Q2 2023 Karuna Therapeutics Inc Earnings Call
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Welcome to the Corona Therapeutics second quarter 'twenty to 'twenty three financial results conference call.
All participants are in a listen only mode. Please note that this call is being recorded I will now turn the call over to Alexis Smith head of Investor Relations.
Good morning, everyone and thank you for joining our second quarter 2023 financial results Conference call I'm joined on the call today by Bill Murray, President and Chief Executive Officer interact now the Chief Financial Officer, who will begin our call with prepared remarks, as well as Andrew Miller, founder and Chief operating Officer, and Wilkins, Chief Commercial officer, who will join us Phil and Troy for the.
The Q&A portion of our call.
Before we begin I encourage everyone to visit the investors page of our website at investors Dot Carina, TX dot com to find our press release and presentation related to today's call.
Forward looking statements related to our product development regulatory and commercialization plans, our research activities and financial outlook may be presented during this call. Please refer to today's press release, and our SEC filings for important risk factors that could cause our actual performance and results to differ materially from those expressed or implied in these forward looking statements.
Now I'll hand, it over to Bill.
Thanks, <unk> and good morning, everyone. We're now midway through 2023 and have made excellent progress in terms of our NDA advancing our development programs for new indications and the pre commercialization work for the anticipated launch of <unk> in the second half of next year assuming approval.
First I'll start with where we are on our NDA for schizophrenia and outline what's ahead as we shared last quarter, we had a productive meeting with the FDA in April where we discuss various aspects of our submission, including those related to our data package and timing.
That meeting and the subsequent meeting minutes and May confirmed our key assumptions and we continue to work towards a submission in September as planned.
Here's where we are the clinical data needed for the submission is in hand. This is data that we've generated across our three positive efficacy and safety trials emergent one two and three.
As well as the necessary long term safety data from a version four and five this is the data that will make up the bulk of our clinical module the.
The data has been collected cleaned and analyze and now we're in the final stages of writing the ISC and ISS.
Additionally, the other key technical sections of the NDA, including CMC, non clinical pharmacology, and toxicology and human pharmacokinetics and bioavailability are complete or near complete.
Our NDA consists of several hundred thousand pages in a seamless sort of assembling formatting and publishing and our submission document in the next several weeks the NDA filing team of Corona has done an excellent job to produce a timely and high quality submission.
As it relates to other aspects of our submission we will be providing additional safety data from our ongoing trials of de 120 as discussed and aligned on with the agency during our pre NDA meeting. This includes the latest data from emerging four and five as well as data from our phase <unk> trial, which completed enrollment ahead of schedule.
In the second quarter.
Moving onto our other ongoing phase III development programs arrived and adapt.
And arrived reactivated nearly 20 additional clinical trial sites in Bulgaria, and Serbia last quarter. These sites along with the existing U S sites will support recruitment in the trial with data on track for the second half of next year.
As we talked about data from arise will be used to support a supplemental NDA for the adjunctive treatment of schizophrenia in 2025, assuming approval in schizophrenia next year.
The treatments are used extensively for serious mental health conditions, such as depression, bipolar sewer and all timers, where there are multiple classes of drugs approved for treatment <unk> has the potential to be the first and only adjunctive treatment for schizophrenia, which would be a major advance for patients in the field of psychiatry.
Our debt program evaluating <unk> T in psychosis, and Alzheimers continues to advance as well.
The Def one a randomized withdrawal trial is underway and the first patient enrolled in a depth three the one year open label extension trial last month, we will be initiating adapt to a double blind placebo controlled trial in the coming months.
Data from a depth one and two are anticipated in 2025.
As a reminder, while the debt program focuses on evaluating the efficacy and safety of <unk> in treating elucidation and delusions associated with Alzheimers.
So collecting data on other prominent symptoms such as agitation aggression, and cognition, which may inform future development efforts with <unk>.
This is an important third indication for us the potential to car T and psychosis related to all Simers is as significant as that in schizophrenia, and we look forward to updating you on this program in the future.
Beyond our three primary indications, we're evaluating additional opportunities for our car ex TNC, Ias and agitation as well as in autism and made here and have ongoing formulation efforts related to <unk>.
Hi, QD and bid dosing in the elderly we have some work to do here and plan to share more updates on the status of these programs early next year.
Now since the start of the year, we've made excellent progress building our operational capabilities. We expanded key teams such as managed care Medical affairs and started pre commercialization activities that lay the groundwork for our anticipated launch next year.
And this spring we attended several key psychiatry Congresses, where we shared additional new data from our emergent program that further highlights <unk> unique and differentiated profile.
We presented data from our merchant three where <unk> demonstrated a statistically significant improvement in the clinical global impression of severity score at all time points in the trial.
Specifically patients entered the study with an average <unk> score of five or six out of seven meaning markedly or severely ill by week five approximately 40% of patients were rated a score of one not at all L to three mildly versus 22% in placebo.
It is an important finding the CGI S. Clinicians assessment of the patient's global functioning which takes into account all available information, including symptoms behavior function. Among other factors in other words, it's a judgment about the total picture of the patient at each visit it's more than a symptom checklist and it correlates well with well known <unk>.
Search efficacy scales.
We also shared exploratory data evaluating the effects of <unk> card cognition from emerging two and three.
Using the Cambridge cognition tests to evaluate memory attention and executive function. We showed statistically significant improvements in cognition in the car T O arm relative to placebo in patients who are cognitively impaired at baseline.
Further currency was not shown to impair cognition. These.
These findings are consistent with our understanding of the <unk> four mechanism as well as prior clinical data generated with a normally and correct.
This is an important finding given the prevalence of cognitive impairment among patients with schizophrenia is 70% to 90% and there is no FDA approved treatment.
Cognizant is an important predictor of improved functional outcomes and is a key treatment target in schizophrenia.
This is an exploratory analysis, we're encouraged by what we've seen and are actively assessing additional clinical work to explore <unk> effect on cognition.
In the fall, we'll be sharing more data analyses for emergent <unk> III and the broader emerging program, including pans responder rates and pans item analyses. These findings reinforce previous published data from our emerging program, where more than half of patients treated with <unk> experienced at least a 20% 30% reduction.
Positive or negative symptoms of schizophrenia, including improvements on the <unk> motor factors, such as disorganized thoughts uncontrolled hostility and depression and anxiety.
Before we review second quarter financials, I wanted to spend a few minutes on the leadership updates we announced this morning, including the appointment of Jonathan Rosen as Chief Human Resources Officer.
Jonathan joined US in July bring with them extensive experience and proven leadership in building highly effective growth oriented teams, whose appointment comes at a key time for us as we continue to recruit top talent and focus on transitioning to a fully integrated <unk>.
<unk> company.
We also announced the promotion of adjacent Brown Chief Financial Officer, Jason currently serves as senior Vice President Finance and has extensive experience with all aspects of the finance function at P&A accounting audit and more.
And he has also played an integral role in our business development efforts from due diligence to deal evaluation and execution.
Zone internally for us detail oriented mindset and sound judgment.
With that I also like to share our gratitude Detroit for his commitment to the company over the past four years. He has been a key member of our executive leadership team contributing financially and operationally to the company in numerous ways. The letter IPO multiple successful equity financings and help build the court fine.
<unk> capabilities at Corona.
With the NDA submission well in hand, and a strong balance sheet in place. This is a logical time for these transitions I'd like to thank Troy again for his commitment and contributions to the company and congratulate Jason and Jonathan on their new roles and with that I'll hand, it Detroit.
Thank you Bill good morning, everyone and thank you for joining us today.
Before I review, our second quarter financial results I want to take a few minutes to express my gratitude for the opportunity to serve as Corona as CFO over the last four years.
My time at Corona has been nothing short of exciting it was a little over four years ago that we took the company public with the help and continued support of the investment community.
And have since made significant progress towards our mission of developing and delivering <unk> to patients.
It's been a pleasure working alongside the leadership team talented members of our finance communications and it.
Departments and the broader organization as well as our board of directors I am proud of all we've accomplished together and look forward to seeing the continued success of Corona.
Now turning to our second quarter financial results our balance sheet remains very strong. We ended Q2 with one 4 billion in cash cash equivalents and investments compared to $1 1 billion at the end of 2022.
The increase was primarily the result of our follow on public offering in March that resulted in net proceeds of approximately $437 million we.
<unk>, our current cash runway to continue to support our business operations through the end of 2026, which includes two full years. After the anticipated launch of <unk> T. In schizophrenia in the second half of 2024.
I'm also pleased to share that our operating expenses for the second quarter continued to track with our full year 2023 guidance that we previously provided at our first quarter business update <unk>.
Combined R&D and G&A costs for the second quarter were $119 $9 million, which was.
Partially offset by interest and other income, resulting in a net loss of $103 2 million before income tax.
R&D expenses for the second quarter were $92 5 million compared.
Compared to $52 5 million for the same period in 2022.
The increase of $40 million was primarily driven by expenses related to <unk> clinical programs.
The structure.
With that I'll hand, it back to bill.
Thanks, Roy I'll turn it over to the operator to begin Q&A.
Thank you in order to ask a question.
Then the number one on your telephone keypad and we kindly ask you to limit it to one question, we would pose for just a moment to compile the Q&A roster.
Your first question comes from.
Machias from Stifel.
Please go ahead.
Hey, thanks, so much uhm congrats.
Next venture and congrats.
Congrats Jason on the promotion.
I I was just curious as you get towards the NDA filing for car X T. What's your base case expansion expectation for priority review or lack thereof in an AD Tom and then just really quickly can you flag for us the timing and upcoming read outs for the bone compound.
Watching for the for the as it relates to the M licence asset from goldfinch. Thanks, so much.
Thanks, Paul This is bill will make a few comments and then I think Andrew Kim can expand I think.
Our base case.
Famed root beer is you know we'll find out.
60 days after the submission.
Whether we've earned a primary review, but we're assuming a standard review at this point at which would be 10 months from the from the acceptance of the NDA, which we expect the submit as you know at the at the end of September .
Uhm.
It relates to.
The second part of the question.
But we just have to be prepared for one I don't anticipate that we'll have one I don't view it as a negative or a positive development. We're already planning for one if the F. D. A decides to schedule. It. This was a as you know a fairly standard development program wildcard.
T as a novel compound the studies that we conducted we're very consistent with precedence as you know there's roughly a dozen atypical antipsychotics that are approved it is a novel compound I think we've.
You said, it pretty hard high bar as it relates to efficacy and safety and side effects data, but it's not obvious to me why they would schedule an AD, but if they do will be ready and then finally as it relates to the barrier angled I'm compounds.
For the Behringer ingelheim compound their trip C. Four five.
We anticipate that there could be results available sometime in the second half of this year and then in early 2024 based on what we've read in the in the public domain started their first study M. P. T S D.
Seconds excuse me the person that he was in borderline personality disorder very different than the indications that we would we would study with our trips you for five second indication or second condition was P. T. S D and the third was N D.
And look it's we'll have to wait and see whether the results from the B I studies to the extent that they share them are instructive, they're different compounds. As you know there are a lot of different factors.
That can impact the outcomes of a study.
We'll wait and see and did you want anything.
<unk>, yes.
Next question comes from David Enslen Piper Sandler David go ahead.
Thanks, So an adjunctive usage in practice I I know you have the the adjunctive studies.
Ongoing but is it your view bill that some practitioners as a means of gaining early experience with car X T may use it as as an add on therapy.
Data not notwithstanding we've heard different things from different practitioners and wanted to pick your brain on that and then also looking at early commercialization.
Thinking any differently about <unk> early on with the recent <unk> failure and just wanted to pick your brain on on that and how you were thinking about the the potential impact on kirksey now that that product failed. It's recent phase III. Thanks.
They'll take the the first part of that question I'll ask will gain our chief commercial officer to.
To expand as it leads to a junk the views I think I think there are too.
Two statistics to keep in mind first of all today based.
Based on both market research and data for my <unk>.
<unk> 30 per cent of patients with schizophrenia, receiving two D. Two attacking us so there's effectively.
Non fixed combination market or in a drunk give treatment market that it exists today of course, none of the currently available a typical have an F. D. A approved vindication for adjunctive adjunctive treatment, but there's clearly a high need they're given that they're taking.
Two compounds that are much more similar than different in order to generally achieve higher response rates. We also know that in the literature. There are some studies dating back.
You know almost 20 years when die.
<unk> and <unk> and <unk> will launch that upwards of 60% of patients were receiving Polly palm pharmacy with two different compounds. So I expect that.
If we can produce positive data from the arise trial.
<unk>.
This could trigger a fundamental change in the management of schizophrenia. We know that atypical for example are used on top of S. S. R I's and partial or Nonresponders 20 per cent of the time.
We know and David you know this category fairly well and all Simers. The Mendez used on top of Aricept, almost 40 per cent of the time and it has the indication.
Or junk the treatment and moderate to severe all sivers disease, and so I think the anticipation that psychiatry community.
Is that the effects of <unk> on top of a D. Two are complementary.
An additive and pharmacologically that makes sense.
And from an efficacy and safety profile, we have efficacy results at the top end of the range. Although we have no head to head studies and then more importantly, when you look at safety and side effects, you don't have overlapping profiles and so you're not adding to some of the common side effects such as weight gain EPS akathisia.
<unk>.
You know how.
How the psychiatry community is gonna manage this before we produce data.
That's of course.
<unk> to be seen but my sense is there is gonna be there's gonna be some adjunctive treatment. Obviously, we can only promote the data that we've produced and that's in our label and we are you know.
We are impatient about getting the results of the rise study available and then the the next question related to pre commercialization.
And <unk>.
But I've never viewed that this was a one of one market I've never viewed the schizophrenia market as a market. Your battle, it's not a zero sum game and I think we see that in the current segment of the main antagonists.
And and I feel that way about muscarinic that are in development, yes from a commercial perspective, we do have a higher share of voice and and of course, we can we can take advantage of that our job right now is to focus on roughly 30000 psychiatrist convinced.
Then that the data that we produced justifies trial with colleagues T and I think if we generate trial.
And the real world experience with <unk> represents.
<unk>, what we've observed in the clinical trials. This is gonna be an important launch and and a fairly big launch and that's how I think about it will do you want to add anything.
I have two brief things one in to the first question I just want to reinforce that in our conversations with the psychiatry community. They need strong monotherapies bones, adjunctive therapy and the data set that we have an immersion program is.
<unk> is quite solid and there's a lot of excitement.
About that specifically for their needs with patients, who they would consider switching or they've lapsed and therefore, they need any treatment option and so it's not a question of adding is getting them back on therapy, and then as bill pointed out there is clearly a lot of interest in and excitement about uhm potential hi, Jonathan has an approval for that use because it is such an unmet need.
In this marketplace. The second question I, just want to underscore that in our conversations as well you know the need for new therapies in this market is hi.
Schizophrenia is very challenging disease with with the same approach to treatment for the past several decades. So the <unk> an order on trials no.
Disappointment I would say from my own personal perspective doesn't help the market because there are needs for new therapies me here that I've been all the time, but our plan to go to market is unchanged based on on any changes in this movie and program et cetera, We will bring a strong effort to that launched thanks David.
Alright.
Next question comes from miles Minter from William Blair miles. Please go ahead.
Hi, Thanks for taking the questions and I can <unk>.
That's probably the thing right with you.
Congrats stripes on that on the next week.
Oh, you just mentioned that the same same packages complaint on your complaint while components in the complaint that's the first one and the second one is just on the commercial viability of <unk> site prices and the plan.
<unk> I think for that product would that be done after the at that studies unit breaching study format. Thank you.
Thanks miles with a question I'm Gonna turn it over to Andrew.
Sure with respect to the NDA submission.
This mission this a five modules and administrative module summary module Nonclinical CMC clinical I think with respect you nonclinical on CMC. All the information is available those modules are essentially final at this point, it's really in the final process of compiling with respect to clinical as we've been.
Speaking about really for the last year the last piece of information to come in it's really around long term safety. That's here. It's analyzed it's also in the process of being compiled and obviously an NDA submission itself is a pretty substantial documents, probably an order of 450000 pages.
So we're in that final push to pull that together in anticipation of submission here prior to the end of September .
And then the second question on dosing.
Oh, you want to speak very well.
So I would just say obviously the incentives to move towards a V I D b.
The I D dosing regimen however.
However in a market research we've done there was a place where tid 13 option, particularly in patients in the Alzheimer's population, obviously loved her giving support and so while we would want to clearly move in a direction to reduce the brings you've gotta, saying there was viability for it yet he does.
And maybe they pick up on that last point with respect to R&D activities, we do have a number of.
Formulation development work screams ongoing including currently ongoing phase one clinical work within a bad sore a formulation of crushed T, which could offer the potential.
Including that transition from T I D to the idea and the elderly that village.
Next question comes from Jason Butler from J N T. Securitas. Please go ahead.
Hi, Thanks for taking the question I just want a arise can you just maybe ran right.
Color here around enrollment dynamics for the study obviously timelines on track, but that just your your focus on priority on and getting the right patients and that in that trial and you know thinking again about making sure the placebo rate stays within your expectations. Thank you.
Thanks, James and go ahead, and yeah sure happy to speak to that and we provided some updates operationally around the Orion study at our our previous earnings release, Yeah, I've seen has initiate additional sites and Serbian Bulgaria over the last quarter.
Obviously.
Getting there getting patients into the study of the appropriate pace, but also monitoring for variety of quality and placebo response related strategies continues to be a focus for us. So obviously been a substantial focus across the emerging program that the inpatient and outpatient studies, it's been a focus in gaming P. M study, which recruited.
Quite quickly and finished left or finished enrollment last quarter.
With respect in general to placebo response expectation bias in.
India Ryan study, we're following all the same strategies that we followed across the immersion program to highlight a couple of those specifically we continue to pursue flexible dosing, which allows us to one to one ran my subject. So 50 per cent of and see about 50 per cent off drug.
It's important because expectation if therapeutic benefit is an important driver of placebo response across psychiatric indications and so the higher percentage of patience you can have on going to see that on your studies, therefore lowered the expectation of benefit on both sites and investigators as well as patients you see that again consistent that one to one randomization.
An emergency one two and three as well as a rash as well as Ah depth wanted too that's a common strategy for us and I think it's been effective.
In addition, you know.
Typically employ a variety of other strategies when we speak about frequently as the idea that we have those same <unk> centralized wrote Raiders used the remote Raiders is a quality control tool, we can verify ratings against recordings better than rerated by the Raiders, but I think actually the most important aspect.
With that being that's sites in sight Raiders know that we're recording ratings. They know we're gonna rewrite those ratings.
And so the idea that there is a stream of accountability about what's being done I think it's really important sort of behavioral modification her behavior all effect as.
As well as a number of other strategies that we use but those are the two that we speak about less frequently again I think it's always a concern we're always.
Thoughtful about a conscious about it uhm and will continue to be a focus for us for it.
As for the question.
Next question from Halloween wish time Goldman Sachs Halloween. Please go ahead.
Good morning. This is <unk> congratulations on the <unk> the package so far could you speak to some of your ongoing efforts on the commercial infrastructure and let's get to find out my cat I have the potential of <unk> and 24, and then could you just fame expectations around the upcoming data from the.
<unk> either patients that are involved in that study.
Similar in terms of baseline Caritas next to the <unk>. Thank you.
Great. Thanks for the question will will take the first part Andrew can take the second part sure Zoe on the the Bill that you will have a commercial organisation, we're making strong and steady progress on those friends. We've opened our head of sales two months ago now and she was fully immersed in planning for refill for sizing structure and deployment we've added additional strong.
<unk> talents I worked puts in the past two that's gonna be up much experience, particularly in to see in this area too.
To strengthen and enhance our preparations and so things are moving right on schedule and.
We'll be ready and I would just add that.
You know in this pre commercialization phase the two most important groups or the managed care account team, which under the Pie Act as the ability to approach pears with scientific information about about <unk>, which allows us.
To at least clear a path from a payer perspective for launch at the end of 2024 and.
That group is is in place right now we have 10 to 15 account managers.
And then we have a medical affairs team.
Of equal size.
That is conducting all scientific exchanged for the company so.
All the capabilities for the sort of 12 to 18 month period, leading up to launch are in place and then as it relates to the launch.
Will came the head of marketing the head of sales.
Our head of Athletics, all have extensive experience with biopharma launches and look this isn't a lunar lander planning, we know exactly what to do we will make the right strategic decisions operationally.
We're going to get things done and of course, the launch boats before approval and after approval will be appropriately funded and I think we're good place you want to think Andrew. This question about AVP M. Yeah with Recirculated began study I think there are a lot of similarities in terms of the patients that we would expect.
To recruit Navy PM in comparison to a merchant one two and three.
And also point out that we have the exact same dosing paradigm <unk>, we do an a b P M.
That he has conducted.
<unk> said you conduct in the U S for the vast majority of subjects.
Just made it an urgent wanted two or three were from we had an average age and the generally in the mid forty's across the emerging program. We expect similar any of the PM study.
The average characteristic and stuff.
Study.
Thank you for the question.
Next question comes from our Goodman from Leerink Partners Mark. Please go ahead.
Okay. Thanks for taking my question this Judy and I liked congrats on the progress with a quarter to help question regarding the <unk>.
Can you remind us how to copy some benefits will have you you spend crises opportunities regarding eligible patients and marcie potential and I know you mentioned that in making that other <unk> you should maybe can provide more counterpin dose studies.
Thanks for the question Andrew I'll, let him take the first part and then I can answer the second for sure I mean with respect to what we've been able to demonstrate safari technician at the relevance of that.
It's it's been an endpoint that's collected across the merger one two and three it was also in that point that was collected and historical so normally and monotherapy studies and all timer set and schizophrenic conducted by by Eli Lilly across all of those studies consistently we see benefit on cognition SA importantly, when you look at what we.
Scene and emerge at one two and three.
Yeah. Those are studies for acute psychosis, but in general there's a non significant to small correlation of cognitive benefits seen in those studies with your overall symptomatic treatment set another way the.
The.
It's really and it's a way to address any sort of specificity concerns. We believe there is a real cock and a benefit there is not as cocky Alzheimers you senior across all of our studies <unk>.
Cognition continues to be using asking area of unmet need and schizophrenia Bill mentioned on the call that 70% to 90% of patients with schizophrenia have a level of cognitive impairment. They're currently no treatment specifically approved by the F. D. A for the treatment of cognitive symptoms.
So I think any benefit that we can have their is a further enhancement of the potential profile of course T. I'd also point out that even the lack of any detrimental effect on cognition, giving existing agents have a warning for both motor and cognitive impairment is actually a substantial improvement over currently available treatments. So we continue to be excited about what we've seen.
<unk> from our cognition standpoint, we are collecting cognitive data across both the arrive in depth programs that are ongoing uhm and we are contemplating.
And planning additional work in cognition exactly what that will look like will be.
The details of which were you at or or reveal at a future time, but I think there's a range of potential considerations from something that looks more like a pilot study to fully powered phase two proof of concept study to Registrational program seeking specific labeling force yeah, yeah. So it would remind people that our expectation of labeling.
Based on the emergency program.
Plea for the treatment of schizophrenia in adults doesn't have a restriction towards particular symptom severity or symptoms that means.
But we do think there is an opportunity to further demonstrate the cognate benefits of car S. T and we look forward to it that's all.
Great. Thanks, that's good thank you.
For the question.
Next question from J also from Oppenheimer J go ahead.
Oh, Hey, congrats on all the progress and thank you for taking the questions could you talk about the key unmet needs in autism and which features of autism may be treated by car X T types of patients you could enroll in study design you might run in that population. Thank you.
Sure. Thanks, J I'll I'll take the first part of the question and ask Andrew to expand as it relates to autism, we're focused on the behavioral problems or disturbances and autism, namely agitation and aggression in terms of unmet needs. There's only two as you know J F D. A approved data vehicles.
Aaron Prep resolve and Risperidone and if you talk to any psychiatrist there's two problems with giving those products to kids first one is weight gain.
And the second one is is akathisia and so when you look at the F.
<unk> safety data from the emerging program and the profile for car X T.
It looks pretty good on those two fronts and so you know.
The benefit risk profile of this product and a pediatric population.
Is is fairly fairly compelling and from a farmer logical standpoint, we would expect that it would produce.
A positive result, it's one of the few areas where atypical or used.
Where you have such a vulnerable population and so the safety and side effect profile car X T seems well suited for it.
Yeah, I think specifically with respect to clinical study designs I think.
The appropriate benchmark should really be the Arab papers all of our spirit of studies that have previously then conducted this focus on so overall behavioral symptoms or your ability, there's established and pointed inventories track the symptoms and tend to be relatively short term studies.
One to two months or less and a double blind placebo controlled manner.
Not so dissimilar to the emergency program.
Schizophrenia, So I think there's some well precedented studies well precedent in terms of how they translate into labeling that are good examples for us certainly the type of designs that we would think about with respect to future studies persisting.
Thanks Jay.
Next question comes from Ya <unk> Guggenheim partner. Please go ahead.
Thank you so much it's been a pleasure working with you <unk> a good luck with the with the next nine children and Jason Congrats to come forward to working with you as well.
So I have two clarification question and this is regarding E for N T. Five so they are part of the finding.
<unk> <unk> <unk>. This study done, but it seems like the data will be shared.
Later, this year and I'm not near any of those are done and and will there be just curious how the data from those two studies.
There'll be communicated to the F. D N. So that's one and then the second question is on the a B P. M study.
Did you get any communication from the F. D. A that when you submitted at the 120 would it be with a decline to set up an amendment.
Be just part of a <unk>.
Yeah, maybe I can address the second part of that first with respect to the 80 PM study in our submission strategy and timing, including specifically submitting the AVP M study at 820 safety update was part of our pre NDA meeting with FDA captured into the meeting minutes that we got it may as well.
Yeah, I think there's a lot of confidence in our part based on that interaction and confirmation that submitting data from a phase one safety study inside of that day 120 safety update as a common strategy in a reasonable acceptable strategy uhm again, emphasizing that D. V. P. M study assembly, providing a more definitive supplementary.
Set to our existing vital signs assessments that are conducted as part of all of our clinical program suddenly we have a high degree of confidence that <unk> is online and obviously, having already completed enrollment in this study high level of confidence that will be on time with that data set up getting to the agency with respect to emerge and four and five.
<unk> the studies remain ongoing emerging for completing enrollment in the second half of last year.
In 2023 emergent five completed enrollment here in a second quarter of 2023.
And.
Those studies.
Typical for an NDA submission you set a date of cut date in which you're the quantity of data you have is sufficient to support your submission and then you submit to FDA all the data collected prior to that date you provide a similar update update 120th you say that date is approximately 120 days after the the submission data cut date. So it is.
Both of those studies will continue to be ongoing during the submission and review process and.
And it's simply about having a database that's appropriately sized eating ice th guidelines to support your submission review, that's what we have in hand.
Until we will provide obviously ongoing updates about the studies with respect to win that data will be available at final. Those are things that we would anticipate really being able to share it per cent in the first half of 2024.
Next question comes from Laura Chico from Wedbush Securities. Laura. Please go ahead.
Hey, good morning, guys. Thanks, very much for taking my question congratulations to Jason and try all of that I'm wondering if you could kind of answer them or have a question just send that muscarinic class in general set out we're seeing and for selective M. Unplug the patient's advances pipeline.
I'm wondering if you could comment at all on how you would see the key points of decoration differentiation for car X T beyond receptor subtype activity, how would that possibly play out in a clinical setting thanks very much.
Yeah. Thanks for the question, where I can make a couple comments as it relates to sort of the broader pharmacology you know the.
Expectation, we see this.
In our in our data from the emerging program.
Is broader efficacy and we certainly have a signal.
We saw in the Lily study.
We see in preclinical studies and now we have the exploratory analysis from emerging two and three we see a pro cognitive effects with with <unk>.
And that's something is Andrew talked about.
A few questions ago, we need to explore more and a dedicated a clinical trial, but that is not insignificant you know if you talk to.
Physicians, who were diagnosed in treating patients <unk>.
Mission is a significant problem once they resolve so deposit of symptoms of the condition I would also say that no two muscarinic receptor anti psychotics are gonna be the same even with overlapping pharmacology and when you look at just the basic efficacy data that we produced in the emerging program.
We've set a a fairly a fairly high bar here I mean, the effect size. When you look across the three programs isn't that 0.67 range and the changes on the pans or anywhere from eight or nine to 11 points.
And I think that's also important that as it relates to.
Uhm saved.
Safety and side effects, it's hard to make any comparisons between <unk> and other muscarinic because we have exposure 1500 patients and we have a full you know efficacy and safety program into longterm safety studies, but there again.
Pretty compelling safety and side effect profile and so my sense is the selling proposition here the value proposition is not predicated on one aspect of the profile.
There are several different aspects to it and which would be highly relevant psychiatrist.
Yeah, I think I just add to that you know from basic science perspective.
Paul myself and a few others here publishing mechanistic review paper actually not too long ago in the air control psychiatry, highlighting the potential role of different muscarinic receptors I Wanna. Thank you look at the profile specifically it's normally.
Obviously see that M. Four has a role Indiana psychotic properties.
But not an exclusive.
Property, you can knock out the M. Four receptor and you attenuate, but don't eliminate the end is kotick benefits in preclinical models and then as Bill mentioned the M. One receptor.
Place a substantial role I think the primary role really in zebra cognitive effects that we see clinically and also pre clinically with Emily.
But also I think has a role in that and it's a kind of properties and to Bill's point I think.
At this juncture, it's difficult to offer a comparison simply.
Simply because we don't have large scale registrational data for any other program at this point I think once that comes into focus that'd be more informative about how this clinical profiles prepare but I think to Bill's point, we've been able to demonstrate I think a very compelling and robust efficacy of signal with car say that we're quite excited about it.
<unk>. Thank you guys.
Next question comes from Jason Gregory from Bank of America, Jason. Please go ahead.
Hi, Good morning. This is <unk> and congrats on your progress is clearer and thank you. So much for taking our questions. We just wanted to drill down a bit on the recent recruitment neuropsych trial.
Uhm are you see any potential structural dynamics for the horizon of depth trials beyond ensuring high quality child sites that could impact timelines our ability to mitigate placebo response, and then just a quick one on the goldfinch asset.
Besides following the signs what are other factors that are driving which your mood or anxiety indications that you plan to assess and could we see a trial initiation in the second half of this year. Thank you so much.
Thanks for the question I think with respect to the first question around.
Structural are sort of macro factors with respect to recruitment timelines et cetera.
I don't think we see substantial shifts there obviously the.
People speak a lot about the pandemic and it's over all shifting many industries uhm and there's certainly been impacts of that with respect to clinical studies and recruitment.
But in general I think the the types of issues and considerations and the strategies used to mitigate those are really mostly unchanged.
Every study is unique every study has its own challenges.
We had to mitigate and address challenges ongoing emergent program that study same types of things are gonna happen across any future study that we run so I think from our perspective, we don't see substantial headwind specifics neuroscience are specific to these days.
Types of studies.
It's all the same challenges around design and execution that I've always been there. So I think that's sort of.
The discussion about the <unk> what was the second part of the <unk> Yeah as it relates to the the trip C. Four five and and how we're thinking about well first of all following the science is really important and I would just make it a couple of general comments that when we think about and this is true for courage to you and any additional work we do there.
Do you think about.
Indications for the trip C four or five.
We have to look at.
Medical need probability of technical and regulatory success <unk>.
Commercial potential and the return profile for any investment right now when you think about mood and anxiety disorders were thinking is M. D D and G E D and those are well developed regulatory paths large populations and while there are a number of different classes of medications.
Approved.
Of course, not without limitations most of the drugs today, a surgeon erdrich your adrenergic doberman urgent glutamatergic and this would be a fundamentally different.
Approach.
Not dissimilar to car X T and schizophrenia, and as we get closer to the end of the year will be able to sort of describe in a little bit more detail. What our plans are for the trips before five if you.
You want anything that as it relates to the science.
I think again I think it's important for us to really be thoughtful about what is the probability of title in successive whenever studies figure out and that involves both the basic science and rationale as well as your ability to execute them in a timely fashion uhm on a study that can provide you a definitive data point other positive or negative and so I think.
That comes into focus.
M D N. J E is certainly think it's at the top priority list for US. There's certainly other things that we would consider as well I think we're going to be a physician to provide a more definitive update about that through the second half of this year I wouldn't anticipate a clinical start coming in second half of 2023 from that program.
Next question comes from <unk> from H C. Wainwright Sam. Please go ahead <unk> go ahead.
Thanks, So much for taking my question just with respect to the longterm commercial outlook for car S. T. I was wondering if you could touch upon first of all what you expect the impact of car X T on negative symptoms to be with respect to the potential market positioning and market uptake in schizophrenia.
And then secondly, if you could also give us a sense of whether you're thinking about potential applicability of correct in that population of patients that exhibits mixed features of both schizophrenia and depression. Thank you.
Thanks for the question as it relates to the.
I think your question is the impact of an effect on negative symptoms and the commercial potential of of <unk>.
And I said this earlier and I really do mean, it I don't think that the success of the uptake the adoption of car X T. In psychiatry is predicated on one aspect of the profile.
Interesting convincing data from the emerging program, but in order to get an indication for negative symptoms, we'd have to do a a dedicated trial, which which work in which we're considering.
I think the adoption of car X T.
Is going to be predicated and all the data that we have from the emerging program name.
Namely.
Its efficacy I'm positive symptoms, which is still a a a need in this area.
The fact that it could be used the junk diddly.
I would say is number two.
Number three.
It appears to have a pro cognitive effect more work is needed and then I think from a safety side effects standpoint, it's completely obvious that this is a fundamentally different profile and while the the psychiatry community and including all of us at.
Corona are interested in exploring the benefits.
<unk> feeling negative symptoms.
I don't see it as essential to the adoption uptake of the problem and to be fair. If we do more work here. It would be a couple of several years before we produced produced actual data that we could actually use and and and the commercialization of the of the product and the second part of the question.
Okay.
That was <unk>.
Yes.
And did you want to comment on mixed features of schizophrenia and depression.
Yeah, I mean, I think with any psychiatric illness, I think there's a degree of symptomatic overlap. When you think about depression more I would think about bipolar disorder with respect to schizophrenia.
And people often receive one diagnosis may move onto the next to the at a different point of their illness.
I think specifically with respect to car S. T will be able to demonstrate I think very clearly at this point is a robust effect on the symptoms of psychosis since you get your friends.
The extent to someone has a diagnosis of schizophrenia I think I'll look at the clinical evidence center today, demonstrating that we can treat the symptoms.
Pacific a second negative symptoms had dude and there's a conversation about how those may or may not overlap with some of the types of symptoms associated with depressed.
Depression, and neither bipolar disorder or M E given things like lack of motivation and Indonesia and other features are commonly associated of both of those orders, it's really difficult to predict how.
How <unk>.
Work or be effective in patients without a diagnosis of schizophrenia uhm that being said to Bill's point I think our data provides a motivation and and a demonstration of a broad and robust ask is your profile that we can continue to refine it study over time.
And that will help inform physicians about how they might use the product.
Thanks.
Thank you.
Next question comes from just hung from Morgan Stanley .
Please.
Thanks for taking my question with multiple companies developing candidates for psychosis and all Timer's disease.
Are you concerned that this may lead to slow enrollment or lower quality and patient what steps are you taking to mitigate that potential headwind and psychosis and all timer's disease, and then and then you are there any updates on potential partnership discussions for X U S right <unk>. Thanks.
Thanks, Jeff Andrew will take the first part of the question I think specifically with respect to recruiting in enrolling at the in depth program. It's always a competitive space, obviously alzheimers, it's an indication where there are a large number of ongoing studies does tend to be more around disease modification or or cognitive outcome measures.
There are obviously a number of of agents being pursued for the agitation and aggression associated with Alzheimer's disease, or just a secondary endpoint any adapt to study.
There are other studies ongoing or reading for loose nations and delusions again that's.
Whenever you're in an area with significant unmet need you're likely to face some competitive dynamics with respect to clinical trial recruitment. So I don't think we see anything, particularly unique there with respect E. A deft program.
I think it's.
You you see a pretty broad footprint for that program for us across the U S as well as multiple X U S countries, you'll continue to see that for a depth to as well again, not really reflective a competitive dynamic in particular really just the idea of where the best places to conduct these studies.
How do we get the right patients into those trials and have a high quality and you read out the same way we had with the merchant 123.
It relates to R X U S. Partnering plans are thinking here has not changed.
And of course will make sense operationally to find a partner with regulatory development and commercial capabilities and we will provide an update at the at the right time, we're talking to companies all the time, but no update at this point.
Thanks for the question.
I will now turn the call back over to <unk>, President and Chief Executive Officer for closing remarks.
Thank you for being with US. This morning, we appreciate the questions I look forward to talking to export.
Ladies and gentlemen that concludes today's call. Thank you all for joining you may now disconnect.
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