Q4 2022 ACADIA Pharmaceuticals Inc Earnings Call
Speaker 1: Hi. And you. Yes.
Gigi: Good day, ladies and gentlemen, and welcome to Acadia Pharmaceuticals' fourth quarter and full year 2022 Financial Results Conference Call. My name is Gigi, and I will be your coordinator for today. At this time, all participants are in listen-only mode. We will be facilitating a question-and-answer session towards the end of today's call. I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at Acadia. Please proceed.
Speaker 2: Good day, ladies and gentlemen, and welcome to Acadia Pharmaceuticals' fourth quarter and full year 2022 Financial Results Conference call. My name is Gigi, and I will be your coordinator for today. At this time, all participants are in listen-only mode. We will be facilitating a question-and-answer session towards the end of today's call.
Speaker 2: I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at Acadia. Please proceed.
Mark C. Johnson: Thank you. Good afternoon, and thank you for joining us on today's call to discuss Acadia's fourth quarter and full year 2022 financial results. Joining me on the call today from Acadia are Steve Davis, our chief executive officer, who will provide an overview of our performance and a review of our business. Mark Schneier, our chief financial officer, will discuss our financial results and guidance. Then Brennan, our chief operating officer, head of commercial, will provide updates on our new plaza commercial performance before being joined by Kathy Bishop, our chief scientific officer and head of rare disease, to provide an overview of Trefinite.
Speaker 3: Thank you. Good afternoon and thank you for joining us on today's call to discuss Acadia's fourth quarter and full year 2022 financial results. Joining me on the call today from Acadia are Steve Davis, our Chief Executive Officer, who will provide an overview of our performance and a review of our business.
Speaker 3: Mark Schneier, our Chief Financial Officer, will discuss our financial results and guidance. And then Brendan Thien, our Chief Operating Officer, Head of Commercial, will provide updates on our new private commercial performance before being joined by Kathy Bishop, our Chief Scientific Officer and Head of Brodasease, to provide an overview on Trifinatize.
Mark C. Johnson: Our newly appointed head of research and development, Doug Williamson, will provide an update on our pipeline programs before turning it back to Steve for final remarks and opening the call to your questions. I would also like to point out that we are using supplemental slides, which are available in the events and presentation section of the website.
Speaker 3: Our newly appointed head of research and development, Doug Williamson, will provide an update of our pipeline programs before turning it back to Steve for final remarks and opening the call up for your question.
Speaker 3: I would also like to point out that we are using supplemental slides which are available on the events and presentation section of the website.
Mark C. Johnson: Before we proceed, I would first like to remind you that during our call today, we will be making a number of 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 a number of risks and uncertainties that may cause actual results to differ materially.
Speaker 3: Before we proceed, I would first like to remind you that during our call today, we will be making a number of forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward looking statements include goals, expectations, plans, prospects, growth potential, timing of events, or future results.
Speaker 3: or based on current information, assumptions, and expectations that are inherently subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially.
Mark C. Johnson: These factors and other risks associated with our business can be found in our filings made with the, Please be careful not to place undue reliance on these forward-looking statements, which are made only as of today's day. I'll now turn the call over to Mark. Good afternoon, everyone, and thank you for joining us. Please turn to slide by.
Speaker 3: These factors and other risks associated with our business can be found in our filings made with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of today's date. I'll now turn the call over to Steve.
Stephen R. Davis: The execution of our strategic priorities in 2022 has set us up for 2023 to be an important and transformational year for a. Last year, our new plans and franchise in PDP achieved $517.2 million in net sales, a 7% increase year over year. We submitted our new drug application for Trepinotide, the potential first ever approved treatment for Red Syndrome, with an upcoming PDUFA date of March 12. We are advancing our phase three negative symptoms and schizophrenia program and expect a complete enrollment around the middle of this year.
Speaker 3: Thank you, Mark. Good afternoon, everyone, and thank you for joining us today.
Speaker 3: Thank you, Mark. Good afternoon, everyone, and thank you for joining us today. Please turn to slide 5.
Speaker 3: The execution of our strategic priorities in 2022 has set us up for 2023 to be an important and transformational year for Acadia. Last year our New Finance franchise and PDP achieved $517.2 million in net sales, a 7% increase year over year.
Speaker 3: We submitted our new drug application for tryfenotide, the potential first ever approved treatment for Rett syndrome with an upcoming PDUFA date of March 12th.
Speaker 3: We advance our Phase III negative symptoms and schizophrenia program and expect a complete enrollment around middle of this year.
Stephen R. Davis: And we advanced our next generation 5HT2A program with ACP 204, which is currently in phase one clinical development. With the cash flows from our new closet franchise and a strong balance sheet, we are well positioned to deliver on these four strategic priorities that will shape our success in 2023 and beyond without the need for additional capital. Let's review our PDP business further on slides. We continue to maximize the value of our new plaza franchise and DD.
Speaker 3: And we advanced our next generation 5HT2A program with ACP204, which is currently in Phase 1 clinical development.
Speaker 3: With cash flows from our new climate franchise and a strong balance sheet, we are well positioned to deliver on these four strategic priorities that will shape our success in 2023 and beyond, without the need for additional capital.
Speaker 3: Let's review our PDP business further on slide 6.
Brennan: Over the past few years, we've thoughtfully and strategically grown our share for Nuclacid in the current PDP market environment. We're delivering steady volumes while concurrently optimizing and reducing our commercial expenses. As a result, we've been able to significantly grow cash flow from this franchise every year since it turned profitable in 2019. Looking back at 2022, our New Plysm Performance was led by continued improvement in the long-term care channel, which represents approximately 25% of our total. In the LTC channel, demand growth was up 4% sequentially for the fourth quarter and 5% for the full year. In fact, the fourth quarter represented a record high for new class volume in the LTC2.
Speaker 3: We continue to maximize the value of our applied to franchise and PDP.
Speaker 3: Over the past few years, we've thoughtfully and strategically grown share for Nuplacid in the current PDP market environment.
Speaker 3: We are delivering steady volumes while concurrently optimizing and reducing our commercial expense base.
Speaker 3: As a result, we've been able to significantly grow cash flow from this franchise every year since it turned profitable in 2019.
Speaker 3: Looking back at 2022, our new Pfizer performance was led by continued improvement in the long-term care channel, which represents approximately 25% of our total business.
Speaker 3: In the LTC channel, demand growth was up 4% sequentially for the fourth quarter and 5% for the full year.
Brennan: Our previous high was Q4 of 2019, the last quarter before the pandemic. In the office-based channel, which makes up about 75% of our business, we continue to gain market share in a declining Parkinson's disease market still impacted by the pandemic conditions. This netted out to an overall 3% decline in demand in this channel for the year compared to 2021.
Speaker 3: In fact, the fourth quarter represented a record high for NUFLASA volume in the LTC channel.
Speaker 3: Our previous high was Q4 2019 the last quarter before the pandemic hit.
Speaker 3: In the office space channel, which makes up about 75% of our business, we continue to gain market share in a declining Parkinson's disease market, still impacted by pandemic conditions. This netted out to an overall 3% decline in demand in this channel for the year compared to 2021. More recently, we've experienced relatively steady demand sequentially in the fourth quarter.
Brennan: More recently, we've experienced relatively steady demand sequentially in the fourth quarter. Overall, across all channels for the full year, demand growth for the new prices franchise was steady compared to 20. Given the current market conditions and our profitability objectives for the franchise, we will continue to optimize our PDB commercial spin and expect stable demand volumes in the near-term environment. There are two important factors with the potential to catalyze near to intermediate term volume growth. One is a change in the pandemic conditions related to Parkinson's disease psychosis market. In other words, we believe this is a temporary situation which will normalize at some point in the future.
Speaker 3: There are two important factors with the potential to catalyze near to intermediate term volume growth.
Speaker 3: One is a change in the pandemic conditions related to Parkinson's disease psychosis market.
Speaker 3: In other words, we believe this is a temporal situation which will normalize at some point in the future.
Speaker 3: We believe we're seeing early indicators of that in the LTC channel. And second is assimilation in the medical community of three very important new publications that demonstrate the benefits of pimavantrin, relatively off-label atypical antipsychotics, which were historically used before duplicitous approval.
Speaker 3: Today, we are providing 2023 New Clives of net sales guidance of $520 to $550 million, which incorporates a range of assumptions which Mark will describe further in his section.
Speaker 3: Turning to slide 7, we are very much looking forward to and preparing for the upcoming March 12th PDUFA Action Day for Triphinitide.
Stephen R. Davis: We believe we're seeing early indicators of that in the LTC channel. And second, there are three very important new publications that demonstrate the benefits of Pimavanserin, relatively off-label, atypical antipsychotics, which were historically used before duplazate's approval. Today we are providing 2023 Nuclizance of $520 to $550 million, which incorporates a range of assumptions which Mark will describe further in his. Turning to side seven, we're very much looking forward to and preparing for the upcoming March 12th Perdufa action date for Truffinus.
Speaker 3: Later, Brendan will describe in greater detail some of the key launch initiatives we are working on.
Speaker 3: The first I'd like to take a moment to remind everyone what an important drug for phenetide could be for a community with such a large unmet need. As you know, Ritz Syndrome is a rare genetic neurodevelopmental disorder that severely impacts the lives of patients and their families.
Speaker 3: The approval of Turfinatide would represent a significant step forward in the treatment of rest syndrome. Turfinatide's established efficacy profile is supported by positive broad improvements across two co-prime re-employment and randomized double-wide Phase III study.
Speaker 3: Kathy will review these results in greater detail in her section, as well as provide initial top-line results from a recently completed open-label extension study.
Stephen R. Davis: Later, Brendan will describe in greater detail some of the key launch initiatives we're working on. But first, I'd like to take a moment to remind everyone what an important drug phenotide could be for a community with such a large unmet need. As you know, Red Syndrome is a rare genetic neurodevelopmental disorder that severely impacts the lives of patients and their families. The approval of Trophenitide would represent a significant step forward in the treatment of red syndrome.
Speaker 3: And from a regulatory and IP perspective, Trufinitide has orphan drug status and is protected by a method of abuse patent for the treatment of breast syndrome, which provides exclusivity with expected hatch waxman patent extension into early 2036.
Speaker 3: We are very excited about the prospect of bringing each tenant out to the market and eagerly await our PDUFA date. Let's briefly discuss our next two programs on slide 8.
Speaker 3: The negative symptoms of schizophrenia, characterized by social withdrawal, lack of emotion, or flat affect, is frequently referred to as the most significant unmet need for people living with schizophrenia. Our adjunct to PIM-adanserim program is designed to treat those patients whose positive symptoms are hallucinations, delusions, and paranoia.
Stephen R. Davis: Trepenetized established efficacy profile is supported by positive broad improvements across two co-primary endpoints in a randomized double-line phase three study. Kathy will review these results in greater detail in her section, as well as provide initial top-line results from a recently completed open-label study of, And from a regulatory and IP perspective, epinotide has orphaned drug status and is protected by a method abuse patent for the treatment of breast syndrome, which provides exclusivity with an expected hatch waxman patent into early 2030.
Speaker 3: are adequately controlled, but who still suffer from persistent and uncontrolled negative symptoms. Negative symptoms has been an exceedingly difficult area with lots of industry failures over multiple decades.
Speaker 3: With PIM advancing, we've achieved something very rare in this population, a positive pivotal study, our Advanced 1 study. We expect a complete enrollment in our second pivotal study, Advanced 2, around the middle of this year, with results expected in early 2024. And finally, in our next generation 5HC2A program, we are investing in a novel molecule — with the
Stephen R. Davis: We're very excited about the prospect of bringing you to Finanita in the market and eagerly await our producers. Let's briefly discuss our next two programs on Sliding. Negative symptoms of schizophrenia, characterized by social withdrawal, lack of emotion, or flat affect, are frequently referred to as the most significant unmet need for people living with schizophrenia.
Speaker 3: with ACP204, we're seeking to improve further on the learnings from PIM Advanced.
Speaker 3: Doug will speak to this further in a few minutes.
Stephen R. Davis: Our adjunctive Him of Answering Program is designed to treat those patients who are positive, the hallucinations, delusions, and paranoia are adequately controlled, but who still suffer from persistent and uncontrolled negative symptoms. Negative symptoms have been an exceedingly difficult area with lots of industry failures over multiple decades. With PIMAvanser, we've achieved something very rare in this population. A positive pivotal study, our advanced one. We expect complete enrollment in our second fiscal study, advanced two around the middle of this year, with results expected in early 2020.
Speaker 3: Currently, we are working on completing Phase I development and look forward to advancing eC Q2 04 into Phase II studies later this year.
Speaker 3: I'll now turn it over to Mark to discuss our 2022 financial performance and 2023 guidance.
Speaker 4: Let's start by reviewing our quarterly and full year performance on slide 10.
Speaker 4: In the fourth quarter, we recorded $136.5 million in net sales, up 4% from the fourth quarter of last year. Our gross net adjustment for the quarter was 23.8%.
Speaker 4: For the full year 2022, we recorded $517.2 million in net sales, up 7% year over year.
Stephen R. Davis: And finally, in our next generation 5HT2A program, we are investing in a novel molecule, ACP204, targeted for Alzheimer's Disease, sarcoesis, or ADP. Similar to Pimovanser, ACP204 works primarily by blocking 5H2A. We believe this mechanism is ideally suited to the frail and elderly population.
Speaker 4: Our gross net adjustment for the year was 20.8%.
Speaker 4: This adjustment was relatively unchanged compared to 2021, excluding the impact of the IRA legislation.
Speaker 4: As Steve mentioned, demand was relatively steady for full year 2022 over 2021, and in channel inventory at the end of 2022 was relatively unchanged compared to the end of 2021. That RMD expenses increased to $361.6 million in 2022.
Mark C. Schneyer: And with ACP 204, we're seeking to improve further on the learnings from PIMAVAN; Doug will speak to this further in a few minutes. Currently, we are working on completing phase one development and look forward to advancing AC2O4 into phase two studies later. I'll now turn it over to Mark to discuss our 2022 financial performance and $223. Please, Steve, let's start by reviewing our quarterly and full year performance on slide 10. In the fourth quarter, we recorded $136.5 million in net sales, a 4% increase from the fourth quarter of last year.
Speaker 4: from $239.4 million in 2021. Investments in our portfolio in 2022 included a $60 million upfront payment for our Stoke collaboration, a $10 million milestone payment to our partner Neuren, and $23 million in cumulative payments related to as of yet still undisclosed BD trends.
Speaker 4: $96 million in 2021, representing a 7% decrease year over year.
Speaker 4: 2021, representing a 7% decrease year over year. There are two important considerations here.
Mark C. Schneyer: Our gross to net adjustment for the quarter was 23.8%. For the full year 2022, we recorded $517.2 million in net sales, 7% year over year. Our gross to net adjustment for the year was 20.8%. This adjustment was relatively unchanged compared to 2021, excluding the impact of the IRA legislation.
Speaker 4: One, we significantly reduced our PDP franchise expense base by approximately $60 million from 2021, optimizing the business and increasing cash flows from the franchise.
Speaker 4: And two, we have been making the right investments to be well prepared for the upcoming propinatide launch.
Speaker 4: We ended the year with a cash balance of $416.8 million compared to $520.7 million at the end of 2021. Our balance sheet remains strong and we continue to be confident in our ability to generate sustainable growth with our existing cash resources.
Mark C. Schneyer: As Steve mentioned, demand was relatively steady for full year 2022 over 2021, and in-channel inventory at the end of 2022 was relatively unchanged compared to the end of 2021. Gap R&D expenses increased to $361.6 million in 2022 from $239.4 million in 2021. Investments in our portfolio in 2022 included a $60 million upfront payment for our Stoke collaboration, a $10 million milestone payment to our partner Nuren, and $23 million in cumulative payments related to, as of yet, still undisclosed BD transacts.
Speaker 4: Let's review our 2023 guidance on the next slide. Please note that while our expense guidance for 2023 assumes a potential Tripenetide launch, we are not providing sales guidance for Tripenetide this year.
Speaker 4: As a result, we are also not providing guidance on our future cash balance.
Speaker 4: For our New Placid PDP business, we are providing net sales guidance to be between $520 and $550 million this year. The Miller range assumes approximately 1% volume growth and about a 2.5% net price increase for New Placid in 2023.
Speaker 4: We are projecting rosinets to be between 22 and 25% for the full year, given the need to approve from Medicare rebates related to the IRA.
Mark C. Schneyer: Also, in 2022, there was a total spend of approximately $30 million on Trinitide Commercial Supply Bill. Gap SG&A expenses decreased to $369.1 million in 2022 from $396 million in 2021, representing a 7% decrease year over year. There are two important considerations here.
Speaker 4: As a reminder, Q1 is the highest gross to net quarter for the year. Given the first time impact of the IRA on our full year gross to net, we are providing gross to net guidance for Q1 this year, which we expect to be between 28 and 30%.
Speaker 4: As for the remainder of the year, we anticipate growth net for Q2, Q3, and Q4 will be relatively consistent with patterns we've seen in prior years, with Q2 and Q3 being our lowest quarters than an increase in Q4.
Mark C. Schneyer: One, we significantly reduced our PDP franchise expense base by approximately $60 million from 2021, optimizing the business and increasing cash flows from the franchise, and two, we have been making the right investments to be well prepared for the upcoming Trinotide Law. We ended the year with a cash balance of $416.8 million compared to $520.7 million at the end of 2021. Our balance sheet remains strong, and we continue to be confident in our ability to generate sustainable growth with our existing cash resources.
Speaker 4: On the expense side for 2023, we expect GAP R&D expenses to be between $235 and $255 million including approximately $20 million in stock-based compensation. Our R&D range does not guide for incremental spend for business development transactions. We expect GAP SDNA expense to be between $360 and $308 million.
Mark C. Schneyer: Let's review our 2023 guidance on the next slide. Please note that while our expense guidance for 2023 assumes a potential Trapinitide launch, we are not providing sales guidance for Trapinitide this year. As a result, we are also not providing guidance on our future cash balance.
Speaker 4: spend by an additional $50 million. In aggregate, since 2021, we have reduced our PDP spend by approximately $110 million, significantly enhancing the cash flow generation from this franchise.
Mark C. Schneyer: For our new Placid PDP business, we are providing net sales guidance of between $520 and $550 million this year. The Murrilla range assumes approximately 1% volume growth and about a 2.5% net price increase for New Placid in 2023. We are projecting Grossmanette to be between 22 and 25% for the full year, given the need to accrue for Medicare rebates related to the IRA.
Speaker 3: And now I'd like to turn the call over to Brenda. Thank you, Mark. I'm now going to discuss our new Clad the Brand and we'll return later after Kathy speaks to discuss our Trafinatide Commercial Launch Plan.
Speaker 3: Please turn to slide 13.
Speaker 3: For Newplazid, we continue to drive share growth in a smaller PD market, delivering steady volumes and growing cash flow. We are accomplishing these goals by optimizing promotion of the brand.
Speaker 3: As Steve mentioned, the PDP franchise has been profitable since 2019, and we have continued to build share while optimizing expenses.
Mark C. Schneyer: As a reminder, Q1 is the highest gross net quarterly for the year. Given the first time impact of the IRA on our full year gross to net, we are providing gross to net guidance for Q1 this year, which we expect to be between 28 and 30%. As for the remainder of the year, we anticipate growth net for Q2, Q3, and Q4 will be relatively consistent with patterns we've seen in prior years, with Q2 and Q3 being our lowest quarters, then an increase in Q4. On the expense side, for 2023, we expect GAAP R&D expenses to be between $235 million, including approximately $20 million in stock-based compensation. Our R&D range does not guide for incremental spend for business development transactions.
Speaker 3: Beyond these efforts, there are two important areas that could catalyze future growth. One is a change in pandemic conditions related to the PDP market.
Speaker 3: We have already seen some early improvement in the LTC channel with new admissions returning to pre-pandemic levels and census levels continuing to improve.
Speaker 3: Both present further opportunities to identify the signs and symptoms of PDP and to treat with new plasm. In the community setting, which represents approximately 75% of our total business, we've not yet observed this type of improvement as patient in-person visit volumes remain down double digits.
Speaker 3: versus prior to the pandemic. The second potential catalyst is the promotion of three important real-world evidence studies that have been recently published, which demonstrate the differential benefits of initiating treatment in patients with pima vanterine for PDP as opposed to off-label atypical antipsychotics.
Mark C. Schneyer: We expect GAAPSDNA expense to be between $360 and $380 million for the full year, including approximately $45 million in stock-based compensation. While SG&A expense is expected to be relatively flat year over year, we will be investing to fully support a successful commercial launch of Trinatide, while at the same time further optimizing and reducing our PDP franchise spend by an additional $50 million. In aggregate, since 2021, we have reduced our PDP spend by approximately $110 million, significantly enhancing the cash flow generation from this franchise. Now, I'd like to turn the call over to Brendan.
Speaker 3: I have already discussed the key conclusions before, and they are presented on the slides. While we are still in the early days of engaging healthcare professionals, or HCPs, long-term care facilities and payers with these important new data sets, we are encouraged by the level of engagement we are seeing.
Speaker 3: This data is creating an important dialogue with treaters and is giving us a patient-focused and critically important message to further differentiate new plazas.
Speaker 3: In the Office Space channel, we have only just recently begun sharing and discussing these datasets at the top of this slide with HCPs. We look forward to the opportunity to share these very important datasets and we'll update you on our progress.
Speaker 3: In long-term care facilities, we've been sharing the conclusions from the Kumar et al. paper shown at the bottom of the slide since the latter portion of 2022.
Brendan: Thank you, Mark. I'm now going to discuss our new closet brand, and we're returning later after Kathy to discuss our Trafinitide commercial launch. Please turn to slide 13. For New Plaza, we continue to drive share growth in a smaller PD market, delivering steady volumes and growing cash. We are accomplishing these goals by optimizing promotion of the brand. As Steve mentioned, the PTP franchise has been profitable since 2019, and we have continued to build share while optimizing. Beyond these efforts, there are two important areas that could catalyze future growth.
Speaker 3: The study compares healthcare resource utilization, specifically around hospitalizations, ER visits, and nursing home stays in patients who receive Nuplaazid versus other off-label antipsychotics. These data have been well received as they clearly suggest the use of pimavantrin may improve important outcomes that directly impact facility star ratings.
Speaker 3: which could make a real difference in patient care and favorably impact their business. Again, we will update you on our progress. Now I'd like to turn it over to Kathy to discuss our exciting second potential commercial product, Trufinitide, starting on slide 14. Thank you, Brendan.
Brendan: One is the change in pandemic conditions related to We have already seen some early improvement in the LT new admissions returning to pre-pandemic levels and census levels continuing. Both present further opportunities to identify the signs and symptoms of PDP and to treat with new platy. In the community setting, which represents approximately 75% of our total, We've not yet observed this type of improvement as patient in-person visit volumes remain down double-digit versus prior to the pandemic.
Speaker 5: I would like to begin by noting that tomorrow, February 28th, is Rare Disease Day. On behalf of Acadia, we support the mission to raise awareness and generate change for the 300 million people worldwide living with a rare disease, their families, and those who care for them. We have been very touched and grateful for the involvement and support of the National
Brendan: The second potential catalyst is the promotion of three important real-world evidence studies that have recently been published and demonstrate the differential benefits of initiating treatment in patients with Team of Answers as opposed to off-label atypical antipsychics. I have already discussed the key conclusions before, and they are presented on the slide. While we are still in the early days of engaging healthcare professionals or long-term care facilities and payers with these important new data, we are encouraged by the level of engagement that is creating an important dialogue with providers and is giving us a patient-focused and critically important message to further differentiate new. On the Office-based channel, we have only recently begun sharing and discussing these data sets at the top of this slide.
Speaker 5: of normal development followed by a loss of skills, leaving a typical child unable to use their hands, walk, eat, or speak.
Speaker 5: Rett syndrome affects the broad set of core symptoms, including deficits in breathing, hand movements or stereotypies, repetitive behavior, nighttime behavior, vocalizations, facial expressions, eye gaze and mood.
Speaker 5: Despite this complex, very involved disorder, many individuals with RET live into adulthood but do require one-to-one care for their entire lives. There are no FDA-approved treatments for the core symptoms of RET syndrome, and as such, this is a tremendous unmet need. Let's discuss trypanotype as a potential treatment starting on slide 16.
Brendan: We look forward to the opportunity to share these very important data sets, and we'll update you on our progress. In long-term care facilities, we've been sharing the conclusions from the Kumar at all paper shown at the bottom of the slide since the latter portion of 20, The study compares healthcare resources specifically around hospitalizations, ER visits, and nursing homestays and patients who receive New Plaza versus other off-label antipsychicals. These data have been well received as they clearly suggest the use of Pima Vanturn may improve important facility start times, which could make a real difference in patient care and favorably impact patient outcomes. Again, we will update you on our progress.
Speaker 5: The History Lavender Study was overwhelmingly positive and demonstrates a compelling benefit profile for patients.
Speaker 5: The study met both of its co-primary endpoints, achieving statistically significant separation from placebo, on both the rest syndrome behavioral questionnaire or RRFQ at caregiver assessment and the clinical global impression of improvement or CGII, a physician assessment tool.
Brendan: Now I'd like to turn it over to Kathy to discuss our exciting second potential commercial product, Trinitide, starting on slides. Thank you, Brendan. I would like to begin by noting that tomorrow, February 28th, is Rare Disease Day.
Speaker 5: The RSDQ was positive with a p-value of 0.0175 and an effect size of 0.37.
Speaker 5: Overall, a mean 5.1 improvement was observed for patients in the trypanotide group at 12 weeks compared to baseline.
Kathie M. Bishop: of Acadia, we support the mission to raise awareness and generate change for the 300 million people worldwide living with a rare disease, their families, and those who care for them.
Speaker 5: In addition, there are eight domains in the RSPQ which capture the broad array of symptoms. There was a directional improvement across all eight domains in favor of tryphinotype compared to placebo. The co-primary endpoint CGII was also positive with a p-value of 0.003 and an effect size of 0.47. In addition, there were three domains in the RSPQ which capture the broad array of symptoms.
Kathie M. Bishop: We have been very touched and grateful for the involvement and support of the RET disease community as we develop.
Kathie M. Bishop: as we develop Trifenit. Please turn to slide 15.
Kathie M. Bishop: RET syndrome is an extraordinarily debilitating disorder affecting not
Kathie M. Bishop: Not only the patients but their caregivers and family.
Speaker 5: The advocacy results were consistent across all age groups and severity of disease. In addition, the key secondary endpoint, which was related to non-verbal communication, was also positive. Upon completion of lavender, patients could continue into lilac.
Kathie M. Bishop: There is a period of normal development followed by a loss of skills, leaving a typical child unable to use their hands, walk, eat, or speak. RET syndrome affects a broad set of core symptoms, including
Kathie M. Bishop: Decreased breathing, hand movements or stereotypies, repetitive behavior, nighttime behavior,
Speaker 5: Slide 18 shows the study design for this 40-week open-label extension study which recently completed. 154 patients rolled over to the Lilac study from Lavender.
Kathie M. Bishop: Nighttime behaviors, vocalizations, facial expressions, eye gaze, and mood.
Speaker 5: Upon completion of Lilac, patients could continue into Lilac II and can remain in that study until we transition them to commercially available product if Trefenatide is approved. Let's review some of the key findings of the Lilac study starting on slide 19.
Kathie M. Bishop: Despite this complex, very involved disorder, many individuals with RET live into adulthood.
Kathie M. Bishop: with RETs live into adulthood, but do require one-to-one care for their entire life. There are no FDA-approved treatments for the core symptoms of rest syndrome, and as such, this is a tremendous unmet need. Let's discuss Tripinotide as a potential treatment starting on slide 16. We evaluated Trinotide in a robust phase-free clinical study, Lavender.
Speaker 5: Regarding efficacy, we are pleased that for both of the co-primary lab leader endpoints, we observed a sustained and continued improvement in lilac. For the RSVQ, the Caregiver Assessment, we observed an improvement of more than seven appointments compared to the lab leader baseline.
Kathie M. Bishop: involving 187 young women and girls with RET syndrome.
Speaker 5: Importantly, this magnitude of effect was also observed for patients who transitioned from placebo to a trifinatite for the Lilac Study. Let's review the CGII scores on slide 20.
Kathie M. Bishop: The 12-week double-blind study design is shown here. Please turn to slide 17.
Kathie M. Bishop: The Phase 3 Lavender Study was overwhelmingly positive and demonstrates a compelling benefit profile for patients. The study met both of its co-primary endpoints, achieving statistically significant separation from placebo on both the RETS syndrome behavioral questionnaire, or RRQ, a caregiver assessment, and the clinical global impression of improvement, or CGIII, a physician assessment tool. The RSCQ was positive, with a P value of 0.0175 and an effect size of 0.37.
Speaker 5: As a reminder, the CDII is assessed by physicians on a 7-point Likert scale. Thus, a score of 4 indicates the physician saw no improvement.
Speaker 5: Cours greater than four, you know, a worsening of disease, as course less than four indicate an improvement.
Speaker 5: Recall that in Lavender, Chifinidai patients improved approximately half a point in 12 weeks to a score of 3.5. And in the Lilac study, their baselines were reset and over the next 40 weeks all patients who completed the study demonstrated additional improvement on average of almost 1 full point.
Kathie M. Bishop: Overall, a mean 5.1 improvement was observed for patients in the Trifinity study.
Kathie M. Bishop: Affinatide Group at 12 weeks compared to baseline. In addition, there are eight domains in the RSBQ, which capture a broad array of symptoms. There was a directional improvement across all eight domains in favor of Trophenotide compared to placebo. The co-primary endpoint CGIII was also positive, with a p-value of 0.003 and an effect size of 0.47. The advocacy results were consistent across all age groups and severity of disease.
Speaker 5: with a mean score of 3.1 at the end of 40 weeks. These are very meaningful findings in both the RFPQ and CGII and important for patients and caregivers.
Speaker 5: I'd like to briefly review the top-line safety and tolerability findings on slide 21. In the 40-week Lilac study, we observed a consistent adverse event profile compared to the Lavender study. Importantly, no new safety or tolerability findings were reported. Over the course of the study, the most common adverse events reported were diarrhea, vomiting, and COVID-19.
Kathie M. Bishop: In addition, the key secondary endpoint, which was
Kathie M. Bishop: Which was related to nonverbal communication was also positive.
Kathie M. Bishop: Upon completion of lavender, patients continue into lilac. Slide 18 shows the study designed for this 40-week open-label extension study, which has recently been completed.
Kathie M. Bishop: 154 patients rolled over to the Lilac Study from Lavender. Upon completion of Lilac, patients could continue on Lilac Tube and can remain in that study until we transition them to a commercially available product if troughenetide is approved. Let's review some of the key findings of the Lilac study starting on slide 19.
Speaker 5: There was no single reason contributing to the additional discontinuations and this rate is not uncommon when compared to other long-term open label studies.
Speaker 5: For context, patients continued and completed Lilac over the span of several years.
Speaker 5: GI management plans were only added towards the end of the study and this would not have made much of a difference in the overall data collected.
Kathie M. Bishop: Starting on slide 19.
Speaker 5: However, discontinuations did decrease the longer patient's state on therapy. This is further evidenced by a much smaller discontinuation rate in the ongoing Lilac II extension, and notably so far in Lilac II, we have had no discontinuations due to diarrhea. I'll now turn it back to Brendan to outline our launch initiative.
Kathie M. Bishop: Regarding efficacy, we are pleased that for both of the co-primary lavator endpoints, we observed a sustained and continued improvement in lilac. For the RSPQ, the caregiver assessment, we observed an improvement of more than seven points compared to the lavender baseline. Importantly, this magnitude of improvement is
Speaker 3: Thank you, Kathy. Please turn to slide 22. We're very excited to be on the verge of potentially bringing the first-ever treatment of Rett syndrome to the patients, families, and HCPs looking for novel solutions. As you would expect, we're making significant investments and progress in preparing for the successful launch of Provenetide. Let me break down our priorities to three areas of focus.
Kathie M. Bishop: was also observed for patients who transitioned from placebo
Kathie M. Bishop: Botechutrophenitite for the Lilac study. Let's review the CGII scores on slide 20. As a reminder, the CDII is assessed by physicians on a seven point Lycurt scale. Thus, a score of four indicates that physicians see no improvement. Scores greater than four denote a worsening of disease, as scores less than four indicate an improvement. Recall that in lavender, patients improved approximately half a point in 12 weeks to a score of 3.5. And in the Lilac study, their baselines were reset, and over the next 40 weeks, all patients who completed the study demonstrated a
Speaker 3: disease awareness, patient identification, and ongoing support. Our first priority is to drive disease state awareness and education about the core symptoms of Rett. An important part of the foundation we're laying now is continuing to build the awareness of the core symptoms of Rett.
Speaker 3: so that physicians and caregivers are better equipped to recognize the unique benefits trifenatide stands poised to deliver. It is equally important to educate HCPs and caregivers on the potential therapeutic value of trifenatide and to set up the right expectations for both efficacy and tolerability to ensure patients receive the full long-term benefits of trifenatide.
Kathie M. Bishop: of additional improvement on average of almost one full point with a mean score of 3.1 at the end of 40 weeks.
Kathie M. Bishop: These are very meaningful findings in both the RSQ and CGIII and important for patients and caregivers. I'd like to briefly review the top line safety and tolerability findings.
Speaker 3: of treatment. Our second priority is to fully characterize the identified 4,500 patients who are currently diagnosed in the United States. Red patients are primarily cared for in three principal treatment settings. About 25% of patients are treated in centers of excellence, as designated by Red Patient Advocacy Foundations. There are currently 22 centers of excellence with more that are in the processing.
Kathie M. Bishop: on slide 21. In the 40-week Lila study,
Kathie M. Bishop: In this study, we observed a consistent adverse event profile compared to the Lavender Study. Importantly, no new safety or tolerability features were reported.
Kathie M. Bishop: Over the course of the study, the most common errors were
Kathie M. Bishop: Adverse events reported were diarrhea, and vomiting.
Kathie M. Bishop: and COVID-19. Diarrhea and vomiting rates were consistent with those from the Lavender Study and were
Kathie M. Bishop: almost all mild or modern in nature; discontinuations in the study related to an adverse event.
Kathie M. Bishop: of diarrhea were 21% over the 40 weight, the overall discontinuation rate was approximately 46%. There was no single reason contributing to the additional discontinuations, and this rate is not on
Speaker 3: we've hired a highly seasoned commercial leadership team with significant experience in rare disease to build out a field force sized to address this relatively concentrated HCP audience.
Speaker 3: And the third critical launch priority is continuing to develop best in class support services for patients and their families and to leverage the strong support we have in the red community.
Kathie M. Bishop: is not uncommon when compared to other long-term open-label studies.
Kathie M. Bishop: For context, patients continued and completed Lilac over the span of several years. GI management plans were only added towards the end of the study, and this would
Speaker 3: At the center of this support is our hub, Acadia Connect. Here we've developed comprehensive resources that will soon provide patients, caregivers, and HCPs with the extensive support they need. Our people are at the center of our service model, including our field-based family access managers, as well as on-call pharmacists and nurse care professionals.
Kathie M. Bishop: And this would not make much of a difference in the overall data collected. However, discontinuations did decrease the longer patients stayed on therapy.
Kathie M. Bishop: This is further evidenced by a much smaller discontinuation rate in the ongoing Lilac II extension, and notably, so far in Lilac II, we have had no discontinuations due to dire.
Brendan: I'll now turn it back to Brendan to outline our launch in more detail.
Speaker 3: investing in 24-7 support to ensure every patient journey on to be a benefit if the best it can be from day one. We are in great shape to launch and we are eager to get to March 12. And with that, I'll turn it over to Doug Williamson, our newly appointed head of R&D. Doug?
Brendan: Thank you, Kathy. Please turn to slide 22.
Brendan: We're very excited to be on the verge of potentially bringing the first ever treatment of RET syndrome to patients, families, and healthcare professionals looking for novel solutions. As you would expect, we're making significant investments and progress in preparing for the successful launch of Provinatide. Let me break down our priorities to three areas of focus: disease awareness, patient identification, and ongoing support. Our first priority is to drive disease state awareness and education about the core symptoms of rheumatoid arthritis.
Speaker 6: Thank you, Brendan. Please turn to slide 24. I'd like to begin by just taking a moment to introduce myself before sharing some thoughts on Acadia's R&D programs and some of the exciting potential we have in front of us. I'm a psychiatrist by training and following a few years spent in clinical practice and academic research, I've spent almost 30 years in neuroscience drug development in both I'm a nurse, who can be my best friend.
Brendan: An important part of the foundation we're laying now is continuing to build the awareness of the core symptoms of RET so that physicians and caregivers are better equipped to recognize the unique benefits Trafinitide stands poised to deliver. It is equally important to educate HCPs and caregivers on the potential therapeutic value of Trinatide and to set up the right expectations for both efficacy and tolerability to ensure patients receive the full, long-term benefits of treatment.
Speaker 6: in contrast to other antipsychotics which target dopamine and other receptors. And this has provided a safe and effective treatment for tens of thousands of families affected by Parkinson's disease psychosis.
Brendan: Our second priority is to fully characterize the identified 4,500 patients who are currently diagnosed in the United States. RET patients are primarily cared for in three principal treatment settings. About 25% of patients are treated in Centers of Excellence, as designated by the RET Patient Advocacy Foundation. There are currently 22 centers of excellence, with more that are in the process of receiving the designation. Beyond these COEs, a significant majority of current rep patients are cared for at other large institutions, including academic hospitals. And finally, there are a small percentage of patients cared for out in the community setting in standalone neurology offices not associated with the hospital.
Speaker 6: Tofenotide, meanwhile, is poised to potentially become the first and only therapy approved to treat Rett syndrome, as well as being Acadia's second commercial product. Neuroscience drug development is full of unique challenges. We're still a long way from understanding the brain, as well as we're beginning to understand the rest of the body. But the unmet need and the cost to society of brain disorders is huge.
Speaker 6: and it will require focus and persistence to achieve success.
Speaker 6: One of the main reasons I joined Acadia is because we have consistently demonstrated those qualities throughout the company's history.
Speaker 6: Beyond PDP and REV syndrome, I'm very excited to help lead the development of two other areas of significant unmet need, our negative symptoms of schizophrenia and Alzheimer's disease psychosis programs. Let's continue with the negative symptoms program on slide 25.
Speaker 6: Persistent negative symptoms remain one of the largest unmet needs in schizophrenia, and as of today, there are still no approved treatments for these symptoms. Once the acute psychotic symptoms have been controlled, it is the crippling lack of motivation, no energy, social withdrawal, and blunted mood.
Brendan: In preparation for the launch of Trufinitide, we've hired a highly seasoned commercial leadership team with significant experience in rare disease to build out a field force to address this relatively concentrated HCP audience. And the third critical launch priority is continuing to develop best-in-class support services for patients and their families and to leverage the strong support we have in the WREC community. At the center of this support is our hub, Acadia Connect.
Speaker 6: which prevent those living with schizophrenia from returning to the relationships, employment opportunities, and quality of life which we often take for granted. Unable to care for themselves, the burden of looking after them often passes to the caregivers instead. We are evaluating Pilvanzrin for the estimated 700,000 people living with schizophrenia in the US today, whose positive symptoms are adequately controlled on currently available antipsychotics, but who continue to experience predominant negative symptoms.
Brendan: Here, we've developed comprehensive resources that will soon provide patients, caregivers, and HCPs with extensive support. Our people are at the center of our service model, including our field-based family access managers, as well as on-call pharmacists and nurse care coordinators at our hub. These team members will be educating caregivers and families on the benefits they should observe with treatment, as well as appropriate implementation of our GI management plan. To ensure we are the best partners we can be to the RET community, we are investing in 24-7 support to ensure every patient journey on Troufinetide is the best it can be from day one. We are in great shape to launch, and we are eager to get to March 12th. And with that, I'll turn it over to Doug Williamson, our newly appointed head of R&D. Doug?
Speaker 6: We believe that Pym of answering as a negative treatment has the potential to alleviate negative symptoms and enable them to take that next step to a more fulfilling life.
Speaker 6: Slide 26. As Steve mentioned earlier, as part of our development program, we have one positive physical study, advance 1. Our next study, advance 2, had an important modification.
Speaker 6: The Advanced 1 study included some dose ranging, and while we achieved the primary endpoint, we clearly observed more robust results in patients who took the 34mg dose, as shown on the slide.
Speaker 6: Note that this is the same commercially available dose which demonstrated the strongest efficacy for PDP. Advance 2 is now close to completing enrollment, which should occur around mid-year. If all continues to go well, we should have top-line results in early 2024, and we look forward to keeping you updated on our progress. Now let's discuss our ACP-204 program.
Douglas J. Williamson: Thank you, Brendan. Please turn to slide 24.
Douglas J. Williamson: I'd like to begin by just taking a moment to introduce myself before sharing some thoughts on KDS R&D programs and some of the exciting potential we have in front of us. I'm a psychiatrist by training, and following a few years spent in clinical practice and academic research, I've spent almost 30 years in neuroscience drug development in both large and small pharma,
Speaker 6: to optimize the efficacy potential, while also reducing the risk of QT prolongation, and all with a potentially faster onset of action.
Douglas J. Williamson: span all phases of clinical development and medical affairs.
Douglas J. Williamson: We've already discussed plazas and troughenotides, so I won't spend too much time. But I would like to reiterate the importance of these two drugs. Neufrazid selectivity for the 5HT2A receptor represents an important and differentiating feature.
Speaker 6: We're currently finalizing our phase 1 work, and once complete, we will engage the FDA on a potential development plan for ACP204 as a treatment for Alzheimer's disease psychosis. Following discussion with the FDA, we plan to initiate phase 2 trials in patients with ADP later this year. We anticipate being able to leverage our familiarity with this class of compounds to be aggressive in late stage development.
Douglas J. Williamson: differentiated approach to antipsychotic treatment, in contrast to other antipsychotics which target dopamine and other receptors.
Douglas J. Williamson: And this has provided safe and effective treatment for tens of thousands of families.
Speaker 6: but it will still be very important to appropriately characterize the pharmacology of this novel asset prior to entering Phase 3. With that, I'll turn it over to Steve for closing remarks. Thanks much, Doug. Please turn to slide 29. I'd like to end today's prepared remarks with a slide outlining our key development milestones. First, our upcoming PDUFA for Trufina's dad is just two weeks away.
Douglas J. Williamson: of families affected by Parkinson's disease psychosis. Tracetide, meanwhile, is poised to potentially become the first and only therapy approved to treat LET syndrome, as long as it is KG's second commercial product.
Speaker 3: Second, we should complete enrollment in our second pivotal study for the negative symptoms of schizophrenia around the middle of the year with top-line results expected in early 2024. And we plan on advancing ACP-204 into ADP patient paralysis later this year. And finally, given the cash flows from our PDP franchise and our strong cash balance, we have the ability to execute our current operating plan.
Douglas J. Williamson: Neuroscience drug development is full of unique challenges. We're still a long way from understanding the brain, as well as we're beginning to understand the rest of the body. But the unmet need and the cost to society of brain disorders are huge.
Douglas J. Williamson: and it will require focus and persistence to achieve success. One of the main reasons I joined Acadia is because we have consistently demonstrated those qualities throughout the company's history. Beyond PDP and RET syndrome, I'm very excited to help lead the development of two other areas of significant unmet need, our negative symptoms of schizophrenia and Alzheimer's disease psychosis program.
Speaker 2: without the need to raise additional capital. As always, I would like to thank our employees for their accomplishments and their ongoing commitment and passion as we continue our mission to elevate lives. And with that, I'll now turn things back over to the operator for Q&A. Ladies and gentlemen, if you wish to ask a question, please press star 1 1 on your touchstone telephone. If your question has been answered or you wish to withdraw your question, please press star 1 1 again.
Douglas J. Williamson: Let's continue with the Negative Symptoms Program on slide 25.
Douglas J. Williamson: Persistent negative symptoms remain one of the largest unmet,
Douglas J. Williamson: unmet needs in schizophrenia. And as of today, there are still no approved treatments for these symptoms.
Douglas J. Williamson: Once the acute psychotic symptoms have been controlled, it is the crippling lack of motivation, low energy, social withdrawal, and blunted mood that is most noticeable.
Douglas J. Williamson: those living with schizophrenia from returning to the relationships, employment opportunities, and quality of life which we often take for granted; unable to care for themselves, the burden of looking after them often passes.
Speaker 2: a little bit more on the Diary and Management Plan that you alluded to in the Appedia Connect program. I guess it's what the Nurse Care Coordinator and on-call pharmacists will help manage. It can you describe what you're going to recommend to the support and then.
Douglas J. Williamson: to the caregivers instead. We are evaluating Pilvancerin for the estimated 700,000 people living with schizophrenia in the U.S. today, whose positive symptoms are adequately controlled on currently available antipsychotics, but who continue to experience predominant negative symptoms.
Speaker 2: Do you think that your assumptions for diarrhea discontinuation rate will resemble what you've featured today in LILAC? Thanks. Yeah, thanks much for the question. I'm going to to ask Brendan to answer your question as it relates to the activities that we've...
Douglas J. Williamson: We believe that Pimavansarin as an adjunctive treatment has the potential to alleviate negative symptoms.
Speaker 3: stood up in terms of how we will offer very comprehensive care and support to patients and their families. And then we'll take the very last part of your question.
Douglas J. Williamson: and enable them to take that next step to a more fulfilling life. Slide 26. As Steve mentioned earlier, as part of our development program,
Speaker 3: Sure, thanks for the question. As we said in our prepared remarks, we are building our caregiver and patient support around our hub, also known as Acadia Connect. This is intended to provide comprehensive end-to-end support to both caregivers and patients. It's critical to do that to help patients not only start, but stay on track.
Douglas J. Williamson: In the program, we have one positive principal study, Advance 1.
Douglas J. Williamson: Our next study, advanced two, had an important modification.
Douglas J. Williamson: The Advanced One study included some dose ranging, and while we achieved the primary endpoint, we clearly observed more robust results in patients who took the 34 milligram dose, as shown on the slide. Note that this is the same commercially available dose which demonstrated the strongest efficacy for PDP.
Douglas J. Williamson: Advance 2 is now close to completing enrollment, which should occur around mid-year. Paul continues
Speaker 3: with families as they start and then begin to stay on for phenytoid.
Douglas J. Williamson: If all continues to go well, we should have top-line results in early 2024, and we look forward to keeping you updated on our progress. Now, let's discuss our ACP 204 program. ACP 204 is a novel molecule, but one which is designed to build on our experience with Penramp. With ACP 204, we may have an opportunity to optimize the efficacy potential while also reducing the risk of QT prolongation, and all with a potentially faster onset of action. We're currently finalizing our phase one work.
Speaker 2: Great. Thanks, Brennan. In response to the last part of your question regarding diarrhea, dyscontinuation rates, I think, you know, with any drug, sometimes there can be differences between what you see in clinical studies and what you see in verbal practice.
Speaker 3: And I think the way I would think about this, and as we said very consistently, with drugs that have symptomatic relief on subjective endpoints, you will have a certain amount of discontinuations in the early months of therapy.
Speaker 2: We see that in neuropsychiatry a lot. We see that with compliancy. And so you'll see that. I would think of this population in two components. One is the prevalent population. So there's the sizable prevalent population that we will access the drug first. We'll work through that population. And then there's an incident population.
Douglas J. Williamson: And once complete, we will engage the FDA on a potential development plan for
Douglas J. Williamson: Development Plan for ACP 204 as a treatment for Alzheimer's Disease Psychosis. Following discussions with the FDA, we plan to initiate phase two trials in patients with ADP later this year. We anticipate being able to leverage our familiarity with this class of compounds to be aggressive in late-stage development, but it will still be very important to appropriately characterize the pharmacology of this novel asset prior to entering phase three.
Speaker 7: beyond that. And so as we think about the dynamics of this molecule, we recognize that there's, it's a very, very highly debilitating disease. There's no approved therapy. The...
the benefits that we see which are fin and tied offer hope for the first time to these families. And so I think there will be a high motivation to access the therapy. And then what we anticipate over time is as it worked through their prevalent population and the early months of therapy where we have a lot of patients going through that simultaneously.
Stephen R. Davis: With that, I'll turn it over to Steve for closing the mark. Thank you much, Doug. Please turn to slide 29. I'd like to end today's prepared remarks with a slide outlining our key development milestones. First, our upcoming Fedufa for Trinathad is just two weeks away. Second, we should complete enrollment in our second pivotal study for the negative symptoms of schizophrenia around the middle of the year, with top-line results expected in early 2024.
then the discontinuation rates will flat-mount and settle into much more normal cycles. So I hope that's helpful. Thank you. One moment for our next question. Our next question comes from the line of tests Romero from JP Morgan. Hey guys, thanks so much for taking our question.
Stephen R. Davis: And we plan on advancing ACP 204 into ADP patient trials later this year. And finally, given the cash flows from our PDP franchise and our strong cash balance, we have the ability to execute our current operating plan without the need to raise additional cash costs. As always, I would like to thank our employees for their accomplishments and their ongoing commitment and passion, as we continue our mission to improve. And with that, I'll now turn things back over to the operator for Q&A.
So just one for my son, Trifinatide. So can you just remind us, in your prepared remarks, you talked a little bit about your healthcare practitioner audience here. How do these different practices from your centers of excellence to your academic hospitals, to your community centers, compare on average with respect to number of rep patients treated, physician awareness of Trifinatide, or any other kind of key distinguishings?
Operator: Ladies and gentlemen, if you wish to ask a question, please press star 1-1 on your touchtone telephone. If your question has been answered or you wish to withdraw your question, please press star 1-1 again. Please limit yourself to one question. I repeat, please limit yourself to one question. Press Star 1 to begin. Please stand by for your first question. Our first question comes from the line of Ritu Baral from Cowan.
Ritu Subhalaksmi Baral: Good afternoon, guys. Thanks for taking the question. On Tresanetide, can you elaborate just a little bit more on the diarrhea management plan that you alluded to in the Acadia Connect program?
to the thousands. We've already identified the 4,500 or so already diagnosed and cared for patients in the United States. So from that perspective we don't see finding where to locate our patients as rate limiting. When you think in terms of both the prescribing community and where we're going to find those patients they do as you pointed out break into three principal groups.
unknown: I guess that's what the nurse care coordinators and on-call pharmacists will help.
unknown: will help manage. Can you describe what you're going to recommend for support, and then do you think that your assumptions are correct?
unknown: for diarrhea, the discontinuation rate will resemble what you featured today in Lime.
unknown: featured today in Lilac.
Stephen R. Davis: Yeah, thanks much for the question, me too. I'm going to ask Brendan to answer your question as it relates to the activities that we have planned in terms of how we will offer very comprehensive care and support to patients and their families, and then we'll take the very last part here. Sure, thanks.
The first would be those centers of excellence of which there are 22 currently designated and there are roughly 25% of the Rett population treated in those centers. The vast majority of patients are then treated at high volume institutions, principally academic centers and children's hospitals with strong neuroscience capabilities. And then there's a smaller percentage of patients that are treated at individual neurology practices. So that's principally how the audience breaks down.
Brendan: As we said in our prepared remarks, we are building our caregiver and patient support around our hub, also known as Acadia Connect. This is intended to provide comprehensive end-end support to both caregivers and patients, and it's critical to do that to help patients not only start but stay on therapy and ensure the optimal treatment experience. We will also have 24-7 clinical pharmacists, clinical nurse coordinators at the hub, and then in the field, we're supplementing that with Family Access Coordinators, Family Access managers that are intended to be face-to-face with families as they start and then begin to stay on for phenotype.
families with patients that are on the younger end of the spectrum. So I wouldn't be surprised if we skew towards younger patients and younger families in the early days for treatment.
Stephen R. Davis: Great, thanks, Brent. In response to the last part of your question regarding diarrhea discontinuation rates, I think, you know, with any drug, sometimes there can be differences between what you see in clinical studies and what you see in real world practice. And I think the way I would think about this, and as we have said very consistently, with drugs that have symptomatic relief on subjective endpoints, you will have a certain amount of discontinuations in the early months of therapy. We see that in neuropsychiatry a lot. We see that with new planes it.
Also, with the volumes that we're seeing at Centers of Excellence and at these high-volume institutions, that's where we principally expect the majority of patients to be given the opportunity to be treated with Trofinitide in the early days. That is, I think, important to be...it's important to understand that while there is...
Stephen R. Davis: And so you'll see that. I would think of this population in two components. One is the prevalent population. So there's a sizable prevalent population that we will, that will access the drug first. We'll work through that population. And then there's an incident population beyond that. And so as we think about the dynamics of this molecule, we recognize that there is a very, very highly debilitating disease.
Our next question comes from the line of Mark Goodman from SVB Laring. Just as a follow-up on these 4,500 diagnosed and cared for patients, that number seems to be the same number that you all have been using for, I don't know, the past year or so. I was just curious...
Stephen R. Davis: There's no approved therapy, and the benefits that we see with Trinotide offer hope for the first time to these families. And so I think there'll be a high motivation to access therapy. And then what we anticipate over time is that as we work through their prevalent population, the early months of therapy when we have a lot of patients going through that simultaneously, then the discontinuation rates will settle in, will flatten out, and settle into a much more normal cycle. So I hope that's helpful. Now we'll go to the next question.
I've kind of made a turn here. Thanks. Sure, thanks for both questions, Mark. Brendan, do you want to take each of these? Sure, and thanks for the question.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Tess Romero from J.P. Morgan.
We have access to databases so we're able to track, diagnose, and treat patients with Rett. As mentioned in the prepared remarks, there's a prevalent population of six to nine thousand and it is not uncommon after the introduction of a first to market therapy that...
Tessa Thomas Romero: Hey guys, thanks so much for taking our question. So, just one from us on Trinatide.
Tessa Thomas Romero: So can you just remind us, in your prepared remarks, you talked a little bit about your healthcare practitioner audience here. How do these different practices from your Centers of Excellence to your academic hospitals to your community centers compare on average with respect to the number of RET patients treated, physician awareness of troughinatide, or any other kind of key distinguishing characteristics we should be thinking about? Thanks so much.
the claims databases available to us while there is an incident population that will be introduced over time. It's still roughly in the 4,500 or so range for those diagnosed and treated in the United States.
Stephen R. Davis: Yeah, thanks much for the question. Brendan, do you want to take that?
Brendan: Sure, thanks for the question. Many times, with a rare disease, you'd expect it to be a little challenging depending on where you find your patients. We do not see that in the RET community. This is a well-organized group with advocacy groups that have membership lists well into the thousands. We've already identified the 4,500 or so already diagnosed and cared for patients in the United States. So from that perspective, we don't see finding where to locate our patients as rate-limiting.
The separate question you had refers to New Plaza in LTC. And I think we are encouraged by the early signs we've seen on two fronts. One, we know that the long-term care portion of the market had a more profound drop as a function of the pandemic.
frankly patients residents passed away and we saw that trough in the middle of 2021 from which we've seen a steady increase in census over time, slow but steady, and that's been driven by new resident, new residents entering long-term care facilities. The reason that's so important to New Plaza is that is the time where the science...
Brendan: When you think in terms of both the prescribing community and where we're going to find those RIP patients, they do, as you pointed out, break into three principal groups. The first would be those centers of excellence, of which there are 22 currently designated, and roughly 25% of the RET population is treated in those centers. The vast majority of patients are then treated at high volume institutions, principally academic centers and children's hospitals with strong neuroscience capabilities. And then there is a smaller percentage of patients that are treated at individual neurology practices. So that's principally how the audience breaks.
unknown: Do you expect the kind of cadence of patients starting treatment to be different, dependent on the type of practice, just as a quick follow-up?
other studies that are being introduced in the community setting have provided a strong basis for why New Plasid is a logical choice in the first line setting for those residents. The two of those coupled to create our highest bottle volume in long-term care since Steve noted the fourth quarter of 2019 the highest we've had in the history of...
Brendan: A fair question, a couple of things. I think we would expect, given the results of the Lavender Program, that we would see a motivated group of families with patients that are on the younger end of the spectrum. So I wouldn't be surprised if we skew towards younger patients and younger families in the early days of treatment. Also, with the volumes that we're seeing at Centers of Excellence and at these high-volume institutions, that's where we principally expect the majority of patients to be given the opportunity to be treated with troughinotide in the early days.
for long-term care. I think that it's fair to say that that segment has led the way. When we look at the in-office setting, we still see in-person patient visits down double digits. So using the same logic, the challenge there is physicians really want to see a patient face-to-face if they're going to.
Brendan: That is, I think, important to be; it's important to understand that while there is high interest in treatment, we will still be working through access with each of the payer organizations and the logistics of families simply getting to these facilities to have an opportunity to be treated.
prescribed branded therapy. So we're encouraged that in-patient or in-office visits are dominant and we're not seeing much telemedicine anymore. We would just like to see the frequency of those visits increase. I hope that's helpful. Thank you. One moment for our next question.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Mark Goodman from SVB Layering.
Marc Harold Goodman: Just as a follow-up on these 4,500 diagnosed and cared for patients, that number seems to be the same number that you all have been using for, I don't know, the past year or so. I was just curious, as you've kind of dug into this market, is that just a number that you're just using conservatively, or are you finding more patients? It just seems like
Our next question comes from the line of Tezin Ahmad from Bank of America, Merrill Lynch. Okay. Hi, guys. Maybe another Tracenotyce question or two from me. How should we be thinking about the initial days of uptake? So, you've got patients identified, but for meaningful uptake, do you think you're going to need a J code? Yes, I do. I'm going to need a J code.
Marc Harold Goodman: Just as a follow-up on these 4,500 diagnosed and cared for patients, that number seems to be the same number that y'all have been using for, I don't know, the past year or so. I was just curious, as you've kind of dug into this market, is that just a number that you're just using conservatively, or are you finding more patients? And it just seems like, you know, as you look back over the past years, I would have, have, you know, kind of made a turn here.
or because of the rare nature of the disease and lack of any therapies, that won't matter. And then secondly, I know you'll be announcing pricing at the time of approval, but what's the appropriate range that we should be thinking about for modeling purposes as we get closer? Thanks. Yeah, thanks much. Brendan, do you want to take these questions? Sure. So, thanks for the question, Tizine. In terms of the early days of launch, let's be clear, we definitely want to establish the phenotype as the foundational treatment for...
Stephen R. Davis: Thanks. Yeah, sure. Thanks for both questions, Mark. Brendan, do you want to take each of these?
Brendan: Sure, and thanks for the question. We have access to databases, so we're able to track diagnosed and treated patients with RET. As mentioned in the prepared remarks, there is a prevalent population of 6 to 9,000, and it is not uncommon after the introduction of a first-to-market therapy that there could be an increase in diagnosis rates, particularly in older patients who may have been clinical. diagnosed earlier on in life but for which there hasn't been perhaps a confirmatory genetic test. Other than that, using the claims databases available to us, while there is an incident population that will be introduced over time, still roughly in the 4,500 or so range for those diagnosed and treated in the United States.
counterbalancing. We know there will be a high interest in prescribing the drug. We know that payers have proven receptive to letters of medical exception and an opportunity to get patients started, perhaps before they've made a coverage decision.
but we still expect there to be a linear shaped uptake curve. Unlike some other rare diseases where there might be an early access program where you might create a bolus of patients.
Brendan: The separate question you had refers to New Plaza and LTC, and I think we are encouraged by the early signs we've seen on two fronts. One, we know that the long-term care portion of the market had a more profound drop as a function of the pandemic; frankly, residents passed away, and we saw that trough in the middle of 2021, from which we've seen a steady increase in census over time, slow but steady, and that's been driven by new residents entering long-term care facilities.
That's not really what we had here. As Kathy described, there is an open-label extension in Lilac 2, and we do expect the majority of those patients to transition over to commercial drug, but that's going to be a function of and subject to their individual payer access timelines by geography.
I think your second question was around pricing. So we're not going to disclose pricing before approval.
to level set we can add a little bit of context. With rare disease therapies there tends to be, you know, an established range of prices and there are several elements that tend to contribute to where products tend to price. The first is the severity of the disease. The second is the level of unmet medical need and the ability of a product to address those needs. And then the third is record number of spread.
Brendan: The reason that's so important to New Plaza is that it's the time when the signs and symptoms of Parkinson's disease psychosis are identified. It's a great opportunity for New Plasid to be chosen as a treatment. That sort of dynamic, coupled with the fact that we had the real-world evidence from the Kumar-At-All study in the second half of 2022, and that really preceded some of the other studies that are being introduced in the community setting, has provided a strong basis for why New Plaza is a logical choice in the first line setting for those residents.
Brendan: The two of those coupled to create our highest bottle volume in long-term care since, as Steve noted, the fourth quarter of 2019, the highest we've had in the history of long-term care. I think that it's fair to say that that segment has led the way.
care to patients. The unmet medical need is equally high here with no approved therapies available to address the core neurodevelopmental symptoms of Rett syndrome, creating a critical void that needs to be filled. Given the robust response seen in our phase three studies 1e2,
Brendan: When we look at the in-office setting, we still see in-person patient visits down double digits. So using the same logic, the challenge there is that physicians really want to see a patient face-to-face if they're going to prescribe a branded therapy. So we're encouraged that in-patient or in-office visits are, um, are, um, dominant, and we're not seeing much telemedicine anymore. We would just like to see the frequency of those visits increase.
it is potentially poised to address that unmet need. And then finally, there is the relatively small prevalent population estimated at six to 9,000 in the United States with the 4,500 or so currently diagnosed and treated patients. So with that background, I think you should expect us to price Trufinitide as the first and only therapy poised to address that high level of unmet need.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Tazine Ahmad from Bank of America in Maryland. Okay, hi guys.
and to ensure broad access for patients and families who stand to benefit from treatment. Thank you. One moment for our next question. Our next question comes from the line of Charles Duncan from Cantor Fitzgerald. Yes, good afternoon. Thank you for sharing the Lilac information that you did today. I guess I'm on...
Tazeen Ahmad: Okay, hi guys, maybe another Tricana-type question or two from me. How should we be thinking about the initial days of uptake? So you've got patients identified, but for meaningful uptake, do you think you're going to need a J-code, or because of the rare nature of the disease and lack of any therapies, that won't matter? And then, secondly, I know you'll be announcing pricing at the time of approval, but what's the appropriate range that we should be thinking about for modeling purposes as we get closer?
Stephen R. Davis: Yeah, thanks a lot. Brendan, do you want to take these questions?
Brendan: So thanks for the question to Zine. In terms of the early days of launch, let's be clear, we definitely want to establish Trafinitide as the foundational treatment for the treatment of RET syndrome, and we will be working from the outset to ensure access. If you look at other rare disease launches, you'll see that there tends to be high demand, but that's mitigated by some of the logistical issues that one would handle, particularly access, the second being the time it takes for patients to get to their appropriate physicians. So for us, those are counterbalancing.
Hi, Charles. Thanks for the question. With regards to the pattern of disinclination, can you guys Teaable techniques.
due to diarrhea associated with your phenotides. I will say that the pattern discontinuations in lilac was very similar to that in lavender in that we have a very similar discontinuation rate within about the first three months and then a smaller rate after that. And as I mentioned on the call.
In the subsequent study, Lyla 2, we have a very low discontinuation rate and none due to diarrhea to date. So one pattern that emerges from this is that the longer you're on traphinitide, the longer you're able to stay on it. As I mentioned, it's also notable, though, that in the early years of these trials, because they did extend over several years.
Brendan: We know there will be a high interest in prescribing the drug. We know that payers have proven receptive to letters of medical exception and an opportunity to get patients started, perhaps before they've made a coverage decision. But we still expect there to be a linear-shaped uptake curve.
we did not have the diarrhea management plan in place. So, as we think ahead to launch, we are instituting that plan, and Brendan is prepared to provide many resources to caregivers and the patients to manage the diarrhea to be able to keep them on drug. Yeah, I think, Charles, our standard response when we're in registration is not to comment on back and forth. We have with the agency, but I simply say that, you know, they've been very engaged. We're eager to get to our pepidufa, Dave, but we don't comment on things otherwise. There's one important contextual point I just want to mention in terms of diarrhea. I know we've said it before. It's a really important point, though.
Brendan: Unlike some other rare diseases where there might be an early access program where you might create a bolus of patients, That's not really what we had here. As Kathy described, there is an open label extension and Lilac 2, and we do expect the majority of those patients to transition over to the commercial drug, but that's going to be a function of and subject to their individual payer access timelines by geography. I think your second question was around pricing. So we're not going to disclose pricing before approval. To level the playing field, we can add a little bit of context.
Red patients on average have about 80% of them have significant constipation. And it can get quite severe. It can lead to impaction, hospitalization. There have even been a few reported cases of death due to sepsis associated with constipation and impaction. So this is very top of mind in the Rett community with physicians as well as caregivers.
Brendan: With rare disease therapies, there tends to be, you know, an established range of prices, and there are several elements that tend to contribute to where products tend to price. The first is the severity of the disease. The second is the level of unmet medical need and the ability of a product to address those needs. And then third is the relative rarity of the disease itself. So if we're thinking about RET syndrome in particular and then the value of trophenotide, RET syndrome is a very devastating disease.
And so in some respects, the diarrhea effect that we see with Trefenatide can be somewhat of a trade-off. And you also have a situation where almost all of these patients wear diaper-type garments their entire life. And so just some additional context around that, and as Kathy mentioned, a lot of the diarrhea management, mitigation regimen steps that we took late in, or that we developed late in the lavender study, by that time, significant majority of patients in Lilac had already completed that 40-week.
Brendan: It causes substantial disability to patients, and it disrupts the lives of families and caregivers, who provide essentially around-the-clock care to patients. The unmet medical need is equally high here, with no approved therapies available to address the core neurodevelopmental symptoms of RET syndrome, creating a critical void that needs to be filled. Given the robust response seen in our phase three studies for Trinotide, it is potentially poised to address that unmet need. And then finally, there is the relatively small prevalent population estimated at 6 to 9,000 in the United States with 4,500 or so currently diagnosed and treated patients.
program as well. So we're very eager to get to the finish line here and as Brenda described here we have a lot of resources that we'll put it that we'll we'll bring to bear to help families manage the tolerability of the tide which we think is.
significantly outweighed by the significant benefits that we see, which we see continuing sustained and continuing to grow through the LILAC study. Thanks, Steve, Kathy. Thank you. One moment for our next
Brendan: So with that background, I think you should expect us to price Trinotide as the first and only therapy poised to address that high level of unmet need and to ensure broad access for patients and families who stand to benefit from treatment.
Our next question comes from the line of Nina from Citi. Thanks for taking my question. Just to follow up on the last question on the impact of diarrhea on discontinuation, I'm curious if you can comment on what happened when you did implement the diarrhea management program in the Lilac.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Charles Duncan from Cantor Fitzgerald.
Charles Cliff Duncan: Kathy, do you want to take that question?
Kathie M. Bishop: Hi Charles, thanks for the question. With regard to the pattern of distant joint condition, due to the phonetize, due to diarrhea associated with trifinotide. I will say that the pattern of discontinuations in Lilac was very similar to that 11 in that we had a very similar discontinuation rate within about the first three months and then a smaller rate after that. And as I mentioned on the call, in the subsequent study Lilac 2, we have a very low discontinuation rate and none due to diarrhea to date. So one pattern that emerges from this is that the longer you're on affinitide, the longer you're able to stay on. As I mentioned, it is also notable, though, that in the
Open Label Extension Study, did you see that patients who were maybe earlier in the OLE did have a lower discontinuation rate? I'm just trying to contextualize how to think about the impact of the diarrhea management on the discontinuation rate. Thanks.
Yes, thanks for the question. So as we implemented the diarrhea management plan, which as Steve mentioned, it's really important to keep into context that 80% of these patients have constipation, which can be very severe. The first step in the plan is to stop taking your anti-constipation medications.
Stephen R. Davis: During the years of these trials, because they did extend over several years, we did not have the diarrhea management plan in place. So as we think ahead to launch, we are instituting that plan, and Brendan's is prepared to provide many resources to caregivers and patients to manage the diarrhea to be able to keep them on drugs. Um, Oh, yeah, I think Charles' standard response when we're in registration is not to comment on the back and forth we have with the agency but, you know, to simply say that they've been very engaged, we're eager to get through our Budufidavit, but we don't comment on things otherwise. There's one important contextual point I just want to mention in terms of diarrhea. I know we've said it before, but it's a really important point, though.
by the caregivers and the physicians and the trial. We certainly hear a feedback that those steps are helping to control the diarrhea and later on in the trial keep patients on drip and it died.
I should also add, as we're talking about diarrhea, remember that the diarrhea is almost all mild or moderate in nature and is not a safety concern. It does not lead to dehydration, does not lead to weight loss, does not lead to hospitalizations. So this is really a management issue. And through the trials and working with some of the study nurses and clinicians, we have
Stephen R. Davis: Red patients, on average, about 80% of them have significant constipation, and it can get quite severe. It can lead to impaction, hospitalization, and there have even been a few reported cases of death through sepsis associated with constipation and impact. So this is very top of mine in the recreational community with physicians as well as care providers. And so, in some respects, the diarrhea effect that we see with troughinotide can be somewhat of a trade-off.
Our next question comes from the line of Yatin Sunneha from Guggenheim Partners.
Hey, this is Eddie on free out and congrats on the quarter. Do you expect any impact on the trip in a tide filing or review now that Billy Dunn has departed and do you expect to have any restrictions or limitations on the label or have to complete any post marketing studies after potential approval? Thanks. Yeah, I'll take the first part of that. We don't anticipate any impact from Billy Dunn leaving FDA.
Stephen R. Davis: And you also have a situation where almost all of these ret patients wear diaper-type garments their entire life. And so, just some additional context around that. And as Kathy mentioned, a lot of the diarrhea management, mediation regimen steps that we took late in, or that we developed late in, the Lavender study; by that time, a significant majority of patients in Lailak had already been, had already completed that 40-week program as well.
We, as you might expect, we reached out to FDA today, heard back from them. They expressly confirmed that we should not have any impact on our application. Dr. Baraccio has been acting deputy director of the Office of Neuroscience for some time and will continue that role as well as the director of the Neurology I Division. So understand that.
reason for asking the question, but we don't think it'll have any impact on our application. And second part of the question with respect to, I think you talked about post marketing requirements and labeling. Since we're under review, we don't comment on that at this point. Do you think you could clarify how many Lilac 2 patients you currently have on drugs? Yeah, so the Lilac 2 study is currently ongoing. So at this time we can't get into any of the general comments or whatever they came up with.
Stephen R. Davis: So we're very eager to get to the finish line here, and as Brendan described here, we have a lot of resources that will be put to bear to help families manage the tolerability of the phenotype, which we think is significantly outweighed by the significant benefits that we see, which we see continuing to sustain and continuing to grow through the Lileaks.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Nina Betrido Garg from City.
Neena Marie Bitritto: Hey guys, thanks for taking my questions.
Neena Marie Bitritto: Just to follow up on the last question on the impact of diarrhea on discontinuations, I'm just curious if you could comment on what happened when you did implement the Diarrhea Management Program at the Lilac Open Label Extension Center.
Great, thanks Steve and congrats on the progress and thanks for taking my question. Steve, maybe just a question on perhaps longer term or even post the March PDUFA for Trifinitide. Just on the premise of a potential Trifinitide approval and it entering the market, how does that shape your prioritization of your pipeline and maybe looking externally?
Neena Marie Bitritto: study, Did you see that patients who were maybe early
Neena Marie Bitritto: in the OLE did have a lower discontinuation rate. I'm just trying to contextualize how to think about
Neena Marie Bitritto: contextualize how to think about the impact of diarrhea management on the discontinuation rate
Kathie M. Bishop: Yes, thanks for the question. So, we implemented the diarrhea management plan, which, as Steve mentioned, is really important to keep up.
Kathie M. Bishop: into contacts that 80% of these patients have constipation, which can be very severe.
Greg, I'm sorry, I didn't hear the, I heard the first part relating to what impact we have on our portfolio.
Kathie M. Bishop: The first step in the plan is to stop taking your anti-constipation medications, and many of these patients are on two or three of those. And then to implement anti-daria over-the-counter measures such as an increase in fiber in the diet and over-the-counter low paramed. So as that plan rolled out and then became implemented by the caregiver,
Yeah, just with respect to within your pipeline, the ASO program and how you're thinking about the pipeline and external, how an approval would shape your prioritization and focus there. Thank you. Yeah, okay. Thanks much. So, you know, the short answers of wouldn't.
Kathie M. Bishop: caregivers and the physicians in the trial, we certainly hear feedback that those steps are helping to control the diarrhea and, later on in the trial, keep patients on the dripena diet.
I think that we've always viewed, since we got data from the study of Trufinedad, where we had both co-primary endpoints, recognized a very dramatic unmet need, we have felt like this is a drug that's needed and with a high likelihood of approval. So we plan our business accordingly.
Kathie M. Bishop: I should also add, as we're talking about diarrhea, remember that diarrhea is almost always mild or
Kathie M. Bishop: moderate in nature and is not a safety concern. It does not lead to dehydration, does not lead to weight loss, and does not lead to hospitalizations. So this is really a management issue. And through the trials and working with some of the study nurses
We'll continue, we're very excited about other assets we have, including our early assets, including the programs we have partnered with, the STOKE Therapeutics that you referred to. From a business development perspective, our strategy remains the same as we've discovered for the last couple of years, and that is, it's a very important part of our business.
Kathie M. Bishop: Nurses and clinicians, I think we should put in place steps to help parents better manage it, and that's what we intend to do as we move towards hopeful commercialization.
As we've described in the most recent quarters, the fluctuations in the capital markets have significantly impacted business development opportunity set. And that really works to the advantage of companies like us, companies that have strong balance sheets, established revenues, and don't need to go back to the capital markets versus those that do. And so as a consequence of that, we're seeing opportunities that continue to improve. We're well positioned to leverage them.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Yatine Zuneha from Guggenheim Partners.
Yatin Suneja: Hey, this is Eddie on Friatan. Congratulations on the Quarter. Do you expect any impact on the Trinitide filing or review now that Bailey Dunn has departed? And do you expect to have any restrictions or limitations on the label or have to complete any post-marketing studies after potential approval? Thanks.
Thanks, Steve. Appreciate it. Thank you. One moment for our next question. Our next question comes from the line of Jeff Hung from Morgan Stanley . Thanks for taking my question. Can you share with us some of the recent feedback you've been hearing from your conversations about what you hear from people including your first donation?
Stephen R. Davis: Yeah, yeah, I'll take the first part of that. We don't anticipate any impact from Billy Dunn leaving FDA. We, as you might expect, we reached out the FDA today, heard back from him, they expressly confirmed that we should not have any impact on our application. Dr. Braccio has been acting deputy director of the Office of Neuroscience for some time, and we'll continue with that role as well as the director of the director of the Neuroscience for some time, and we'll continue with that role as well as the director of the, neurology So I understand the reason for asking the question, but we don't think it'll have any impact on our application. And the second part of the question,
conversations, I would say that payers have very logical questions that we're able to address. The first is many many payers simply don't know what Rett syndrome is. We have to describe this as a devastating disease, the fact that it requires around-the-clock support, and dimensionalize it for them from the outset. They are very well aware that your phenytoide would be the only FDA approved drug for treating the
Stephen R. Davis: To, I think you talked about post-marketing requirements and labeling. Since we're under review, we don't have to comment on that at this point. Gotcha.
Stephen R. Davis: Gotcha. Do you think you could clarify how many Lilac 2 patients you currently have on drugs?
Kathie M. Bishop: Yeah, so the Lilac 2 study is currently ongoing, so at this time, we can't get into any further specifications rather than what I mentioned in a prepared remark.
Operator: One moment for our next question. Our next question comes from the line of Gregory Renza from RBC Capital.
Gregory James Renza: Great, thanks Steve and team. Congratulations on the progress, and thanks for taking my question.
come to expect and that this is a very rare and defined patient population.
Gregory James Renza: Steve, maybe just a question on perhaps longer term or even post the March Padufa for Trisinotide, just on the
So given that, we feel confident that we're going to be able to assure access to patients, to appropriate patients and their families if we are lucky enough to have an approval in the near term.
that we feel confident that we're going to be able to assure access to patients, to appropriate patients and their families, if we are lucky enough to have an approval in the near term. Thank you.
Gregory James Renza: Just on the premise of a potential Trifincide approval and entering the market, how does that shape your prioritization of your pipeline and, maybe, looking externally, as you and Brendan certainly mentioned, Trifinitide as foundational to RET patients? I'm curious if you have any input on whether it's the ASO program or others that you think are important to tack on to our... when it comes to serving these patients. Thanks so much.
Thank you. One moment for our next question. Our next question comes from the line of Paul Matias from Stifel. Hi, thanks for taking our question. This is Catherine from PAW. Just on Trifenatide, on the regulatory side, what do you see as the greatest risk to approval at this point, if any? And then on the launch, how are you thinking about the cadence post-approval and how soon after you can expect to start treating patients? Thanks.
Stephen R. Davis: Greg, I'm sorry; I didn't hear this. I heard the first part relating to what impact it would have on our portfolio, but I didn't hear the second part.
Yeah, thanks much for the, for each of your questions. Brittany, you want to take the second question first? Sure. Thanks for the question. As you would expect, we're doing everything that you would expect of a company getting ready to launch a first-in-class product in a rare disease. And we will be ready to go pretty quickly after approval. There are really just a few things from a logistical perspective that take some time. One is the finalization of a label, obviously, because it has lots of implications about product drug availability. Also, training our field force to make sure that they are 100 percent prepared.
Stephen R. Davis: Yeah, just with respect to within your pipeline, the ASO program, and how you're thinking about the pipeline and external, how an approval would shape your prioritization and focus there. Thank you. Okay, okay. Thanks a lot. So, you know, the short answer is it wouldn't.
Stephen R. Davis: I think that, you know, we've always viewed, since we got data from a study with Trinidad where we have both co-primer endpoints, recognized a very dramatic on-met need. We have felt like this is a drug that's needed and with a high lack of approval. So we plan our business accordingly. We'll continue; we're very excited about other assets. we have included our early assets and including the programs we have partnered with Stoke therapeutics, which you, From a business development perspective, our strategy, you know, remains the same as we've described it for the last couple of years, and that is, it's a very important part of our business.
to support the physicians that want to prescribe and the families that want to get started. But other than those simple logistics, we see no other reasons for delay and we know that the community is waiting. Thanks Brendan. I'll take the second part of the question. I think in terms of risks to an approval, I'll start by repeating what we said before and that is, please don't comment on back and forth with the agency. And when we're under review, that's just always been our standing policy. And having said that, as we've said, we're eager to get to March 12th. The FDA, we're very happy with the level of engagement we've had with FDA. And as noted a second ago, they've just confirmed this recently, this morning that.
Stephen R. Davis: As we've described in the most recent quarters, the fluctuations in the capital markets have significantly impacted business development opportunities, and that really works to the advantage of companies like us, companies that have strong balance sheets, established revenues, and don't need to go back to the capital markets versus those that do. And so as a consequence of that, we're seeing opportunities that continue to improve, and we're well positioned to lower them.
Operator: Thank you. One moment for our next question. Our next question comes from Jeff Hung from Morgan Stanley.
Jeff Hung: Thanks for taking my question. Can you share with us some of the recent feedback you've been hearing from your conversations with Ayers? Bennett, is there anything that you found surprising?
Brendan: Yeah, thanks a lot for the question, Brendan. Do you want to take that? Sure, yes, thanks for the question.
of the franchise and whether we could see a reacceleration of growth in 2024? And then second, does your guidance range in 2023 assume kind of improving inpatient volumes and whatnot to take place sometime this year? Thank you.
Brendan: Sure, yes, thanks for the question. Just in context, we have had discussions with payers really since we acquired the program, which dates back over a year at this point. But even in recent conversations, I would say that payers have very logical questions that we were able to address. The first is that many payers simply don't know what RET syndrome is. We have to describe this as a devastating disease, the fact that it requires around-the-clock support, and dimensionize it for them from the outset.
I'll briefly answer the first question. We don't guide beyond the current year, so as we progress this year, we'll continue to offer as much color as we can, if it feels appropriate. Brittany, do you want to take the second part of the question?
Sure, and thanks for the question. When we look at 2023, I think we described in our prepared remarks where we think things are. We do see some improvement in the long-term care channel. We will certainly look to continue to capitalize on that. In the in-office channel, we're focused on market share and new patient starts.
Brendan: They are very well aware that Trophenitide would be the only FDA-approved drug for treating the core symptoms of redness and that it is different than some of the individual symptomatic types of medications that may have preceded it. They're aware now, from our education for phenotides, of the positive benefit risk profile, and understand that this is a rare disease base with a pricing model for products like this that they've come to expect, and that this is a very rare and defined patient population. So given that, we feel confident that we're going to be able to assure access to patients, to appropriate patients and their families, if we are lucky enough to have an approval in the near-tariff.
Operator: Thank you. One moment for our next question. Our next question goes on the line with Paul Matias from Steefel.
Paul Matias: Hi, thanks for taking that question. This is Catherine on behalf of Paul.
in that market dynamic and I believe our guidance reflects that. There are two areas where we could see catalysts for growth.
Paul Matias: Just on the trial front, what do you see as the greatest risk to approval at this point, if any? And then on the launch, how are you thinking about Kaden post-approval and how soon after you can expect to start treating patients?
The first is, if in addition to in office visits being the preferred route for patients to see their clinicians, which we know is the case, we just need to see a frequency there increase because frequency is going to get those patients back in front of a doctor who can see the signs and symptoms of Parkinson's disease psychosis and treat. We're confident in the story for a new plaza in that environment. We just need to see a frequency.
Stephen R. Davis: Yeah, thanks much for the for each question. Bernie, do you want to take the second question first? Sure, thanks for the question.
Brendan: As you would expect, we're doing everything that you would expect of a company getting ready to launch a first-in-class product and a rare disease, and we will be ready to go pretty quickly after approval. There are really just a few things from a logistical perspective that take some time. One is the finalization of a label, obviously, because it has lots of implications about product drug availability. Also, training our field force to make sure that they are 100% percent.
Brendan: We are prepared to support the physicians that want to prescribe them and the families that want to get started. But other than those simple logistics, we see no other reasons for delay, and we know that the community is waiting. Thanks, Brendan. I'll take the second part of the question.
really didn't come out until late December . So it's really early days in the in office environment to be describing that. I will say anecdotally that the audience has found the information interesting, compelling, and very much patient focused. So we look forward to talking about that further as the year progresses again.
Stephen R. Davis: I think in terms of risks to an approval, I'll start just by repeating what we said before, and that is, we should comment back and forth with the agency and wouldn't run a review. That's just always been our standard policy. Having said that, as we've said, we're eager to get to March 12th. The FDA, we're very happy with the level of engagement we've had with FDA. And as noted a second ago, they've just confirmed this morning that Billy Dunn's departure will not have any impact. So we're eager to get to March 12, and everything appears to be on.
early days, but that's kind of the market dynamic we're operating in. Thank you. One moment for our next question.
Pardon me, one more moment for our next question.
Thanks for taking the question. Congrats to Dr. Doug Williamson on joining Acadia. I was wondering if he could talk about his vision for the future of R&D and the pipeline at Acadia. Are there any gaps in the pipeline that you would like to know? Thank you. Thank you.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Ami Fadia from Needham.
Ami Fadia: Hi, good afternoon. This is Vison Leon from AMI.
Ami Fadia: Thanks for taking our question. Maybe just a two-parter on PDP. First, could you comment on kind of the longer-term trajectory of the franchise and whether we could see the re-acceleration of growth in 2024? And then second, does your guidance range for 2023 assume, you know, kind of improving inpatient volumes or whatnot, you know, to take place sometime this year? Thank you.
Yeah, Doug? Thanks, I appreciate the question. I think I've been here seven weeks now, so I'm still taking the time to understand fully the existing pipeline and its potential, let alone look to the future. I can tell you that I'm very excited to be at Acadia. I've spent most of my career in neuroscience clinical research, and I think it's one of the most difficult areas.
Stephen R. Davis: I'll briefly answer the first question. We don't guide beyond the current year, so as we progress this year, we'll continue to offer as much color as we can feel as appropriate. Brendan, do you want to take the second part of the question? Sure, and thanks for the question.
of drug development. So one of the things that appeals to me about Acadia is the focus and persistence this company has always shown in taking on, I think, the challenges of developing novel treatments for people suffering from brain disorders, where of course there's significant unmet needs. So I don't really wanna get into detail about gaps or where we're headed except that.
Brendan: When we look at 2023, I think we described in our prepared remarks where we think things are. We do see some improvement in the long-term care channel, and we will certainly look to continue to capitalize on that.
Brendan: In the in office channel, we're focused on market share and new patients. You see that as evidenced by the use of the real-world evidence studies that help us differentiate New Plaza further from off-label atypical antipsychotics that have proceeded. So in terms of market dynamics, we're operating in that market dynamic, and I believe our guidance reflects that. There are two areas where we could see catalysts for growth. The first is if, in addition to in-office visits being the preferred route for patients to see their clinicians, which we know is the case, we just need to see frequency there increase because frequency is going to get those patients back in front of a doctor who can see the signs and symptoms of Parkinson's disease psychosis and treatment.
We will be developing over the, shortly in the future we'll be developing more clarity around what direction we're headed, but I can't give you any more detail on that right now. Let me just add one annotation. Mark Schneider mentioned in his remarks that there's some deals that we've done that we don't disclose. So when we do a deal, we determine from a SEC perspective, do we need to disclose it? And if we do, of course we disclose it. If we don't, sometimes we...
take programs on and once you get to a certain destination or answer certain questions before talking publicly about it, we've got some of those programs. So as Doug alluded to, as we progress this year, we'll talk more about some of these programs that we haven't discussed yet. That's great. Thanks for taking the question. Thank you. One moment for our next question. Our next question comes in the line of David Huang from SMBCNICO.
Brendan: We're confident in the story for a new plaza in that environment. We just want more opportunities for a patient to be identified. The second, which could catalyze growth, is the real-world evidence data, in the form of the Moss Holder study and the Layton study. The Moss Holder study was really a fourth quarter introduction, and the Layton article really didn't come out until late December. So it's really early days in the in office environment to be describing that.
Brendan: I will say anecdotally that the audience has found the information interesting, compelling, and very patient-focused. So we look forward to talking about that further as the year progresses. It's early days, but that's kind of the market dynamic we're operating in.
Hi. Thanks for the update and taking my question. So, I just had a follow-up or two on the in-office channel for New Plasmid and PDP. How long do you think, or do you have any estimate about how long you think the presentation of the real-world evidence will take before that becomes reflected to any extent in script volumes?
Operator: Right. Thank you. Thank you. One moment for our next question.
Operator: Pardon me, one more moment for our next question. Thank you. The next question comes from the line of Jay Olsen from Oppen.
Jay Olson: Oh, hey, thanks for your FD and for taking the time to ask me a question.
And do you have any sense of the decreased patients, patient, sorry, patient visit? Is there any feedback of the prescriber end as to what they're seeing and if they expect those number of visits to rebound? Brindin, you want to take that? Yes.
Jay Olson: Congratulations to Dr. Doug Williamson on joining Acadia. I was wondering if he could talk about his vision for
Jay Olson: about his vision for the future of R&D and the pipeline at Acadia, and are there any gaps in the pipeline that you'd like to know? Thank you.
Douglas J. Williamson: Thanks, I appreciate the question. I think I've been here for seven weeks now, so
Sure, and thanks for the question. As you would expect, we ever since the beginning of the pandemic, we've been paying a very close attention to what we think are leading indicators for patient return to in office, to the in office setting. We saw a dramatic rise in telemedicine, obviously, but that's largely gone away. What we've seen, however, is
Douglas J. Williamson: I'm still taking the time to fully understand the existing pipeline.
Douglas J. Williamson: and its potential, let alone look to the future. I can tell you that I'm very excited to be at Acadia. I've spent most of my career
Douglas J. Williamson: in neuroscience clinical research, and I
Douglas J. Williamson: I think it's one of the most difficult areas.
Douglas J. Williamson: of drug development. So one of the things that appeals to me about
Douglas J. Williamson: Al-Qaeda is the focus and persistence this company has always shown in taking on, I think, the challenges of developing novel treatments for people suffering from brain disorders, where, of course, there's a significant unmet need.
we're still down double digits for inpatient volumes of visits. And that's a function of two things. One, I think there was mortality in the PD, a patient population during the pandemic. We see that in a surrogate marker for carbidopa-levodopa scripts. One would expect carbidopa-levodopa as a treatment to rise with an incident population just as you would in the broader community. Over the pandemic, use of carbidopa-levodopa is still down about 5%. That's sort of the top of the funnel for the treatment of patients. So what we're looking for is, and I think what we've started...
Douglas J. Williamson: and unmet need.
Douglas J. Williamson: I don't really want to get into detail about, you know, gaps or where we're headed, except that, you know, we will be developing over the... Shortly in the future, we'll be developing more clarity around, you know, what direction we're headed, but I can't give you any more detail on that right now.
Stephen R. Davis: Mark Schneier mentioned in his remarks that, "There are some deals that we've done that we don't disclose. So when we do a deal, we determine, from an SEC perspective, do we need to disclose it?" And if we do, of course, we disclose it. If we don't, sometimes we take programs on and want to get to a certain destination or answer a certain question before talking publicly about it. We've got some of these programs. So, as Doug alluded to, as we progress this year, we'll talk more about some of these programs that we haven't discussed yet. That's great!
Operator: That's great. Thanks for taking the question.
David Timothy Hoang: One moment for our next question. Our next question comes from David Huang from SMBC Nico. Hi.
David Timothy Hoang: Hi, thanks for the update and taking my question. So I just had a follow-up or two on the in-office channel for Neuplazid and PDP. Do you have any sense, you know, of the decreased patient visits? Is there any feedback from the prescriber end as to, you know, what they're seeing and if they expect those numbers of visits to rebound? Brendan, do you want to take that?
Brendan: And that's a function of two things. One, I think there was mortality in the PD population, a patient population during the pandemic. We see that in a surrogate marker for Carbidopa Levitopa script, One would expect Carbadole Leipidopa as a treatment to rise with an incident population just as you would in the broader community. However, over the pandemic, use of Carbidoba Leipidopo is still down about 5%.
is very helpful in the midterm and longer term for a neoplasmic growth.
Thank you. We have time for one more question.
Our next question comes from the line of Kyle Keon from Canaco or Genuity. Hello, this is Kyle speaking on behalf of Sumant Kulkarni. Thanks for squeezing us in. Team advancement in mea symptoms of schizophrenia, given you have a positive phase 3 already, what point do you expect to run from the FDA as to exactly what your second phase 3 child may be?
Brendan: That's sort of the top of the funnel for the treatment of patients. So what we're looking for, and I think what we've started to see, is some stabilization in those office visits. What we want to see is a rise. A rise helps us in two ways. One, we believe, as I said, early days on the real-world evidence, but we do know that we're getting time with physicians. They find the information compelling, and there's an opportunity for us to use that as a real platform for differentiation of New Plaza versus the atypical antipsychotics that preceded it. The second is the audience to treat. And if we can get more patients to return to the office, I think that combination is very helpful in the midterm and longer term for New Placid growth.
the negative symptoms of schizophrenia. In terms of where we stand, so we, again, as Doug mentioned in our prepared remarks, we have something very unusual in this space. It's been a very difficult space for decades.
It's long been talked about as the most significant unmet need in schizophrenia. So it's very rare to have a positive pivotal study, which we have in the case of Advanced I. So we're running our second study now, Advanced II. We should complete enrollment there in the middle of this year and then have results early next year. So at that point, with two positive pivotal studies, if Advanced II is successful, we'll be applying to submit on that basis.
Operator: We have time for one more question. Our next question comes from Kyle Kean from Kanakor Genuity.
Kyle Kean: Hello, this is Kyle speaking on behalf of Sumant Kukarni. Thanks for speaking with him.
Kyle Kean: Pima Vance and May is something, the schizophrenia, given you have a positive phase three already. At what point do you expect to learn from the FDA as to exactly what your second phase three child may need to show? And related to that, will a trend be enough given no product has ever been approved specifically for the indication? You know, You were mixing up a little bit. I think I've got the questions, let me just try. If I don't answer everything you ask,
And we follow the difficult path there where we would have a pre-sumission meeting with FDA, we'd submit, and then I go through the normal review process. Did that answer both your questions? Yes, so in the second phase three, we'll trendy enough given no color types in the proof indication, as in the time it did not hate. Well, I think until we, at this point, we just need to complete the study and get the results. We're eager to do that. You know, as Doug mentioned, having very strong results at the dose that we're testing now in advance to in our advance one state, you know, certainly gives us, so you can mean for optimism here.
Stephen R. Davis: There's nothing to treat the negative symptoms of schizophrenia. In terms of where we stand, so we, again, as Doug mentioned in his prepared remarks, we have something very unusual in this space. It's been a very difficult space.
Stephen R. Davis: It's long been talked about as the most significant unmet need in schizophrenia, so it's very rare to have a positive pivotal study, which we have in the case of the advanced one. Still running our second study now, advanced two. We should complete enrollment there in the middle of this year, and then have results serving. So at that point, the two positive federal studies, if it gains too successful, we'll plan to submit on that basis, and we'd follow the difficult path there, where we would have a pre-submission meeting with FDA, we'd submit, I go through the norm. Did that answer both of your questions?
Stephen R. Davis: Yes, so in the second phase, three, will trend be enough, given though products had been approved indication, as in if the primary did not hate them?
Stephen R. Davis: Well, I think until we, at this point, we just need to complete the study and get the results. We're eager to do that. You know, as Doug mentioned, having very strong results at the dose that we're testing now in advanced two in our advanced one study certainly gives us significant means for optimism here. And the two things that Doug pointed out that are different between advanced one and advanced two should both improve the chances of success. So I think until we actually open the envelope we're due, there's not a lot more than
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Stephen R. Davis: Thank you. Mr. Davis, please proceed to your closing remarks.
Stephen R. Davis: Great, thanks much, operator. Thanks again, everyone for joining us today. This will be a very significant year for us, a year to get to March 12th, as I mentioned. Thank you for your participation in today's conference call. This concludes the presentation. You may now disconnect. Good day, we will begin shortly. To raise and lower your hand during Q&A, you can dial star 1-1. Thank you.
Operator: Thank you for your participation in today's conference call. This concludes the presentation. You may now disconnect. Good day.
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