Q4 2023 ACADIA Pharmaceuticals Inc Earnings Call
Operator: ACADIA Pharmaceuticals Inc. Good day, ladies and gentlemen, and welcome to ACADIA Pharmaceuticals' fourth quarter and full year 2023 Financial Results Conference Call. My name is Abigail, and I will be your coordinator for today. At this time, all participants are in a listen-only mode.
Yeah.
Abigail: Good day, ladies and gentlemen, and welcome to Acadia Pharmaceuticals fourth quarter and full year 2023 financial results Conference call. My name is Abigail and I will be your coordinator for today at this time all participants are in a listen only mode. We will be facilitating a question and answer session towards the end of today's call.
Operator: We will be facilitating a question and answer session towards the end of today's call. To ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. I would now like to turn the presentation over to Al Kaldani, Senior Vice President of Investor Relations and Corporate Communications at ACADIA. Please proceed. Good afternoon, and thank you for joining us on today's call to discuss ACADIA's fourth quarter and full year 2023 earnings results. Joining me on the call today from ACADIA are Steve Davis, our Chief Executive Officer, who will provide some opening remarks, followed by Brendan Tien, our Chief Operating Officer and Head of Commercial, who will discuss our strong commercial franchises, Dayview and New Plaza.
Abigail: To ask a question you will need to press star one on your telephone and wait for your name to be announced.
Abigail: I'd now like to turn the presentation over to Al Qahtani Senior Vice President of Investor Relations and corporate communications at Acadia. Please proceed.
Sumant Kulkarni: Good afternoon, and thank you for joining us on today's call to discuss the Kbr's fourth quarter and full year 2023 earnings results.
Sumant Kulkarni: Joining me on the call today from Acadia are Steve Davis, our Chief Executive Officer, who will provide some opening remarks, followed by Brendan <unk>, our chief operating officer and head of commercial who will discuss our strong commercial franchises debut of NUPLAZID.
Operator: Doug Williamson, our Head of Research and Development, will provide an update on our pipeline programs, and Marc Schneier, our Chief Financial Officer, will review the financial highlights. Steve will then provide some closing thoughts before we open up the call to your questions. In addition, Parag Miswani, Senior Vice President for Phenetide Rare Disease Franchise, will be available for the Q&A session. Additionally, we are using supplemental slides which are available on our website's events and presentations section.
Brendan: Doug Williams, and our head of research and development will provide an update on our pipeline programs and Mark Schneider, Our Chief Financial Officer will review the financial highlights.
Brendan: He will then provide some closing thoughts before we open up the call to your questions. In addition, parag Suwannee senior Vice President for phenotype rare disease franchise will be available for the Q&A session.
Brendan: We are using supplemental slides, which are available on our website events and presentations section.
Operator: Before proceeding, I would like to remind you that during our call today, we will be making several forward-looking statements 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.
Brendan: Before proceeding I would like to remind you that during our call today, we will be making several forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995.
Brendan: 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.
Brendan: 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.
Operator: 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 for his opening remarks. Thank you, Al. Good afternoon, everyone, and thank you for joining us. Please turn to slide five.
Brendan: I'll now turn the call over to Steve for opening remarks.
Stephen R. Davis: Thank you al good afternoon, everyone and thank you for joining US please turn to slide five.
Stephen R. Davis: We transformed our business in 2023. Today, we are a cash flow positive company with two first-class commercial assets. We have three late-stage assets and a robust early-stage pipeline, and we continue to invest in future growth through business development. Let's begin with our commercial franchises, which delivered record revenue of $231 million in the fourth quarter of 2023 and $726.4 million for the full year.
Stephen R. Davis: We transformed our business in 2023 today, we are a cash flow positive company with two first in class commercial assets.
Stephen R. Davis: We have three late stage assets and a robust early stage pipeline and we continue to invest in future growth through business development.
Stephen R. Davis: Let's begin with our commercial franchises, which delivered record revenues of $231 million in the fourth quarter of 2023 and.
Stephen R. Davis: $726 $4 million for the full year.
Stephen R. Davis: Debut, the first and only drug approved to treat Brett syndrome, generated fourth quarter sales of $87.1 million in its second full quarter of sales since it was launched in April of last year. We're proud of our early success with the launch and excited about the future of DayVu. New Plastic continues to deliver and be strongly cash flow positive. Sales in the fourth quarter were $143.9 million and reflect our ability to gain market share and grow the revenue base while continuing to manage expenses, in addition to our two successful commercial franchises. We have a deep and growing pipeline, and ACADIA is making significant advances, including programs in the negative symptoms of schizophrenia, Potter-Willey syndrome, and Alzheimer's disease psychosis. ACADIA has never been in a stronger financial position.
Stephen R. Davis: Debuted the first and only drug approved to treat breast syndrome generated fourth quarter sales of $87 1 million.
Stephen R. Davis: In its second full quarter of sales since it was launched in April of last year.
Stephen R. Davis: We're proud of our early success with the launch and excited about the future of debut.
Stephen R. Davis: NUPLAZID continues to deliver and be strongly cash flow positive.
Stephen R. Davis: Sales in the fourth quarter or $143 $9 million and reflect our ability to gain market share and grow the revenue base, while continuing to manage the expense base.
Stephen R. Davis: In addition to our two successful commercial franchises, we have a deep and growing pipeline, which is making significant advances including programs in the negative symptoms of schizophrenia product Willi syndrome in Alzheimer's disease psychosis.
Stephen R. Davis: Acadia has never been in a stronger financial position.
Stephen R. Davis: We delivered 40% revenue growth in 2023 on the strength of our successful debut. We are now in a position to generate substantial, sustainable cash flow to fund further growth in our business. We ended the year with $438.9 million in cash, even after deploying a little over $100 million for business development. We expect our cash balance to grow to between $585 and $655 million by the end of 2020.
Stephen R. Davis: We delivered 40% revenue growth in 2023 on the strength of our successful debut launch.
Stephen R. Davis: We're now in a position to generate substantial sustainable cash flow to fund further growth in our business.
We ended the year with $438 $9 million in cash even after deploying a little over $100 million for business development and.
Stephen R. Davis: And expect our cash balance to grow to between 585 and $655 million.
Stephen R. Davis: The end of 2024.
Stephen R. Davis: ACADIA is relatively unique amongst our biotech peers, combining successful commercial franchises. I'm here to talk about the exciting late and early-stage assets and the financial strength to capitalize on these opportunities. This includes further expanding our portfolio and building on our success with Daybu and Nupliazid in the central nervous system and rare diseases. Let's next turn to a snapshot of our current products and pipeline on slide six. Duplazid is our treatment for Parkinson's disease psychosis, which today remains the only drug approved for the treatment of this condition.
Stephen R. Davis: The kidney is relatively unique amongst our biotech peers combining successful commercial franchises.
Stephen R. Davis: Exciting late and early stage assets and the financial strength to capitalize on these opportunities.
Stephen R. Davis: This includes further expanding our portfolio and building on our successful debut of NUPLAZID and central nervous system and rare diseases.
Stephen R. Davis: Let's next turn to a snapshot of our current products and pipeline on slide six.
Stephen R. Davis: NUPLAZID is our treatment for Parkinson's disease, psychosis, which today remains the only drug approved for the treatment of this condition.
Stephen R. Davis: In 2023, we added significant growth potential to our business with the introduction of Debut for the treatment of Red Syndrome. Here, too, they used the first and only drug approved for the treatment of RET. Behind these two successful commercial franchises, we have numerous late and early stage pipeline assets, including our Negative Symptoms of Schizophrenia Program with Pimivans. There are no FDA-approved treatments for this disorder, so the unmet need is high. And we look forward to having top-line results of our ADVANCE II study by the end of this quarter. As a side note, obviously, we do not have results as yet. ACP 101 and Prader-Willi Syndrome, where we are currently in rolling subject. Prader-Willi is a rare and highly debilitating genetic disease. Patients have an unrelenting drive to eat called hyperphagia.
Stephen R. Davis: In 2023, we added significant growth potential to our business with the introduction of debut for the treatment of Ret syndrome.
Stephen R. Davis: Year to date view as the first and only drug approved for the treatment of breath.
Behind these two successful commercial franchises, we have numerous late and early stage pipeline assets, including our negative symptoms of schizophrenia program with Timothy answering.
Stephen R. Davis: There are no FDA approved treatments.
Stephen R. Davis: For this disorder, so the unmet need is high.
Stephen R. Davis: And we look forward to having top line results of our advance two study by the end of this quarter.
Speaker Change: As a side note obviously, we do not have results as of today.
Speaker Change: ACP would've wanted product Willi syndrome, where we are currently rolling subjects.
Speaker Change: But it really is a rare and highly debilitating genetic disease, where patients have an unrelenting drive to eat pulp hyperphagia.
Brendan Tien: The severity of this disorder translates into an average lifespan of 30 years. Here, too, there are no FDA-approved treatments. We're also currently enrolling our Seamless Phase 2, and Phase 3 programs with ACP 204 in Alzheimer's disease psychosis, another disorder where there are no appropriate... ACP 204 is our second generation 5HT2A blocker, where we are leveraging our learnings from Pimivans. And beyond that, we have a rich pipeline of early-stage disclosed and undisclosed programs; that position is for the future. I'll now turn the call over to Brendan to discuss our commercial performance on slide seven. Thank you, Steve.
Speaker Change: The severity of this disorder translates into an average lifespan.
Speaker Change: Of 30 years.
Speaker Change: Here too there are no FDA approved treatments.
Speaker Change: We're also currently enrolling our seamless phase III phase III program with ACP tool for in Alzheimer's disease psychosis patients.
Speaker Change: Another disorder, where there are no approved treatments.
Speaker Change: ACP 204 is our second generation <unk> blocker, where we're leveraging our learnings from kind of answering.
Speaker Change: And beyond that we have a rich pipeline of early stage disclosed and undisclosed programs.
Speaker Change: <unk> for future growth.
Speaker Change: I'll now turn the call over to Brendan to discuss our commercial performance on slide seven.
Brendan: Thank you Steve.
Brendan: I am pleased to provide additional commentary on our two commercial franchises debut on NUPLAZID and the terrific performance both delivered in the quarter.
Brendan Tien: I'm pleased to provide additional commentary on our two commercial franchises, Debut and New Plazid, and the terrific performances both delivered during the course. Please turn to slide 8, beginning with Debut. We're now roughly 10 months into launch, and I'd like to begin by summarizing our accomplishments to date. The launch of Debut has been one of the most successful recent launches in rare disease. We've had the privilege of bringing this therapy to patients and their caregivers, who previously had no approved therapeutic options to help them deal with the debilitating condition. With an estimated 5,000 diagnosed RET patients in the United States and a prevalent population of 6,000 to 9,000, there is a substantial opportunity in front of us to bring the benefits of this therapy to many more patients. We anticipate this will drive meaningful revenue growth well beyond this year. As the first drug approved for the treatment of Rett syndrome, we've experienced strong interest and demand from Rett families.
Brendan: Please turn to slide eight beginning with debut.
Brendan: We're now roughly.
Brendan: 10 months into launch and I'd like to begin by summarizing our accomplishments to date. The launch of debut has been one of the most successful recent launches in rare diseases.
Brendan: We've had the privilege of bringing this therapy to patients and their caregivers who.
Brendan: Who previously had no approved therapeutic options to help them deal with the debilitating condition.
Brendan: With an estimated 5000 diagnosed patients in the United States and a prevalent population of six to 9000, there is a substantial opportunity in front of us to bring the benefits of the steroid therapy to many more patients.
Brendan: We anticipate this will drive meaningful revenue growth well beyond this year.
Brendan: As the first drug approved for the treatment of Ret syndrome, we've experienced strong interest and demand from families.
Brendan: As we've previously reported this strong interest produced a surge of new patient starts in the first four months of the launch followed by a demand curve that is much closer to our prelaunch expectations and the linear shaped curve, we typically see in rare disease drugs.
From a from a prescriber perspective. This initial surge was met was concentrated in ret centers of excellence or Coes.
Brendan Tien: As we've previously reported, this strong interest produced a surge of new patient starts in the first four months of the launch, followed by a demand curve that is much closer to our pre-launch expectations and the linear-shaped curve we typically see in rare disease drugs. From a prescriber perspective, this initial surge was concentrated in Rett Centers of Excellence, or COE, and we have since significantly expanded the breadth and depth of prescribers. This search has produced multiple benefits.
Brendan: And we have significantly expanded the breadth and depth of prescribers.
Brendan: This surge is produced multiple benefits.
Brendan: It has enabled us to reach a critical mass of experience in the medical and caregiver communities dramatically faster than we otherwise would have.
Brendan: This has also enabled us to rapidly gain real world insights that we've been able to use to further educate the medical and caregiver communities.
Brendan Tien: It's enabled us to reach a critical mass of experience in the medical and caregiver communities dramatically faster than we otherwise would have. This has also enabled us to rapidly gain real-world insights that we've been able to use to further educate the medical and caregiver communities. 10 months into the launch, COEs continue to represent a rich source of new patient starts. In fact, today, approximately 40% of our new patient prescriptions come from COEs, and we are continuing to add depth in this sector. Non-COE high-volume institutions account for approximately 30% of our new patient prescriptions. This sector represents an additional important growth opportunity as we continue to increase our breadth and depth in these institutions. I'd like to focus now on seasonal dynamics we observed in the latter part of the fourth quarter and early part of the first quarter.
Brendan: 10 months into the launch.
Brendan: <unk> continued to represent a rich source of new patient starts in fact today approximately 40% of our new patient prescriptions come from Coes and we are continuing to add depth in this sector non.
Brendan: Non Coa high volume institutions account for approximately 30% of our new patient prescriptions. This sector represents an additional important growth opportunity as we continue to increase our breadth and depth in these institutions.
Speaker Change: I'd like to focus now on seasonal dynamics, we observed in the latter part of the fourth quarter and early part of the first quarter.
Speaker Change: In December in particular, we experienced higher than average refill rates as families prepared for the holidays and health plan changes or re authorizations in the new year.
Speaker Change: In January we saw a decline in new prescriptions written driven by seasonal and significant decline in clinic visits following the holiday period, where approximately 50% of Coes had either no clinic days or reduced clinic days available.
Brendan Tien: In December, in particular, we experienced higher-than-average refill rates as families prepared for the holidays and health plan changes or reauthorizations in the new year. In January, we saw a decline in new prescriptions written, driven by seasonal and significant declines in Rett Clinic visits following the holiday period, where approximately 50% of COEs had either no clinic days or reduced clinic days available. We have since seen a return of Rett Clinic days in February, tracking back to historical levels, and new patient prescription rates returning to the trends we observed prior to January. In January, we also saw a reduction in refills and conversion rates due to typical beginning of the year reauthorization and re-enrollment processes.
Speaker Change: We have since seen a return of Ret clinic days in February tracking back to historical levels and new patient prescription rates returning to the trends we observed prior to January.
Speaker Change: In January we also saw a reduction in refills and conversion rates due to typical beginning of the year reauthorization and re enrollment processes. This resulted in delays in patients receiving their first page shipments in the new year, we are working through those authorizations and do not see any long term issues associated.
Speaker Change: With processing these.
Speaker Change: Let's turn to persistency on slide nine.
Speaker Change: What you see on this slide is updated persistency information there are two key points I'd like to highlight.
Speaker Change: First we continue to track at least 10 percentage points above our clinical trial experience specifically the lilac one open label extension, where patients rolled over to tryphena tied from placebo and this differential has continued to be very consistent for several months now.
Brendan Tien: This resulted in delays in patients receiving their first paid shipments in the new year. We're working through those authorizations and do not see any long-term issues associated with processing. Let's turn to persistency on slide nine. What you see on this slide is updated persistency information.
Speaker Change: Second when we look at these monthly milestones they are improving.
Brendan Tien: First, we continue to track at least 10 percentage points above our clinical trial experience, specifically the Lilac One Open Label Extension, where patients rolled over to trafenatide from placebo, and this differential has continued to be very consistent for several months. Second, when we look at these monthly milestones, they're improving. For example, our month four persistency number was 75% when we reported on our earnings call in November. And now, at month four, you see that with many more patients, we're at 80% persistence. And our month six persistency, which we reported at J.P. Morgan last month, was 68 percent and has now risen to 70 percent.
Speaker Change: For example, our month for Persistency number was 75% when we reported on our earnings call in November and now at month four you see that with many more patients were at 80% persistency.
Speaker Change: And our month of six persistent C, which we reported at Jpmorgan last month was 68% and now has risen to 70% and we continue to see this data improve at all time points thus far.
Speaker Change: We are seeing improvements and persistency as patients and Hcp's gained more experience with the safety and Tolerability profile of debut.
Speaker Change: For clarity the persistency rates were including here are calculated based on the confirmed discontinuation plus those that are 60 days beyond their scheduled refill date counted as a discontinuation.
Brendan Tien: And we continue to see this data improve at all time points thus far. We are seeing improvements in persistency as patients and HCPs gain more experience with the safety and tolerability profile of Debut. For clarity, the persistency rates we're including here are calculated based on the confirmed discontinuations plus those that are 60 days beyond their scheduled refill date counted as a discontinuation. Please turn to slide 10. As I mentioned earlier, we continue to generate and share data supporting the long-term benefits observed in patients treated with Day-D. Here we describe two important posters that we presented recently at the American Epilepsy Society, or AES, meeting in December that emphasize the benefits of daytime duty.
Speaker Change: Please turn to slide 10.
Speaker Change: As I mentioned earlier, we continue to generate a shared data supporting the long term benefit observed in patients treated with debut.
Speaker Change: Here, we describe two important posters that we presented recently at the American Epilepsy Society or Aes meeting in December that underscore the benefits of debut.
Speaker Change: The first poster details the long term outcomes in patients who completed our lavender study and then continued into our open label Lilac, one and then lilac two studies.
Speaker Change: Data presented in the poster demonstrated that patients treated with <unk> and lilac to continued to experience improvement in symptoms for up to 32 months. In addition, safety and Tolerability were consistent with prior studies.
Brendan Tien: The first poster details the long-term outcomes in patients who completed our Lavender study and then continued into our open-label Lilac 1 and then Lilac 2 studies. Data presented in the poster demonstrated that patients treated with profenitide and LILAC2 continued to experience improvement in symptoms for up to 32 months. In addition, safety and tolerability were consistent with prior studies.
Speaker Change: Let's now turn to slide 11 for the second poster presented at Aes.
Speaker Change: This poster presented the results of the caregiver exit interviews for ret patients treated with <unk> and the <unk> and lilac studies.
Speaker Change: You can see in the table on the left some of those specific real world improvements caregivers cited in their interviews <unk>.
Speaker Change: Consistent with the unmet need often highlighted by caregivers the top three areas of improvement noted by these respondents and their children were improvement in engagement improvement in hand use an improvement and gains.
Brendan Tien: Let's now turn to slide 11 for the second poster presented at AES. This poster presented the results of caregiver exit interviews for Rett patients treated with trophinatide in the Lavender and Lilac Studies. You can see in the table on the left some of those specific real-world improvements caregivers cited in their interviews. Consistent with the unmet need often highlighted by caregivers, the top three areas of improvement noted by these respondents and their children were improvement in engagement, improvement in hand use, and improvement in eye gaze. We're pleased to have feedback regarding the impact of Trophinatide on the very symptoms that matter most to Rett families, and we're using this information to educate HCPs and Rett families about the potential benefits of DayView. Now, let's turn to slide 12.
Speaker Change: We're pleased to have the feedback regarding the impact of tryphena tied on the various symptoms that matter most to rep families and we're using this information to educate hcp's and ret families about the potential benefits of debut.
Speaker Change: Let's turn to slide 12.
Speaker Change: These quotes from caregivers reinforce some of the observations described above.
Speaker Change: Consistent with the types of things we've been hearing for many months such as caregivers, noting higher levels of engagement improvement in speech with a broadening vocabulary and improved engagement in conversations.
Speaker Change: More purposeful use of hands and decreased hand wringing in stereotypes.
Speaker Change: We also regularly hear feedback about our loved ones increased cognitive ability or increased alertness with patients now being able to better follow conversations.
Speaker Change: These testimonials all speak to the promise of treatment with debut and underscore exactly why we at Acadia do what we do.
Brendan Tien: These quotes from caregivers reinforce some of the observations described above, which are consistent with the types of things we've been hearing for many months, such as caregivers noting higher levels of engagement. For example, improvement in speech with a broadening vocabulary and improved engagement in conversation; more purposeful use of hands, and decreased hand wringing and stereotyping.
Speaker Change: To support and benefit those with greatest needs.
Speaker Change: Let's next turn to our plans to make <unk> available to patients outside the United States on slide 13.
Speaker Change: We see a clear opportunity to launch debut outside the United States and leverage the insights and learnings from the very successful U S launch to help many more patients suffering from Rep syndrome.
Speaker Change: Starting in Europe. It's estimated there are 9% to 14000 patients between Europe and the UK.
Brendan Tien: We also regularly hear feedback about a loved one's increased cognitive ability or increased alertness, with patients now being able to better follow conversation. These testimonials all speak to the promise of treatment with DayVu and underscore exactly why we at ACADIA do what we do, to support and benefit those with the greatest needs. Let's next turn to our plans to make Debut available to patients outside the United States on slide 13. We see a clear opportunity to launch Debut outside the United States and leverage the insights and learnings from the very successful U.S. launch to help many more patients suffering from Rett syndrome, starting in Europe. It's estimated there are 9,000 to 14,000 RET patients between Europe and the UK. We have engaged with EMA this quarter, and we anticipate filing a marketing authorization application with the European Medicines Agency in the first half of next year. In Canada, it's estimated that there are 600 to 900 red patients.
Speaker Change: We've engaged with EMEA this quarter, and we anticipate filing a marketing authorization application with the European Medicines agency in the first half of next year.
Speaker Change: In Canada. It's estimated there are 600 to 900 rep patients, we expect to file our new drug submission later this quarter with the potential approval around year end 2024.
Speaker Change: And in Japan, there are an estimated one to 2000 <unk> patients and this year, we're engaging the Japanese regulatory agency to kick off our efforts to pursue approval.
Speaker Change: Let's turn to slide 14 for a discussion of our NUPLAZID franchise.
Speaker Change: Product sales of NUPLAZID in 2023 were $549 2 million.
Speaker Change: An increase of 6% over 2022, as we continue to grow new patient starts and increased market share.
Speaker Change: Our primary financial objective for NUPLAZID is to optimize cash flow in that franchise and we do that in two ways first we're continuing to grow bottle shipments and market share. The most effective lever to drive growth recently has been the broad educational campaign, we launched last year to bring it.
Brendan Tien: We expect to file our new drug submission later this quarter with potential approval around year-end 2024. In Japan, there are an estimated 1,000 to 2,000 RET patients. And this year, we're engaging the Japanese Regulatory Agency to kick off our efforts to pursue approval.
Speaker Change: Tension to our real World evidence studies.
Speaker Change: These efforts have allowed us to grow new patient starts faster than the market. In fact in 2023, new patient starts were up 12% year over year.
Brendan Tien: Let's turn to slide 14 for a discussion of our new Plazid franchise. Product sales of Duplazid in 2023 were $549.2 million, an increase of 6% over 2022 as we continue to grow new patient starts and increase market share. Our primary financial objective for New Plazid is to optimize cash flow in that franchise, and we do that in two ways. First, we're continuing to grow bottle shipments and market share. The most effective lever to drive growth recently has been the broad educational campaign we launched last year to bring attention to our real-world evidence studies.
The second way, we optimize NUPLAZID franchise cash flow is by carefully managing expenses and we will continue to do that throughout 2024.
Speaker Change: These combined efforts have enabled us to generate over $300 million on a standalone fully burden basis and annual cash flow, we look forward to continuing to grow this franchise.
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 15.
Doug Williamson: Thank you Brendan.
Doug Williamson: In addition to our conventional products, we have a strong pipeline of clinical programs, providing us with several opportunities to further expand our growth.
Brendan Tien: These efforts have allowed us to grow new patient starts faster than the market. In fact, in 2023, new patient starts were up 12% year over year. The second way we optimize New Plaza's franchise cash flow is by carefully managing expenses, and we'll continue to do that throughout 2020. These combined efforts have enabled us to generate over $300 million on a stand-alone, fully burdened basis in annual cash flow.
Doug Williamson: Let's start with <unk> as a potential treatment for the negative symptoms of schizophrenia on slide 16.
Doug Williamson: Predominant negative symptoms remained the largest unmet needs in schizophrenia and as of today.
Doug Williamson: Still no approved treatments for these symptoms.
Doug Williamson: It's important to understand the distinction between treating the positive and negative symptoms of schizophrenia.
Doug Williamson: Positive or psychotic symptoms hallucinations delusions unsold disorders than typically resolved with antipsychotic treatment.
Doug Williamson: We look forward to continuing to grow this franchise. 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 15. Thank you, Brendan.
Negative symptoms are social withdrawal.
Doug Williamson: <unk> speech lack of emotion loss of motivation and blunted affect.
Doug Williamson: In addition to our commercial products, we have a strong pipeline of clinical programs providing us with several opportunities to further expand our, Let's start with pemivamstrin as a potential treatment for the negative symptoms of schizophrenia, on slide 16. Negative symptoms remain one of the largest unmet needs in schizophrenia. And as of today, there are still no approved treatments for these symptoms. It's important to understand the distinction between treating the positive and negative symptoms of schizophrenia. Positive or psychotic symptoms are hallucinations, delusions, and thought disorders that typically resolve with antipsychotic treatment. Negative symptoms are social withdrawal, restricted speech, lack of emotion, loss of motivation, and blunted athletic ability.
Doug Williamson: Our adjunctive prove answering program is designed to treat the approximately 700000 patients in the U S. Who is positive psychotic symptoms are adequately controlled with antipsychotic treatments, but who still suffer from persistent and uncontrolled negative symptoms inhibiting our ability to lead a normal productive life.
Doug Williamson: Please turn to the next slide to discuss our <unk> clinical program for negative symptoms of schizophrenia.
Doug Williamson: Let's discuss the details of our program. The advance two study is designed to treat patients whose positive symptoms are adequately controlled but still suffer from persistent uncontrolled negative symptoms.
Doug Williamson: Negative symptoms of schizophrenia have proven to be an exceedingly difficult drug development challenge with multiple industry failures over several decades.
Doug Williamson: Therefore, with our previous positive advanced one study in <unk>, we achieved something very rare in this population.
Doug Williamson: Our Adjunctive Pivot of Answering Program is designed to treat the approximately 700,000 patients in the U.S. whose positive psychotic symptoms are adequately controlled with an antipsychotic treatment but who still suffer from persistent and uncontrolled negative symptoms, inhibiting their ability to lead a normal, productive life. Please turn to the next slide to discuss our Pimivansirin Clinical Program for Negative Symptoms of Schizophrenia. Let's discuss the details of our program. The ADVANCE II study is designed to treat patients whose positive symptoms are adequately controlled but still suffer from persistent uncontrolled negative symptoms. Negative symptoms of schizophrenia have proven to be an exceedingly difficult drug development challenge with multiple industry failures over several decades. Therefore, with our previous positive and advanced one study of covalantrin, we achieved something very rare in this population.
Advance to our second six months study is designed to evaluate the impact on persistent negative symptoms in patients with acute psychosis has been controlled with antipsychotic treatment.
Doug Williamson: As Steve said, we don't know the results yet, but remain on track to share them by the end of the quarter.
Doug Williamson: Please turn to slide 18 to discuss our late stage ACP 101 program for the treatment of hyperphagia and product release syndrome.
Doug Williamson: Let me start with just a brief reminder of their disease.
Doug Williamson: Probably syndrome is a rare genetic neuro behavioral syndrome that affects approximately 8% to 10000 patients in the United States and represents a significant unmet need.
Doug Williamson: There are currently no therapies approved to treat the hyperphagia and patients with T. W. S.
Jayson: I would say Jayson.
Jayson: Finding characteristic of Gws uncommonly begins between the ages of three and eight.
Jayson: It's characterized by unrelenting hunger that often leads to obesity and behavioral challenges such as anxiety and aggression and is extremely distressing for patients parents and caregivers.
Jayson: To illustrate just how devastating this disorder is the average life expectancy is approximately 30 years, largely due to obesity and cardiovascular related disease.
Doug Williamson: ADVANCE 2, our second six-month study, is designed to evaluate the impact on persistent negative symptoms in patients whose acute psychosis has been controlled with antipsychotic drugs. As Steve said, we don't know the results yet but remain on track to share them by the end of the quarter. Please turn to slide 18 to discuss our late-stage ACP 101 program for the treatment of hyperphagia in Prader-Willi syndrome. But let me start with just a brief reminder of the disease. Prader-Willi syndrome is a rare genetic neurobehavioral syndrome that affects approximately 8 to 10,000 patients in the United States and represents a significant unmet need. It is characterized by unrelenting hunger that often leads to obesity and behavioral challenges such as anxiety and aggression and is extremely distressing for patients, parents, and caregivers. To illustrate just how devastating this disorder is, the average life expectancy is approximately 30 years, largely due to obesity
Jayson: Please turn to slide 19, where I will speak to our clinical program and probably really syndrome.
Jayson: Okay.
Jayson: Late last year, we initiated a phase III study of ACP 101 for the treatment of hyperphagia and PWM.
Jayson: Before getting into the details of the study I'd like to note that the PWM community has shown an incredibly high level of enthusiasm for this opportunity and interest in our study.
Jayson: On this slide we've laid out the design of the campus Phase III Global multi center randomized double blind 12 week placebo controlled study evaluating the efficacy and safety of ACP 101 in approximately 170 prior when we patients.
Jayson: The primary efficacy endpoint is improvement of hyperphagia as measured by the hyperphagia questionnaire for clinical trials or HQ Cte scale.
Jayson: Those patients who complete the study will be eligible to enroll in an open label long term extension study.
Jayson: If data from this phase III study is positive we plan to submit a new drug application for the treatment of hyperphagia and <unk> to the FDA.
Jayson: We look forward to working with our prior Willi community and clinical excellence as we continue to advance development of this program.
Jayson: Please turn to slide 20.
Jayson: Okay.
Jayson: Yeah.
Doug Williamson: The primary efficacy endpoint is improvement in hyperphagia, as measured by the Hyperphagia Questionnaire for Clinical Trials, or HQCT scale. Those patients who complete the study will be eligible to enroll in an open-label long-term extension study. If data from this Phase 3 study is positive, we plan to submit a new drug application for the treatment of hyperphagia in PWS to the FDA. Additionally, we're advancing ACP 204, our next generation 5HT2A compound, which we're developing as a potential treatment for Alzheimer's disease psychosis. As we previously described, ACP-204, like pivivanserin, works primarily as an inverse agonist of the 5-HT2A receptor, and a steady state concentration is achieved in less than half the time of privilege.
Jayson: We are advancing ICT tool for our next generation <unk> compound, which we're developing as a potential treatment for Alzheimer's disease psychosis.
Jayson: As we previously described ACP tool for like <unk>, where it's primarily as an inverse agonist of the five <unk> receptor.
Jayson: With ACP tour before we're seeking to build on our extensive learnings from timberlands from I believe it has an exciting future.
Jayson: Our work completed to date includes a comprehensive phase one program and supports our target product profile for ACP to reform, including no sign of Qt prolongation of planned doses in our studies a wide dose range supporting the potential for a dose approximately equivalent to two times that.
Jayson: <unk> of 34 milligrams approved <unk>.
And a steady state concentration achieved in less than half the time frame.
Doug Williamson: As you can see on the slide, ACP-204's profile could represent a significant improvement over an already strong product profile for Covavance. Please turn to slide 21. Our seamless Phase 2, and Phase 3 program for ACP 204 is now underway. This plan includes a Phase 2 study with over 300 patients, which we've aligned on with the FDA and which is designed to roll seamlessly into two Phase 3 studies. The phase 2 study has been designed and sized in such a way that, if successful, it could be considered a pivotal registration. Once the full study allocation of patients for Phase 2 is complete, we will analyze and report the Phase 2 results, by which time the two Phase 3 studies will already be underway. This plan will ultimately provide three potential pivotal studies for submission. We look forward to continuing to advance this program and providing future updates. Now, I'll turn it over to Marc for a financial update, beginning on slide 22. Thank you, Doug.
Jayson: As you can see on the slide <unk> profile could represent a significant improvement over an already strong product profile for <unk>.
Please turn to slide 21.
Jayson: Our seamless phase III phase III program for ACP tool for is now underway.
Jayson: This plan includes a phase II study with over 300 patients, which we've aligned with the FDA, which is designed to role seamlessly into two phase III studies.
Jayson: The phase II Phase III study has been designed and sized in such a way that if successful it could be considered a pivotal registration study.
Jayson: Once the full study of allocation of patients for phase two is complete we will analyze and report phase II results by which time the two phase III studies will already be underway.
Jayson: This plan will ultimately provide three potential pivotal studies for submission.
Jayson: We look forward to continuing to advance this program and providing future updates.
Jayson: And now I'll turn it over to Mark for his financial update beginning on slide 22.
Mark Schneider: Thank you, Doug, let's start by reviewing our fourth quarter and full year performance on slide 23.
Marc Schneier: Let's start by reviewing our fourth quarter and full year performance on slide 23. In the fourth quarter, we recorded $231 million in total revenue, up 69% from the fourth quarter of last year. For the full year 2023, we recorded $726.4 million of total revenue, up 40% from the prior year. Fourth quarter debut net product sales were $87.1 million, and full year debut sales were $177.2 million in the first eight and a half months of commercialization. In the fourth quarter, New Plaza net product sales were $143.9 million, up 5% versus the prior year. And our gross net adjustment was 27.5% in the quarter for New Plaza. For the year, New Plaza Net Product Sales were $549.2 million, up 6% compared to $517.2 million in the prior year. Additionally, our new Plazid franchise achieved 3% demand bottle growth year over year driven by increases in new patient starts in both markets. Sell-in growth increased by 2% as we experienced a modest reduction in in-channel inventory over the course of the year.
Mark Schneider: In the fourth quarter, we recorded $231 million in total revenue up 69% from the fourth quarter of last year for the full year 2023, we recorded $726 4 million of total revenue up 40% from the prior year.
Mark Schneider: Fourth quarter debut net product sales were $87 1 million.
Mark Schneider: Full year debut sales were $177 $2 million in the first eight five months of commercialization.
Mark Schneider: Fourth quarter NUPLAZID net product sales were $143 $9 million up 5% versus the prior year and our gross to net adjustment was 27, 5% in the quarter for NUPLAZID.
Mark Schneider: For the year NUPLAZID net product sales were $549 $2 million up 6% compared to $517 2 million in the prior year, our NUPLAZID franchise achieved 3% demand bottle growth year over year, driven by increases in new patient starts in both market segments.
Mark Schneider: Selling growth increased by 2% as we experienced a modest reduction in channel inventory over the course of the year.
Marc Schneier: The Nuclosid gross net adjustment for the full year was 24.3 percent, as compared to 20.8% last year. This increase is primarily due to increased accruals related to the inflation reduction. For 2023, our new Plazid franchise generated over $300 million of cash flow on a fully allocated cost basis. R&D expenses decreased to $351.6 million in 2023 from $361.6 million in 2022. The decrease was mainly due to the Trufenetide commercial supply bill in 2022 that was accounted for as R&D expense as those expenditures took place prior to the FDA approval of Debut. We had a similar level of clinical spend and business development investments year over year. SG&A expenses increased to $406.6 million in 2023 from $369.1 million in 2022.
Mark Schneider: NUPLAZID gross to net adjustment for the full year was 24, 3% as compared to 28% last year. This increase was primarily due to increased accruals related to the inflation reduction Act.
Mark Schneider: For 2023, our NUPLAZID franchise generated over $300 million of cash flow on a fully allocated cost basis.
Mark Schneider: R&D expenses decreased to $351 6 million in 2023 from $361 $6 million in 2022. The decrease was mainly due to the tryphena tied commercial supply build in 2022 that was accounted for as R&D expense as those expenditures took place pre.
Mark Schneider: Meyer to the FDA approval of debut we.
Mark Schneider: We had a similar level of clinical spend and business development investments year over year.
Mark Schneider: SG&A expenses increased to $406 6 million in 2023 from $369 1 million in 2022.
Marc Schneier: The increase was primarily driven by debut commercialization expenses, partially offset by reductions in new plazid specifications. Our cash balance increased year over year as we ended the year with $438.9 million in cash compared to $416.8 million at the end of 2022. Let's turn to slide 24 for discussion of our 2024 guidance. Beginning with Debut, we expect net sales for Debut in 2024 to be in the range of $370 to $420 million. In our 2024 full-year guidance, we project new patient prescriptions from the beginning of February forward that are consistent with the linear growth trend we observed in the fourth quarter, persistency rates that continue to be 10 percentage points above our clinical trial experience, and compliance to dose continuing in the range of 75% to 80%. I'd also like to offer some financial perspective on the seasonal dynamics impacting the first quarter of 2024. Let's start with December.
Mark Schneider: The increase was primarily driven by debut commercialization expenses, partially offset by reductions in NUPLAZID specced.
Mark Schneider: Our cash balance increased year over year as we ended the year with $438 9 million of cash compared to $416 8 million at the end of 2022.
Mark Schneider: Let's turn to slide 24 for a discussion of our 2020 for guidance.
Beginning with debut we expect net sales for debut in 2024 to be in the range of $370 million to $420 million.
Mark Schneider: In our 2020 for full year guidance, we project new patient prescriptions from the beginning of February forward that are consistent with a linear growth trend we observed in the fourth quarter.
Mark Schneider: Persistency rates that continue to be 10 percentage points above our clinical trial experience <unk>.
Mark Schneider: Compliance to dose continuing in the range of 75% to 80%.
Speaker Change: I'd also like to offer some financial perspective on the seasonal dynamics impacting the first quarter of 2024.
Speaker Change: Let's start with December as Brendan discussed Q4, net sales were positively impacted by a seasonal increase in refill rates as families prepared for the holidays.
Marc Schneier: As Brendan discussed, Q4 net sales were positively impacted by a seasonal increase in refill rates as families prepared for the holidays. Health Flare Changes, and Copay Reset In January, we saw a reduction in new patient prescriptions due to fewer office visits and red clinic days, together with reductions in conversion and refill rates as patients went through the payer re-enrollment process. And in February, we have seen strong recovery across these metrics. Factoring in the seasonal dynamics and expected higher growth in net sales in the first quarter, we anticipate first quarter net sales to be in the range of $76 to $82 million.
Speaker Change: <unk> changes and co pay resets.
Speaker Change: In January we saw a reduction in new patient prescriptions due to fewer office visits and Red clinic days together with reductions in conversion and refill rates as patients went through the payer re enrollment process.
Speaker Change: And in February we have seen strong recovery across these metrics.
Speaker Change: Factoring these seasonal dynamics and expected higher gross to net in the first quarter, we anticipate first quarter net sales to be in the range of $76 million to $82 million.
Marc Schneier: This is reflected in our annual guidance range of $370 to $420 million. Moving to New Plazid, we are providing net sales guidance between $560 and $590 million for 2024. The midpoint of the range assumes approximately 1.5% volume growth and 3% net price.
Speaker Change: This is reflected in our annual guidance range of $370 million to $420 million.
Speaker Change: Moving to NUPLAZID, we are providing net sales guidance between $560 and $590 million for 2020 for the.
Speaker Change: The midpoint of the range assumes approximately one 5% volume growth and 3% net price growth.
Marc Schneier: We are protecting gross net for New Plazid to be between 25 and 29% for the full year and between 33 and 35% for Q1. We expect gross to net to be of similar levels for the remaining quarters of the year as we don't anticipate an increase in gross to net for the fourth quarter of 2024 because of the Medicare Part D redesign that is expected to take place in 2025. We expect R&D expenses to be between $305 and $325 million, including approximately $20 million in stock-based compensation. We will be increasing our clinical spend year-over-year as we progress ACP 204, ACP 201, and our early-stage programs and reduce our spend on trefinitol. As a reminder, our R&D range does not guide for incremental spend for business development transactions. We expect SG&A expense to be between $455 and $480 million for the full year, including approximately $50 million in stock-based compensation.
Speaker Change: We are protecting gross to net for NUPLAZID to be between 25% and 29% for the full year and between 33 and 35% for Q1.
We expect gross to net to be a similar levels for the remaining quarters of the year as we don't anticipate an increase in gross to net for the fourth quarter of 2024 because of the Medicare part D. Redesign that is expected to take place in 2025.
Speaker Change: We expect R&D expense to be between $305 and $325 million, including approximately $20 million in stock based compensation.
We will be increasing our clinic clinical spend year over year as we progress ACP two of four <unk> hundred one and our early stage programs and reduced our spend on <unk> as a reminder.
Speaker Change: Minder, our R&D range does not guide for incremental spend for business development transactions.
Speaker Change: We expect SG&A expense to be between $455 and $480 million for the full year, including approximately $50 million in stock based compensation the growth in SG&A year over year is primarily due to increased investment in our U S debut franchise as well as the annualized <unk> of expenses.
Speaker Change: From being on the market for a full year in 2024.
Marc Schneier: The growth in SG&A year over year is primarily due to increased investment in our U.S. debut franchise as well as the annualization of expenses from being on the market for a full year in 2024 and Foundational Investments Preparing for Trophinetide-XUS Launch. Our SG&A guidance does not include pre-launch investment for negative symptoms of schizophrenia, which is contingent on positive results in advanced two. Finally, we expect our 2024 year-end cash balance to be approximately $585 to $655 million, based on our expected range of operational cash flows, excluding any expenditures for future business development transactions.
Speaker Change: <unk> foundational investments preparing for Trinity drove <unk> ex U S launches.
Speaker Change: Our SG&A guidance does not include prelaunch investment for negative symptoms of schizophrenia, which is contingent on positive results of advanced too.
Speaker Change: Finally, we expect our 2020 for year end cash balance to be approximately $585 million to $655 million based on our expected range of operational cash flows excluding any expenditures for future business development transactions.
Speaker Change: With that I'll turn it over to Steve for closing remarks. Thanks, So much Mark please turn to slide 25.
Stephen R. Davis: I'll close by briefly recapping 2023, and highlighting our opportunities in 2024 and beyond.
Stephen R. Davis: 2023 was a transformational year for us with.
Stephen R. Davis: We launched our second commercial drug debuts, we achieved 40% revenue growth from two commercial franchises debut of NUPLAZID.
Stephen R. Davis: And we've completed enrollment in our advanced two study in negative symptoms in schizophrenia.
Stephen R. Davis: With that, I'll turn it over to Steve for closing remarks. Thanks much, Marc. Please turn to slide 25.
Stephen R. Davis: We also acquired worldwide rights to <unk>, we initiated our phase III program of ACP 101 in <unk> Willi syndrome and.
Stephen R. Davis: I'll close by briefly recapping 2023 and highlighting our opportunities in 2024. 2023 was a transformational year. We launched our second commercial drug debut. We achieved 40% revenue growth from two commercial franchises and new clients. And we completed enrollment in our Advanced 2 Study in Negative Symptoms of Schizophrenia. We also acquired worldwide rights to rice tetraphenidide.
Stephen R. Davis: And we initiated our seamless phase III phase III study of ACP tool for in Alzheimer's disease psychosis.
Stephen R. Davis: Looking to this year and beyond we continue to capitalize on the successful launch of debut and strong project strong revenue streams from debut and NUPLAZID.
Stephen R. Davis: We will have the topline results from our advance two study by the end of this quarter.
Stephen R. Davis: Pursuing expansion to debut in Europe, Canada and Japan.
Stephen R. Davis: We're now well on our way to determining the potential of ACP 101, and broader Willi syndrome with the potential new therapy there.
Stephen R. Davis: Likewise with ACP Tau for Alzheimer's disease psychosis.
Stephen R. Davis: We're now at a point, where we have sustainable and growing cash flow from operations to fund future growth.
Speaker Change: With that I'll turn it over to the operator for our Q&A operator.
Stephen R. Davis: We initiated our phase 3 program of ACP 101 and Prader-Willi syndrome, and we initiated our seamless phase 2, phase 3 study of ACP 204 and Alzheimer's disease. Looking to this year and beyond, we continue to capitalize on the successful launch of Debut and project strong revenue streams from Debut and New Plastics. We will have the top-line results from our ADVANCE II study by the end of this quarter. We're pursuing expansion of ABU in Europe, Canada, and Japan. We're now well on our way to determining the potential of ACP101 in Prader-Willi syndrome.
Speaker Change: Thank you at this time, we will conduct a question and answer session. As a reminder to ask a question you will need to press star one on your telephone and wait for your name to be announced if your question has been answered or you wish to withdraw. Your question. Please press star one again, we ask that you limit yourself to one question.
Speaker Change: Our first question.
Cash: Our first question comes from cash from Al <unk> with Jpmorgan. Your line is open.
Cash: Good afternoon, guys. Thanks, so much for taking our question.
Cash: So first one from me.
Cash: What drove your decision to provide full year, Dave your guidance at this time, rather than just a quarterly guide, which I think was your base case at the time of our conference in January.
Operator: There's a potential new therapy there, and likewise, with ACP-204 for Alzheimer's disease echoes. And we're now at a point where we have sustainable and growing cash flow from operations to fund future growth. With that, I'll turn it over to the operator for our Q&A. Operator.
Second question is.
Cash: Just around your guide are you able to clarify the assumption around where you are estimating real World Christmas Kinsey is at 12 months and are you able to give us an update on the number of patients that are currently on DBM. Thanks, so much.
Operator: Thank you. At this time, we'll conduct the question and answer session. As a reminder, to ask a question, you will need to press star one on your telephone and wait for your name to be announced.
Speaker Change: Sure Mark do you want to pick up.
Mark Schneider: Yes, I think as we as we approach every conversation with Wall Street, we just wanted to give.
Operator: If your question has been answered or you wish to withdraw your question, please press star one one again. We ask that you limit yourself to one question. One moment for our first question. Our first question comes from Tess Romero with JP Morgan. Your line is open. Good afternoon, guys.
Mark Schneider: The most relevant information and context of the business as a whole.
Mark Schneider: As we went through kind.
Through our year end process and saw the seasonality that we experienced at the beginning of the year.
Mark Schneider: We thought it was important to provide context, not only on that kind of one forward quarter guidance, but designed to provide perspective on where we see.
Tazeen Ahmad: Thanks so much for taking our questions. The first one for me is, what drove your decision to provide full-year debut guidance at this time, rather than just a quarterly guide, which I think was your base case at the time of our conference in January? And second question is, just around your guide, are you able to clarify the assumption around where you are estimating real-world persistency at 12 months? And are you able to give us an update on the number of patients that are currently on debut? Thanks so much.
Mark Schneider: Debut for the entire year and our confidence in growing the brand.
Mark Schneider: Over the course of the year and beyond so that led to our discussion.
Mark Schneider: <unk>.
Mark Schneider: <unk> got different the two periods of guidance range.
Mark Schneider: On the persistency level.
Mark Schneider: When we we continue within our guidance to expect kind of 10 percentage points above the clinical.
Mark Schneider: I'll experience from the levels that <unk>.
Mark Schneider: Brendan experienced Brendan suggested and I think for for long term.
Marc Schneier: Sure, Marc, if you want to take that. Yeah, I think as we approach every conversation with Wall Street, we just want to give the most relevant information in context of the business as a whole. As we went through kind of our year-end process and saw the seasonality that we experienced at the beginning of the year, we thought it was important to provide context, not only on that, you know, kind of a one forward quarter guidance but also provide perspective on where we see the brand debut for the entire year and our confidence in growing the brand over the course of the year and beyond. So that led to our discussion on the two periods of guidance. On the persistency level, when we continue within our guidance to expect kind of 10 percentage points above the clinical trial experience from the levels that Brendan suggested, and I think for the long term, you know, I think if you think more like 50% plus over a 12-month and beyond period, that's a good early sign.
Mark Schneider: I think if you if you think more like 50% plus over a 12 month and beyond period.
Mark Schneider: A good early sign obviously I'll point out we don't have patients out that far in the commercial setting. So that's the data that we'll evaluate but I think that's a good reasonable ballpark assumption to make to take at this time.
Mark Schneider: And.
Mark Schneider: As far as getting back to the number of patients on therapy in a second but.
Mark Schneider: Since a pause there let me just add a little bit of more color to that so of all the patients who initiated therapy on.
Mark Schneider: Terrific that her debut in clinical trials and lavender to get into those that rolled over to drug and lilac.
Mark Schneider: 40% of them remain on therapy today, and Thats, two plus years since they've been on therapy.
Mark Schneider: As Mark mentioned and as we've described before we continue to attract 10 percentage points above our clinical trial experience. So that's the.
Mark Schneider: Just to Mark's comment that we expect longer term and again when we look at our clinical trial experience. We're looking at two plus years on therapy.
Stephen R. Davis: Obviously, I'll point out, we don't have patients out that far in the commercial setting. So that's some data that we'll evaluate. But I think that's a good reasonable assumption to make to take at this point, and actually, I'm going to ask Mark to come back to the number of patients on therapy in a second. But since he paused there, let me just add a little bit of more color to that.
Mark Schneider: 40% of them on we're tracking 10% above that so that's the basis of our of our.
Mark Schneider: The projection that we expect to have a more patients to stay on therapy over the long term.
Mark Schneider: I would also note that of all of those patients at 40% of patients.
Mark Schneider: We're on track.
Mark Schneider: Terrific.
Mark Schneider: At her debut in clinical trials that have now rolled over we've had zero dropouts from those patients since since launch.
Mark Schneider: So we so it has created a very.
Stephen R. Davis: So of all the patients who initiated therapy on terifinidat, or debut in clinical trials in lavender, together with those that rolled over to a drug in lilac, 40 percent of them remain on therapy today, and that's two-plus years that they've been on therapy. As Marc mentioned, and as we've described before, we continue to track 10-plus percentage points above our clinical trial. So that's the gist of Marc's comment, that we expect longer term. And again, when we look at our clinical trial experience, we're looking at two plus years on therapy. We're tracking 10% above that, so that's the basis of our projection that half or more patients will stay on therapy over the long term. I would also note that of all those patients, 40% of patients that were on Trufenadide or debuted in clinical trials that have now rolled over, we've had zero dropouts from those patients for a long time. So it's created a very persistent and consistent enduring population.
Mark Schneider: Persistent and consistent enduring population Mark you want to address a number of pure I think as you recall, we had just over 800 patients at the end of the third quarter when we closed.
Mark Schneider: 2023, we had close to 900 patients on therapy.
And just to give a little further context as we described we had a seasonal decline in January and as a consequence fewer patients initiated therapy and then in February we saw a significant rebound and rebound in new patient starts.
Mark Schneider: And together with improvements in conversion and refill rates.
And today, we have taking that all together, we have approximately 860 patients on therapy.
Speaker Change: One moment our next question.
Speaker Change: Okay.
Speaker Change: Our next question comes from Ash Verma with UBS. Your line is open.
Ash Verma: Yes, thanks for taking our questions and congrats on all the progress.
Ash Verma: So on debut can you quantify what was the.
Ash Verma: Seasonality benefit in December and we're just trying to wrap my head around so what you're run rating AD based off a cold.
Speaker Change: <unk> and <unk>.
Ash Verma: 370 to 120 million guide it seems to predict in the radio.
Marc Schneier: Marc, do you want to address the number of patients on therapy? Sure. I think, as you recall, we had just over 800 patients at the end of the third quarter. And when we closed 2023, we had close to 900 patients on therapy. And just to give a little further context, as we described, we had a seasonal decline in January. And as a consequence, fewer patients initiated therapy.
Ash Verma: Even that we're so early in the launch this it would be helpful to understand like in terms of new patient.
Ash Verma: What are your expectations.
Ash Verma: For the remainder of the thanks.
Speaker Change: Yes, thanks, so much I'm going to ask Mark to answer the first question Brendan in the segment.
Mark Schneider: Yes, so for the seasonality.
Mark Schneider: And maybe one time benefits and revenue that we experienced in the fourth quarter.
Mark Schneider: Total about $5 million.
Mark Schneider: Positive to revenue in the fourth quarter, and we quantify that as $3 million due to seasonality and $2 million due to a favorable gross to net in the quarter.
Marc Schneier: And then in February, we saw a significant rebound in new patient starts, and together with improvements in conversion and refill rates, and today we have, you know, taking that all together, we have approximately 860 patients on therapy. One moment for our next question. Our next question comes from Ash Verma with EBS. Your line is open.
Speaker Change: Thanks Al I'll go from there.
Speaker Change: So in our prepared remarks, we talked about the seasonality in terms of new patient starts.
Speaker Change: Following a surge that.
Speaker Change: That sort of characterize the first four months of the launch of debut very interested families that queued up to get started we then.
Ash Verma: You guys, yeah, thanks for taking our questions. Congrats on all the progress. So on Debut, can you quantify what was the seasonality benefit in December? And I'm just trying to wrap my head around, so where are you running the rating ad based off 4Q?
Speaker Change: Hit a growth trajectory or a launch trajectory that was very much like what we expected linear growth third quarter and fourth quarter through December.
Speaker Change: The one place where there was a slowdown in new patient starts was January significant slowdown driven by lack of co pay.
Marc Schneier: And is this $370 to $420 million guide? It seems pretty conservative, given that we are so early in the launch. It would be helpful to understand, in terms of new patient growth, what are your expectations for the remainder of the year? Yeah, thanks much.
Speaker Change: Patient days in patient visits we saw a snapback or however, you want to describe it in February to a similar trajectory for new patient starts moving forward, so thinking about 2024 and the midpoint of our guidance we would anticipate.
Marc Schneier: I'm going to ask Marc to answer the first question and Brendan the second. So, for the seasonality, I would, you know, and maybe one-time benefits and revenue that we experienced in the fourth quarter, a total of about $5 million positive to revenue in the fourth quarter, and we quantify that as $3 million due to seasonality and $2 million due to favorable growth to net in the quarter. Thanks, I'll go from there.
Speaker Change: The linear curve replicating what we saw in the third and fourth quarter of last year.
Speaker Change: For new patient starts.
Speaker Change: One moment our next question.
Speaker Change: Our next question comes from David Wang with Citigroup. Your line is open.
David Wang: Hi, Congrats on the progress and taking my question.
David Wang: I'm, just trying to get a better handle on the higher end of your guidance range for debut in 2024.
Brendan Tien: So in our prepared remarks, we talked about the seasonality in terms of new patient starts. Following a surge that sort of characterized the first four months of the launch of Debut, very interested families that queued up to get started, we then hit a growth trajectory or a launch trajectory that was very much like what we expected. Linear growth, third quarter and fourth quarter through December. The one place where there was a slowdown in new patient starts was January, a significant slowdown driven by a lack of COE RET patient days and RET patient visits. We saw a snapback, or however you want to describe it, in February to a similar trajectory for new patient starts moving forward. So thinking about 2024, at the midpoint of our guidance, we would anticipate a linear curve replicating what we saw in the third and fourth quarter of last year for new patient starts. One moment for our next question. The next question comes from David Huang with Citigroup. Your line is open.
David Wang: What type of element would you need to see to drive towards the higher end of guidance. Thanks a lot.
Speaker Change: Yes, sure Mark can we take that yes, I think the whole I mean, the three main assumptions.
Speaker Change: Driving our forecast our new patient starts.
Speaker Change: Persistency rates and overall compliance and obviously, we run many scenarios to get to the informed guidance range that we've shared to you and it's not necessarily one in particular assumption that you would change that would get you from the middle to the high or to the low so I think as.
Speaker Change: The midpoint of the range is more towards what Brendan just mentioned on new patient starts having our persistency continued to be 10 percentage points above.
Speaker Change: Our clinical trial experience and compliance to dose to be within the range of 75% to 80% and as you branch out from the middle you're just flex any are there any or all of the assumptions up we'll get you towards the high end of the range.
Speaker Change: One moment our next question.
Speaker Change: Our next question comes from Charles Duncan with Cantor Your line is open.
David Huang: Hi, congrats on the progress and taking my question. I'm just trying to get a better handle on the higher end of your guidance range for debut in 2024. What types of elements would you need to see to drive towards the higher end of guidance?
Charles C. Duncan: Hey, good afternoon, Steve and team congrats on your progress.
Charles C. Duncan: And all the information on debut that's very helpful.
Marc Schneier: Thanks a lot. Sure, Marc, do you want to take this? Yeah, I think the whole thing, you know, the three main assumptions driving our forecast are new patient starts, persistency rates, and overall compliance. And obviously, we run many scenarios to get to the informed guidance range that we've shared with you. And it's not necessarily one in particular assumption that you would change that would get you from the middle to the high or to the low.
Charles C. Duncan: I wanted to ask a question on the pipeline specific to advance to the negative symptom subscale.
Charles C. Duncan: Schizophrenia, I know that you don't have the data in house, yet, but I guess I'm wondering are you tracking concurrent medications.
Charles C. Duncan: And if you could provide us a little bit of color.
Marc Schneier: So I think, you know, the midpoint of the range is more towards what Brendan just mentioned about new patient starts, having our persistency continue to be 10 percentage points above our clinical trial experience, and compliance to dose to be within the range of 75 to 80%. And as you branch out from the middle, you just flex any or any or all those assumptions will get you towards the high end of the range. One moment for our next question. Our next question comes from Charles Duncan with Cantor. Your line is open.
Charles C. Duncan: Clinically meaningful results versus statistically meaningful results and then finally do you anticipate needing a 12 month exposure beyond the six months study or do you think that the current safety.
Yeah.
Charles C. Duncan: Profile of NUPLAZID Wahid. Thanks.
Speaker Change: Yes, thanks for the question.
Wahid: Doug three parts to that question Ivy.
Ivy: Yes, and I've already forgotten the first two.
Ivy: Yes.
Charles C. Duncan: Hey, good afternoon, Steve and team. Congratulations on a good year of progress. And all the information on Debut, that's very helpful. I wanted to ask a question on the pipeline, specific to the advanced to negative symptoms of schizophrenia. I know that you don't have the data in house yet. But I guess I'm wondering, are you tracking concurrent medications? And if you could provide us with a little bit of color on clinically meaningful results versus statistically meaningful results?
Speaker Change: In terms of safety, we have an extensive safety database of kind of answering in schizophrenia as well as other conditions. So we have comfortably more patient exposures than we would need to get an approval.
Speaker Change: First question Longs again.
Speaker Change: Steve Charles good.
Speaker Change: Charles the first two questions.
Charles C. Duncan: Yes, concurrent medication Terry track on that do you have good coverage and then clinically meaningful versus characteristically significant results.
Doug Williamson: And then finally, do you anticipate needing a 12-month exposure beyond a six-month study? Or do you think that the current safety, you know, profile of New Pleset will handle it? Thanks. Yeah, thanks so much for the question, Charles. Doug, there are three parts to that question. Yeah, and I've already forgotten the first two.
Speaker Change: Yeah.
Charles C. Duncan: Yes, we're tracking obviously.
Charles C. Duncan: Carefully tracking concurrent medications.
Charles C. Duncan: Any antipsychotic is allowed.
Charles C. Duncan: We haven't analyzed the data yet obviously, but we expect.
Charles C. Duncan: <unk> to be similar to advance one where it was the.
Charles C. Duncan: The three most commonly used.
Psychotics, olanzapine and Risperidone or <unk>, where the main concomitant medications.
Doug Williamson: But in terms of safety, we have an extensive safety database for herovanserine in schizophrenia as well as other conditions. So we have comfortably more patient exposures than we would need to get an approval. The first question was, again, sorry, Charles. Good. Charles, the first two questions.
Charles C. Duncan: Clinically and statistically significant well obviously system is significant will be defined by the primary for clinically significant.
Doug Williamson: Yeah, concurrent medications. Are you tracking that? Do you have good coverage? And then clinically meaningful versus statistically significant results? What do you like?
Charles C. Duncan: Nothing has been approved yet so there's no kind of benchmark.
Charles C. Duncan: But in the <unk>.
Charles C. Duncan: Psychiatric studies in general.
Doug Williamson: Yeah, we're tracking, obviously, we're carefully tracking concurrent medications; you know, any antipsychotic is allowed. And, you know, we haven't analyzed the data yet, obviously, but we expect the results to be similar to advance one, where it was the three most commonly used antipsychotics, olanzapine, risperidone, and aripiprazole, that were the main concomit Clinically and statistically significant, well, obviously, statistically significant will be defined by the primary.
Charles C. Duncan: <unk> sighs of sort of 'twenty two.
Two to three is generally regarded as clinically significant and advanced one at the 34 milligram dose we saw an effect size of <unk> three four so something around the two to three level.
Charles C. Duncan: FX size, we would regard as in the field with regard to <unk>.
Charles C. Duncan: Highly clinically significant.
Charles C. Duncan: Yeah.
Speaker Change: One moment our next question.
Speaker Change: Yes.
Ritu Baral: Our next question comes from Ritu barrel with TD Cowen Your line is open.
Ritu Baral: Hi, guys. Thanks for taking the question.
Doug Williamson: For clinically significant, you know, nothing has been approved yet, so there's no kind of benchmark. But in the, you know, in psychiatric studies in general, an effect size of sort of 20 to 0.2 to 0.3 is generally regarded as clinically significant. In advance one at the 34 milligram dose, we saw an effect size of 0.34. So, you know, something around the 0.2 to 0.3 level of effect size we would regard as, and the field would regard as, highly clinically significant. One moment for our next question. The next question comes from Ritu Baral, with TD Cowan. Your line is open.
Ritu Baral: Wanted to ask about Europe, you mentioned that youre going to be filing.
Ritu Baral: Next year I wanted to ask in the first half of 2020 I wanted to ask what the gating items were for the MAA filing or do you have to generate any more clinical data do you have to generate.
Ritu Baral: Any sort of data can help with health technology assessments of the bar.
Ritu Baral: Any potential direction, you can give us on what sort of European price.
Speaker Change: You may.
Speaker Change: That you think that you can get.
Speaker Change: Yes, I think to answer the question Richard we don't need to do any we don't believe we'll need to do any more clinical work.
Ritu Baral: Hi guys. Thanks for taking the question. I wanted to ask you about Europe.
Speaker Change: The principal gating item is.
Speaker Change: No Pip was done before we acquired rights to the program. So so we've got to get alignment on that.
Stephen R. Davis: You mentioned that you're going to be filing next year. I wanted to ask, in the first half of 2025, what the gating items were for the MAA filing. Do you have to generate any more clinical data? Do you have to generate any sort of data to help with health technology assessments over there?
With the with the <unk>.
Speaker Change: European agencies and.
Speaker Change: And there is some additional work running in parallel.
Speaker Change: Sometimes oftentimes the excipient requirements on formulations differ between the U S and the EU and Theres a little bit of work. We're doing there just to button that up we don't anticipate that being a rate limiting issue, but its just running in parallel with other work we're doing.
Stephen R. Davis: And any potential direction you can give us on what sort of European price you may, that you think that you can get. Yeah, thanks so much for the question, Ritu. We don't need to do any, we don't believe we'll need to do any more clinical work. We, the principal gating item is that no PIP was done before we acquired the ROTC program. So we've got to get alignment on that with the European agencies. And there's some additional work running in parallel.
Speaker Change: And then I'll ask Brandon to address the pricing question.
Brandon: 232, Thanks for the question one is.
Brandon: There will obviously be work already ongoing with our global value dossier in <unk>.
Brandon: Reinforcing the value proposition for tryphena tied in Ret syndrome, and then we're still a ways off in terms of.
Brandon: Determining price for debut in Europe ill simply suggest that obviously, we would be pricing it for the value added parts on patients caregivers and the health system and.
Stephen R. Davis: Sometimes, oftentimes, the excipient requirements on formulations differ between the U.S. and the EU, and there's a little bit of work we're doing there just to button that up. We don't anticipate that being a rate-limiting issue, but it's just running in parallel with other work we're doing. And then I'll ask Brendan to address the pricing. Yeah, two points, Ritu.
Brandon: I know you all would look at other rare disease launches first in the United States and then in the EU.
Brandon: I think you see an opportunity there tends to be less of a difference seen with rare disease products that are seen in broader market assets.
Brendan Tien: Thanks for the question. One is there will obviously be work already ongoing with our global value dossier and reinforcing the value proposition for triphenatide in Rett syndrome. And then we're still a ways off in terms of determining the price for debut in Europe.
Speaker Change: One moment our next question.
Speaker Change: Our next question comes from Jeff Hung with Morgan Stanley. Your line is open.
Jeff Hung: And thanks for taking my question for negative symptoms of schizophrenia can you just talk about your commercial launch strategy and the timing of key initiatives and about how many additional reps might be needed.
Brendan Tien: I'll simply suggest that obviously, we would be pricing it for the value it imparts on patients, caregivers, and the health system. And I know you would look at other rare disease launches first in the United States and then in the EU. Where I think you see an opportunity, there tends to be less of a difference seen with rare disease products than is seen in broader market assets.
Brendan: Yes, sure Jeff Brendan you want to take that sure. Thanks for the question. Obviously, we're excited and looking forward to turning the card over and hopefully having an opportunity to be the first therapy ever approved is to support that patient population, we have a footprint and in CNS and.
Operator: Thank you. Thank you. Thank you.
Speaker Change: We do call on a subset of physicians that would would help treat the disease. I think you would expect us to expand from that footprint incrementally.
Operator: One moment for our next question. Our next question comes from Jeff Hung with Morgan Stanley. Your line is open.
Speaker Change: And address an opportunity that is more in the psychiatry space than in the neurology space, but we will leverage.
Jeff Hung: Thanks for taking my question. For the negative symptoms of schizophrenia, can you just talk about your commercial launch strategy and the timing of key initiatives and about how many additional reps might be needed? Yeah, sure, Jeff. Brendan, do you want to take that?
Speaker Change: Existing field footprint.
Speaker Change: Our resources to support that we also have lots of people that have worked in the broader CNS space that work at Acadia.
Speaker Change: Work done on similar assets and we have lots of internal capabilities that will leverage as well.
Brendan Tien: Sure. Thanks for the question. Obviously, we're excited and looking forward to turning the card over and hopefully having an opportunity to be the first therapy ever approved to support that patient population. We have a footprint in CNS, and we do call on a subset of physicians that would help treat the disease. I think you would expect us to expand from that footprint incrementally and address an opportunity that is more in the psychiatry space than in the neurology space, but we will leverage existing field footprint and resources to support that. We also have lots of people that have worked in the broader CNS space that work at ACADIA that have worked on similar assets, and we have lots of internal capabilities that we'll leverage as well. And I would look at us continuing to ramp up post a positive result towards the latter half of this year and into 2025.
Speaker Change: And I would look at us continuing to ramp up post a positive result.
Speaker Change: Towards the latter half of this year and into 2025.
Speaker Change: Okay.
Speaker Change: One moment our next question.
Speaker Change: Our next question comes from Gregory <unk> with RBC capital markets. Your line is open.
Gregory: Hey, good afternoon, Steve and team congrats on the progress in the quarter. Thanks for taking my question, Steve maybe a question for Brendan.
Gregory: Well and just revisiting the seasonal patterns, just curious Brendan and the team.
Gregory: What learnings are you taking away from this to perhaps address.
Gregory: Maybe the situation or the seasonality that you look forward with 2000 2004 to 2025, especially when it could be encountering certainly greater patient numbers on debuted just curious how surprising some of those dynamics from December January and February were just in the context of the public comps too to usual patterns with <unk>.
Gregory: Often visits.
Gregory: Is that which could be unique to <unk>.
Speaker Change: Thanks, so much.
Speaker Change: Yeah. Thanks, Let me, let me answer that at a high level, then I'll turn it over to Brendan.
Brendan: So the seasonality that we saw as something it's just very common in our industry, we see it a lot.
Brendan: <unk> to a greater or lesser extent with most drugs summit has more of an impact than others.
Operator: One moment for our next question. Our next question comes from Gregory Renza with RBC Capital Markets. Your line is open. Hey, good afternoon, Steve and team.
Brendan: Rare disease.
Brendan: Face it seems to bounce around more than others.
Brendan: We saw a more pronounced effect of the seasonality than we anticipated.
Gregory Renza: Congratulations on the progress in the quarter. Maybe a question for you about... well, patterns.
Brendan: A much more significant.
Brendan: Impact, particularly in January and we would have anticipated, but the dynamics are very similar across the industry and one of the learnings we have from this is that.
Operator: Thank you. Thank you. Thank you. What learnings are you taking away from this?
Stephen R. Davis: ACADIA Pharmaceuticals Inc, ®MD-BO I'm curious how surprised... ACADIA Pharmaceuticals Inc, January and February were just in the content, comp to the usual patterns with reoff. ACADIA Pharmaceuticals Inc. Yeah, thank you. Let me answer that at a high level, and I'll turn it over to Brendan. So the seasonality that we saw is something that's just very common in our industry. We see that a lot happens to a greater or lesser extent with most drugs. Some have more of an impact than others.
Brendan: A lot of the ret centers and this just sufficed to a certain extent also even outside of the coes, but a lot of the coes dramatically.
Brendan: Reduce it Red clinic days and that just had a significant impact on our prescriptions in that timeframe.
Speaker Change: Color you'd like to add.
Speaker Change: I agree and Greg.
Speaker Change: Thanks for the question I think one of the key learnings is just the level of preparation that these families have around the holiday season, whether you are seeking treatment for the first time I think we saw.
Brendan Tien: In the rare disease space, things do bounce around more than others, and we saw a more pronounced effect of this seasonality than we anticipated. We saw a much more significant impact, particularly in January, than we would have anticipated, but the dynamics are very similar across the industry. And one of the learnings we have from this is that a lot of the Rett centers, and this applies to a certain extent also even outside of the COEs, but a lot of the COEs dramatically reduced their Rett clinic days, and that just had a significant impact on our prescriptions. Brendan, any additional callers you'd like to add? Yeah, I agree, and Greg, thanks for the question. I think one of the key learnings is just the level of preparation that these families do around the holiday season.
Speaker Change: Nice.
Speaker Change: A nice trajectory for new patient starts in December.
And obviously not a similar trajectory in in January which I think makes sense. These are.
Speaker Change: There are fewer rychlik days and there are fewer theres less interest and I think Rick clinic visits at the time, but I think more notably is the continuing patients that wants to make sure they have appropriate supply throughout the holiday season, which probably bolsters refill rates in December.
Speaker Change: And may have some impact on January but I don't think it changes the way we would approach or.
Speaker Change: Our promotional efforts to this audience and the return in February to what we're seeing for both patient visits and new patient prescriptions.
Brendan Tien: Whether you are seeking treatment for the first time, I think we saw, you know, a nice trajectory for new patient starts in December and obviously not a similar trajectory in January, which I think makes sense because these are, there are fewer recreation clinic days, and there are fewer, there's less interest in, I think, recreation clinic visits at the time. But I think more notably is the continuing patient that wants to make sure they have an appropriate supply throughout the holiday season, which probably bolsters refill rates in December and may have some impact on January. But I don't think it changes the way we would approach our promotional efforts to this audience. And the return in February to what we're seeing for both patient visits and new patient prescriptions puts us on the trajectory we would have expected. Next question. Our next question comes from Amy Fadio with Needham. Your line is open. Hi, good evening. Thanks for taking my question. I've got two of them.
Speaker Change: Have us on the trajectory we would have expected.
Speaker Change: Amendment.
Speaker Change: Question.
Speaker Change: Our next question comes from Amy <unk> with Needham Your line is open.
Amy: Good evening. Thanks for taking my question I've got two plus can you just took off to debut.
Amy: A few more months under the belt can you give us a sense of what where you see the peak market share evolving and if you can give us some color on penetration in <unk>.
Amy: Center of excellence, and then penetration, but then.
Amy: Different age groups and I don't know about 'twenty.
Amy: And with regard to.
Amy: The trial.
Amy: <unk> in Alzheimer's disease psychosis.
Amy: And private any thing Ken.
Amy Fadio: Firstly, just with regard to debut. A few more months under the belt, can you give us a sense of where you see the peak market share evolving? And if you can give us some color on penetration in centers of excellence versus non-centers, and then penetration within different age groups under and over 20.
Speaker Change: When can we anticipate to see any big data could we see some data next year. Thank you.
Speaker Change: Thanks, Jeremy let.
Speaker Change: Let me take the last question and then I'll ask.
Speaker Change: Brendan and Mark to respond to the first two.
Speaker Change: With respect to data on.
Stephen R. Davis: And with regard to the trials that you've initiated in Alzheimer's disease psychosis and Prior Relief Syndrome, when can we expect to see any data? Could we see some data next year? Thank you. Thanks, Tommy.
Speaker Change: On ADP and dws.
Speaker Change: We like to get a little bit deeper into these studies before we.
Speaker Change: Narrowed the aperture on.
Stephen R. Davis: Let me take the last question, and then I'll ask Brendan and Marc to respond to the first two. With respect to data on ADP and PWS, we'd like to get a little bit deeper into these studies before we narrow the aperture on when we expect to complete enrollment and when we would have results. So it's a little bit premature for us to comment on that yet. But what I will say in ADP is these studies usually take a couple of years. And in Prader-Willi, it's probably a fairly similar time frame.
Speaker Change: We expect to complete enrollment and when we'd have results.
Speaker Change: So it's a little bit premature for us to comment on that yet, but I will say in ADP. <unk> study is usually take a couple of years.
Speaker Change: And a product really it's probably a fairly similar timeframe. So obviously a much smaller study, but in a rare disease populations you have a smaller patient foliar pulling from.
Speaker Change: So Brendan do you want to take the first.
Speaker Change: I'm, sorry, Mark I'm going to say Mark Mark you want take the first question on on peak and peak I think just as a matter of kind of our corporate policy. We don't talk about peak market share in peak sales, but qualitatively what I would say is we have a significant potential in both from where we started it stand today as far as penetration.
Stephen R. Davis: It's obviously a much smaller study, but in a rare disease population, you just have a smaller patient pool that you're pulling from. So Brendan, do you want to take the first? I'm sorry, Marc.
Marc Schneier: I meant to say Marc. Marc, do you want to take the first question on peak? Yeah, on peak, I think just as a matter of our corporate policy, we don't talk about peak market share and peak sales. But qualitatively, what I would say is we have significant potential in both. From where we stand today as far as penetration is concerned, there are a significant number of patients that we believe can benefit from debut across all market segments. And then, as far as peak sales is concerned, we obviously see meaningful improvement in sales this year as per our guidance. And we expect that sales can increase significantly above those levels in the years ahead.
Speaker Change: There are significant number of patients that we believe can benefit from debut across all.
Speaker Change: Market segments.
Speaker Change: And then as far as peak sales is concerned.
Speaker Change: We obviously see meaningfully improvement in sales this year as per our guidance and we expect that sales.
Speaker Change: Increased significantly above those levels in the years to come.
And maybe I'll address the sort of the market characteristics, you're asking about as well.
Speaker Change: And yes, I think we have we have ample opportunity to continue to grow our penetration. The question was around Coes and non coes in Coes, we're getting about 40% of our prescriptions today from them, 30% from high volume institutions in CRE like and then 30% in the <unk>.
Marc Schneier: And maybe I'll address the sort of market characteristics you were asking about as well. And yes, I think we have ample opportunity to continue to grow our penetration. The question was around COEs and non-COEs.
Speaker Change: Immunity or penetration, while we don't speak to absolutes is the highest in coes, but we still have ample opportunity to grow new patient share in coes.
Brendan Tien: In COEs, we're getting about 40% of our prescriptions today from them, 30% from high-volume institutions and COE-like, and then 30% in the community. Our penetration, while we don't speak to absolutes, is the highest in COEs, but we still have ample opportunity to grow new patient share in COEs, then followed by the high-volume institutions and then the community thereafter. I think you also asked about age groups.
Speaker Change: <unk> followed by.
Speaker Change: The high volume institutions, and then then the community thereafter, I think you also asked about age groups, what I can say is quarter over quarter. After the kind of the initial surge what we see is.
Speaker Change: Very consistent.
Speaker Change: Distribution of of patients getting started on debut that is reflective of the rec community I think that can give you a good sense of where we're sourcing business.
Brendan Tien: What I can say is, quarter over quarter, after the kind of the initial surge, what we see is a very consistent distribution of patients getting started on debut that is reflective of the rec community. I think that can give you a good sense of where we're sourcing. Ami, your line was breaking up a little bit.
Speaker Change: Amit Your line was breaking up a little bit did you also have a component of your question related to negative symptoms or did I mishear that.
Amit: No I think you've covered all my question.
Operator: Did you also have a component of your question related to negative symptoms, or did I mishear that? No, I think you covered all my questions. Thank you so much.
Speaker Change: Thank you.
Speaker Change: One moment our next question.
Speaker Change: Our next question comes from <unk> with Mizuho. Your line is open.
Operator: Thank you. One moment, our next question comes from Oyir with Mizzou. Your line is open.
Mizuho: Hey, guys. Thanks for taking our question.
Mizuho: Just first a clarification question did you say that youre engaged with.
Oyir: Guys, thanks for taking our question. Just one clarification question. Did you say that you engaged with the EMA? And if you did, did they specifically say that you didn't have to do another study?
Mizuho: The MAA.
Mizuho: And if you did did they specifically said that you didn't have to do another study.
Doug Williamson: And our second question is, You know, based on what Minova put out, is there any learnings from their CRLs that you can apply to your own SNDA for negative symptoms? Thank you. Yeah, Doug, two questions. One on debut and or to prevent that in Europe and the other on negative, Yeah, so on trufenazide, we've had preliminary communications with EMA, but obviously, they don't, you know, confirm that we don't need to do an extra study until we're until we've formally sought scientific advice, um, But we don't we don't anticipate having to do any any further clinical work, um, On negative symptoms, we don't normally comment on other companies' submissions, but I think since in the press release they spelt out the reasons for the CRL, it's worth noting that, you know, the concerns were that there was only one study and they need two, so obviously we were doing a second study, that they didn't have a sufficient size safety database. We have an extensive database with Povansrin, that they'd failed to show the clinical significance. We're engaged with the agency, you know, answering their questions about the clinical significance of the NSA 16 data that we're providing, and I always forget the fourth thing. But whatever it was is not an issue for us either.
Speaker Change: Second question is.
Speaker Change:
Speaker Change: Based on what.
Speaker Change: <unk> put out is there any learnings from their CRM that you can apply to your own.
Speaker Change: S NDA for negative symptoms. Thank you.
Speaker Change: Yes, Doug two questions.
Speaker Change: One on debut in Finfet in Europe, and the other on negative symptoms.
Speaker Change: Yeah, so on <unk> side.
Speaker Change: We've had preliminary communications with the EMA, but obviously they don't.
Doug: Confirm that we don't need to do an extra study until we're until we formally scientific advice.
Speaker Change: But we don't we don't anticipate having to do any any further clinical work.
Speaker Change: On negative symptoms.
Speaker Change: We don't normally comment on other companies.
Speaker Change: Submissions, but I think since in the press release based on the reasons for the CRM.
Speaker Change: Whereas now we're taking that in the.
Speaker Change: Our concerns were there was there was only one study and the two so obviously, we're doing a second study.
Speaker Change: They didn't have sufficient.
Speaker Change: <unk> safety database, we have an extensive database for <unk>.
Speaker Change: They had failed to show the clinical significance, we're engaged with the agency.
Speaker Change: Im showing that questions about the clinical significance of the NSA 16 data that we're providing.
Speaker Change: <unk>.
Speaker Change: And I always forget the forcing.
Speaker Change: Hi, Tom.
Speaker Change: Whatever it was.
Speaker Change: <unk> is not an issue for us either.
Doug Williamson: So, so I think, I think, I think, I think that, uh, they were also looking at this drug as monotherapy, and of course, we're looking at it as adjunctive therapy. That's right, yeah, yeah, the FDA wanted to see a you know concomitant data for their air asset because they know that's how it's going to be used in the real world. And obviously, ours is an adjunctive treatment anyway, so that's not new. One moment for our next question. Our next question comes from Joel Beattie with Baird. Your line is open.
Speaker Change: So I think I think I think Doug.
Tom: Thank you.
Tom: They were also looking at this drug as monotherapy and of course, we're looking at as adjunct over there that's right.
Tom: Yes, yes.
Tom: The FDA wanted wanted to see.
Tom: Can comment on.
Tom: Data for <unk>.
Tom: Our asset because they know that's how it is going to be used in the real world.
Tom: Obviously ours is an adjunctive treatment anyway, so that's not an issue.
Tom: One moment for our next question.
Tom: Yeah.
Tom: Our next question comes from Joel Beatty with Baird. Your line is open.
Joel Beattie: Thanks. What's the exclusivity period look like for Nuplazid now that favorable legal rulings have come in December? And also, is that a long enough period for a launch in the negative symptoms of schizophrenia to add much? Yeah, thanks much for the question. Let me kind of sum up where we stand. As you recall, we have two patents or two families of patents that protect payment of answering. One is our composition of matter patent.
Joel Beatty: What's the exclusivity period look like for NUPLAZID.
Joel Beatty: The favorable legal rulings have come in December and then also.
Joel Beatty: A long enough period for lunch and negative symptoms in schizophrenia to add much.
Joel Beatty: Yes. Thanks, so much for the question, let me kind of sum up where we stand as you recall we have two.
Joel Beatty: <unk>.
Joel Beatty: Yes.
Joel Beatty: Patents.
Joel Beatty: Two families of patents that protect pivot.
Joel Beatty: <unk> answering one is our composition of matter patent.
Stephen R. Davis: We won at the trial court level on that in the fall. We submitted two arguments, and we only needed one to win on one.
Joel Beatty: We won at the trial court level on that.
Joel Beatty: In the fall.
Joel Beatty: We submitted two arguments we only needed one to win on one we both on what we wanted excuse me on both arguments.
Stephen R. Davis: We both won on both arguments. That is being appealed, as we fully expected it would be. The schedule I anticipate there is, We'll probably go through a series of briefings in the second quarter of this year, and then we expect oral arguments to be in the third quarter of this year. And the decision would likely come probably in the first half of next year. So that's where we stand on that front. Again, I'll just repeat what we said before. We feel like we're in a very good position there. We won at the trial court level. This is being appealed, and so we will be continuing to aggressively protect our rights there.
Joel Beatty: That is being appealed as we fully expected it would be.
Joel Beatty: The schedule I anticipate there is we'll probably go through a series of briefings in the second quarter of this year and then we expect oral arguments to be probably in the third quarter of this year and the decision would would likely come in probably in the first half of next year.
Joel Beatty: That's where we stand on that front again I'll just repeat what we said before we feel like we're in very good position. There. We wanted the trial court level. This is being appealed so we will be continuing to aggressively protect our rights there.
Stephen R. Davis: On the other family patents, dealing with four formulation patents around the 34 milligram capsule formulation of pimivanserin, and we also, as an aside, have a method of use patent on the 10 milligram tablet. Those are the only two marketed forms of the drug.
Joel Beatty: The other family patents dealing with where for formulation patents around the 34 milligram capsule formulation of <unk> and it also as an aside method of use patent on the 10 milligram tablet those are the only two marketed forms of the drug on the formulation patents.
Stephen R. Davis: On the formulation patents, we, In the fall, we also won a Markman ruling in that case, which puts us in a favorable position, advancing into the trial court that is scheduled for December of this year. And we would anticipate a decision from that trial on these formulation patents in the first half of next year also. So that's kind of where things stand. So when you work through all of that,
Joel Beatty: We.
Joel Beatty: In the fall. We also won a markman ruling in that case, which is which.
Joel Beatty: Puts us in a favorable position advancing into the.
Joel Beatty: Two the trial court.
Joel Beatty: That is.
Joel Beatty: Scheduled for December of this year hearing or excuse me. The trial is scheduled for December of this year and we would anticipate a decision from that trial on these formulation patents.
Joel Beatty: And.
Joel Beatty: The first half of next year also.
Stephen R. Davis: Today, we have Composition of Matter Protection that takes us to April of 2030 with a six-month pediatric extension, which we anticipate that would get us to October of 2030. That's all on the Composition of Matter Patent, which we won at the draw-for level, now under appeal. On the formulation patents, those run to 2038. We have already settled and yielded a little bit of ground there, which you typically do when you start settling on something like that. And we've settled with all but two companies, I should say, on the formulation patents. And so that would pull us back to late 2037 on those patents. That family patent, again, will come to trial in December, and we expect a decision on that in the first half. One moment for that question. ACADIA Pharmaceuticals Inc. Our next question comes from Marc Goodman with Lee Rink. Your line is open. Yes, for my debut, just a little bit more color. Can you help us with dosing? What is the dose for most of these patients relative to the target dose?
Joel Beatty: So thats kind of where things stand. So when you when you worked through all of that.
Joel Beatty: Today, we have composition of matter protection that takes us to.
Joel Beatty: April 2030, with a six month pediatric extension, which we anticipate that would go just to October 2030, that's all on the composition of matter patent, which we wanted to drop where level Dow under appeal.
Joel Beatty: On the <unk>.
Joel Beatty: Formulation patents those run to 2038, we have already settled.
Joel Beatty: In <unk>.
Joel Beatty: Yielded a little bit of ground, there, which you typically do when you start settling on that and that we've settled with all of the two companies I should say on the formulation patents and so that would pull us back to late 2037 on those patents that family packs again being will come to trial in December and we expect a decision.
Joel Beatty: On that in the first half of next year.
Speaker Change: One moment a question.
Joel Beatty: Steve.
Joel Beatty: Okay.
Joel Beatty: Our next question comes from Marc Goodman with Leerink. Your line is open.
Joel Beatty: Yes.
Marc Goodman: Dave you, just a little bit more color.
Marc Goodman: Can you help us with dosing.
Marc Goodman: With the.
Marc Goodman: Dosing for most of these patients relative to the target dose and then also like average age and weight of the patients if you could help us with that thanks.
Marc Goodman: And then also like the average age and weight of the patients, if you can help us with that. Sure. Before we answer that question, there was a question on profitability that I realized we didn't answer. So, Marc, do you want to take that? Yeah, happy to. I think just on the previous question, the simple answer is, can we make a launch and investment in the negative symptoms of schizophrenia profitable? The simple answer is yes.
Marc Goodman: Sure.
Speaker Change: Before we answer that question. There was a question of profitability that arose we didn't answer so mark you want to take that yes happy to I think just on the previous question. The simple answer is can we make a launch an investment in negative symptoms of schizophrenia profitable simple answer is yes.
Marc Schneier: Obviously, we will be mindful of the potential ranges for exclusivity for remaining for permanent answering. So, our launch will be a little different than if we knew that we would have a much, you know, longer dated life. But if we, as we get into 2030 and beyond, we can adjust investment. And also keep in mind, you know, there's a significant number of synergies between the negative symptoms of schizophrenia and Parkinson's disease psychosis.
Speaker Change: Obviously, we will be mindful of the potential of ranges for.
Speaker Change: For exclusivity for our remaining for permanent answering so.
Speaker Change: So our launch with <unk> that will be a little different than if we knew that we would have a much longer.
Speaker Change: Longer dated life, but if we as we get into 2030 and beyond.
Marc Goodman: Just investment and also keep in mind there is.
Marc Goodman: Significant number of synergies between negative symptoms of schizophrenia, and Parkinsons disease psychosis. So we're not starting from scratch and altogether can make we can make this franchise profitable to Acadia on a variety of ranges for ultimate exclusivity for the molecule.
Marc Schneier: So, we're not starting from scratch. And all together, we can make this franchise profitable for ACADIA on a variety of ranges for ultimate exclusivity for them all. Thanks, Marc. Okay, we've got two questions. Yeah, sure, Marc.
Speaker Change: Thanks, Mark Okay, Brendan two questions Yeah sure Mark Thanks for the question.
Brendan Tien: Thanks for the question. In terms of dosing, we think in terms of compliance to the label dose, you know, it's a weight-based product. The average compliance to dose is in the 75 to 80 percent range at this point. You also asked questions about weight and age. The weight has remained in the low 30-kilogram range, between 32-34, and the age is in the mid-teens, about 16 for an average age.
Brendan: In terms of dosing, we think in terms of compliance to the labeled dose you know, it's a weight based product.
Brendan: The.
Brendan: Average compliance to doses in the 75% to 80% range at this point.
Brendan: You also ask questions about weight and age the weight has remained in the low 30 kilogram range between 32 to 34 and the.
Brendan: The ages in the mid teens about 16 for an average age.
Operator: One moment, our next question. ACADIA Pharmaceuticals Inc. Our last question comes from Jatin Sinesha with Guggenheim. Your line is open. Boom! This is too quick one for me.
Speaker Change: One moment our next question.
Speaker Change: Okay.
Speaker Change: Our last question comes from Yadkin Dyskinesia with Guggenheim Your line is open.
Yadkin Dyskinesia: I guess two quick ones for me could you comment on gross to net or where you are on debut.
Jatin Sinesha: Could you comment on gross to net where you are on debut? If you can also characterize the OUS opportunity in dollars, would you be willing to say anything on New Plastic from a Q1 sales perspective? How should we think about seasonality there similar to what you have experienced in the past few years? are a little bit different.
Yadkin Dyskinesia: You can also characterize the whole U S opportunity in dollar perspective, and then are you willing to say anything on NUPLAZID from Q1 sales perspective, how should we think about seasonality there similar to what you have experienced in the past few years.
Speaker Change: A little bit different.
Marc Schneier: OK, I think it's going to be Mark, Brendan Mark. Yeah, on gross to net, maybe I'll do a go forward and a look back on my debut. I think going forward, we expect gross to net to be, you know, in the 20 percent range for debut. And it shouldn't really fluctuate quarter to quarter. When we look backwards, it was a little lower over the course of the entire year. So it was 17.7 percent through fiscal year 2023. And we did have favorability to that in the fourth quarter.
Speaker Change: <unk>.
Speaker Change: Okay, I think thats going to be.
Speaker Change: Mark Brendan Mark.
Mark Brendan: Yeah on gross to net.
Mark Brendan: Maybe I'll do a go forward and the look back on debut.
Mark Brendan: Going forward, we expect gross to net to be in the 20% range for debut and it shouldn't really fluctuate.
Mark Brendan: Quarter to quarter.
Mark Brendan: When we look backwards.
Mark Brendan: It was a little lower over the course of the entire year. So was 17, 7% through fiscal year 2023, and we did have favorability to that in the fourth quarter and the gross to net for debut was 15, 4% in the fourth quarter of last year.
Marc Schneier: And the gross to net for debut was 15.4 percent in the fourth quarter of last year. From just thinking about debuting outside the United States, obviously, we see a tremendous opportunity. I would speak to it in terms of the prevalent population, which is slightly larger than the United States and EU.
Mark Brendan: From just thinking about debut outside the United States, Obviously, we see a tremendous opportunity.
Mark Brendan: Would speak to it in terms of the prevalent population, which is slightly larger than the United States need you.
Brendan Tien: Canada, where we'll be first, is on the order of 600 to 900 patients. And then Japan is likely between 1,000 and 2,000 patients. So, in terms of value, I think I spoke a little bit about what we see, which is you can take a look at our U.S. pricing, and you can look at other rare disease products that launched in the U.S. to see their proximity to a U.S. price for their EU approach, and I think there's a narrower band than existed for broad range or broad indication products. It's too early for us to, you know, really talk about what the price per EU nation will be at this point, but that should give some sense of direction.
Mark Brendan: Canada, where we'll be first is on the order of 600 to 900 patients.
Speaker Change: And then Kent.
Speaker Change: Japan is likely between the 1002 thousand 2000 patients.
Speaker Change: So in terms of value I think I spoke a little bit to what we see which is you can take a look at our U S pricing and you can look at other rare disease products that launched in the U S to see their proximity.
Speaker Change: <unk> U S price for their for their EU approach and I think there is a narrower band than existed four four broad range or broad indication products, it's too early for us to two.
Speaker Change: Talk about what the price per.
Speaker Change: Per EU nation will be at this point, but that should give some sense of direction.
Marc Schneier: And then on New Plazid, you know, I think dynamics should be consistent this year, except for the gross to net dynamic that I mentioned for the fourth quarter. So we gave, you know, kind of seasonal dynamics, and across the quarter should be the same in terms of volumes. And then I gave the gross to net guidance for the first quarter just to make sure people can think in the right range as we go through the Medicare Part D dynamics for the first quarter. And there'll just be less of that in the fourth quarter of this year, just due to the anticipated Medicare Part D redesign in twenty twenty.
Speaker Change: And then on on NUPLAZID, I think dynamics should be consistent this year, except for the gross to net dynamic that I mentioned for the fourth quarter. So we gave kind of seasonal dynamics across the quarter should be the same in terms of volumes.
Speaker Change: When I gave the gross to net guidance for the first quarter just to make sure people can think.
Speaker Change: In the right range as we go through the Medicare part D dynamics for the first quarter and they will just be less of that in the fourth quarter of this year just due to the anticipated Medicare part D redesign in 2025.
Marc Schneier: That concludes the question and answer session. I would like to turn the call back to Steve Davis for closing remarks.
Speaker Change: That concludes the question and answer session I would like to turn the call back to Steve Davis for closing remarks.
Stephen R. Davis: Thank you, Operator. Thanks again, everyone, for joining us today. We look forward to updating you on our progress next quarter. ACADIA Pharmaceuticals Inc. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
Stephen R. Davis: Great. Thank you operator, thanks again, everyone for joining US today, we look forward to updating you on our progress next quarter.
Speaker Change: Thank you for your participation in today's conference. This does conclude the program you may now disconnect.
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