Q2 2023 Cerevel Therapeutics Holdings Inc Earnings Call
Yeah.
Good morning, and welcome to the fear about Therapeutics second 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.
Now I'll hand, the call over to Makela Street, Vice President of Investor Relations.
Thank you good morning, everyone. We appreciate you joining us for our second quarter 2023 earnings call on today's call you'll be hearing from Rhondda now, our president and Chief Executive Officer, Dr. Rey Sanchez, our Chief Medical Officer, Dr. John Wrangler, Our Chief Scientific Officer, and Dr. Susan offshore our Chief financial office.
Sure.
During our call today, please refer to our press release from this morning detailing our second quarter 2023 financial performance as well as our updated corporate presentation, both of which are available on our website I would like to remind you that we will be making forward looking statements that reflect our current views related to among other things the potential attributes and benefits.
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 I will now hand, the call over to Robert now President and CEO of share Bell to provide an overview of our achievements and outlook good.
Morning, everyone and thank you for joining us for our second quarter 2023 business results call I'm.
I am pleased to be here with all of you today as the new President and CEO of this exceptional company.
And my time at Cerro belt, so far I've seen immense passion and dedication from our team and I'm incredibly enthusiastic about our science and innovation as we aim to build a world class Neuroscience company.
Before getting into the specifics, let me share some of my initial observations of this organization.
Service comprised of smart energized with deep experience in neuroscience drug energize people with deep experience in neuroscience drug development and notable track records of success.
We have an unparalleled pipeline with the potential to bring new treatments to some of the most challenging neuroscience diseases.
We're also focused on disciplined execution aware that patients and loved ones are waiting for these important new treatment options.
Before I joined the company I was impressed with its enviable portfolio now that I've had an opportunity to work with this team and dive deep into the details of the science and the programs I'm, even more excited about all we have ahead of us.
Turning to our lead programs, let me start with <unk> or M for selective positive allosteric modulator of Pam.
I'd say, we're about we're exploring all aspects of the M. Four muscarinic pathway as we seek to build a franchise that can address a broad range of diseases via this mechanism.
<unk> is a highly selective for them for and we believe it has the potential to change the way, we view and treat schizophrenia.
All timers disease psychosis, and other serious mental illnesses.
We announced this morning that arm rack with each base to empower program is now expected to read out in the second half of 2024.
A change resulting from recent slower than expected enrollment.
We are deploying measures to restore our pace of enrollment and I am personally working closely with ray and the team on mitigation strategies.
Ray will provide more details, including our go forward approach and our reasons for confidence in our updated timing.
As always we're focused on ensuring the quality of Iraq within data and we'll be thoughtful in our plans to add new sites are countries to ensure we maintain a rigorous standards.
Moving now to wrap it on the first day, one Deepak partial agonist in development for treatment of Parkinson's disease.
We believe our Registrational phase III tempo program has the potential to establish the map it onto the backbone treatment across the spectrum of Parkinson's disease therapy.
<unk> has the opportunity to serve as both the preferred mono therapy for newly diagnosed patients and the ideal adjunctive therapy to love adult, but as the disease progresses.
We expect sample three to be our first data readout of 2024, while data from Tampa. One example, two will read out in the second half of 2024.
Turning now to the rig about our selective alpha <unk> three five Gaba Pam currently in development for both epilepsy and panic disorder.
Yeah.
Our phase II realized trial in focal epilepsy is designed to address an area of tremendous unmet medical need for patients who need better control. Their seizures. We expect this program to be our second data readout next year coming mid year 2024.
We also recently initiated the adapt trial during about a phase II proof of concept trial and panic disorder.
We have confidence in the potential of the rig about to treat anxiety related disorders, given its selective receptor subtype profile and it is avoidance of Alpha one receptor subunit. We believe is the main driver of side effects for benzodiazepines.
On the financial front, we have a strong balance sheet that is expected to support all of our anticipated late stage data Readouts next year.
Before I hand, it over to Ray I wanted to take a moment to welcome the newest members to this arabel executive team, Dr. Susan Altshuler, Chief Financial Officer, and Paul Burgess, Chief business development and strategic operations Officer.
Susan brings financial management, Investor Relations and business planning experience from leading Biopharma companies.
Paul brings deep experience in corporate development business development and operations his skills. During this important juncture for Ceragon.
All three of us have been warmly welcomed by serve all senior leaders seasoned leadership team.
I am proud of how in just seven weeks, we come together as a new invigorated executive team I'm energized by all that we will do together along with all of our survey will colleagues to build a world class Neuroscience company with multiple commercial products.
With that 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.
Let me start with <unk>, our highly selective and for positive allosteric modulator or Tam, which we are currently developing in schizophrenia, alzheimers disease psychosis or ADP.
And 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 in this important indication.
Turning to schizophrenia, and our phase II empower program as a reminder, in power one and empower to our two adequately powered three arm trial does that each include 372 adults living with schizophrenia and experiencing an acute exacerbation of psychotic symptoms.
The first trial studying them rapidly at 10 milligrams and 30 milligrams once daily versus placebo and a second trial <unk> milligrams and 30 milligrams once daily versus placebo with.
We designed these trials to potentially meet the criteria necessary to service pivotal trials based on what we expect the FDA will evaluate in a registrational package.
We're also enrolling in power three our 52 week open label safety extension trial and prioritizing the completion of non clinical and clinical pharmacology studies to accelerate a potential registrational package for a record unit schizophrenia.
As Ron discussed.
We have seen a recent slowdown in enrollment enrollment in this program had strong momentum at the outset, but we've observed a slowing of that initial pace in recent months with some ex U S sites, taking longer to standup and planned and several U S sites, yielding slower enrollment.
We are responding accordingly, with mitigation measures, including increased site and investigator outreach and plans to enhance enrollment in existing sites. We will also look to add additional high quality sites in the U S and one to two more countries without going beyond a total of 30 sites per trial.
Reserve data quality and mitigate the placebo response risk.
We will continue to stay laser focused on executing these trials, while maintaining the quality of the data with.
We recognize the central importance of in record into cerebellum, our investors and the patients we seek to serve and we are acting with deliberate speed to address these potential headwinds and restore our prior pace of enrollment.
With the strong efforts of the team I am highly confident in our ability to deliver within these revised timelines.
Turning now to tap it or D $1 five partial agonist, our phase III trials known collectively as the tempo trials are ongoing along with the corresponding open label extension and which we are encouraged by high rollover rate of 90% or more.
We expect data for temporal three to be our first data readout in 2024 with data for <unk>, one and two coming in the second half of 2024.
I will now discuss the rig about our selective Gaba Pam which is currently in development for epilepsy and panic disorder.
We believe the rig that has the potential for both anti epileptic that anxiolytic activity comparable to currently available benzodiazepines.
<unk> side effects.
<unk> novel mechanism of action and expected Tolerability profile provides the potential for a new treatment option that may be used chronically.
Our phase III realized in focal epilepsy is progressing and we expect results in mid year 2024.
Here. We also are encouraged by our continued high rollover rate into the realized open label extension.
Beyond epilepsy, we're excited about expanding the potential applications of <unk> through the initiation of the adapt trial, a phase II trial and panic disorder.
The adapt trial will evaluate <unk> about 25 milligrams twice daily versus placebo and enrolled 228 patients with panic disorder.
The primary endpoint will be the proportion of subjects, who are free of panic attacks. During the last two weeks of the maintenance period and key secondary endpoints will be the change from baseline in the panic disorder symptoms scale or <unk> total score at week 14, and the change from baseline in panic attack frequency during the last two weeks of the maintenance period.
A new drug has not been approved and panic disorder in nearly 20 years. So we are excited about the potential of providing drink about to patients in need of new therapies 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.
Thank you Rick and good morning, everyone.
I am very pleased with the progress that we've made in discovery research and early clinical development.
Let's begin with our Kappa opioid receptor antagonist recorder program also known as CBL 354.
We recently completed both our single and multiple ascending dose trials in which a broad range of doses were administered and considered well tolerated.
These trials will enable us to interrogate a wide range of receptor occupancy is at both the Kappa opioid receptors.
This dose range of buyers with the potential for a selection of doses that can either preferentially target the kappa receptor or provide a dual inhibitory activity at both capa and <unk> receptor is simply by increasing exposures.
We anticipate that this dose flexibility will enable us to explore efficacy and better understand tolerability across a number of populations of interest which include major depressive disorder post traumatic stress disorder and substance use disorder.
Our results to date demonstrate pharmacokinetics to support once a day administration and the ability to dose without regard for meals.
In addition, we demonstrated a predictive dose related change in serum biomarkers are consistent with opioid antagonists.
We're also pleased to announce that we received additional night it.
National Institutes of drug abuse, Nida grant funding of up to $8 $1 million over three years to support the ongoing clinical development of CVR three quarter, including our recently initiated phase one receptor occupancy trial that will include determination of both capa and <unk> receptor pet tracer displacement for displacement to further characterize <unk>.
<unk> cross compound exposures we.
We anticipate providing updates on our internal phase one data and plans for next steps in the future.
Moving to other exciting news in our early stage pipeline. We recently received a grant from the Michael J Fox Foundation for Parkinson's research to advance our internally initiated T. NIM 175 program, which is aimed at slowing and stopping the progression of Parkinson's disease.
As context, <unk> 175, or transmembrane protein 175 is the recently identified and structurally unique protein, which is believed to be an Indo lysosomal potassium in proton channel.
Target has been a particular interest to our team because of its strong generic relationship to idiopathic Parkinson's disease.
Our team in 175 program consist solely of internally to identify compounds that have been discovered by our share of Bell <unk> and sciences.
It represents one of our initial efforts to develop potentially disease modifying therapies continue to.
Intended to stop the progression of debilitating neurodegenerative disease.
We look forward to working closely with the Michael J Fox Foundation.
This grant will support our programs research efforts and enable progress we made in finding promising new chemical matter I look forward to sharing more details of the compelling science behind this effort as we continue to advance this program.
And now going to turn it over to <unk>, Chief Financial Officer, Dr. Susan <unk> Schuller, Who's going to review our financial performance for the second quarter Susan.
Thank you John .
The second quarter of 2023 operating expenses were approximately $97 million.
Rise of $74 million of research and development expenses and $23 million of general and administrative expenses.
We ended the second quarter with roughly $825 million in cash and marketable securities on the balance sheet, which provides us runway comfortably into 2025.
Opportunistically bolstering the balance sheet remains a priority for the company to ensure we maintain the financial strength to maximize the value of our broad pipeline.
As our track record shows we will be thoughtful about how we access capital and will consider a variety of options, including evaluating partnerships and regional collaborations in service of meaningful value creation for our patients and our shareholders.
With that I will hand, the call back over to Ron for his concluding remarks. Thanks Susan.
<unk>, we believe we have an unparalleled pipeline in neuroscience with.
We're thinking big and as I started my tenure as CEO I can tell you that the potential of this company is inspiring.
We are committed to bringing important new treatment options to patients facing some of the most devastating neuroscience conditions, including schizophrenia Alzheimers.
Alzheimer's disease psychosis, Parkinson's disease, Parkinson's disease, epilepsy, and panic disorder.
I am pleased and honored to be at the helm of this company and to be part of the incredible work, we're doing together here.
I've gone under the Hood and we've taken a close look at our operations and I can assure you. We are focused on execution. Our entire executive team is working together to deliver on promises to bring new medicines to patients as quickly as possible.
With our to that but on temporal three data expected in the first half of 'twenty four.
Followed by during about realized data mid year and the busy second half of 'twenty, four with empower and remaining tempo readouts.
I look forward to updating you as we advance this robust portfolio.
I'd like to conclude with my sincere thanks to our employees and to the patients and investigators in our clinical trials, who graciously make everything we do possible.
With that let's open the call for questions.
As a reminder to ask a question. Please press star one one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one one again, please stand by while we compile the Q&A roster.
As a reminder to ask a question. Please press star one one on your telephone and wait for your name to be announced.
To withdraw your question. Please press star one one again.
At this time I would now like to turn the conference back over to Ron Renaud for closing remarks.
Operator, I think there should be some folks in the queue.
I would say demand here, so could you double check please.
One moment.
Yes, our first question one moment for our first question.
Our first question comes from the line of Amit <unk> from Evercore ISI.
Hi, This is Mike <unk> on for Omar Thanks, So much for.
Question Welcome Ron looking very forward to working with you a few for me I just wanted to better understand the drivers of the.
Schizophrenia trial delays.
Second if you can.
Is the CRO that youre using and Ron.
Just as an outsider coming in with a wealth of experience that theres something seems to be that different in the conduct of.
Psychosis schizophrenia studies, what do you think it is that in general is causing.
Them to be more delayed maybe reasons outside of Covid. Thank you.
Yes, so thanks for the questions.
I'll, let ray provide some some colors on some of the some color on some of the logistical issues but.
Basically.
We said this in our prepared remarks, we'll say it again.
We know the importance of <unk> the potential for this to be a truly transformative therapy for patients.
And I think you can you can hear in our comments that we're moving to bring this ahead as quickly as possible, but while we do this we're going to continue to be incredibly rigorous in our site selection with an eye towards minimizing variability in some of the other factors that that Ray can talk about in terms of things that play.
Our role in placebo effect, but we're not going to we're not going to compromise on this at all.
To your point, yes, undeniably we've reported delays in the past with some of our other programs dovap. It on the rig about and now in rack with Ian I think what I would tell you here is as I'm, New Susan is new here Paul is new year, we're taking a fresh look at everything we're putting a fresh set of eyes on how do we do everything.
And how can we do a better job at forecasting these enrollment timelines. We know that this is critical given the importance of <unk> in their respective indications and what I can tell you is we do need to do a better job of this and we're committed to getting this right and these are these are some of the things that we're looking at right now with regard to some of.
Some of the specific issues around.
The factors driving delay in the CRO.
I'll, let ray take that yes. Thank you Ron and good morning, Mike So Mike what I can tell you is that all of the principal investigators I continue to talk to you in the rapid ink program are extremely excited about this new class specifically them rapidly and because of its once daily dosing and no need for titration. So theres a lot of excitement there we are.
We're continuing to understand the root cause of some of these delays at the site level.
Accordingly, because we strive to use the best sites, we're not going to compromise on data quality data integrity trying to manage and mitigate placebo response.
Just to understand that each of the sites also.
They rely on referrals to ensure that we get the right patients and Thats the key thing getting the right patients and so.
In doing so some months are better than others, but collectively that those are some of the bottlenecks that really hold getting the right patients into the trial, but again because we are so focused so laser focused as I said in the call earlier.
Getting this right, making sure that we just don't exacerbate the placebo response that we work closely which we are with the investigators who are heightening our communication plan.
With them to ensure the greatest likelihood of success for these trials. So that's really our main focus.
And and those are some of the challenges that we're up against in terms of the.
The sites and what they're experiencing.
Okay.
Got it thanks, so much.
Thank you all enrollments for our next question.
Our next question comes from the line of Mohit Bansal from Wells Fargo.
Great. Thank you very much for taking my question and welcome Ron Susan.
Yep.
Looking forward to working with you.
So my question is also on the same line because so Ron let me in.
The limited and you have expanded the company.
When you look at the timeline I mean.
There could be one or two reasons one is obviously.
Was this the case.
Little bit providing aggressive timelines to investors and now realizing thats, probably not fair or it is a little bit on where.
There is something fundamentally changing in the marketplace.
It is hard to enroll these patients I'm asking this because I mean.
As expected <unk> trials. This looks like it is a chart trial. So it is still we haven't still ways away from.
From the point, where we can say that the trial is fully enrolled so just trying to understand if it is like what exactly is the underlying causes.
And then the second part of my question is that.
So you mentioned that you are doing some more work.
In terms of figuring out.
The stride data package for the.
The filing for <unk>.
Asset.
How should we think about the timeline, particularly <unk> in terms of filing timelines and how much data you need to generate there. Thank you.
Yes, so thanks for the thanks for the good words.
First of all again, I'll keep coming back to this and you'll hear US say this over and over again, our focus remains on ensuring the quality of data and we're going to be rigorous in our in our site selection, we're going to be rigorous and the investigators that we work with and our focus on placebo variability reduction strategies.
You've seen in the industry what happens as the number of sites increase as the number of patients increase that variability increases and that is something that we are really focused on on minimizing and so we are just not going to compromise in any way shape or form on the quality of the site.
That we work with I know there is theres going to be a natural theres always a natural inclination at the sponsor to to.
So want to speed things up to want to hurry up and meet the timeline. It's unfortunate that we pushed this out on the other hand again, we're not going to compromise the quality.
Of the sites that we're using here and so we're going to continue to stay focused on that and so with that data reading out in the second half.
Don't want to point towards exactly when we would file anything with the with the agency that being said, we're putting all of the pieces in place and we've been putting all the pieces in place to be prepared to file an NDA for firmer equity in here and so we're working down that pathway at the same.
I'm that we're focused on on execution of this program and that's all happening.
In conjunction with each other.
Thank you.
Thank you one moment for our next question.
Our next question comes from the line of Greg <unk> from Mizuho Securities.
Hey, thanks.
Thank you for taking my question, Ron Susan and Paul My Congrats on the new positions and I look forward to working with and partnering with you I have two questions. If I may 1st Ron just just bigger picture as you.
Step in as new CEO .
Maybe just a broad question on <unk>.
Whether you are coming in with a view that.
We need to do a review of the business and you need six months before making any changes any kind of thoughts on like overall strategy.
Bigger picture thoughts and then my second question.
Maybe it's best for array with regards to this.
<unk>.
Trials and I just wanted to ask in light of the phase III negative readout for the Synovia and Otsuka Tar one program, where it was.
Ascribed to a very large placebo response can you just remind us.
The measures that you're putting in place in order to best minimize the chance that you'll potentially see a high placebo response in order to ensure that we minimize the risk of a negative trial outcome. Thanks.
Yes. So thanks for the question and I'll take the first part of that and then as.
You are asked to let ray take the I think the second part so absolutely coming in were seven 7% or eight weeks into this.
Obviously.
I want to turn it over as many stones and make sure from an operational perspective, we are working as as as efficiently and as effectively as we possibly can there is a lot going on here we have.
More than 2000 patients on <unk> studies right now.
Double digit number of studies not to mentioned the number of those studies that are part of Registrational pathways and so I will tell you my initial views on everything here at <unk> is that our company. Our fundamentals are very strong I believe we have an unparalleled pipeline of neuroscience.
<unk> assets I think you'd be I think it struggled to find another portfolio of neuroscience assets in the industry.
That looks as broad and as robust as what we have here in <unk>.
A few moments ago was quite so bring anything to the field. So what we're doing and what we've mentioned before is you know is ensuring that we get the right patient so.
And how you do that is really critical and so we have a process in place to do that that really looks at the patient qualification because as you know and others know that the patient profile really drive the outcome of these trials as does the quality of the Raiders of the site is when we say quality sites were talking not just about the ability to access the right patients, but their ability <unk>.
Actually to have competent really robust raiders and so we have a plan in place to address that other things that we're doing is we have a placebo mitigation protocol at each of the sites that allows for certain interventions to be made or not be made to ensure that the placebo response skeptic pay as much as possible, but also limiting the number of.
Sites limiting the number of countries and when you do that invariably you're gonna see waxing and waning of the enrollment. However at no point do you to lose the data any position you trough with the greatest likelihood does that so collectively that's the confidence that we have the <unk> physician for the greatest likelihood of success and up.
Thank you one moment for next question.
Our next question comes from the liner to Xena MA from Bank of America.
Hi, Good morning, an also ran in team congrats on the new Ross and we look forward to working with you I just wanted to clarify you've mentioned now on a call several times.
Find the right patients.
Or any other program can you give us a little bit of color on on what the right patient looks like and how that might translate into what you ultimately think.
The market opportunity would be in schizophrenia would it be for the broader population or are you thinking that there is a a subset of the population, which could still be quite large that might be best suited for your child and then secondly can you just remind us what your cash runway S. Thanks.
So from.
From the first part of your question over to Ray and Susan I'm Gonna start compared to being a good morning. Thank you for that question. So so the the trials are meant for the generalized schizophrenia population when we talk about the right patient I remembered we're conducting clinical trial. So we're trying to detach the signals. This therapy has and so in order to do that <unk>.
To refine the patient population in terms of the severity of disease. So as you know we have a pan score of at least 85 up to 120 in those crazy and and a variety of other criteria truly to define the patient population. That's gonna really give you the best opportunity to detect the signal oven rack is going to be.
A robust therapeutic in the population.
Over it doesn't mean that you're restricting the population in any way to suggest that it only works in certain patients and not others. It's really for the general schizophrenic population, but because you are conducting a clinical experiment you have to have certain controls in place to ensure the greatest likelihood of success.
Great.
Thank you as noted we are well capitalized and ended the.
The second quarter with 825 million on the balance sheet, so that funds us through all our key data Readouts next year and comfortably into 2025. So we will continue to be thoughtful about resource allocation an opportunistic is in bolstering the balance sheet, but we feel very good about our cash position.
Thank you one moment for next question.
Our next question comes from the line of <unk> iPhone.
Hey, Thanks, so much for taking my questions are and Mercury Dean we we noticed that a drug drug interaction study was put on clinical trials Dot Gov is that just a typical study check the box for 90, a or are you actually expecting to elucidate and interaction that could.
Significant as it relates to how people prescribed the drug and then separately I had a couple of pipeline questions on the cabinet program I was curious from your perspective now that it seems like we have a couple of external studies, suggesting this target has an anti depressant effect I just do you agree with that.
Do you plan on moving more quickly now and depression, and then John to your point on our dose range as it relates to Kappa and you do we want to be targeting new as well I was under the impression that that produce more side effects or maybe you could just kind of speak to that scientific hypothesis behind your compound and how you're thinking about it.
Thanks, so much.
It sounds like drunk and take.
[laughter] you don't Wanna trailer.
Alright baseball appreciate.
<unk> questions here, so yeah. The D D. I profiling is a standard for Registrational package and so.
As you know you have to inform the label and potential <unk> in any kind of a dose adjustments to the physician can make the right decision for each patient based on their background therapies and so.
These are pretty much standard.
<unk> yeah. So we're really excited so now as you mentioned the second company has shown uhm.
You know the Bruce Bruce.
Carly company USA showed a nice potential for looking at the core mechanism of action as an adjunct understand or care and M. D. D. Major depressive disorder. Now recently, we've seen another colleague company showing the amount of therapy also showed a nice nice perfect positive benefit and the M. D D as.
As a mono therapy. So we will we think this is very consistent with the mechanism of action. What's been published quite extensively preclinical models. As you know there's a lot of potential for this mechanism to actually go beyond M D D and so.
That's that's gonna lead into the answer to the next one which is.
As you know we've been working closely with night, we received like I mentioned this morning, an additional funding to go.
Four to BB more studies, there and the clinic.
<unk> I can see being one of them and so you know when you think about what it is that you want to achieve.
So both if you look at the boat competitor molecules. The first one is a very kind of.
Selective approach that we've seen as the adjunct and what you see with the more recent data is one that we consider to be highly selected to captain so.
Both cases, you have a nice demonstration that either mixed activity or highly selective activity is effective.
However, as you think across the different potential indications could be <unk>.
Some of those may actually benefit from having some you activity and so what we wanted to do is be able to think about how we take this particular molecule and actually look at dose ranges that are appropriate for different indications. So as an example, if you went into substance used to store or study an opioid patients you definitely did.
I don't want to have new activity, because you could induce withdrawal, which is extremely unprison unpleasant for the patient and so and that it would be a different dose range and potentially.
Another indication, where you would actually benefit from having some new new activity. So.
With this molecule knowing that we can cover a pretty broad range and it will tolerate his passion. It gives us a potential to actually look at those ranges are appropriate for different indications based on what we know about <unk>.
You know the ideology of the disease and what benefit each group and so it's a it's a really exciting molecule really exciting science, so stay tuned and we'll share more as we can.
Extra.
Thank you for.
Thank you one moment for next question.
Our next question comes in the line of Joseph phone from T D Cowan.
Good morning, and thank you for taking my questions. Maybe the first one is there anything about marketing and and the ADP I guess, what would you be looking for in that healthy volunteers thirty-two advanced the next level and I guess, how tied or the empower resolved to advancement in ADP do you want to wait for the empower studies to read out uhm before committing.
To the next step and then maybe just a quick one on the drink about panic disorder study can you come in a little bit on how severe patients symptoms are at baseline in terms of pretreatment or or I guess, just baseline severity and then when we think about through the titration of maintenance.
Period can patients use any rescue medications, if they do have an attack. Thank you.
So I'll I'll turn it over to John M right.
Sure. So I'll have to speak to the ADP questions first and then can address a second sir so.
You know.
No.
The popular for ADP is differentiated from the schizophrenia population, primarily by age and so what we have to do is a healthy elderly TK.
TK study and then what you were going to do is then go into the patient population and so what will we be looking for.
We wanted to demonstrate is that we can achieve the exposures of drug that.
We have related previously to pet receptor occupancy data. So that we're confident that we are able to achieve.
CNS receptor occupancies that will test the mechanism of the M. Four in the ADP patients.
So what we're looking for his safety into our ability at the exposures that we want to achieve to take forward into the the ultimate patient population.
So.
As you know what we were in the middle of visit multiple sending dose study to do that and so that data will help US then demonstrate that we have a pair for and so what we're looking for is really just to see that we have the same kind of well tolerated profile that we've demonstrated previously.
As you know, it's a very different population than the schizophrenia population. So it's difficult I think to make any conclusions about whether one would inform and the other at this point.
Obviously this rationale to believe it will be effective in both so that's the question that we need to answer but we are going as quickly as we can and we're not waiting for anything else to gate, our decision to progress in this indication or potentially others. So that they can.
It's not a wait and see type of approach is go go as fast as we can safely as we can.
Good morning, Joseph So listen we're really excited about the potential to come up with a new therapy, which is much needed in the landscape or panic disorder with nearly 20 years ago that was the last medication approved for that so the population that we're using is a moderate population and so we're stuck.
Looking at the panic disorder symptoms scale severity of 12.
Greater.
Being the threshold moderate disease. They also have to have at least eight panic attacks with no free week panic attacks in the month prior to the screening visited in the two weeks leading to the baseline visit had at least or panic attacks and so that's.
That's something that you know the severity does drive in <unk>. Appreciate that question is February there's just drive the outcome and a lot of the study. So we're using the right population to ensure the greatest likelihood of success no rescue medication is allowed in the trial is you know that potentially could confound. The outcome. So rescue medication is not allowed in we're all.
Also at every visit doing screens to make sure that they're not using other therapies as rescue so those patients will be censored or discontinued appropriately. So all in all in terms of how do you design the trial with the right methodology to ensure the greatest likelihood of success and that's what we're trying to achieve.
Great. Thank you very much.
Thank you.
Thank you one moment for next question.
Our next question comes from the line of check hung from Morgan Stanley .
Thanks for taking my questions and also my congrats to Ron Susan upon the new rules two questions for me first can you talk about the challenges for identifying the appropriate patient population for dementia related apathy and in the context of challenges identifying appropriate patients.
What is your latest thinking on the size of the market opportunity for this medication.
And then second for the adapt studying panic disorder housing enrollment going and can you remind us of what you need to see to consider the proof of concept of success. Thanks.
Against German right, Yeah, So I'll I'll start with thank you to ask for with the dementia related App. If he was you know that this is a new path or carving forward. We received fast track designation from the F. D. A in order to do so so we will be working very closely with them, but it is an experiment to try to work on that.
He is truly experimental we're looking at areas primary endpoints and so forth in terms of scale, but nothing there's no formal hypothesis testing per se one of the challenges of course B b.
The landscape recognizing who these patients are so the families that caregivers practitioners really really understanding what apathy is so we've been working very closely with the <unk> I S. CPM grouped which F. D. A has been involved with in order to understand the criteria to identify these patients so.
That is the biggest challenge is really to identify the patients that are out there because we know that half of the patients with dementia.
Suffer from apathy, it's the leading neuropsychiatric syndrome, and a predictor of a disease.
Progression.
So we're continuing to say laser focused on that trial and also helping the site identify the right patients.
The panic disorder trial.
So as you know it's 14, we trial Lily with a 12 week maintenance phase, it's 80% power to detect a difference of 20% in the proportion of patients been between active and see both in the proportion of patients who are free of panic attacks. During the last two weeks of the maintenance phase and why that end point, because that's the end point.
It's been that the president has been settled at the F. D. A has historically wanted to understanding as you know it takes time presentations to respond to therapy. So that seems like an appropriate endpoint. So those are the parameters and so where we are excited about continuing at that trial is you know just initiate it.
Within the last few weeks. So we have not provided any timelines at this point.
But we're excited about the progression of the program moving forward is so stay tuned as the as the.
Program continues.
Right.
Thank you.
Thank you one moment for next question.
Our next question comes on the line I'm Michaeline from Geoffrey.
Pardon me Michael from Jeffries. Your line is now open.
Hello can you hear me.
Again.
For me.
Yeah.
Right.
Following up on the questions around the enrollment for schizophrenia.
Wanted to ask.
Around clarification in color.
D C T dot Gov, you've got a lot of sites listed up there I think some of them overlap.
Centres at some of the competitor enrollment center and so I just wanted to understand is it cites getting up and said Hey, we've got the site but.
We don't really like the criteria or the patients that are coming in and we're not really happy with some of that maybe just shut off light on that because what we see is a lot of centers and we're just trying to think about what the actual glacier sharp.
And then related to that I know that you are running non clinical studies and other studies that are related to N D. A and other competitors taken many months, but typically it's standard to file an NDA around six months after a.
The data set so do you feel comfortable based on the timeline set up your data comes out in second half of 24.
And of all the non cyclic studies and all that should have a filing and first half of 25 seconds.
Yeah, Alright, yeah, so Michael the morning so.
As you know we are some we're always seeking the best sites and of course, everyone else potentially R. As what they are as well so there aren't going to be some overlapping sites with other other sponsors to that and it's really around to your point really looking at getting the right patients and so we have a method by which we help the site at <unk>.
That that's independent of the actual site.
Proposing the patient exclusively so we have another independent committee that looks at the criteria to make sure. We have the right patients in the trial and that waxes and wanes over time, it's really patient accessibility that sometimes can be a bit of the bottleneck.
<unk> <unk>, we're working with a size closer to measure that and continue to understand the root causes of what's holding them up in certain cases, but just to remind you that we started with a bulbous.
Bolus of patients really an exciting very ahead of schedule type of enrollment initially in the last few months, we've seen this slowing down.
And in the U S. Secondly for X P. U S sites and of course, we choose countries, where historically we've had good data that we know the sights well there's been also a slowing down of getting those protocols approved really in the bottleneck. There is really at the country level at the IRB level and those at those countries and I do think it's.
Just a volume issue that they're grappling with but we are.
Have all the sites that we need at currently up and running and will looking at new countries in new site potentially in the future and again always focused on.
Data quality not diluting the data in any way <unk> exacerbating placebo response, so you know.
We want to get this therapy out to the patient sooner than later, but we also know in order to do that we need very robust data and that's what we're trying to achieve as well.
Mike speak to the second question so.
In reference to.
Mmm Prestore preparedness for for submission.
So obviously, we are all over the the timelines to make sure that we have all of the preclinical data CMC data for the CMC module in Enda and also all the Clinton required Quinn firm studies to inform on dozing in those types of things and so we will definitely I'm not I'm not <unk>.
Commit to how much time it is but we will definitely position to have the data in hand, when we get the the read outs. So we are very focused on minimizing that timeline from data Rita two submission.
We're doing all the work necessary to make sure that we get the NBA completed as quickly as possible.
I think that can't be Underemphasize, it's pretty important part of the package. Besides the face for data. Thank you.
[laughter].
Thank you one moment for next question.
Our next question comes in the line of Charles Duncan from Cantor Fitzgerald.
Good morning Uhm.
<unk>, thanks for taking our questions congrats to the new joiners on the call.
<unk> I had a question and lastly, Dean and then actually <unk> with regard to and lastly, Dean and the over in the in the sites, where you see overlap with a direct egg N. S. I guess I'm wondering if you if you have any feedback to.
Sure with regard to investigate or interest and then in addition to enroll ma'am right can you provide any color on on Drafthouse from that study and then also and empower three do you have any patients that have rolled over to that opened Michael.
Thanks for the questions Charles I'll I'll erase it goes so Charles Yes, we've seen yes, we have patience rolling over and that's the way the program and set up that patients have the opportunity when they complete the six weeks trials to rollover into the 52 week open label extension and of course that is for us to continue to.
Gather the exposure data the long term exposure data that we need when we do file that N D. A in terms of an <unk> and.
And the investigators as I mentioned earlier in the call that one of the things that I've been really comforted by an excited by is really the level of enthusiasm that the investigator community has for <unk>, specifically for this new class really giving patients a better alternative to treat these psychotic symptoms. So.
So you know again, we're working closely with them to ensure we get the right patients as we've been mentoring mentioning through the morning.
And and so I hope that answers. Your question is there anything else you'd want to know about that.
Yeah, I think I think that's clear and I appreciate all the teller that you've you've provided on your efforts for for a moment just moving on quickly to read it back again.
I guess I'm wondering about the high rollover rate that you mention in the open label extension I'm quite intrigued with that to me and and epilepsy patients that that perhaps reflects.
Enthusiasm about the therapeutic profile. So I guess I'm wondering if you could provide any any further color on that.
Yeah. So it's it's it's always a difficult to predict the rollover right in terms of patients rolling over so when you see robust rollovers as we're seeing you know we get excited about the potential of the therapy and that patient population and they're quite eager as you know to try to come up with a therapy that really.
Depressed or seizure activity so.
We continue to be.
Excited about the rollover Reagan were monitoring it closely we're getting the exposure is ultimately over time, they will need when we do file in pain after our phase III.
Three program. So so it speaks to all of that.
Might might the rollover rate as well as persistence within open label speak to the Tolerability as well differentiated tolerability.
You know it made at this point you.
You know it'll be conjecture, because we have this you have to look at the data, but obviously if somebody rolls over and stays on your therapy for a long period of time then.
Puts tolerability in a good light, but in terms of what the what that would look like I think we should just wait for the data to Rio.
Okay. Thanks for taking my questions. Thank you.
Thank you one moment for next question.
Our next question comes from the line of Douglas L from H ceiling right.
Hi, good morning, and thanks for taking my questions and congrats to everybody for joining Mccain.
Maybe to start with and <unk> not to beat a dead horse, but ray I'm just curious in terms of finding the right patients are you taking any.
Sort of logistical or any additional screening issues I mean, obviously, we have you know the patient inclusion exclusion criteria to you get the right patients, but is there any logistical things that are perhaps.
Slowing down the process a little bit.
Yeah, what benefits.
It provides.
So so so <unk>.
There's nothing that's slowing down the process remember that.
We started with great momentum in the process hasn't changed from that so what we've seen in the last few months, we have a very robust.
Safety net like to make sure that as I mentioned earlier that the investigators you know stay true to form to make sure that.
We get the right patient and ultimately drive the success of the trial. So that's not slowing the trial down I think it's really around that it's really around finding the right patients and that waxes and wanes overtime.
We have to stay steadfast and we've got to stay very committed and focused to ensuring that at no time, we get the wrong patients.
N N N again, that's what we're doing and positioning these trials with the greatest slices of success based on.
<unk>.
Okay, great. Thanks, and then just as a follow up.
And some of the moving parts with the pipeline and obviously some studies are now reading out later than was originally plan does that.
How you think about moving some of the earlier stage assets until later stage development just as you think about sort of managing your cash right away. Thank you.
Yeah, you know I'll take that one you know look we we're we're we're very conscious of of the balance sheet, we pay close attention to that and as soon as I mentioned.
We're gonna we're gonna do you know what we need to do to be you know <unk> opportunistic to make sure that that that balance sheet can continue to support not only the late stage programs that we spent most of our time talking about today, but many of these really interesting and important early stage programs and so you know.
The early stage program, we won't we won't short changed that as well and so this is something that is equally as important as making sure we get the.
Program right.
Okay, great. Thank you so much huh.
Yeah, you bet.
Thank you at this time I would now like to turn the conference back over to run right now for closing remarks.
So I want to first of all thank everybody for the questions. This morning, but also for the for the warm welcome I you know I know.
Oh that that Susan and fall and I are are super excited to be here to be part of you know one.
One of the most exciting pipelines in neuroscience and to really be part of building. This world class Neuroscience company.
It is something that I am incredibly excited about where.
Well funded with the resources to maintain all the work we're doing well into 2025.
You know, we're looking at things with a fresh set of eyes, and we will have lots of discussions with all of you and many more over the coming months is who you know the the.
The things, we're learning along the way, but I think on balance what you're gonna find is is there's a lot of.
Incredibly important work going on here it serve out too late stage programs two N D. A registrational programs underway here and then a significant number of programs right behind that that's going to keep us busy not only with these N D as for the next.
12 to 24 months, but for the foreseeable future after that and that's that's incredibly exciting. So I look forward to having more discussions with all of you on all of these programs as as we move at thanks, a lot and I hope everyone has a great day.
This concludes today's conference call. Thank you for participating you may now disconnect.
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