurs, we obviously intervene at the site level to make sure that the Raiders are doing what they need to do or they need to have a refresher and that validation of course occurs frequently with the Raiders. In terms of having the confidence that we're mitigating that placebo response, it's really around all the measures that I mentioned earlier. And Michael's question in terms of looking at the right patients and how do we do that?

Speaker 4: clinically understand what that profile looks like. So that's been a limiting step for that program. But we're continuing to move it along. We're continuing to identify the sites that have access to the right patients because that's really critical to get the signal detection that we need for success. So that's where we are with that program.

Clinically understand what that profile looks like so thats been a limiting step for that program, but we're continuing to move it along we're continuing to identify those sites that have access to the right patients because thats really critical to get the signal detection that we need for success.

So that's where we are with that program now and then.

Speaker 4: And then the other question was, for the realized study, what are you looking for for success? What are you looking for? So for epilepsy, for the rigabat, remember, it's 80% powered to detect that at least a 30% placebo adjusted difference in reduction of seizure frequency. So if we achieve that, that's terrific. As you know, we've got.

Paul Matteis: We have an independent committee that really looks at the patient qualifications to ensure that they meet the criteria for the profile that needs to occur for them to be enrolled in the trials. So, and then we have a placebo protocol at each site that allows us to standardize the way we actually approach each patient at every site to increase the likelihood of success and mitigate that placebo response. So really we've taken the learnings from so many years as well as the advice from key advisors who understand placebo response and have infused them into our programs.

The other question was a trigger for the realized study what are you looking for for success.

Right right so for epilepsy for direct about it. So remember it's 80% powered to detect at least a 30% placebo adjusted difference in reduction of seizure frequency. So if we achieve that thats terrific.

Speaker 4: seen on product. We've got Sinovamate that have had very compelling outcomes, which fall into the mid-30s. Capra falls around 28%. So if we achieve our 30% threshold and above,

Got seen on product.

Paul Matteis: So we're confident that we're taking all measures to give to ensure that that placebo response is mitigated if we are also limiting the number of countries limiting the number of sites, all which contribute to placebo response. If you look at the trials that you've mentioned, the recent trial that you know over six countries over 35 sites in those trials. And so all of that contributes to variability, everything that we're trying to minimize to ensure the greatest likelihood of success.

So <unk> made that have had very compelling.

Very compelling outcomes.

Each fall into the mid Thirty's.

<unk> thoughts around 28%, so if we achieve our 30% threshold and above that would be.

Speaker 4: that would be really a successful outcome for us. So we'll stay tuned for that. And based on that data, it'll allow us to then tailor our phase three program accordingly. But based on the mechanism of action and selectivity of this GABA-APAM compound, we are very hopeful that this will introduce a novel therapy that will benefit patients with epilepsy. Great, thank you.

Really a successful outcome for us so we'll stay tuned for that and based on that data and allow us to tailor our phase III program Accordingly, but based on the mechanism of action selectivity of the Gaba Pam compound. We are very hopeful that this will introduce a novel therapy that will benefit patients.

With Odyssey.

Great. Thank you.

Thank you Jeff.

Thank you one moment for our next question.

John Renger: Paul and Paul, thanks for the question and I, the Camp Hope Viewer, Seth and Tagonist. So, yeah, to your question about what does you provide in terms of potential therapeutic benefit and indications? And so, as an example, what I would do is point it to opioid withdrawal syndrome patients. And so, if you think about what it is, you want to achieve potentially with our compound, with our profile. But we can do it.

John Renger: As we can go through a receptor occupancy range at Kappa, where we can have selectivity to Kappa. But if we continue to go up the receptor occupancy curve and exposure curves, we can bring in view. And so why does that provide something to us that seems exciting? Because what you can get is a therapeutic benefit from Kappa. And what we believe the potential there is is to reduce things like the Q and Duce reinstatement data that you see in the preclinical models where you can remove some of the things that would cause relapse and patients that are undergoing withdrawal or undergoing abstinence from use of opioids.

Okay.

Speaker 2: And our next question comes from Greg Svanovesh of Missouho.

And our next question comes from Greg <unk> of Mizuho.

Speaker 14: Hi, this is Wayne for Greg's advantage. Good morning and thank you for taking.

Hi, This is <unk> for Greg Savannah, Richard Good morning, and thank you for taking my question Congrats to the team for the recent capital raise and just two quick questions from us or bracketing, what has been what is needed from non clinical and clinical pharmacology studies in order to support it.

Speaker 14: Congrats to the team for the recent capital raise and just too quick.

Speaker 14: for marketing what is needed from non-clinical and clinical pharmacology.

Speaker 14: in order to support a potential registrational package in schizophrenia and to what drove the decision to proactively raise equity capital ahead of your multiple clinical data.

A potential registrational package and schizophrenia.

What drove the decision to proactively raised equity capital to help your multiple clinical data events in 2024. Thank you.

Speaker 3: Sure, thanks for the question. Yeah, so we have been looking forward to getting the package ready to submit to the NDA. So,

Sure. Thanks for the question.

Yes, so we have.

And looking forward to getting the package ready to submit to the NDA. So.

Speaker 3: summarized briefly, we've done almost all the work that we need to do actually to prepare the preclinical section of the NDA already. So we have we have a few things to finish up, but there is nothing that's going to be on the critical path from from that area at all. So hope that addresses your question.

To summarize briefly we've done almost all of the work that we need to do actually to prepare the preclinical sections of the NDA already. So we are we have a few things that finish up but there is nothing thats going to be on the critical path from that area at all so.

John Renger: But if you think about what you're actually trying to achieve in the long term, it's also reducing the potential for exposure to new agonists. And so, if you think about how you could approach that population, you could actually begin with the lower dose range, gain the benefit of the Kappa without having any kind of new antagonism that might induce withdrawal symptoms. And then as the patient progresses, you can actually increase the dose so you actually bring in the new antagonism potential.

Speaker 6: Yeah, and then, you know, I think on the cap of ways, you know, I, I'll, I'll, I'll add Susan at to this as well, but I, you know, I think largely this was, you know, one, one thing that, you know, we have been talking to a number of investors about over the last few months and, and, and there was a significant amount of interest in, in, you know, doing the raise from, from outside investors. And so we thought it was a good time to do that so that we could really be focused on execution in, in 2024. As we mentioned, is, you know, we're, we're gonna be working on, We're gonna be working on, we're gonna be working

I hope that addresses your question.

Yeah, and then I think on the capital raise.

I'll, let Susan add to this as well but.

Largely this was.

One thing that we've been talking to a number of investors about over the last few months and.

John Renger: What that does is, it has the ability to block opioid activation, if there is an exposure to an opioid in the future of that patient. So let's say they have a relapse, they take an opioid agonist at that point, having an antagonist could benefit that patient population, both as the safety measures in terms of blocking activation with an opioid so you could prevent the potential for harm. But you can also potentially depending on what exposure they get to what opioid, you can actually prevent the rewarding benefit.

And there was a significant amount of interest in doing the raise from from outside investors and so we thought it was a good time to do that so that we could really be focused on execution in 2024, as we mentioned.

As you know, we're going to be working on <unk> in parallel and so to be able to you know.

Speaker 6: in parallel. And so to be able to, you know, have the balance sheet, short off and really have a line of sight and focus on execution on those lead programs.

We have the balance sheet shored up and really have a line of sight and focus on execution on those lead programs.

Speaker 5: was really the primary driver behind that. I'm not sure if this is anything bad, that's using it. You know, we'll continue to be judicious with our spending. I mean, ultimately, what the capital rate enabled us to do, as Ron said, was focus on execution, then runway gets us into 2026, so we can turn over the data cards next year and not have any overhang limiting our upside potential.

It was really the primary driver behind that I'm not sure if there's anything that we can.

John Renger: And so you can imagine where you would start a patient going through the phase of withdrawal, starting with more of a Kappa selectivity dose range. And we could do is build up that dose range over time so that there, if there is an exposure, you get the protection of having a new antagonism benefit on board and that same patient. So that's how we're thinking about it.

We will continue to be judicious with our spending I mean, ultimately what the capital raise enabled us to do as Brian said was focused on execution that runway gets us into 2026. So we can turn it over to the data cards next year and.

Paul Matteis: Thanks a lot. Thanks Paul. Thank you one moment for our next question.

And not have any overhang limiting our upside potential.

Alright, thank you.

Thank you one moment for our next question.

Mohit Bansal: And our next question comes from Mohit Pencil, as well as Fargo. Great. Thank you for taking my question and thank you for having an uneventful quarter.

Speaker 2: And our next question comes from Charles Duncan of Cantor Fitzgerald.

And our next question comes from Charles Duncan of Cantor Fitzgerald.

Speaker 12: Good morning, Ron and team. Thanks for taking the question. Congrats on the progress. Had a quick question on emraclidine and one follow-up on darigabat. On emraclidine, the ADP study, I'm wondering if you could give us a little more color on timing of data.

Mohit Bansal: I have two questions. One is on Tibetan. In our chat, doctors are suggesting that the dopamine agonist are a little bit out of fashion. They're not used as much. So could you talk a little bit about how you're thinking about the bar for success clinically, not just static benefit? What? and then the second one, can you remind me about what was the reason for so enrollment and how you are mitigating that.

Good morning, Brian and team. Thanks for taking the question congrats on the progress.

Had a quick question on <unk> and one follow up on <unk>.

<unk>.

<unk> D. The ADP study.

Wondering if you could give us a little more color on timing of data.

Speaker 12: and really the kind of rate limiting step for enrollment of that study. And what would, you know, what's the key parameter that you're looking for or looking at to decide whether or not to move forward in?

And really the kind of rate limiting step for enrollment of that study.

What.

What's the key parameters that you're looking for are looking at to decide whether or not to move forward in ADP.

Mohit Bansal: Thank you. So, Mohit, thanks for that question and to wrap it on. So, if you think about the novel mechanism of, of to wrap it on being a D15 partial agonist that subtlactically targets those receptors of the direct nitro strato pathway, it really gives us the confidence that it's going to be transformative therapy and symptomatically treating Parkinson's disease. You know, clinically we've designed the program to show the benefits of both the model therapy and as an adjunctive therapy and the model therapy, 27 with trials, looking at the UPDRS, you know, parts two, which looks at the daily functioning and parts three that looks at the motor symptoms.

Sure.

Speaker 6: Yeah, Charles, so as we've talked about in the past, this is more or less a first-of-its-kind type of study, and right now we're in healthy elderly volunteers.

Yes Charles.

As we've talked about in the past this is more or less a first of its kind type of type of study and right now we're in health with healthy elderly volunteers and so we haven't to that end, we haven't given any guidance on when we expect to enroll that study in terms of.

Speaker 6: And so to that end, we haven't given any guidance on when we expect to enroll that study in terms of, I'll add Ray addressed how we're thinking about the indication itself. But just stay tuned on that. That's something that we're looking to move ahead and we're looking forward to. But we're not going to provide any guidance on enrollment on that program at this time.

Mohit Bansal: And that's the primary end point in change from baseline is the primary end point. So, to show really the benefits and not only motor symptoms, but the quality of life as impacted by motor symptoms for the adjunctive trial, which is a first trial to read out in the first half of next year. We're looking at the benefit of to wrap it on as an as the best adjunctive treatment with levido, but to decrease the off time, but importantly, increase the on time without troublesome dyskinesis, which is the primary end point and really what's clinically relevant.

I'll, let ray address.

How we're thinking about the indication itself, but just stay tuned on that that's something that we will continue to move ahead, and we're looking forward to but.

We're not going to we're not going to provide any guidance on enrollment on that on that program at this time.

Speaker 4: And to follow up with that Charles, for ADP, currently we're doing, as Ron mentioned, multiple ascending dose trial and healthy volunteers. There's other work that needs to be done subsequent to that, that will allow us to understand the dosing in that population, which is important because.

Yes.

To follow up with that Charles or ADP currently were doing as Ron mentioned multiple ascending dose trial in healthy volunteers.

Theres other work that needs to be done subsequent to that that will allow us to understand the dosing in that population.

Speaker 4: Very different manifestation of, it's thematically, but also population in terms of the psychotic symptoms that...

Which is important because it's very very different a very different manifestation of symptomatically, but also population in terms of the psychotic symptoms.

Speaker 4: that they experienced, mostly hallucinations and delusions. The good news is we got fast track from the FDA, which will allow us to work closely with them in terms of what does that development program look like. So stay tuned for that. Okay.

They experienced mostly hallucinations and delusions. The good news is we got fast track from the FDA, which will allow us to work closely with them in terms of what this does that development program looks like so stay tuned for that.

Mohit Bansal: So, that's how we are thinking about that program. And really we're thinking of it as really backbone therapy, meaning that when the patient is first diagnosed as being the best therapy to initiate patients on and then when levido, but needs to be introduced as the best adjunctive treatment. So, we're hoping that if the results read out as we expect that they will next year, that we will then proceed to file an NDA and give patients a transformative therapy for symptomatic treatment of Parkinson's.

Okay.

Charles Let me give it a follow up on very good luck.

Speaker 15: Yep, yep. Quickly, I think Ray mentioned that he's encouraged with high rollover rate, probably not a surprise in focal onset epilepsy if there is perceived efficacy. So, I'm just wondering what a high rollover rate means. And more importantly, what do you see in terms of persistence in that open label part of that study?

Yep Yep quickly just I.

I think ray mentioned that he's encouraged with high rollover rate.

Probably not a surprise in Coca Cola onset epilepsy.

If there is perceived efficacy Tom I'm, just wondering what a high roller rollover rate been and more importantly, what what are you seeing in terms of persistence in that open label part of that study.

Mohit Bansal: It's not the dirty back question matter. So, can you repeat that question? Yeah, I mean, so the question was, can you remind me what was the reason for slow enrollment in the beginning and how are you trying to mitigate that? I think it was more to do with the fact that you were taking patients off the background medication, right? What was the issue now?

Speaker 4: So Charles obviously we're always encouraged by patients rolling over into the open label extension, meaning that they are tolerating the therapy well in terms of efficacy. It's really hard to really understand that because the data is blinded and it's in the patient's purview to roll over. They feel that they're spend if it or they want to continue with the therapy.

Yes.

Charles You know obviously, we're always encouraged by.

Ah patients rolling over into the open label extension.

Meaning that they are tolerating the that therapy well in terms of efficacy, it's really hard to really understand that because the data is blinded and.

Ray Sanchez: You know, so there are a couple of a couple of reasons for the enrollment issues with the epilepsy program. Remember, these are patients who are drug resistant. They're at least one and no more than three antiethylaphthics. They continue on those therapies at the static dose so those that's not changed. One of the challenges that that that program has had is the fact that the concomitant medications, concomitant antiethylaphthics are three a four inducers.

It's in the patient's purview to rollover they feel that there is benefit or they want to continue with the therapy. We can't comment on the open label extension data that will be disclosed when we locked that database and that data becomes available mid year next year.

Speaker 15: We can't comment on the open label extension data that'll be disclosed when we lock that database and that data becomes available mid year next year. So, while we review the data for data quality, we don't review it in terms of patterns of anything other than that at this at this juncture. So we'll stay tuned for that data readout in in mid 2024. Thank you look forward to the progress.

So while we review the data for data quality, we don't review it in terms of patterns of anything other than that at this at this juncture. So we'll stay tuned for that data readout in mid 2024.

Ray Sanchez: In fact, they are all three a four inducers and we, as you know, cannot allow patients who are untrugged, they're three a four inducers because it impacts the pharmacokinetic profile of the therapy and it will impact the outcome of the trial. So the challenge there has been to find the right patient profile, but there are not a concomitant medications like Carbamazepine, Xcarbazepine and other therapies that are three a four inducers. So we've been challenged by that.

Okay. Thank you look forward to the progress.

Thank you Charles.

Thank you one moment for our next question.

Okay.

Speaker 2: And our next question comes from David N. Fallam of Piper, San Luis Obispo.

And our next question comes from David <unk> of Piper Sandler.

Speaker 4: Hey, thanks. So just a couple of quick ones. Looking more broadly at Imraq Ladeen, how important is it to develop it and and explore

Ray Sanchez: The good news is that John and his team have conducted a drug interaction trial that will allow us to then overcome that obstacle in phase three. But we really had to know that the actual dose data based on those individuals that are not on those concomitant medications that would impact the the pharmacokinetic profile. So what we've done is we've been heightened the number of sites, the number of countries that we know well to increase the enrollment.

Hey, Thanks, So just a couple of quick ones looking more broadly at <unk>, how important is it.

Two <unk>.

Develop it.

And explore.

Speaker 16: clinical work as an adjunct to D2 blockers? How do you think about that commercially? And then secondly, as you look at the CAPA, can you talk about what you think?

Clinical work as an adjunct.

Two.

Two <unk> blockers.

How do you think about that.

Commercially and then secondly.

As you look at the cap.

Ray Sanchez: We've seen great momentum. And so the good news is that we are planning to read out in mid year next year, and if the results are what they are, then we can proceed with the robust phase three program.

Can you talk about what you think makes sense and MDT vis vis monotherapy or adjunctive therapy.

Speaker 16: in MDD vis-a-vis monotherapy or adjunctive therapy and how you're thinking about it based on the body of data for your competitors and what you've seen to date.

And how youre thinking about it based on the body of data for the year competitors.

Ronald Renaud: The other thing I might add here, I know there's going to be more questions on Tvapodon, Mohit, and as I mentioned in my prepared comments, we're going to host an investor webcast focused on Tvapodon on December 11th at 10am, so tune into that and I think if you have additional questions, that'll be a good forum to get some clarity. Thank you very much, go ahead to the progress.

And what <unk> seen to date.

Thank you.

Speaker 4: Okay. So, hi, David. So, in terms of adjunctive treatment, so, you know, we are very encouraged that we do believe that imraclidine will be a best-in-class muscarinic agent with once-a-day dosing, no need for titration, and a very benign tolerability profile.

Okay. So hi, David So in terms of adjunctive treatment. So we are very encouraged that we do believe that <unk> will be a best in class muscarinic agent with once a day dosing no need for titration.

<unk>.

Benign tolerability profile.

Jeff Hung: Thank you, one moment for our next question and our next question comes from Joseph Thorn of PD Cowan, Joseph Thorn of the line is open, please check your mute. One moment for our next question and our next question comes from Jeff Hung of Morgan Stanley. Thanks for taking my question, for CDL 871, can you talk about the challenges clinical sites are facing on patient identification for dementia related apathy, and then for the Derigabak Realized Study in Folkwap, what do you need to see next year to consider the proof of concept of success, you know, their particular bar for reduction in seizure frequency, thanks.

Speaker 4: No doubt that a junk of treatment plays a role in the clinical landscape and probably has utility. The first step is for us to really understand that dose range in the trials will read out in the second half of next year.

No doubt that adjunctive treatment plays a role in the clinical landscape and probably has utility.

First step is for us to really understand the dose range in the trials that will readout in the second half of next year following that.

Speaker 4: Following that, then we will pursue other programs in schizophrenia. I jump to three, may I?

And we will pursue other other programs in schizophrenia junk.

<unk> treatment may.

Speaker 4: potentially be one of them. So we're not going to comment on that just yet, because we really want to understand the profile of, I'm racially didn't get to frame here first before we consider it as an adjunctive treatment.

Potentially be one of them so.

Not going to comment on that just yet because we really want to understand the profile.

Academia in schizophrenia first before we consider it as an adjunctive treatment.

Speaker 4: In terms of core of MDD monotherapy versus adjunctive therapy, as you know, there are two companies that have done, one has done a monotherapy.

In terms of core MDT mono therapy versus adjunctive therapy. As you know there are two companies that have done one has done the mono therapy. A second one is done the adjunctive therapy.

Speaker 4: The second one is done adjunctive therapy. If you look at the outcomes of those trials that really are very similar, the model therapy to what standard of care has shown and the adjunctive treatment is very similar to what.

You look at the outcomes of those trials that.

Really are very similar the model therapy to what standard of care as shown in the adjunctive treatment as very similar to what the standard of care is adjunctive treatment.

Speaker 4: the standard of care as adjunctive treatment, basically the neuroleptics have shown.

Speaker 4: So, if you think about the value proposition of CORA.

Basically the neuroleptic have shown.

If you think about the value proposition of Cora.

Speaker 4: in as adjunctive treatment to displace the neuroleptics because of a better tolerability profile based on the neuroleptic tolerability profile. That seems like a very

And as adjunctive treatment to displace the neuroleptic because of a better tolerability profile based on the neuroleptic Tolerability profile that seems like a very.

Jeff Hung: Hi Jeff, good morning. So the apathy program as you know, the 871 program is a phase 2A trial, that's really experimental in nature. As you know, it's the leading neuropsychiatric syndrome that you see in patients with dementia, and we're conducting in all of the dementia experimentally as a first step. It's also a predictor of disease progression. There's three components and really, you know, decreased goal-directed behavior, decreased emotional responsiveness and lack of motivation.

Speaker 4: Exciting approach and also has great commercial and also potential, but also in the best interest of the patient. So we think that that's probably the best approach, but we're evaluating all that. We're, we're continuing to understand our core compound internally, which we believe has the potential to be another best in class therapy. So we'll stay tuned for all that moving forward. Okay, that's helpful. Thank you.

Exciting approach and also has great commercial and also potential but also in the best interest of the patient so.

We think that Thats, probably the best approach, but we're evaluating all of that work, we're continuing to understand our core compound internally, which we believe has the potential to be another best in class therapy. So we'll stay tuned for all that moving forward.

Jeff Hung: The challenge with that is that the landscape is really still trying to understand what that patient profile looks like. Remember, these are patients that are not agitated, they're not really problem clinically, but it does impact their quality of life. It does impact the longevity of their disease. So one of the challenges is really identifying the right patient profile. So to that end, that's one of the challenges that we've encountered, but we believe that the therapy has a great potential of being a novel therapy that will work in that population.

Okay. That's helpful. Thank you.

Thank you one moment for our next question.

Speaker 2: And our next question comes from Joseph Tomei of TD Cohen. Hi there, good morning.

And our next question comes from Joseph <unk> of TD Cohen.

Hi, there. Good morning are you able to hear me.

Speaker 13: Yep, perfect. Thank you. Great. Just a quick question on the development on filing strategy. I think you was mentioned earlier that it was going to be a 2025 submission. So, what early and late Parkinson's be filed together? And is there anything else besides from the open label?

Hi can you hear us.

Yeah perfect. Thank you great.

Great just a quick question on the active effort on a filing strategy.

I think it was mentioned earlier that it was going to be a 2025 submission. So what early and late Parkinson's the final together and is there anything else aside from the open label.

Jeff Hung: But again, I think the landscape is trying to catch up and really clinically understand what that profile looks like. So that's a limiting step for that program. But we're continuing to move it along, we're continuing to identify the sites that have access to the right patients, because that's really critical to get the signal detection that we need for success.

Speaker 13: that is kind of gating to that submission. And then maybe a second on the panic disorder study for the Rigobat, I know there's a minimum number of panic attacks that patients need to have, but is there a maximum number that patients could have given that the primary endpoint is panic attack alright Brian , 10 Bos ?????? transplant.

That is kind of gating to to that submission and then.

Maybe a second on the panic disorder study for a rig of that I know, there's a minimum number of panic attacks that patients need to have but is there a max number that patients could have given that the primary endpoint is.

Ray Sanchez: So that's where we are with that program now.

Ray Sanchez: The other question was for the Realized Study. What are you looking for for success? Right, right. So for epilepsy, for the Rigomatt, so remember, it's 80% power to detect that at least a 30% placebo adjusted difference in reduction of seizure frequency. So if we achieve that, that's terrific. As you know, we've got that's seen on product because synomate that have had very compelling outcomes, which fall into the mid 30s, capra falls are on 28%.

Panic attack freedom. Thank you.

Speaker 4: Joseph, thank you for the questions. So for Tim Epidon, yes, we plan to file in 20 to 25. As you know, those studies will read out next year. Nothing is gating. In fact, you know, the open label extension has progressed well. And, you know, those exposures have been met. So we were excited about that potential in the Parkinson's arena.

Joseph Thank you for the question so for <unk>, Yes, we plan to file in 'twenty to 'twenty five as you know those studies will read out next year nothing is gaining in fact the.

The open label extension has progressed well.

And.

Those those exposures have been met so we were excited about that potential.

And up in the Parkinson's Arena.

Speaker 4: In terms of the panic program, you are correct that they have to have at least

In terms in terms of the panic program.

You are correct that they have to have at least.

Speaker 4: eight panic attacks and the most prior to screening and then four panic attacks that in the two weeks of screening in order to qualify for the trial.

Ray Sanchez: So if we achieve our 30% threshold and above, that would be really a successful outcome for us. So we'll stay tuned for that and based on that data, it allows us to then tailor our phase three program accordingly, but based on the mechanism of action and selectivity of the SCABBA APAM compound, we are very hopeful that this will introduce a novel therapy that will benefit patients with epilepsy. Great, thank you. Thank you, Jeff. Thank you, one moment for our next question.

Eight panic attacks in the months prior to screening and then or panic attacks.

But in the two weeks of screening in order to qualify for the trial.

Speaker 4: So, we don't have a floor effect. We actually can show that there is potential to reduce panic attack symptoms. But there is no maximum. So, it's really around meeting the, that minimum threshold. And then from there, you can have as many panic attacks as the patient's experiencing. We're really wanting to ensure, though, that we get the right patient profile that really drives success. And that's why that criteria is set that way. And it's, there's precedent to that, for that.

So we don't have a floor effect, we actually can show that there is potential to reduce panic attack symptoms, but there is no maximum so it's.

It's really around meeting deep.

Minimum threshold and then from there you can have as many panic attacks as the patient is experiencing.

We're really wanting to ensure though that we get the right patient profile that really drive success and Thats why that criteria is set that way and it's there is precedent to that for that so we are.

Speaker 4: So we are continuing to enroll in that program and excited about the potential of Derogavat really being an innovative therapy and a needed therapy.

Is continuing to enroll in that program and excited about the potential drug about really being an innovative therapy and are needed therapy in the Indian <unk> disorder space. So we'll stay tuned for that data in the future.

Yael Wang: And our next question comes from Graig Suvannavejh of Masuho. Hi, this is Yael Wang for Graig Suvannavej. Good morning, and thank you for taking my question.

Speaker 4: in the anxiety disorder space. So we'll stay tuned for that data in the future. Part of Joe's question about filing for Tabapedon was, is it early and or late? Could you just give a little more detail on how you think about the filing for Tabapedon? Right. So when we filed the Tabapedon NDA, we will file all three trials.

Part of Joe's question about filing for <unk> in the earlier <unk> could you just give a little more detail on how you think about the filing for <unk> right. So when we filed that to map. It on NDA, we will file all three trials, so and the open label extension. So we will get a label like others that Bruce.

Graig Suvannavejh: Congrats to the team for the recent capra race and just two questions from us. Graig Suvannavejh, what has been needed from nonclinical and clinical pharmacology studies, in order to support a potential registration package in schizophrenia and to what drove the decision to proactively raise equity capital to help your multiple clinical data events in 2024. Thank you. Sure, thanks for the question. Yeah, so we have been looking forward to getting the package ready to submit to the NDA, so to summarize briefly, we've done almost all the work that we need to do actually to prepare the preclinical section of the NDA already.

Speaker 4: So, at the open label extension, so, you know, we will get a label like others have received for the treatment of Parkinson's disease. So, the NDA will consist of the Temple 3 trial, which will read out in the first half of next year, which is the adjunct of the Libidova trial, the 2-mono-thera-b trials that will read out in the second half of next year, as well as the Temple 3, which is actually the...

<unk> for the treatment of Parkinson's disease. So the NDA will consist of the temporal III trial, which will read out in the first half of next year, which would be adjunctive to levodopa trial at two monotherapy trials that will read out in the second half of next year as well as the temple.

<unk>, which is actually.

Speaker 4: Tuesday, September 4, which is actually the open label extension trial.

Excuse me the temp before which is actually be open label extension trial.

Okay.

Perfect. Thank you very much.

Thank you Jos.

Speaker 2: Thank you. I'm showing no further questions at this time. I would like to turn it back to Ron Renaud for closing remarks.

Thank you I'm showing no further questions at this time I would like to turn it back to Ron Renaud for closing remarks.

Graig Suvannavejh: So we have a few things that finish out that there is nothing that's going to be on the critical path from that area at all. So hope that addresses your question. Yeah, and then, I think on the capra race, I'll add Susan at to this as well, but I think largely this was one thing that we have been talking to a number of investors about over the last few months, and there was a significant amount of interest in doing the race from outside investors, and so we thought it was a good time to do that, so that we could really be focused on execution in 2024.

Speaker 6: So, I'd like to thank everybody for joining us this morning. And keep in mind, again, I just want to remind folks about our Tavapidon Investor Event on December 11th. Thanks, and we'll talk soon.

So I'd like to thank everybody for joining us this morning, and keep in mind again, I, just would remind folks how about our tobacco at an investor event on December 11th Thanks, and we'll talk soon.

Speaker 2: This concludes today's conference call. Thank you for participating in you, may now disconnect.

This concludes today's conference call. Thank you for participating and you may now disconnect.

Graig Suvannavejh: As we mentioned, we're going to be working on two NDAs in parallel, and so to be able to have the balance sheet short off and really have a line of sight and focus on execution on those lead programs was really the primary driver behind that. I'm not sure if there's anything that's Susan. We'll continue to be judicious with our spending. Ultimately, what the capra race enabled us to do, as Ron said, was focus on execution, then runway gets us into 2026, so we can turn over the data cards next year and not have any overhang limiting our upside potential. Thank you. Thank you, one moment for our next question.

Speaker 17: here the

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Ronald Renaud: And our next question comes from Charles Duncan of Cantor Fitzgerald. Good morning, Ron and Teen, thanks for taking the question, congrats on the progress. I had a quick question on Immbracadine and one follow-up on Derrick Abot. Immbracadine, the ADP study, I'm wondering if you could give us a little more color on timing of data and really the kind of rate limiting step for enrollment of that study. And what would, you know, what's the key parameter that you're looking for or looking at to decide whether or not to move forward in ADP?

Ronald Renaud: Yeah, yeah, Charles. So, you know, as we've talked about in the past, this is more or less a first of its kind type of study and right now we're in healthily healthy, elderly volunteers. And so, we haven't, you know, to that end, we haven't given any guidance on when we expect to enroll that study in terms of, you know, I'll let Ray address, you know, how we're thinking about the indication itself, but just stay tuned on that, that's something that, you know, we, you know, we're looking to move ahead and we're looking forward to, but we're not going to, we're not going to provide any guidance on enrollment on that, on that program at this time.

Ronald Renaud: Yeah, so we'll follow up with that, Charles. For ADP, currently we're doing, as Ron mentioned, multiple ascending dose trial and healthy volunteers. There's other work that needs to be done subsequent to that that will allow us to understand the dosing in that population, which is important because it's very, a very different, a very different manifestation of thematically, but also population in terms of the psychotic symptoms that, that they experience, mostly hallucinations and delusions, the good news is we got fast track from the FDA, which will allow us to work closely with them in terms of what this, that development program looks like, so stay tuned for that.

Ronald Renaud: Okay. So then we'll try to bring you to the follow up on Dr. Gilbeth. Yeah, yeah, quickly. Just, I think Ray mentioned that he's encouraged with high rollover rate, probably not as prized in FOCA, FOCA onset epilepsy, if there is perceived efficacy. So I'm just wondering what a high rollover rate means. And more importantly, what, what do you see in terms of persistence in that open label part of that study? Thanks.

Ronald Renaud: Yeah. So Charles, obviously we're always encouraged by patients rolling over into the open label extension, meaning that they are tolerating the therapy well in terms of efficacy. It's really hard to really understand that because the data is blinded and it's in the patient's purview to rollover, they feel that there's benefit of they want to continue with the therapy. We can comment on the open label extension data that'll be disclosed when we lock that database and that data becomes available mid year next year. So while we review the data for data quality, we don't review it in terms of patterns of anything other than that at this juncture.

Charles Duncan: So we'll stay tuned for that data readout in mid 2024. Thank you. Report to the progress. Thank you, Charles.

David Amsellem: Thank you one moment for our next question and our next question comes from David and Salem of Piper Sandler. Hey, thanks. So just a couple of quick ones.

David Amsellem: Looking more broadly at Imraclidine, how important is it to develop it and explore clinical work as an adjunct to to do two blockers? How do you think about that commercially?

David Amsellem: And then secondly, as you look at the capa, can you talk about what you think makes sense in MDD vis-a-vis monotherapy or adjunctive therapy and how you're thinking about it based on the body of data for the year competitors and what you've seen today. Thank you. Okay, so hi, David. So in terms of adjunctive treatment, so, you know, we are very encouraged that we do believe that Imraclidine will be a best-in-class must-curine agent with once a day dosing, no need for titration and a very benign tolerability profile.

David Amsellem: No doubt that adjunctive treatment plays a role in the clinical landscape and probably has utility. The first step is for us to really understand that dose range in the trials will read out in the second half of next year following that. Then we will pursue other other programs since schizophrenia. Adjunctive treatment may potentially be one of them, so we're not going to comment on that just yet because we really want to understand the profile of Imraclidine and schizophrenia first before we consider it as an adjunctive treatment.

David Amsellem: In terms of core of MDD model therapy versus adjunctive therapy, as you know, there are two companies that have done one has done a model therapy. A second one has done adjunctive therapy. If you look at the outcomes of those trials that really are very similar, the model therapy to what standard of care has shown and the adjunctive treatment has very similar to what these standard of care as adjunctive treatment basically the neuroleptics have shown.

David Amsellem: If you think about the value proposition of Cora in adjunctive treatment to displace the neuroleptics because of a better tolerability profile based on the neuroleptic tolerability profile, that seems like a very exciting approach and also has great commercial and also potential, but also in the best interest of the patients. So we think that that's probably the best approach, but we're evaluating all that. We're continuing to understand our Cora compound internally, which we believe has the potential to be another best in class therapy. So we'll stay tuned for all that I'm moving forward. That's helpful. Thank you. One moment for our next question.

Joseph Tomay: And our next question comes from Joseph Tomay of TD Cohen. Hi there. Good morning. Are you able to hear me? Yep, perfect. Thank you. Great.

Joseph Tomay: Just a quick question on the development on filing strategy. I think you was mentioned earlier that it was going to be a 2025 submission. So what early and late Parkinson's be filed together? And is there anything else besides from the the open label that is kind of gating to do that submission?

Joseph Tomay: And then maybe a second on the panic disorder study for Derigabat. I know there's a minimum number of panic attacks that patients need to have, but is there a maximum number that patients could have given that the primary endpoint is panic attack freedom? Thank you. Yes, Joseph. Thank you for the questions. So for Tomapidon, yes, we plan to file in 20 to 25. As you know, those studies will read out next year.

Joseph Tomay: Nothing is gating. In fact, you know, the open label extension has progressed well. And you know, those exposures have been met. So we were excited about that potential in the Parkinson's arena. In terms of the panic program, you are correct that they have to have at least eight panic attacks and the most prior to screening and then four panic attacks in the two weeks of screening in order to qualify for the trial.

Joseph Tomay: So we don't have a full effect. We actually can show that there is potential to reduce panic attack symptoms, but there is no maximum. So it's really around meeting the minimum threshold. And then from there, you can have as many panic attacks as the patients experiencing. We're really wanting to ensure though that we get the right patient profile that really drives success. And that's why that criteria is set that way. And there's precedent for that.

Joseph Tomay: So we are continuing to enrol in that program and excited about the potential derivative at really being an innovative therapy and a needed therapy in the anxiety disorder space. So we'll stay tuned for that data in the future.

Joseph Tomay: And a part of Joe's question about filing for tobacco was earlier and or later. Can you see we just give a little more detail on how you think about the filing for tobacco on, right? So when we filed the tobacco on NDA, we will file all three trials. So at the open label extension. So, you know, we will get a label like others have received for the treatment of Parkinson's disease. So the NDA will consist of the tempo three trial, which will read out in the first half of next year, which is the adjunctive delibidopa trial, the two monotherapy trials that will read out in the second half of next year, as well as the tempo three, which is actually the, excuse me step before, which is actually the open label extension trial. Perfect. Thank you very much. Joseph. Thank you.

Ronald Renaud: I'm showing no further questions at this time. I would like to turn it back to Ron Renaud for closing remarks. So I'd like to thank everybody for joining us this morning and keep in mind again, just remind folks about our to vapodon investor event on December 11th. Thanks and we'll talk soon. This concludes today's conference call. Thank you for participating and you may now disconnect.