Q2 2023 ACADIA Pharmaceuticals Inc Earnings Call
My name is Gina and I will be your coordinator for today at this time all participants are in a listen only mode.
We'll be facilitating a question and answer session towards the end of today's call is at any time during the call you require assistance. Please press star followed by you and a coordinator will be happy to assist you I would now like to turn the presentation over to Jessica teasing Associate director of Investor Relations at Acadia. Please proceed.
Yeah.
Thank you good afternoon, and thank you for joining us on today's call to discuss second quarter 2023 earnings.
Joining me on the call today from Acadia are Steve Davis, our Chief Executive Officer, who will provide some opening remarks, followed by Brendan T N. Our chief operating officer and head of commercial who will discuss the debut launch of NUPLAZID execution, Doug Williams, and our head of research and development will provide an update on our pipeline program.
And Marc Schneier, our Chief Financial Officer will review the financial highlights.
Steve will then provide some closing thoughts before we open the call up for your questions.
In addition, Kathy Bishop our head of rare disease in external innovation will be available for the Q&A session.
We're using supplemental slides, which are available on our website events and presentations section.
Before proceeding I would like to remind you that during our call today, we will be making several forward looking statements with them within the meaning of the private Securities Litigation Reform Act of 1995.
These forward looking statements, including goals expectations plans prospects growth potential timing of events or future results are based on current information assumptions and expectations that are inherently subject to change and involve several risks and uncertainties that may cause results to differ materially.
These factors and other risks associated with our business can be found in our filings made with the SEC.
You are cautioned not to place undue reliance on these forward looking statements, which are made only as of today's date I'll now turn the call over to Steve.
Thank you Jess good afternoon, everyone and thank you for joining us please.
Please turn to slide five.
Acadia is ensuring a transformational period of growth as we continue to continue to execute across all strategic priorities.
First NUPLAZID is an increasingly cash flow positive franchise and is the financial foundation to our business.
Our real World evidence studies, which we began rolling out at the beginning of the year have had a positive impact on new patient starts.
Despite a contracted Parkinson's disease market NUPLAZID continues to gain market share and outpace new patient starts over other anti psychotics used off label in the PDP market.
Second the launch of debuts off to an exceptional start we're seeing high demand and broad reach since U S commercial availability on April 17th.
We continued to see broad distribution of prescriptions written across all account types, including high volume institutions and community practices. In addition to centers of excellence.
Brendan will discuss further in his section we're very pleased to be receiving highly positive caregiver feedback regarding the benefits they are seeing.
In addition, we are receiving positive feedback from health care providers and caregivers regarding the level of support they are receiving through our acuity connect services and we're seeing these efforts translate into sustained demand.
Third last month, we announced our expanded licensing agreement for <unk> and we now have worldwide rights to the asset.
The successful launch of debut in the U S underscores the opportunity we have to execute our global strategy.
We expect to file a new drug submission for <unk> in Canada in the next 18 months and we'll engage with European and Japanese regulators soon.
There is a significant unmet medical need worldwide and no approved treatment for ret syndrome outside of the United States.
Incidence rates around the world are similar to those in the U S.
We estimate prevalence in Europe , and UK combined to be between 9014 thousand patients.
Based on birth rates mortality rates and other data, we expect that prevalence in Japan to be between two and 3000 patients.
Fourth we have multiple late stage programs with near term milestones, including our phase III advance two study a team of answering in negative symptoms of schizophrenia, where we have now completed enrollment and expect top line results in the first quarter of 2024.
We have a phase two study of ACP to afford in Alzheimer's disease psychosis that is expected to begin in the fourth quarter later in his section Doug will discuss more about how that study will run seamlessly into two phase III studies, all three of which could potentially support an NDA submission.
And ACP 101 is also expected to start a phase III trial in product really syndrome in the fourth quarter of this year.
Fifth we have a deep early stage portfolio that includes disclosed and undisclosed programs.
Our neuroscience theatrics in rare disorders, and we remain active in business development to further expand our portfolio.
As an important side note to.
Through the success of our debut NUPLAZID franchises, our business has now reached cash flow neutrality.
Let's turn to NUPLAZID on slide six.
The NUPLAZID franchisee has been cash flow positive going back to 2019, and we've generated increasing cash flow from its franchise. Each year. Since then by focusing on both top and bottom line inclusive of reducing expenses by over $100 million.
When comparing 2021 results to our expectations for 2023.
Our second quarter performance of $142 million in net sales was driven by an increase in new patient starts across both office based and long term care channels with particularly strong performance in LTC.
As we've laid out previously there are two dynamics, which we believe can contribute to top line growth for our NUPLAZID franchise, one is the awareness and understanding by health care professionals.
Three we are a world studies that demonstrate the benefits of answering compared to off label atypical anti psychotics.
Yeah.
As Brendan will elaborate further in his section it's clear that these studies are green gaining traction as evidenced by an increase in our market share of new to therapy patients for PDP.
And second is our ability to continue to grow this year. Despite no significant improvements in Parkinson's disease market dynamics, let's.
Let's turn to slide seven to discuss our pipeline highlights.
Here, we have a big picture overview of our two commercial.
Numerous early stage and late stage pipeline programs.
Each of these contribute to our leadership in the development and commercialization of new medicines for central nervous system disease and shape, our long term growth opportunities.
We have phase III programs underway in both negative symptoms in schizophrenia and product Willi syndrome. We also have a phase II slashed III program quickly getting underway in Alzheimer's disease psychosis and behind that we have a rich pipeline of early stage disclosed and undisclosed programs that position us for long term growth.
I'll now turn it over to Brendan to provide additional insights on our debut launch execution and NUPLAZID as commercial performance starting on slide eight.
Thank you Steve let.
Let me provide commentary on both of our commercial franchises debut and NUPLAZID each of which are performing exceptionally well, let's start with debut on slide nine.
We're excited to report that our debut launch continues to exceed our expectations.
Before I get into important metrics today I'd like to first described the most important element of this launch illustrated through the caregiver testimonials you see on this slide regarding day to day improvements in our real world use of debut that these families are sharing with us.
Just 15 months 15 weeks into the launch hearing these important examples about the tangible impact debut is having on patients and families.
Makes the value of this first ever treatment for Ret syndrome, all the more meaningful.
A few examples of benefits families are describing include.
Improvement in speech or speaking for the first time in years.
Broadening vocabulary and improved engagement and conversations.
We also hear regular feedback about increased alertness, such as the testimonials on this slide and which patients are able to better follow conversations or complete activities that were previously unable to complete and decreased handwringing and stereotypes.
These proof points all speak to the promise of treatment with debut and we'll continue to monitor and share those experiences as patients continued treatment.
Let's now turn to prescriber metrics on slide 10.
I'd first like to speak to the significant breadth of demand we're seeing from prescribers.
To date, well over 400 prescribers have written prescriptions for debut.
This demand is coming from all sectors centres of excellence high volume institutions and community practices.
We have received prescriptions from all 18 of the designated centers of excellence within the first five weeks post product availability.
In addition to the broad distribution of prescriptions across account types, we're seeing enrollment forms from every region of the country and from each of our 36 territories.
We're also seeing a significant number of <unk> prescribers, who have written more than one prescription pointing to not only encouraging breath, but also increasing depth of prescribing at this point of launch.
While we're pleased with both the breadth and depth of prescribing there is still significant opportunity to penetrate the broader ret syndrome market.
With respect to advancing these prescriptions to paid therapy to date about seven out of 10 written prescriptions from the second quarter have converted and we expect the remainder to convert in the weeks ahead.
The rate of conversion to paid scripts continues to improve monthly.
In terms of process. The vast majority of centers are treating patients as they come to see them during planned ret syndrome clinic days.
Some centers have increased the number of red collect days.
To accommodate patients and families.
Looking at the mix of patients early on we're seeing characteristics such as weight age and gender that are consistent with the broad label that we have at the demographics of the Rep community.
Including a meaningful number of male patients and patients above the age of 20.
We're pleased to see a high degree of titration to help patients reach their optimal dose.
While many of the patients who started treatment early post launch are now reaching their most appropriate dose more recently added patients will continue to titrate up from their starting point.
Overall, we are very encouraged by what we're seeing at this stage of launch given our broad label.
Let's discuss our patient support services next on slide 11.
We continue to be very proactive in providing a wide range of support services to hcp's and caregivers with a special emphasis on educating about the benefits of debut and providing strategies for our Gi management plan.
Our one Acadia team has received excellent feedback from both the medical community and from caregivers underscoring the benefit of our programs, let me double click on this briefly.
As a reminder, we have fully staffed teams of nurse care coordinators at our hub as well as family access managers, who are paired with each patient and caregiver from the moment the prescription is written.
Our field based family access managers or fans also reach out proactively to the prescribing physicians to develop strong relationships with office staff, leading to faster prior authorizations pull through and approvals.
Our sales team is staffed with rare disease experts, who are highly engaged with the ret centers of excellence high volume institutions as well as the smaller community practices there.
They are educating on the debut package label and clinical program as well as our support services to ensure that all practices are well supported.
Our field based rare disease medical science liaisons provide timely insights based on health care provider requests for further clinical information as they start treating patients with debut over.
Overall, our <unk> approach to supporting the recommended <unk> has been instrumental to our early success.
Let's discuss access dynamics on slide 12.
Since commercial launch coverage written coverage policies policies for Dave you have as expected been accelerating.
At this stage payers have adopted formal policies covering approximately one third of ret lives.
This written policy process has progressed somewhat faster than we anticipated at this stage of the launch and underscores that patients.
Payers understand the severity of rips syndrome, the impact it has on patients and their families as well as the clinical evidence that supports debuts approval.
As we projected Medicaid makes up about 60% of coverage with commercial plans covering about an additional 25% the rest of the mix is Medicare and other federal programs.
For those two thirds of patients who have payers that have not yet adopted a formal policy debut prescriptions are fulfilled through medical exception or letters of medical necessity.
Looking at prescription re authorizations. These are generally consistent with our expectations and reflective of what has been seen for other rare disease specialty products, most reauthorization or at six or 12 months with summit three months then annually thereafter.
Let's now turn to NUPLAZID on slide 13.
As Steve noted the NUPLAZID franchise is significantly cash flow positive and increasingly so year after year.
We have introduced operational efficiencies that have lowered our cost base, while simultaneously, increasing our market share versus off label atypical anti psychotics in our contracted overall harkins.
Parkinson's disease market.
Driven by increased PDP, new patient starts our net product sales of NUPLAZID in the second quarter were $142 million up 6% year over year.
We began our broad educational campaign leveraging newly available real world evidence studies at the beginning of the year and are pleased to see these efforts beginning to drive both NUPLAZID brand preference and most importantly, an increase in new patient starts across across both the community and long term care segments of our business.
Since the beginning of the pandemic the overall Parkinson's disease market has contracted significantly.
Looking at carbon Opel levered over prescriptions over the first half of 2023 versus the second half of 2022, we continue to see this trend.
Despite this during the same timeframe NUPLAZID performance has continued to run against the current and we have grown new patient start significantly.
As you can see on this slide and the office based channel. During this timeframe, we have grown new patient starts 13%, while all other PDP products have declined 3%.
Turning to the LTC channel, where we're seeing improvement in new patient admissions.
<unk> has substantially outpaced the class growing fully 20% during this period, while all other products used to treat PDP and the long term care setting have grown just 1%.
Understanding that the large majority of revenues we record during any given quarter are the result of refills by continuing patients. These significant increases in NUPLAZID, new patient starts in both market segments are encouraging.
I'll now turn it over to Doug Williamson, our head of research and development to provide an update on our pipeline programs starting on slide 14.
Thank you Brendan I'd now like to update you on the continued progress of our clinical programs, starting with <unk> as a potential treatment for the negative symptoms of schizophrenia on slide 15.
As Steve mentioned, we have now completed enrollment on schedule in advance to our second study of <unk> in negative symptoms of schizophrenia and are on track for high level results in the first quarter of 2024.
I want to remind you of the opportunity that we're pursuing in this program.
Predominant negative symptoms remained one of the largest unmet needs in schizophrenia and as of today. There is still no approved treatments for these symptoms.
Let's first understand the distinction between treating the positive and negative symptoms of schizophrenia.
The positive oil psychotic symptoms of schizophrenia are characterized by hallucinations delusions unsold disorders.
They typically resolve with appropriate antipsychotic treatment over a period of weeks and often occur in discrete episodes.
The negative symptoms of schizophrenia are characterized by social withdrawal lack of motivation and blunted affect.
Negative symptoms often persists following acute episodes of psychosis and continue to worsen between episodes. These symptoms can lead to greatly diminished social functioning increased CAGR of a burden poor occupational outcome on long term disability.
Drugs that treat the positive symptoms, including drugs approved to treat schizophrenia. Today typically also show a benefit on negative symptoms during the acute treatment phase, but thereafter fail to resolve the chronic persistent and significant negative symptoms affecting approximately 700000 patients in the U S.
<unk>.
Our late stage Adjunctive prevention program is designed to treat these patients whose positive psychotic symptoms are adequately controlled but who still suffer from persistent and uncontrolled negative symptoms inhibiting their ability to lead a normal productive life.
In order to demonstrate utility in this population and obtain an FDA approval for treatment of negative symptoms is necessary to study patients with predominant negative symptoms with positive symptoms are under control.
Sufficient period of time, usually several months.
Please turn to the next slide.
Let me just highlight a few key elements of our now fully enrolled phase III clinical trial advanced two to treat the negative symptoms of schizophrenia.
Negative symptoms of schizophrenia program to be an exceedingly difficult drug development challenge with multiple industry failures over several decades.
Without previous positive advanced one study of <unk>, we achieved something very rare in this population.
And our second pivotal study advance two we're following the same design as our positive advanced one study with two key differences both of which are aimed at improving the probability of success.
First in the advance one trial, we studied patients on a flexible dose range of 20% to 34 milligrams and while the primary endpoint of improvement in all patients was match, we clearly saw that the patients on 34 milligrams had a meaningfully stronger response, so as a result in advance too.
We're only treating patients with the 34 milligram dose the same dose for which NUPLAZID is approved for Parkinson's patients with or without dementia.
Secondly, advanced two is being conducted solely in sites outside the U S. It's well understood in our industry as well as by the FDA that separating from placebo has become more difficult in the U S. Schizophrenia trials over the past couple of decades, largely because of differences in the way schizophrenia patients are treated.
And the way clinical trials are run here therefore.
And therefore, because we already have all of the U S patients we need advanced two is being run solely outside the U S.
The T W. S.
ACP 101 is an intranasal formulation of carbon Towson, which is a synthetic analog of a naturally occurring hormone oxytocin.
Oxytocin deficiency is believed to play a particularly important role MPW S, resulting in increased appetite and behavioral symptoms such as Anxiousness.
However, oxytocin has a very short half life is usually administered intravenously I'll buy I am injection and accordingly is not a viable treatment for P. W. S.
Carpets Olson has improved drug qualities relative to oxytocin, including a much greater half life, which allows for three times daily dosing.
It also has greater selectivity for oxytocin receptors compared to off target vasopressin receptors, reducing the risk of antique diuretic effects such as hypernatremia.
In addition, ACP 100 ones Intranasal administration of competition provides direct direct delivery of the drug to the brain and greatly reduce the systemic exposure further reducing the potential for side effects.
On this slide we've laid out the design of a phase III global Multicenter randomized double blind 12 week placebo controlled study evaluating the efficacy and safety of ACP 101, and approximately 170 probably patients.
In this study we will evaluate three two milligrams of ACP 101 compared to placebo.
The primary efficacy endpoint is improvement of hyperphagia as measured by the hyperphagia questionnaire for clinical trials or H Q C T scale.
This was the same primary endpoint on which to three two milligram dose group achieved statistically significant separation from placebo in the failure say in the previous phase three study conducted by Leibowitz therapeutics.
Those patients who complete the study will be eligible to enroll in an open label Longterm extension study.
I would like to provide some additional perspective regarding the $3 two milligram dose.
Prior to a cages acquisition Leveaux conducted a phase III multicenter randomized double blind eight week placebo controlled study evaluating two doses of ACP 100, 132 milligrams of $9 six milligrams versus placebo.
The study was underpowered and the nine six milligram dose while it demonstrated improvement compared to placebo did not achieve statistical significance.
However, topline results showed the ACP 101 demonstrated statistically significant efficacy at the three two milligram dose.
With regard to safety and Tolerability 3.2 milligrams of ACP 101 had a very clean profile with no serious adverse events of concern both in the Liberal Phase III study and an open label extension study that followed.
If data from this phase III study is positive we plan to submit a new drug new drug application for the treatment of hyperphagia MPW S to the FDA.
We look forward to working with the product really community in clinical experts as we continue to advance development of this program, we know the patients and their families are waiting for our treatments.
On slide 18, let's shift now to ACP two O for our next generation five ice tea to a compound which were developing as a potential treatments for Alzheimer's disease psychosis.
<unk> continues to make excellent progress and we believe has a potentially exciting future.
ACP to our forward, primarily as an inverse agonist at the five H T. Two a receptor.
Our experience with <unk> suggests that this mechanism is very well suited for elderly populations with multiple comorbidities.
Providing antipsychotic efficacy with a highly tolerable safety profile and a low drug drug interaction liability.
With a C. P 204, we're seeking to build on those learnings.
As Steve mentioned, we have completed a comprehensive phase one program for ACP 204 involving over 100 subjects, including both adult and elderly volunteers.
This phase one effort reflects our goal of Characterising ACP 204, as fully as possible early in development in order to accelerate late stage development.
Our work completed to date supports our target product profile for 204, a profile that could represent a significant improvement over an already strong product profile for kind of <unk>.
Firstly, we wanted to mitigate or eliminate a Q T signal.
This was an important goal is it limited the dose of <unk> to date, we've seen no signals of risk of Q T. Prolongation that plan doses in our studies with ACP 204.
Next we wanted to explore doses of ACP 204 higher than the equivalent of 34 milligrams of <unk> we.
We believe the 30 milligram and 60 milligram doses of ACP through our four wheel taking through to phase two development represent up to two fold that does.
Finally, we wanted ACP 204 to have a faster onset of action.
<unk> has a short half life and to advancement on a reaches a steady state in less than half the time, roughly five days compared to around 12 days.
In addition, and our phase one studies ACP 204 demonstrates a very favorable safety and tolerability profile with a low propensity for drug drug interactions similar to <unk>.
Police tend to slide 19.
Armed with this strong data from phase one we're preparing to start our phase two study of over 300 patients for ACP 204 in the fourth quarter.
We've designed phase two so that if successful it could be considered a pivotal registration study.
As we previously described we recently met with the FDA to get alignment on our phase two three development plan and be able to move seamlessly from phase two into two phase III studies.
With this accelerated development plan.
We can move seamlessly from phase III to two phase III studies with the same sites continuously enrolling patients.
As each site complete star Phase two site allocation they will move directly into enrolling patients for one of the phase three studies once the full study allocation of patients for phase. Two is complete we will analyze and report phase two results by which time the two phase III studies will already be underway.
This plan will ultimately provide three potential pivotal studies for a submission.
Overall, we're very excited with the progress of this program and we've already begun exploring a potentially rich lifecycle plan for 204, which will comprise other indications where five <unk> and division plays a significant role.
And now I will turn it over to Mark for financial update on Slide 20.
Thank you, Doug Let's review, our quarterly performance on Slide 21 [laughter].
And the second quarter, we recorded $165 $2 million a total net sales.
NUPLAZID net product sales with $142 million up 6% from the second quarter of last year, our gross Jeanette adjustment for NUPLAZID was 27% for the quarter.
Year over year demand and selling growth for each up approximately 3% in the quarter driven by an increase in new patients start to cross cross both the office based in long term care channels with particularly strong performance in long term care.
Turning to debut.
Net product sales were twenty-three $2 million in the first quarter of commercial availability as.
As a reminder debut is sold directly to our single specialty distribution partner using a consignment model. Our revenue is recognized when customer orders are filled to the pharmacy warehouse, which is essentially right for for product is shipped to the patient.
Therefore, there is no and channel inventory stocking for debut.
R&D expenses decreased to $58 $8 million in Q2, 2023 from $75.6 million in Q2 2022.
Decrease was mainly due to the inclusion of preapproval manufacturing supply expenses for tryphena tide and last year second quarter.
SG&A expenses increased slightly to $96 million in Q2, 2023 from $89 $9 million and Q2 2000 2000 to the.
The increase was driven by commercial cost associated with the debut launch pardon.
<unk> in our commercial support of new closet.
We ended the quarter with a cash balance of $375 for $1 billion compared to $416 $8 million at the end of 2022.
Decreases primarily due to the 40 million dollar milestone payment to neural related to debuts first commercial sale.
As a reminder are pro forma cash balances approximately $275 million <unk>.
After considering in the $100 million upfront payment related to our expanded licensing agreement with.
For worldwide rights <unk> that we completed in July .
Finally, as Steve mentioned, our existing business as a whole has now reached cash flow neutrality.
Our PDP franchise has been cash flow positive going back to 2019, and we've generated increasing cash flow from this franchise each year. Since then by focusing on both the top and bottom line inclusive of reducing expenses by over $100 million when comparing 2021 results to the midpoint of our 2023.
SG&A expense guidance range.
Turning to slide 2000 2022.
We are reiterating our third quarter debut net sales guidance of 45% to $55 million.
Our full year NUPLAZID guidance also remains unchanged with net sales expected to be in the range of 530 $545 million in gross and net expect it to be in the range of 22 to 25 per cent.
On the expense side for 2023, we now expect R&D expenses to be between 335 and $355 million adjusted for the $100 million upfront payment to <unk> that we will record as R&D expansion in the third quarter.
We are raising our SG&A expense guidance range to $380 million to $400 million the.
The increase is primarily due to an increase in operating costs as a result of favorable business performance.
And now I would like to turn the call over to Steve for closing remarks.
Thanks, much Marc please turn to slide 24.
I'd like to in today's prepared remarks by integrating.
Integrating where I started Ah Katie is entering a transformational period of growth as we continue to execute across all strategic priorities.
And with that I'll turn the call over to the operator to begin kunai.
Thank you.
If you wish to ask a question. Please press pound followed by the one on your Touchtone telephone.
If your question has been answered are you like three strike to withdraw your question. Please press the pound key please limit yourself to one question I repeat please let me yourselves to one question has <unk> to begin please stand by for your first question.
[noise] okay.
<unk> J P. M. Please go ahead.
Alright, thanks, so much for taking my question Hi, Stephen team.
So our question is can you give us a sense of what the new patient starts are looking like months and months qualitatively any <unk> point out.
To the extent you can provide any directional color and catch a lie that may be informing the guide that would be that would be helpful. Thank you. So much.
Yeah. Thanks, so much for the question test Brendan and you want to take that.
Sure. Thanks test.
So I think we're focused on providing.
Output instead of input at this point with the revenue guidance, we provided for the quarter.
We're doing so principally because we know there are a number of adjustments that we make from the time of a new patient start to fully realizing revenue as you know as a weight based prescription. There's also titration that takes place to find that Apple optimal dose, which isn't always reflective of the written prescription.
So rather than give sort of a single metric on patients. We believe it's more productive at this point to guide to revenue, which takes into account each of those variables.
For the quarter.
If and when we get to metrics that we think are dependable and reliable will surely help you will surely help out and share those when we have them but.
But for today I think we've outlined the strong breath of demand we're seeing the number of physicians that have written as well as insights into the patient mixed that we're seeing in these initial months both post launch.
Okay. Thank you so much for taking my question.
Thank you one moment to your next question.
The next question comes from Charles Duncan of Cantor Fitzgerald. Please go ahead.
Hey, Hey.
Hey, good afternoon, Steven Teen congrats on a great quarter of nice to see the.
I'll take debut lots of questions to be asked but all of my mind to just one and that is on the negative symptoms for schizophrenia.
Yeah with <unk> trial, I think does mention this on the call about conducting this study slowly S. U S. I can we assume that that was discussed with the agent fee in advance and secondly.
With regard to the predominant in negative symptoms mercy, possibly did the symptoms may be in the U S. Can you help us understand how that might be a little bit different or wind up a little bit. They find acts you asking is to gauge probability successfully that's right. Thanks.
Yeah, Charles I'll take the first part of that and then I'll ask Doug to answer the second part so in terms of running this study advanced two entirely outside of the United States as Doug mentioned, it's well understood in the community and certainly also at the F. D. A and it's just become increasingly difficult over the last.
A few decades as Doug mentioned.
Two separate from placebo and it goes.
It's based upon some of the things it does refer to that we probably need to go into here.
We have enough patients in the United States today, So we don't need to enroll more in terms of the broad plan for.
Four negative seem schizophrenic, yes, we did discuss that at an early stage of development with the FDA, but we're confident that we have enough patience.
Enough U S patients in the database today, Doug you and take the second part.
Yeah can you can you can you clarify your second question, we are asking about the difference between positive and negative symptoms within the U S and your lungs.
Yeah, just quickly dug you mentioned that it was important to study pre dominate negative symptom patience.
Alright, and I get some laundering, if you would have seen that in the state or is there some something different in the treatment paradigm etsy last that results in that.
No that positive negative symptoms are pretty consistent.
Regardless of what the region is that the reason for conducting it outside of the U S.
<unk> said and as I said on the call is.
The lower placebo right.
The gradual difficulties over the last couple of days.
Decades of separating placebo in U S schizophrenia studies.
But isn't that usually seen in positive symptoms not not I don't know if you have a large database and negatives sometimes it's a general finding across actually all psychiatry studies, not just schizophrenia studies and in fact, we did.
We did we did see this in advance one in our in our first negative symptoms study, we saw a similar pattern.
Okay. Thanks for taking my question.
No. Thank you one moment for my next question.
Your next question comes from my Tech name is leaving please go ahead.
Yes, Hi, can you give us a sense for debut.
The titration plan persistence, what's happening just how the patient are going on.
And staying on drug and just you know give us a sense of the average selling price in the quarter and what's happening there just it's kind of all wrapped together. Thanks.
Mmm Yeah. Thanks, much further question Mark Britain, and you wanted to take out.
Sure. Thanks Mark.
I was gonna start with persistency and simply state that were encouraged by what we're seeing early on as it relates to persistent and C.
As you know <unk> was never intended to be an acute care treatment. We want patients to have the long term benefits of debuts of staying on therapy longer long term is critical.
We learned a lot from the phase III study, obviously and we took a comprehensive approach from the outset to support both the patient family and and the health care professionals from the outset to that to that and we've done a lot of medical education on Ti management with the Hcp's caregiver communities.
We work directly with the families with Nerf care coordinators to essentially certify these caregivers and <unk>.
Comfortable with both the benefits they'll see with with debut but also Gi management strategies as they start the journey.
Our family our family access managers are all paired with each patient and caregiver to further reinforce those clinical benefits and timing.
And to be with them every step of the way and then our teams are the very same thing with our with every HCP before they start treatment with debut so for us that comprehensive patient and caregiver focused programming was expected to deliver deliver benefits in the early days for persistency and we're certainly seeing that early on.
The second part of your question was around titration, which I want to say, we're also having to see.
Acp's families, obviously want nothing more than to find that optimal dose for each individual patient to make sure that they can stay on therapy and get the long term benefit.
To be derived from treatment.
And unlike the clinical trial, where you are essentially trying to defy.
Define the treatment benefit of the product and the real world physicians and families can take all of those learnings for the trial and translate those into a treatment plan that can lead to the highest long term success rate.
I should say separately that payers do approve prescriptions on a monthly basis. So we don't see families ending up with large excesses of product on hand, as a function of that and.
And then in terms of actual titration rates, while it varies from physician and patient they tend to reflect the starting dose in in the area of about 50% of the target dose with a scheduled tight titration right.
Or I.
I should say titration time over a period of about two to six weeks.
That obviously varies from patient to patient with their experience.
And as you would expect we would expect patients to settle it on their optimal dose.
Over that period of time, and then create a consistent dosing schedule from there.
What does that mean for pricing.
Oh, sorry, yes. Good question. So based on what we said prior to launch the fundamentals of how we described pricing for debut remained largely the same many patients are tight trading as we said the average weight is perhaps slightly higher than expected because of our broad label.
And a meaningful number of patients over the age of 20, but other than that the elements of both titration dosing in patient mix support our expectations for a net realized price.
Thanks.
Thank you one minute for your next question.
Okay.
Our next question comes from Gregory Venza of I B C capital market. Please go ahead.
Hey, good afternoon at Steve at team Congrats again on the progress and thanks for taking my question I will keep it to one and maybe just pivoting back to ER negative symptoms schizophrenia.
Doug certainly helpful to hear about the unmet need in characterizing the population there, but maybe Steve as you get closer to their read out I'll be <unk>.
To just hear a little bit about that commercial opportunity maybe how are you.
Thinking about leveraging the existing infrastructure, what that would look like especially as you have a direct NUPLAZID now in the base business to.
To leverage in cash flow positivity any additional caller there on what the arbitrary it looks like pending positive read out would be great. Thanks, so much.
Yeah, Thanks, a bunch of <unk>.
I'll I'll start, bringing feel free to chime in with any additional color you'd like to add so about 700000 patients in the United States have what Doug is described these.
Prevalent negative symptoms that continue on despite the fact that they've got positive symptoms under control and have already received any many times transitory benefit from getting that under control. So it's a cycle population is about five times the size of Parkinson's disease psychosis.
It is a very significant unmet need and there are no drugs approved to treat the negative symptoms of schizophrenia. So when you think about the pricing and penetrating at market.
We do not anticipate any difference on pricing.
In in negative symptoms in or reprice currently to treat.
Parkinson's disease psychosis again, the Niesr very similar no drug approved significant.
So.
When we think about how to leverage the capabilities, we have in place today, obviously, NUPLAZID and PDP, we have a drug.
That treats psychiatric symptoms that are predominantly written.
By a neurologist so we have a strong franchise, both enroll James psychiatry.
Negative symptoms schizophrenia are treated predominantly psychiatrist. So we would anticipate having an expansion of our field force to cover that much broader footprint.
We would we would anticipate that it would be.
Can be an expansion not a separate.
Salesforce that we would stand up we would expand and enforce it we have to cover the same.
Territory's here towards that have to be slightly different size.
Today.
With neuropsychiatric drugs.
Franchises that we standup are dramatically smaller than what we did in the industry feud.
Few decades ago, we think it's all very manageable and of course, there's an opportunity to significantly leverage all of the other components of our commercial.
Franchise.
As we.
As we move into negative schizophrenic. So I think we're very very well positioned to capitalize on on a financial approval here and we're very excited about bringing anything you'd like to add yeah.
Completely agree I was just going to reinforce that final point, we have we are foundational and the CNS space and we have a lot of internal capabilities that are leverageable across indications Sylvia.
So beyond the addressable physician population, which we would we would augment our current field footprint to support we have lots of capabilities internally, whether those are patient support services account management or our marketing leadership team. We're in we're in good shape.
Greg I'm, sorry, just one one other.
Component that I think it's important to remind everyone.
As Doug mentioned the population were seeking to treat is not first line therapy for schizophrenia patients.
For those patients, particularly if they are focused on the positive symptoms.
There are more than a dozen approved drugs that are now generic relatively inexpensive. So we're not trying to displace those drugs, we would be adding on top of those drugs as a jumped of therapy to.
To treat the persistent negative symptoms. So it's a little from a pricing perspective is a little bit different dynamics in.
The way, we would think about the market. If we were seeking to treat positive symptoms as first line therapy.
That's great. Thanks, so much I appreciate it.
Thank you one moment trying next question.
Okay.
Okay.
Your next question comes <unk> <unk>. Please go ahead.
Hi, Thanks, so much for taking my question.
Maybe it got back to the topic of tape you as it relates to monitoring the initial signs of diarrhea, how have doctors found it to get the best way to go about it and uhm alright. They made aware that a patient is having severe diarrhea right away or.
How is it that communication work to get that treatment started thanks.
Yeah. It takes much Dizzy Brendan.
Sure dizzying. Thanks, so much for the question.
I'll go back to all of the preparation work, we did as a function of what we learned from phase III. So the phase III study gave us a pretty clear.
Image of the product profile for for debut as a.
Function of that you've seen us with.
GIM management guidelines that have been written we have a hub that that educates all patients and families in advance of starting treatment. We do the same with with Hcp's and we're grateful that the label for for debut also includes inform.
Nation about discontinuing anti constipation medicines.
So you can prepare the patient for the best treatment journey ahead.
In terms of how the families interact both with our our family access managers and they're treating physicians for sure as they run into.
Any issues that they might have with tolerability. They are alerting their health care professionals and they're looking for guidance on best ways to manage that I think as I said, we're we're pleased with what we've seen in terms of both titration and persistency.
I think those are are intertwined.
A thoughtful approach to finding the optimal dose.
Constant interaction I would say between families and their providers to talk about that treatment journey, and then choosing the appropriate adjustments to get to the best dose for the individual patient.
Oh, Thanks, Brandon you guys stop comfortable providing.
Arrange for for three kids already.
Is that because the initial management of the diarrhea.
Or any similar.
All patients can more accurately predict what patients are kind of drop out.
The the the reason we gave.
Two three guidance as we felt like we have a good handle on exactly what we're seeing overall and we felt like there was a more productive and more useful to you and everyone else that's.
On this call to get the output as opposed to various inputs and hopefully people will get to the right conclusion.
So that was the reason for guiding on Q3 as it relates to persistence and continuation therapy I would just simply repeat what.
What we said earlier and that is we're very encouraged by what we're seeing is still very early and and we don't have perfect line of sight on these things once a patient starts therapy, but we have good.
Access to information, particularly through our Fam our system and what we're hearing we're very very encouraged by.
Okay.
Thank you one moment trying next question.
Your next question comes from some months Kulkarni.
Genuine he prescribed.
Good afternoon. Thanks for taking my question could you comment on what the specific primary endpoint you might be using will be in the face to the child's for a C. P 204 fries that much Dizzy psychosis, and how that compares to the <unk>.
Hey, yeah. Thanks, so much for the questions argument take out.
Yeah, we'll we'll be using the same primary outcome measure the SaaS HD.
Thanks.
Thank you one moment trying next questions.
The next question comes from Jason Butler JMP. Please sir.
Hey, Thanks for taking my question I I'll jump in with a follow up there on the ICP 204 phase two three trial design, if you're using the same endpoint is the 30% improvement in symptoms threshold, but you you you used for responders still irrelevant you know marker for clinical significance.
And what drove the.
Decision to go for a six week can point given that you you saw improving efficacy throw at least eight weeks in the running and the last phase III trial. Thanks.
Doug you and take them.
Sure.
I mean, the 30% improvement is generally kind of regarded as a clinically significant change so we're sticking with that.
And even though we're seeing even though you may see continued improvement past six weeks when we looked at the existing data we have a <unk>. We decided six weeks was the optimal treatment period.
<unk>. Thank you.
Thank you one moment for your next question.
Your next question comes from your end.
Uh-huh <unk>.
<unk>.
[noise] hi, Thanks for taking the question. Another one on two of four could you just comment on how come system was the PK in young and younger how the volunteer versus the outer D. And then with regard to the studies that you are running emanate are these based on what's going on all over to the long term safety study because that to me.
<unk> perspective for some of these new indications.
Yeah, Doug two questions.
Yeah, I'll have to come back to you on the second one because I couldn't hear it properly but.
How consistent was the was the PK findings and.
Young young adults this is elderly.
Was consistent it was consistent with many other studies.
Comparing young adults with elderly, we did see slightly higher exposures and the elderly population.
But.
We've chosen our our doses based on based on that based on on the on the <unk> the elderly volunteers and we study.
And can you repeat the second part of the question again.
Yeah. This is my second question will patrons rollover and don't believe global extinction and the answer is yes, yes.
Thank you.
Thank you one moment for your next question.
Mmm.
The next question comes from on the 30th of Needham and company. Please go ahead.
Hi, Good evening. Thanks for taking my question I'm going back to the negative symptoms, let's look at the <unk> study.
Can you talk to the <unk> off the plant one study.
Between the U S and X U S patient population.
And talk about the.
<unk> the magnitude of effects tie you saw in their patients.
Out of Europe in the 34 milligram dose.
And if you could set up just remind us.
Disclosed any details around poverty, Okay uhm it asked to study thank you.
I'll I'll, maybe start at a very high level in the appropriate chummy. So as Doug mentioned, what we saw in the advanced studies, we did see differential between USAID and extra sides.
Very consistent we see this all the time and schizophrenia. We also saw it by the way when we did a earlier study.
To treat.
Difficult to treat patients with positive and negative Simpson, who saw similar pattern there.
A higher response outside of the U S. As opposed to you. So it's very consistent.
Result that we see and as Doug mentioned the results were in to 34 milligram dose I think you were asking about were highly.
Highly.
Improved over the total population, where where you're allowed dose flexibility down to 20 milligrams.
And with a 34 milligram dose we saw an effect size a 0.34.
It's like anything else you want to add.
No.
I think the effect size was consistent across regions that was really the separation from <unk> and different.
Thank you one moment for our next question.
Your next question comes from Jane Austen of Oppenheimer. Please go ahead.
Oh, Hey, Thank you for taking the question. We're curious about a C. P. 101 can you describe the size of the commercial opportunity.
<unk> really syndrome, and that's been a notoriously challenging therapeutic area. What learnings can you take away from previous studies that should help you increase the probability of success. Thank you.
Yeah. Thanks, so much great Britain, and you want to take them.
Thanks for the question.
As we I think noted.
In a prior call. There is a there is a higher prevalent population for prouder, Willie I would put the unmet medical need similar to what we've seen in the rift syndrome community. There are no approved treatments. This is life a life changing type of opportunity.
For us that's the way we would.
Kind of approach approach 101, and B W. S.
And learning from previous studies.
<unk> I I can I can how 'bout that.
So I I think.
One advantage. We have is we do have access to the full data and a lemonade family those previous space based study that they conducted with exactly this exact product Anthony <unk>.
And.
Very carefully gone over all that data in great detail. This has helped US plan our phase three clinical trial that we're gonna be starting in the fourth quarter here, we'll be talking exactly about child design I think as we start the trial, but we based on that data I think maintain tweaks to the English.
And experts and criteria.
And as we talked about previously.
Crowley made a little bit longer because we do see greater benefit no longer retreat with that previous experience.
Exactly right the private really field is quite experienced in clinical trials, there's been quite a work done there. Unfortunately.
Treatments today, so I think some disappointments in the field, but that's awesome I advantage can because we do have very experienced clinical trial site and are able to use <unk> I think also in the execution of the trial. So what I'm working with experience sites in Seattle is experienced and pregnant Lily.
Trials, two as you mentioned tap into that previous experience.
Great. Thank you very much.
Thank you one moment for your next question.
The next question comes from Kenya.
Raymond James Please go ahead.
Hey, guys. This is Alex on for Danielle. Thanks for taking my question. This question on debut so I know you said the reauthorization requirements were within expectations, but also in reading some of the <unk> of the enacted pay your policies it.
It seems the three authorization requirements are on the more stringent side requiring documented measured treatment benefit not just physician at a station. So we were just curious how you were thinking on a quantitative basis, roughly what percentage of patients major falloff debut therapy, whether by Preauthorization rejections of the <unk>.
My time point over Discontinuations throughout the first six months to one year. Thanks, so much.
Britney you Wanna take Ah yeah.
Thanks appreciate the question.
I would characterize what we've seen among payers to date as seeing them take a thoughtful approach to.
Two debut coverage and looking to ensure appropriate views and so we work very closely with them on a regular basis.
To look at their coverage policies and make sure that these are elements that that payers and families are going to be able to me to continue to not only to get approval to stay on therapy. So we believe by and large when we look at paid claims and the published coverage criteria. The payers are recognizing.
The challenges the unmet needs that are seeing of red syndrome, and are valuing the clinical benefit that they view is bringing to address those patients.
Thank you one moment.
You only have time for one more question, so I appreciate and die for that.
Okay last question comes February too far off as television Cohen. Please. Please go ahead.
Hi, guys. This is Athena on for me too. Thanks for taking my question. Another one until you how long to care peppers.
You tend to shop benefit before determining it does not work for that child.
<unk> I'm Gonna speakers, Yeah sure thing thanks for for the question.
I think we've been encouraged by guidance that the Red community. The traders are giving to caregivers to.
To set appropriate expectations, obviously, the lavender study is 12 weeks in duration, which gives people some sense for what they should be looking forward to see the initial signs of improvement.
Improvement in debut.
Many physicians are saying look this is a a life long.
Illness that we're dealing with here is the first ever drug approved 12, 12 weeks worth of treatment as a relatively short treatment course, and are encouraging families and caregivers to look out to six months.
To make sure that they're seeing the benefits that they would expect to see now with that said are are and are prepared remarks were already very encouraged to hear caregivers note differences day to day improvements that are occurring well before that time period.
So I think it's a balance of those two but at least the guidance given is to is to give the drug Ah thoughtful period of time to work.
Okay. Thank you thanks.
Thank you Mister Davis. Please proceed to closing remarks.
Great. Thank you operator, thanks again, everyone for joining US today, we look forward to updating you on our progress next quarter.
Thank you for your participation in today's conference call that concludes the presentation you may now disconnect.
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