Q2 2024 ACADIA Pharmaceuticals Inc Earnings Call

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Operator: Good day, ladies and gentlemen, and thank you for standing by. Welcome to the ACADIA Pharmaceuticals second quarter 2024 financial results conference. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 11 on your telephone. Please be advised that today's conference is being recorded. I would now like to hand the conference over to Al Kildani, Senior Vice President of Investor Relations and Corporate Communications at ACADIA. Please go ahead.

Speaker Change: Good day, ladies and gentlemen, thank you for standing by welcome.

Speaker Change: Welcome to the Acadia Pharmaceuticals second quarter 2024 financial results Conference call.

Speaker Change: At this time all participants are in a listen only mode.

Speaker Change: After the speaker's presentation, there will be a question and answer session.

Speaker Change: To ask a question during the session you will need to press star one on your telephone.

Speaker Change: Please be advised that today's conference is being recorded.

I would now like to hand, the conference over to.

Speaker Change: Al killed Donnie.

Speaker Change: Senior Vice President of Investor Relations and corporate Communications at Acadia. Please go ahead.

Speaker Change: Thank you Daniel.

Al Kildani: Good afternoon, and thank you for joining us on today's call to discuss ACADIA's second quarter 2024 earnings. Joining me on the call today from ACADIA are Steve Davis, our Chief Executive Officer, who will provide some opening remarks, followed by Brendan Teehan, our Chief Operating Officer and Head of Commercial, who will discuss our commercial franchise's debut and new platform. Also joining us today is Elizabeth Thompson, Ph. D., Executive Vice President, Head of Research and Development.

Speaker Change: Good afternoon, and thank you for joining us on today's call to discuss the <unk> second quarter 2020 for earnings.

Speaker Change: Joining me on the call today from Acadia are Steve Davis, our Chief Executive Officer, who will provide some opening remarks, followed by Brendan <unk>, our chief operating officer and head of commercial who will discuss our commercial franchises debut of NUPLAZID.

Speaker Change: Also joining us today is Elizabeth Thompson Ph D Executive Vice President head of research and development will provide an update on our pipeline programs and Mark Schneider, Our Chief Financial Officer, who will review the financial highlights.

Al Kildani: We'll provide an update on our pipeline programs, and Mark Schneyer, our Chief Financial Officer, will review the financial highlights. Steve will then provide some closing thoughts before we open up the call to your questions. In addition, Parag Meswani, Senior Vice President, Trophinitide Rare Disease Franchise, as well as Kimberly Manhard, Senior Vice President, Global Strategic Planning and Execution, will be available for the Q&A session.

Speaker Change: Steve will then provide some closing thoughts before we open up the call to your questions.

Speaker Change: In addition, our August one as senior Vice President your phenotype rare disease franchise as well as Kimberly men are senior Vice President Global strategic planning and execution will be available for the Q&A session.

Al Kildani: We are using supplemental slides which are available on our website's events and presentations section. Before proceeding, I would like to remind you that during our call today, we will be making several forward-looking statements 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, future results, and financial guidance, are based on current information, assumptions, and expectations that are inherently subject to change and involve several risks and uncertainties that may cause results to differ materially.

Speaker Change: We are using supplemental slides, which are available on our website events and presentations section.

Speaker Change: Before proceeding I would like to remind you that during our call today, we will be making several forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995.

Speaker Change: These forward looking statements, including goals expectations plans prospects growth potential timing of events future results and financial guidance are based on current information assumptions and expectations that are inherently subject to change and involve several risks and uncertainties that may cause results to differ materially.

Speaker Change: 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 and we assume no obligation to update or revise these forward looking statements as circumstances change except as required by law.

Al Kildani: 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, and we assume no obligation to update or revise these forward-looking statements as circumstances change, except as required by law. I'll now turn the call over to Steve for his opening remarks.

Speaker Change: I'll now turn the call over to Steve for opening remarks.

Steve Davis: Thank you, Al. Good afternoon, everyone, and thank you for joining me.

Steve: Thank you al good afternoon, everyone and thank you for joining US please turn to slide five.

Steve Davis: Please turn to slide 5. The foundation of ACADIA's business is built on our two commercial products, which apply them for the treatment of hallucinations and delusions associated with Parkinson's disease and debuts for The Treatment of Red. Together, these commercial franchises delivered $242 million in revenues for the second quarter. In addition to these successful commercial products, we have a deep and growing pipeline, headlined by our Phase III Prader-Willi Syndrome Program and our Phase II, Phase III program in Alzheimer's disease psychosis. Our two profitable franchises drove 46% year-over-year revenue growth and provided Katie with a strong financial foundation. We are a cash flow positive company and now have over $500 million in cash with no debt.

Steve: The foundation of the games business is built on our two commercial products.

Why is it for the treatment of hallucinations and delusions associated with Parkinson's disease and debut for the treatment of Ret syndrome.

Steve: Together these commercial franchises delivered $242 million of revenues for the second quarter.

Steve: In addition.

Steve: And to the successful commercial products, we have a deep and growing pipeline headlined by our phase III audit released syndrome program.

Steve: In our phase II phase III program in Alzheimer's disease psychosis.

Steve: Our two profitable franchises drove 46% year over year revenue growth in.

Steve: And provide acadia with a strong financial foundation.

Steve: We are a cash flow positive company and now have over $500 million in cash.

Speaker Change: Oh depths.

Steve Davis: This gives us a great deal of confidence in our ability to fund future growth by advancing our current pipeline program, as well as investing in future business development. Please turn to slide 16. I'll now discuss some highlights from each of our commercial products that Brendan will expand upon further in his section. I'll begin with David.

Speaker Change: This gives us a great deal of confidence in our ability to fund future growth by advancing our pipeline programs as well as investing in future business development opportunities.

Speaker Change: Please turn to slide six.

Speaker Change: I'll now discuss some highlights from each of our commercial products that Brendan will expand upon further in his section I'll.

Brendan: I'll begin with debut.

Steve Davis: In the second quarter, debut net product sales were $84.6 million, up 11% sequentially. During the quarter, we've returned to growing active patients on therapy. Today, we are at 900, which is back to where we ended 2023 following the surge of new patients we experienced soon after debut's launch and is 66 patients above our low point late in the first quarter, consistent with our expectations. Furthermore, numerical discontinuation has dropped significantly, with the rate of weekly discontinuations decreasing 46% in the second quarter versus the first quarter.

Brendan: In the second quarter <unk> net product sales were $84 $6 million up 11% sequentially.

Brendan: During the quarter, we returned to growing active patients on therapy today.

Brendan: To date, we are at 900, which is back to where we ended 2023 following the surge of new patients. We experience soon after debut launch.

Brendan: And a 66 patients above our low point late in the first quarter.

Brendan: Consistent with our expectations numerical discontinuation has dropped significantly in the quarter with.

Brendan: But the rate of weekly discontinuation decreasing 46%.

Brendan: Second quarter versus the first quarter.

Steve Davis: New patient starts rebounded in the quarter, but the rate of weekly starts increasing 12%. This rate of growth was slower than projected. So while things are moving in the right direction, they have not moved as fast as we anticipated. As a consequence, and as Mark will discuss in his section, we're lowering our guidance range for debut for the year to $340 to $370 million.

Brendan: New patient starts rebounded in the quarter, but with.

Brendan: With the rate of weekly starts increasing 12%.

Brendan: This rate of growth was slower than projected.

Brendan: So while things are moving in the right direction has not moved as fast as we anticipated.

Brendan: As a consequence and as Mark will discuss in his section.

Mark: Lowering our guidance range for debut for the year to $340 million to $370 million.

Steve Davis: Brendan will discuss in his section our outlook for the remainder of the year and beyond. Now turning to new clients, net product sales were up 11% in the second quarter 2024 over the second quarter 2023 to $157.4 million. For the first half of 2024, net product sales were up 10% compared to the first half of 2023. There are two undercurrents supporting this.

Brendan: Brendan will discuss in his section our outlook for the remainder of the year and beyond.

Mark: Now turning to NUPLAZID.

Mark: Net product sales were up 11% in the second quarter 2024 over second quarter of 2023 to $157 4 million.

Mark: For the first half of 2024 net product sales were up 10% compared to the first half of 2023.

Speaker Change: There are two undercurrent supporting its growth.

Steve Davis: First, the Parkinson's disease psychosis market, which was hit very hard during the pandemic, has now stabilized. Second, and more important, and on a positive label change announced late last year, clarifying that Nuplazib can be used in Parkinson's disease patients who also have dementia. Our performance year to date and the favorable undercurrents I've just described have led us to increase our annual sales guidance for Nuclizid in 2024 from a previous range of $560 to $500 million to a new range of $590 to $610,000.

Mark: First the Parkinson's disease psychosis market.

Mark: Which was hit very hard during the pandemic is now stable.

Mark: Second and more importantly, where.

Mark: Getting very good traction on the real World evidence studies, we previously discussed.

Mark: And on a positive label changes announced late last year.

Mark: Clarifying that NUPLAZID can be used in Parkinson's disease psychosis patients, who also have dementia.

Mark: Our performance year to date and a favorable undercurrents I've just described.

Mark: Let us to increase our annual sales guidance for NUPLAZID in 2024 from a previous range of $560 million to $500 million $590 million up to a new range of.

Mark: $590 to $610 million.

Steve Davis: Before I leave New Planset, I want to touch on one other important point. Our market research demonstrates that the awareness of hallucinations and delusions dropped drastically during the course of the pandemic, which means patients many times may be experiencing these symptoms but do not raise them with their dog.

Mark: Before I leave NUPLAZID I wanted to touch on one other important point.

Mark: Our market research demonstrates that the awareness of hallucinations and delusions dropped drastically during the course of the pandemic.

Mark: Which means patients many times may be experiencing these symptoms.

Mark: Do not racing with their doctor.

Steve Davis: This gap creates an opportunity to raise that awareness in a market that is now stable. As Brendan will describe, we are initiating a targeted campaign to close the Hallucinations and Delusions Awareness Gap and capitalize on this opportunity. Our new Plymouth franchise has never been in a stronger position, and we look forward to sharing more details about our growth initiative. Now, let's turn to slide seven.

Mark: This GAAP creates an opportunity to raise that awareness in a market that has now stabilized.

Mark: As Brian will describe we are initiating a targeted campaign to close the hallucinations and delusions awareness gap and capitalize on this opportunity.

Brian: Our NUPLAZID franchise has never been in a stronger position and we look forward to sharing more details about our growth initiatives.

Brian: Let's turn to slide seven.

Steve Davis: Before giving an overview of our current products and pipeline, I'd like to take this opportunity to officially introduce Dr. Elizabeth Thompson, as our Executive Vice President, Head of Research and Development. Liz is a preeminent drug research and development leader with extensive experience, and we're thrilled to have her on board. Liz joins us from Amgen, where she served as Executive Vice President, Research and Development, Rare Disease, following its acquisition by Horizon.

Speaker Change: Before giving an overview of our current products and pipeline I'd like to take this opportunity to officially introduce Dr. Elizabeth Thompson as our executive Vice President head of research and development.

Speaker Change: This is a preeminent drug research and development leader with extensive experience and we're thrilled to have her on board.

Speaker Change: <unk> joins us from Amgen, where she served as executive Vice President Research and development rare disease following its acquisition by horizon.

Speaker Change: Of Horizon Therapeutics.

Steve Davis: Turning to our products and pipelines, as you heard, both Duplazit and Debut form the growing core of our commercial business. In addition to these successful commercial franchises, we have numerous attractive late and early stage pipelines. These include ACP 101 and Parter-Willi Syndrome, where we are currently rolling subjects in our Phase 3 setting. Quater Willie is a rare and debilitating genetic disease where patients have an unrelenting drive to eat called hyperphagia.

Speaker Change: Turning to our products and pipeline.

Speaker Change: As you heard both NUPLAZID and debut form the growing core of our commercial business.

Mark: In addition to the successful commercial franchises, we have numerous attractive late and early stage pipeline assets.

Speaker Change: These include ACP 100 wanted product Willi syndrome or.

Speaker Change: We are currently enrolling subjects in our phase three study.

Speaker Change: But it really is a rare and debilitating genetic disease, where patients have been unrelenting drive to eat all type of Asia.

Brendan Teehan: There are no FDA-approved treatments for this condition. We're also currently enrolling our Phase 2, and Phase 3 programs with ACP 204 in Alzheimer's disease psychosis. Another disorder where there are no approved medicines, HCP 204 is our second generation 5HT2A blocker where we are leveraging our learnings from new clients. It represents an opportunity to expand and extend our neuropsychiatry. And behind that, we have a rich pipeline of early stage disclosed and undisclosed programs that position us for future growth. I'll now turn it over to Brendan to discuss our commercial performance, beginning on slide 16.

Speaker Change: There are no FDA approved treatments for this condition.

Speaker Change: We're also currently enrolling our phase II phase III program with <unk> in Alzheimer's disease psychosis patients.

Speaker Change: Another disorder, where there are no approved treatments.

Speaker Change: <unk> is our second generation <unk> Walker.

Speaker Change: Where we are leveraging our learnings from NUPLAZID.

Speaker Change: It represents an opportunity to expand and extend our neuropsychiatry franchise.

Speaker Change: And behind that we have a rich pipeline of early stage disclosed and undisclosed programs that position us for future growth.

Speaker Change: I'll now turn it over to Brendan to discuss our commercial performance beginning on slide eight.

Brendan: Thank you Steve.

Brendan Teehan: Today I'll be focusing my comments on the current state of business in our new Plazid and Debut franchises. Starting with Debut, my comments will address three key areas: results to date in 2024. New data we are messaging based on the real world experiences from caregivers and health care providers, and core elements of the business that drive long-term value and revenue. Please turn the slides now.

Brendan: Today I'll be focusing my comments on the current state of business and our NUPLAZID and debut franchises.

Brendan: Bearing with debut my comments will address three key areas first.

Brendan: Results to date in 2024.

Brendan: New data, we are messaging based on the real world experiences from caregivers and health care providers and core elements of the business that drive the long term value and revenues. Please turn to slide nine.

Brendan Teehan: Let's start with how the business has progressed thus far in 2024. The second quarter marked a return to growth in total active patients on debut. As you know, the first quarter saw a slowdown in new starts.

Speaker Change: Let's start with how the business has progressed thus far in 2024.

Speaker Change: The second quarter marked a return to growth in total active patients on debut.

Brendan: As you know the first quarter saw a slowdown in new starts that dynamic coupled with the first quarter increase in numerical discontinuation associated with a large surge in new patient starts soon after launch resulted in a decline in total active patients during the first quarter.

Brendan Teehan: That dynamic, coupled with the first quarter increase in numerical discontinuations associated with the large surge in new patient starts soon after launch, resulted in a decline in total active patients during the first quarter. Our second quarter recovery in total active patients was driven by a sequential increase in demand and a decrease in numerical discontinuations. First, we generated an increase in new patient starts on debut, with weekly new starts coming in 12% higher than in the first quarter.

Brendan: Our second quarter recovery in total active patients was driven by a sequential increase in demand and a decrease in numerical discontinuation.

Brendan: First we generated an increase in new patient starts on debut with weekly new starts coming in 12% higher than in the first quarter.

Brendan Teehan: At the same time, we experienced a significantly lower rate of weekly discontinuations, decreasing 46% in the second quarter versus the first quarter. While we made important progress on both fronts in the second quarter, our rate of increasing active patients on therapy was slower than anticipated. This is a function of numerical discontinuations decreasing in line with our expectations.

Brendan: At the same time, we experienced a significantly lower rate of weekly discontinuation decreasing 46% in the second quarter versus the first quarter.

Speaker Change: While we made important progress on both fronts in the second quarter, our rate of increasing active patients on therapy was slower than anticipated.

Speaker Change: This is a function of numerical discontinuation decreasing in line with our expectations, but our rate of new patient starts while growing total patients on therapy has been slower than projected.

Brendan Teehan: But our rate of new patient starts while growing total patients on therapy has been slower than projected. As we expand our penetration in high-volume institutions and community practices, there are obviously substantially more physicians we're engaging, each of whom we need to educate on the clinical benefits of DayVu so they can best communicate those benefits to their caregivers and patients. Our increased penetration in these treatment settings over the past quarter indicates this will happen, and it just takes time to reach this broader audience.

Brendan: As we expand our penetration in high volume institutions and community practices. There are obviously substantially more physicians were engaging each of whom we need to educate on the clinical benefits of debut so they can best communicate those benefits to their caregivers and patients.

Brendan: Our increased penetration in these treatment settings over the past quarter indicates this will happen and it just takes time to reach this broader audience.

Brendan Teehan: With that, let me now turn to our view of the business for the second half of the year and opportunities to accelerate new patient start. As of August 1st, we have 900 active patients on debut therapy, which is fully back to where we were in late 2023. By the close of the second quarter, approximately 30% of all diagnosed RET patients in the United States had initiated their debut treatment after less than 15 months on the market. This, of course, means 70% of the Rett population is still available.

Brendan: With that let me now turn to our view of the business for the second half of the year and opportunities to accelerate new patient starts.

Brendan: As of August 1st we have 900 active patients on debuted therapy, which is fully back to where we were in late 2023.

Brendan: By the close of the second quarter, approximately 30% of all diagnosed <unk> patients in the United States had initiated debut treatment after less than 15 months on the market.

Brendan: This of course means 70% of the population is still available and we've continued to grow our penetration early in the third quarter.

Brendan Teehan: And we've continued to grow our penetration early in the third quarter. Beyond the Centers of Excellence, we have also driven greater penetration in both high-volume COE-like institutions, as well as in community practices, where almost three-quarters of all RET patients are treated. Today, approximately two-thirds of all debut prescriptions are coming from these two segments, with the remaining third continuing to be sourced in COEs, where we see a steady stream of volume. As previously described, we expect this shift in the source of business to continue over time as we achieve greater penetration in high volume and community practice.

Brendan: Beyond the centers of excellence, we have also driven greater penetration in both the high volume Coa like institutions as well as in community practices. We're almost three quarters of all <unk> patients are treated.

Brendan: Today, approximately two thirds of all <unk> prescriptions are coming from these two segments with the remaining third continuing to be sourced and Coes, where we see a steady stream of volume.

Brendan: As previously described we expect this shift in the source of business to continue over time as we achieve greater penetration in the high volume and community practices.

Brendan Teehan: Having launched DEBU in mid-April of last year, we are now at a point where we have a significant body of real-world relevant experiences from both healthcare providers and the caregiver community. We're now communicating these proof points back into these communities to further inform their understanding of the clinical benefits DEBU can provide in the context of their own experiences. We further emphasize how these real-world experiences are consistent with our lavender results and how this body of data can contribute to the establishment of potential best practices. Let's turn to slide 10 to discuss this further.

Brendan: Having launched debut in mid April of last year. We are now at a point, where we have a significant body of real world relevant experiences from from both healthcare providers and the caregiver community.

Brendan: We're now communicating these proof points back into these communities to further inform their understanding of the clinical benefits debut can provide in the context of their own experience.

Brendan: We further underscore how these real world experiences are consistent with our 11th year results and how this body of data can contribute to the establishment of potential best practices.

Brendan: Let's turn to slide 10 to discuss this further.

Brendan Teehan: It's essential that we communicate to physicians and families the benefits of treatment with day view they can expect to experience over time. To that end, we recently presented, at the IRSF conference in June, four posters describing three studies—LILAC 1, LILAC 2, and LOTUS—where caregivers spoke to both the number, diversity, and durability of benefits seen over time, as well as their utilization of GI management strategies. Liz will go into more detail in her section.

Brendan: It's essential that we communicate to physicians and families. The benefits of treatment with debut they can expect to experience over time to that end. We recently presented at the IRS theft conference in June four posters, describing three studies lilac, one lilac to and Lotus.

Brendan: Caregivers speak to both the number diversity and durability of benefit seen overtime as well as their utilization of Gi management strategies.

Brendan: This will go into more detail in her section.

Brendan Teehan: As we enter the third quarter, we are sharing more success stories families are experiencing across a wide range of patient ages, as well as disease severities, all intended to paint the patient picture for debut. Those stories, told by the caregivers whose loved ones are benefiting from debut treatment, show us that the results we're seeing in the real world are very consistent with what we've seen in our clinical studies, but importantly, can now be expressed in more understandable and relevant terms to caregivers.

Brendan: As we entered the third quarter, we are sharing more success stories families are experiencing across a wide range of patient ages as well as disease severities, all intended to paint the patient picture for debut.

Speaker Change: Those stories told by the caregivers, who loved ones are benefiting from debut treatment show us that the results. We're seeing in the real world are very consistent with what we've seen in our clinical studies, but importantly can now be expressed in more understandable and relevant terms to caregivers.

Brendan Teehan: On the GI management front, we are seeing a growing body of evidence that diarrhea may be more manageable in the real world than what was observed in the Lavender Study. As a reminder, there was no proactive GI management protocol associated with the Phase 3 study.

Brendan: On the GI management front, we are seeing a growing body of evidence that diarrhea may be more manageable in the real world than what was observed in the <unk> study.

Brendan: As a reminder, there was no proactive Gi management protocol associated with the Phase III study.

Brendan Teehan: Today, with authentic examples of the benefits patients are seeing, coupled with a proactive GI management plan, our commercial and medical teams are better equipped than ever to educate HCPs and caregivers about DayView's real-world benefits and tolerability. Now, let's turn to slide 11, where I'll discuss my third debut topic, the core elements of our business that drive long-term value and revenue. First, I'll start with the size of the opportunity and physician intent to treat.

Brendan: Today with us authentic examples of the benefits patients are seeing coupled with our proactive Gi management plan, our commercial and medical teams are better equipped than ever to educate hcp's and caregivers about debuts real world benefits and Tolerability.

Brendan: Let's turn to slide 11, where I'll discuss my third debut topic, the core elements of our business that drive long term value and revenues.

Speaker Change: First I'll start with the size of the opportunity and physician intent to treat.

Brendan Teehan: As I noted a few minutes ago, today there is a sizable population of approximately 5,000 diagnosed RET patients in the United States. We expect this diagnosed population to continue to grow and further close the gap with the estimated 6,000 to 9,000 total prevalent population. Of the 5,000 diagnosed patients today, approximately 30% have initiated debut therapy, leaving a very large opportunity to continue to grow the drug. I'd like to share a few key elements of our market research, further informing our view of the attractiveness of the remaining opportunities.

Speaker Change: As I noted a few minutes ago today, there is a sizable population of approximately 5000 diagnosed patients in the United States.

Brendan: We expect this diagnosed population to continue to grow and further closed the gap with the estimated six to 9000 total prevalent population.

Brendan: Of the 5000 diagnosed patients today, approximately 30% have initiated debuted therapy, leaving a very large opportunity to continue to grow the drug.

Brendan: I'd like to share a few key elements of our market research further informing our view of the attractiveness of the remaining opportunity.

Brendan Teehan: Today, 92% of HCPs treating Rett syndrome are aware of Debut. Surveyed ACPs state that, over the next 24 months, they expect to increase their prescriptions of Debut to treat, in the aggregate, more than 70% of their eligible RET patients. Physicians cite improvement in quality of life as the primary reason to expand their day-to-day prescribing. When asked...

Brendan: Today, 92% of Hcp's treating rich syndrome are aware of debut.

Brendan: Surveyed hcp's state debt over the over the next 24 months they expect to increase their prescriptions have debuted to treat in the aggregate more than 70% of their eligible eligible patients.

Brendan: Physicians site improvement in quality of life is the primary reason to expand their debut prescribing.

Brendan Teehan: Fully 60% of physicians reported they were extremely willing to proactively recommend Debut to a caregiver, and approximately 80% were extremely willing to honor a caregiver request for Debut. Second, as we've previously stated, we see the opportunity for a sizable, enduring population on Debut. Real-world persistency on Debut is continuing to track about 10 percentage points higher than what we observed in our clinical trials, specifically the placebo rollover patients from the Lilac One study.

Brendan: When asked fully 60% of physicians reported they are extremely willing to proactively recommend debut to a caregiver and approximately 80% are extremely willing to honor our caregiver request for debut.

Speaker Change: Second as we've previously stated we see the opportunity for a sizable enduring population on debut.

Brendan Teehan: Consistent with our prior reports, today, our real-world persistency rate on debut at nine months remains 58%, with a now much larger number of patients having reached that nine-month point, demonstrating the durability of this measure. Knowing additionally that approximately 40% of patients who initiate debut therapy in our Phase 3 program remain on therapy today and have now been on therapy more than three years, this 10% point improvement informs our expectation that, in the real world, half or more patients who initiate debut therapy will be long-term, enduring patients.

Brendan Teehan: Third, let's turn to debut utilization rates. As we've previously described, upon initiating debut therapy, many physicians choose to titrate their patients up, and some down. In other words, they may start dosing below the labeled dose and work up, or they may start at the full labeled dose, and they may choose to decrease the dose. In both cases, to determine the best therapeutic dose for their patient if that is not 100% of the labeled dose.

Speaker Change: It may start at the full label dose and they may choose to decrease the dose in both cases to determine the best therapeutic dose for their patients.

Speaker Change: That is not 100% of the label dose.

Brendan Teehan: Following any dose adjustments during this treatment initiation period, our data consistently indicate the average dose patients take is between 75 and 80 percent of the labeled dose. When we take into consideration our full patient mix, which includes patients that are titrating, patients at their post-titration dose, and patients who may, from time to time, pause therapy due to comorbidities or other reasons. The product consumption rate across our entire patient population is in the low 70 percent range.

Speaker Change: Following any dose adjustments during this treatment initiation period, our data consistently indicates the average dose patients take is between 75 and 80% of the label dose.

Speaker Change: When we take into consideration our full patient mix.

Speaker Change: Which includes patients that are titrating patients at their post titration dose and patients who made from time to time paused therapy due to comorbidities or other reasons.

Speaker Change: The product consumption rate across our entire patient population is in the low 70 percentage range.

Brendan Teehan: Fourth, for the sake of completeness, we've established access to Debut across multiple payer types, with now greater than 80% of plans having written policies covering Debut, largely on label. We further see conversion rates to paid treatment of approximately 90% over time as our monthly patient cohorts mature. And finally, as I described above, we have a growing body of real-world evidence demonstrating the clinical effectiveness of Debut that is much more relatable to HCPs and caregivers.

Speaker Change: Fourth for the sake of completeness.

Speaker Change: We have established access to debut across multiple payer types with now greater than 80% of plans, having written policies covering debut largely to label.

Speaker Change: We further see conversion rates to paid treatment of approximately 90% over time as our monthly patient cohorts mature.

Speaker Change: And finally as I described above we have a growing body of real world evidence demonstrating the clinical effectiveness of debut that is much more related to hcp's and caregivers.

Brendan Teehan: We believe in these long-term value drivers of Debut and will continue to leverage them. Please turn to slide 12 for an update on new classes. Turning to New Plaza, we had an outstanding second quarter with 11% year-over-year growth.

Speaker Change: We believe in these long term value drivers of debut and will continue to leverage them.

Speaker Change: Please turn to slide slide 12 for an update on NUPLAZID.

Speaker Change: Turning to NUPLAZID, we had an outstanding second quarter with 11% year over year growth.

Brendan Teehan: This performance has been driven by our leveraging of real-world evidence studies demonstrating New Plaza's unique clinical profile for patients suffering from Parkinson's disease-related hallucinations and delusions, as well as last year's labeling. Our sales team has done an excellent job of effectively educating HCPs about the key findings of these important real-world evidence studies published over the past two years, which demonstrate the differential benefits of initiating treatment in patients with Neuplazid for PDP as opposed to off-label atypical antipsychotics.

Brendan Teehan: We've bolstered these efforts with peer-to-peer programming, with PDP experts educating their peers on these data sets and the need to consider New Plazid as the first and best choice for treating PDP. In addition to these important new data sets, last year the FDA approved a positive change to Nuplazid's label, making it clear that Nuplazid can be prescribed to treat patients with Parkinson's disease psychosis with or without dementia, thereby addressing confusion that existed with prescribers about Duplaz's addressable patient population.

Brendan Teehan: Today, our sales teams can address these questions clearly and help clinicians make the best decision for their patients suffering from PDP. Now, let's turn to look at how Neuplazid is performing relative to the broader Parkinson's disease market. Please turn to slide 13.

Brendan Teehan: There are two takeaway points from this slide. First, we've observed that the Parkinson's disease market has now stabilized following significant upheaval during the pandemic years as the Parkinson's community was particularly hard hit given the advanced age and medical condition of people with Parkinson's and the number of patients who reside in long-term care facilities. For several quarters in a row now, utilization of carbidopa-levodopa, the staple of Parkinson's motor therapy, has been stable.

Speaker Change: Parkinson's and the number of patients who reside in long term care facilities.

Speaker Change: For several quarters in a row now utilization of carbon Opel levodopa, the staple of Parkinson's motor therapy has been stable.

Brendan Teehan: More importantly, as you can see in the chart, New Plazid new patient starts in the second quarter grew 4% sequentially, while new patient starts for other antipsychotics declined 8%, leading to New Plazid's share of new starts increasing 11% during this time period. This is terrific progress and sets us up nicely for the second half of the year as new patients start in the first and second quarter become our continuing patients in subsequent quarters.

Speaker Change: More importantly, as you can see in the chart NUPLAZID new patient starts in the second quarter grew 4% sequentially, while new patient starts for other anti Psychotics declined 8% leading to NUPLAZID share of new starts increasing 11% during this time period.

Speaker Change: This is terrific progress and sets us up nicely for the second half of the year as new patient starts in the first and second quarter become our continuing patients in subsequent quarters.

Brendan Teehan: The second quarter also marked a significant new milestone as we ended the quarter with the highest number of patients ever on New Plaza in the community setting. This is a reflection of both strong performance among our continuing patient population, as well as shared gains I described above for new patients. Please turn to slide 14.

Speaker Change: The second quarter also marked a significant new milestone as we ended the quarter with the highest number of patients ever on NUPLAZID in the community setting. This is a reflection of both strong performance among our continuing patient population as well as share gains I described above for new patient starts please turn to slide 14.

Brendan Teehan: With the PDP market now stabilizing, and New Plazid both gaining share from our competitors and growing treated patients, we see an attractive opportunity to further engage patients and caregivers to bridge a gap that exists today regarding the awareness of hallucinations and delusions, as well as New Plazid's central role in treating these non-motor symptoms of Parkinson's. Let's look at the market research that backs this up and what we plan to As you can see from the chart on this slide, among caregivers and patients, unaided awareness of hallucinations and delusions associated with Parkinson's is down significantly from a peak of 33% in May of 2020 to around 8% more recently.

Speaker Change: With the PDP market now, having stabilized and NUPLAZID, both gaining share from our competitors and growing treated patients we see an attractive opportunity to further engage patients and caregivers to bridge a gap that exists today regarding the awareness of hallucinations and delusions as well as NUPLAZID.

Brendan Teehan: To address this decline in patient and caregiver awareness and help identify new patients, we will soon launch a targeted, unbranded DTC campaign intended to raise disease awareness by speaking directly to this audience. As a reminder, this is a dynamic population that has high patient turnover. Thus, many patients suffering with PDP today will not have seen or benefited from our prior educational campaign. It's therefore critical that we continue identifying and educating new patients and caregivers under these improving market conditions, most of whom have not heard this type of message.

Brendan Teehan: On top of this low level of awareness of hallucinations and delusions, we know awareness of Neuplazid among this audience as a treatment option is also low, at approximately 15 percent, according to the latest data. These two dynamics result in fewer discussions with healthcare professionals about the non-motor symptoms of PDP, undoubtedly leading to some patients not receiving the treatment they need. Despite these low levels of awareness of hallucinations and delusions and of Neuplazid, our market research indicates that approximately 65% of physicians, when receiving a request for Neuplazid from a patient or caregiver, indicate they are extremely likely to prescribe it at that request.

Speaker Change: If they are extremely likely to prescribe it upon that request.

Brendan Teehan: We recently launched a branded DTC campaign designed to raise awareness of nuplazid as the only FDA-approved treatment option for patients suffering from hallucinations and delusions associated with Parkinson's disease. It's intended to be a complement to the upcoming disease awareness campaign. We look forward to sharing our progress on both of these programs as they roll out in advance of the upcoming fall months and the holidays, when we know families will get together and assess potential changes they see in their loved ones as a function of their disease.

Speaker Change: We recently launched a branded DTC campaign designed to raise awareness of NUPLAZID as the only FDA approved treatment option for patients suffering from hallucinations and delusions associated with Parkinson's disease.

Speaker Change: It's intended to be a complement to the upcoming disease awareness campaign.

Speaker Change: We look forward to sharing our progress on both of these programs as they rollout in advance of the upcoming fall months and the holidays, where we know families will get together and assess potential changes they see in their loved ones as a function of their disease.

Brendan Teehan: The current strength of our new Plaza business has been driven by both the real-world evidence studies that we've shared with HCPs, as well as the positive label clarification. That success now leads us to increase our guidance for new plasmid sales this year. To be clear, we are not relying on our new DTC campaigns to establish our 2024 revised guidance, as the projected impact of these campaigns is expected to be realized in 2025 and beyond. Equally importantly, we will be able to absorb the investments in these new campaigns without increasing our SG&A guidance for 2024.

Speaker Change: The current strength of our NUPLAZID business has been driven by both the real World evidence studies that we've shared with Hcp's as well as the positive label clarification.

Speaker Change: That success now leads us to increase our guidance for NUPLAZID sales this year.

Speaker Change: To be clear, we are not relying on our new DTC campaigns to establish our 2020 for revised guidance.

Speaker Change: As the projected impact of these campaigns is expected to be realized in 2025 and beyond.

Speaker Change: Equally importantly, we will be able to absorb the investments in these new campaigns without increasing our SG&A guidance for 2024.

Brendan Teehan: Mark will provide the details shortly. I'll now turn it over to Liz Thompson, Executive Vice President, Head of Research and Development, to provide an update on our clinical studies and pipeline programs, starting on slide 15. Liz Thompson Thank you.

Speaker Change: Mark will provide the details shortly.

Liz Thompson: Thank you, Brendan. I'd like to start out by saying that it's a pleasure to be with you all today.

Liz Thompson: I'm pleased to be joining the ACADIA team. I came here based on my enthusiasm for what our market for medicines is bringing to patients, for the potential of our pipeline, and the opportunity to continue to feed and grow that pipeline. I look forward to our conversation today and going forward.

Liz Thompson: Now, turning to today's We continue to make progress on enrollment in our late-stage clinical programs. First, let's turn to slide 16, which gives an overview of our ACP 101 program in Prader-Willi Syndrome. Let me start with some background on the disease. Prader-Willi is a rare genetic neurobehavioral disorder that affects approximately 8 to 10,000 people in the United States. Its defining characteristic is hyperphagia, which is an unrelenting hunger, a constant craving for food that never ends because patients living with Prader-Willing never feel full.

Liz Thompson: This manifests very early in life and can lead to obesity and myriad complications like type 2 diabetes or heart disease, as well as behavioral changes like aggression and anxiety. And unfortunately, life expectancy is currently only around 30 years old, largely due to cardiovascular disease.

Liz Thompson: Please turn to slide 17. As a reminder, we're currently running a Phase 3 study called COMPASS-PWF. This study is global, multicenter, randomized, double-blind, and placebo-controlled. Building on the prior Phase III experience, this trial focuses on the 3.2 mg dose that was previously shown to reduce hyperphagia-related behaviors. We also utilized the same primary endpoint as was used previously, the hyperphagia questionnaire for clinical trials.

Liz Thompson: We anticipate giving more specific guidance on timing as we get further into enrollment, but thus far, it is proceeding well. We've been truly pleased with the enthusiasm we're seeing in the Prader-Willi community, and we look forward to continuing to work with them and clinical experts as we advance through the study. And, of course, if data from this phase three study are positive, we plan to submit a new drug application for the treatment of hyperphagia in PWS to the FDA. Turning to slide 18.

Mark: We plan to submit a new drug application for the treatment of hyperphagia and dws to the FDA.

Mark: Turning to slide 18.

Liz Thompson: Now, on our second late-stage clinical program, ACP 204. You've heard from both Steve and Brendan today about the strong growth in nuplazid. We're looking to build upon that solid foundation with ACP204, our next generation 5-HT2A compound that we're developing with the intent to expand our neuropsychiatry portfolio. We're very encouraged by what we've seen so far with ACP204 in a comprehensive phase one program. No sign of QT prolongation at the doses that we were studying.

Mark: Now on our second late stage clinical program ACP 204.

Speaker Change: You've heard from both Steve and Brendan today about the strong growth in NUPLAZID, we're looking to build upon that solid foundation with ACP tool for our next generation <unk> compound that we're developing with the intent to expand our neuro psychiatry portfolio.

Speaker Change: We're very encouraged by what we've seen so far with <unk> and a comprehensive phase one program no sign of Qt prolongation that the doses, we're studying a wide dose range supporting the potential for a dose equivalent to approximately twice the approved NUPLAZID 34 milligram dose.

Liz Thompson: A wide dose range supporting the potential for a dose equivalent to approximately twice the approved nuplazid 34 milligram dose and steady state PK achieved in less than half the time of nuplazid, suggesting the potential for an earlier onset of activity. ACP 204's profile could represent a significant improvement over the already strong product profile for NuPlas. Please turn to slide 19 to review our ongoing clinical trial. Currently, ACP204 is in development as a potential treatment for Alzheimer's disease psychosis.

Speaker Change: <unk> steady state PK achieved in less than half the time of NUPLAZID, suggesting the potential for an earlier onset of activity.

Mark: <unk> profile could represent a significant improvement over the already strong product profile for NUPLAZID.

Mark: Please turn to slide 19 to review our ongoing clinical trial.

Liz Thompson: The program is global and contains randomized, double-blind, placebo-controlled studies. We've previously discussed our approach to making enrollment in the Phase 2, and Phase 3 programs seamless under a master protocol, which we aligned upon with FDA and other regulators. However, regulators in the EU haven't agreed to this master protocol, so enrollment at sites in that geography will only be limited to Phase II at this time.

Liz Thompson: We continue to plan for a Phase II study with over 300 patients and two Phase III studies of roughly equivalent size. The Safety Study is ongoing and is designed and sized in such a way that, if successful, it could be considered an adequate and well-controlled registrational study. Once the full Phase 2 study data are collected, we will analyze and report results, by which time the two Phase 3 studies will already be underway at all study sites outside of the EU, with the EU sites joining the Phase 3 program a little later. Again, I anticipate getting more specific guidance on timing as we get further into enrollment.

Liz Thompson: Finally, moving to day view on slide 20, where we continue to make progress in our ambition to bring this medicine to patients outside the U.S. living with Rett syndrome. We've made our submission to Health Canada and continue to look forward to a regulatory decision in the fourth quarter. We are also targeting a submission of the marketing authorization application in the EU in the first quarter of next year.

Liz Thompson: And finally, we've had productive conversations with PMDA, the regulatory agency in Japan, regarding the potential to bring Debut to patients there. As is typical, additional clinical work will be necessary to support approval in Japan, and PMDA has given us valuable initial guidance on a potential development plan. We very much look forward to continuing to collaborate with PMDA and Japanese experts to design a clinical program. We will also continue to build the body of evidence around debuts with presentations at medical meetings and in the peer-reviewed literature. A few highlights are included on this slide.

Liz Thompson: I'll start with Lilac 1 and Lilac 2, which were the open-label extensions of Lavender, our pivotal study for Debut. Patients completing the Pivotal Study were first eligible to enroll in Lilac 1 for up to 40 weeks, and then, upon completion, they could enroll in Lilac 2 for an additional three years. So, in total, the studies represent the potential for nearly four years of continuous treatment with babies. And while there are important caveats with long-term open-label studies like this, for instance, patients who aren't doing well tend to drop out, they can give us important insight into the effects that long-term treatment can have.

Liz Thompson: And what we saw in LILAC1 and LILAC2 was that long-term treatment continued to improve symptoms of Rett syndrome without evidence of new safety concerns. And importantly, in those caregivers who chose to participate in exit interviews, 96% said they were satisfied or very satisfied with treatment efficacy, and over half said they'd had changes in their daily lives as a result of their child's improvement. Both of these studies were recently published in Med.

Mark: Without evidence of new safety concerns and importantly in those caregivers who chose to participate in exit interviews, 96% said they were satisfied or very satisfied with treatment efficacy and over half. So they'd had changes in their daily lives as a result of their child's improvement. Both of these studies were recently published in med.

Liz Thompson: LOTUS is a real-world evidence study enrolling patients who have been prescribed commercial debuts. Real-world evidence studies can provide supplemental information to the necessary constraints of a clinical trial. While Lotus is ongoing, and data will continue to accrue, it's notable that there is evidence of significant variation in approaches to titration and diarrhea management, with only a minority of caregivers reporting use of anti-diarrheal medications or supplemental fiber. These data on diarrhea management, in particular, suggest there could be room for continued improvement in the patient experience.

Mark: Lotus is a real world evidence study enrolling patients who are prescribed commercial debut.

Mark: Real World evidence studies can provide supplemental information to the necessary constraints of a clinical trial.

Mark: Although this is ongoing and data will continue to accrue. It's notable but there is evidence of significant variation approach to titration and diarrhea management with only a minority of caregivers reporting use of anti Diarrheal medications are supplemental fiber. These data on diarrhea management in particular suggests there could.

Mark: The room for continued improvement in the patient experience.

Liz Thompson: LOTUS has also allowed us to collect information from caregivers outlining the nature of improvements they see, with nonverbal communication, alertness, and social interaction and connectedness as the most consistently cited. These data were presented at the recent International Rett Syndrome Foundation Annual Meeting. Now, I'll turn it over to Mark for a financial update beginning on slide 21.

Mark: Lotus has also allowed us to collect information from caregivers outlining the nature of improvements they see with nonverbal communication alertness, and social interaction and connectedness as the most consistently.

Mark: Consistently cited these.

Mark: These data were presented at the recent international Ret Syndrome Foundation annual meeting.

Mark: And now I'll turn it over to Mark for a financial update beginning on slide 21.

Mark Schneyer: Thank you, Liz. Let's review our quarterly financial performance on slide 22. In the second quarter, we recorded $242 million in total net sales, up 46% from the second quarter of last year. Debut net product sales were $84.6 million in the second quarter, up from $23.2 million in the second quarter of last year. Sequentially, debut net sales were up 11% from the first quarter, comprised of 7% follow growth and a 4% increase in net price.

Mark Schneyer: New Plazid net product sales were $157.4 million in the second quarter, up 11% versus the prior year's second quarter. Gross to net for New Plazid was 23.8% in Q2. Our New Plazid franchise achieved 4% demand bottle growth and 6% sell-in bottle growth when comparing Q2 2024 to Q2 2023. In this year's quarter, our sell-in modestly outpaced demand, while demand modestly outpaced sell-in in last year's quarter. On a year-to-date basis for 2024, shell-in has equal demand.

Mark Schneyer: R&D expenses increased to $76.2 million in the second quarter of 2024 from $58.8 million in the second quarter of 2023. The increase in research and development expenses was mainly due to increased costs for ACP-101, ACP-204, and early-stage programs, partially offset by a reduction in costs associated with our Pimibanserin negative symptoms of schizophrenia. SD&A expenses increased to $117.1 million in the second quarter of 2024 from $96 million in Q2 2020. The increase was primarily driven by upfront costs related to a new consumer activation program to support our new Plaza franchise, increased marketing costs in the U.S. to support JVU, and investments to support the potential commercialization of triphenatide outside the U.S. We ended the quarter with a cash balance of $500.9 million, which increased $30.4 million versus the first quarter.

Mark Schneyer: Please turn to slide 23 for discussion of our 2024 financial guidance. For New Plaza, we are increasing our guidance for net sales from a range of $560 to $590 million to a range of $590 to $610 million based upon our strong performance year to date. As Ren mentioned, this guidance increase does not rely upon an impact from our new DTC campaigns, the benefits of which will largely be achieved in 2025 and 2026 through a combination of accelerated new patient starts and refills from these new patients.

Mark Schneyer: In terms of growth in Afternoon Plaza, we are narrowing our guidance to a range of 26 to 28% as we are now halfway through the year. When thinking ahead to 2025 for New Plaza Gross Net and considering the specified small manufacturer phase-in as a part of the Inflation Reduction Act, we expect New Plaza Gross Net to reduce by approximately 300 basis points year over year. For Debut, as discussed earlier, while we saw a rebound in new patient starts and a reduction in patient discontinuations, our overall growth in net patient ads has been slower than expected. As a result, we are updating our guidance for debut net sales to a range of $340 to $370 million, down from our previous guidance range of $370 to $420 million.

Mark Schneyer: Taking New Plaza and Debut together, our guidance for total revenues is $930 to $980 million. For both R&D and SG&A, with half of the year completed, we are narrowing our guidance range. We are narrowing SG&A expenses for the year to the higher end of our previous range and now expect between $465 and $480 million for SG&A expenses. As Bren mentioned, we are able to absorb the expenditures associated with the new DTC campaigns without the need to increase our guidance range for SCNA.

Mark Schneyer: We are also narrowing R&D expenses for the year to the lower end of our previous range and now expect between $305 to $315 million for R&D. Lastly, we are updating our cash guidance range to $575 to $625 million, reflecting our updated guidance ranges for net sales and operating. Now, I'll turn the call over to Steve for closing remarks.

Mark: Yeah.

Mark: We are also narrowing R&D expenses for the year to the lower end of our previous range and now expect between $305 million to $315 million, but R&D expenses.

Mark: Lastly, we are updating our cash guidance range to $575 million to $625 million.

Mark: Reflecting our updated guidance ranges for net sales and operating expenses.

Mark: And now I will turn the call over to Steve for closing remarks.

Steve Davis: Thanks so much, Mark. Please turn to slide 24.

Steve: Thanks, So much Mark please turn to slide 24.

Steve Davis: We have a strong foundation for our business today and are excited to build on our successes and drive future growth. We're focused on continuing to execute on this significant opportunity that remains in front of us for both Debut and New Plants. We look forward to further enrolling our two late-stage programs, including our Phase 3 program for Prader-Willi Syndrome and our Phase 2, phase 3 program for Alzheimer's disease psychosis. We're pleased to have these exciting pipeline assets while at the same time being in a position to generate sustainable and increasing cash flow from operations to fund future growth. With that, I'll now turn it over to the operator for Q&A. Operator? Ladies and gentlemen, if you wish to ask something,

Steve: We have a strong foundation for our business today and are excited to build on our successes and drive future growth.

Steve: We're focused on continuing to execute on the significant opportunity that remains in front of us for both debut and NUPLAZID.

Mark: We look forward to further enrolling our two late stage programs, including our phase III program for <unk> Willi syndrome, and our phase II phase III program in Alzheimer's disease psychosis.

We're pleased to have these exciting pipeline assets, while at the same time being in a position to generate sustainable and increasing cash flow from operations to fund future growth.

Speaker Change: With that I'll now turn it over to the operator for Q&A operator.

Operator: Ladies and gentlemen, if you wish to ask a question, please press star followed by one one on your touchtone telephone. If your question hasn't been answered or you wish to remove yourself from the queue, please press star 11 again. In the interest of time, may I ask that you please limit yourself to one question? I repeat, please limit yourself to one question. Press star 1 1 to begin. Please stand by for your first question. And our first question comes from Ritu Baral, with TD Cowan. Your line is open.

Speaker Change: Ladies and gentlemen, if you wish to ask a question. Please press star followed by one one on your Touchtone telephone.

Speaker Change: Question has been answered or you wish to remove yourself from the queue. Please press star one again.

Speaker Change: In the interest of time, we ask that you. Please limit yourself to one question.

Speaker Change: Our repeat please limit yourself to one question.

Speaker Change: Press Star one to begin.

Speaker Change: Please standby for your first question.

Speaker Change: Okay.

Ritu Baral: Good afternoon, everyone. Thanks for taking the time to answer the question. I guess I wanted to ask about the difference that you guys are seeing in the ongoing discontinuation rate and the new start rate between the community and the COEs. I believe you said that two-thirds of the new prescriptions were coming from the COEs, like high volume in the community, but you know, how are those centers and doctors managing discontinuations versus the COEs? And then, the second part of one question, how the dose titration discussion that was featured significantly at IRSF factored into that as well? Thanks.

Steve Davis: Thanks much for the question, Ritu. Brendan, you want to take that? Sure. Thanks, Ritu.

Brendan Teehan: Sure. Thanks, Ritu. So first, just in terms of discontinuation rates between COEs and non-COEs, we see that it's reasonably steady between the both, meaning to say that there's more consistency that we see in our persistency curves whether you're in a COE or a high-volume institution. From a new patient start perspective, our audience will recall that we started in COEs and had excellent uptake. Obviously, these are the practices that were involved in our clinical trials, the vast majority of them.

Brendan Teehan: So our penetration of COEs was and is significantly higher than it is outside of those COEs. So it's logical that as we continue to talk about the Debut message and expand our breadth, the majority of our prescriptions are going to, over time, begin to come from non-COEs and from the community. As a reminder, about a quarter of all Rett patients will be found in centers of excellence, of which there are now 21.

Brendan Teehan: So it gives you a sense of just patient processing ability from that segment. And then the other 75 percent are going to be found in these high volume and community practices. So we continue to increase our penetration there. Two thirds of our new starts come from there. And we still have a steady flow of about a third of our prescriptions coming from COE. I think you also made a reference to IRSF for dose titration. I'll try to touch on that. If I don't answer your question, please ask it differently.

Brendan Teehan: But we did speak at IRSF about dose titration and the ability of physicians, if they deem it appropriate, to start at a lower dose and titrate up. We are definitely seeing that, and we're seeing it both in COEs and outside of COEs. We also have been encouraging families to stay in close contact with their physicians to make sure that if there are needs to make any adjustments to their GI plan, they do that in the first two to four weeks.

Brendan Teehan: All of that is intended to help increase the ability of patients and families to stay on therapy through those first couple of weeks on treatment with Debut and get out to the benefits that we expect they'll see with longer-term treatment.

Operator: And our next question comes from Charles Duncan with Canter. Your line is open.

Charles Duncan: I yeah, thanks for taking the question. Unfortunately, it's a two-parter. And that is related to the bookends in terms of debut guidance. Now that we're in the third quarter, I guess I'm wondering what gives you confidence to hit one end versus the other. What has to happen?

Operator: And then just a clarification from Liz, I wasn't sure I understood, are you going to read out phase two of the ACP 204 study and then phase three? Could you go back and repeat your comments there? Okay. Great.

Steve Davis: Yeah, thanks much for the two-part question, Charles. Mark, do you want to answer the first part? Yes, sure.

Mark Schneyer: Yeah, sure. Thanks for the question.

Mark Schneyer: I guess in terms of day view guidance, where we're tracking today with kind of all the key metrics, I would say we're tracking towards the lower half of our revised guidance range. With all the initiatives that we have in place and the new information and data that we're going to share with HCPs and caregivers about benefits and GI management plans, we think all of that can take us to increasing our metrics and getting towards the high end of the range. And the low end of the range would need to see, you know, our metrics, you know, turn a little backwards from what we're achieving today.

Liz Thompson: Okay, Liz? Absolutely.

Liz Thompson: So, for clarification, how this is going to work is that sites can enroll in Phase 2, and then sites that are not in the EU, once they're done enrolling in Phase 2, move over and start enrolling in Phase 3. So, practically speaking, that means that Phase 2 data is going to come out while Phase 3 is still enrolling. So we think that's actually going to be a helpful thing to then continue to spur enrollment thereafter, and it will help the EU to come on quickly because Phase 2 data are always motivational for physicians and for patients. So hopefully, that's cleared that up. Thank you. Our next question comes from Gregory Renza with RBC Capital Markets. Your line is open. Hi guys, it's Anish on for Greg.

Operator: Thank you. Our next question comes from Gregory Renza with RBC Capital Markets. Your line is open.

Speaker Change: With that have stopped have not restarted thanks, so much.

Steve Davis: Thanks so much for the question, Brendan. Do you want to take these? Sure, thanks.

Speaker Change: Thanks, So much for the question Brendan do you want to take these sure. Thanks.

Brendan Teehan: Sure, thanks. So, I would say that summer looks like summer in terms of what we see for just patient cycling. In July, there are patients that are taking holidays; there are also HCPs taking holidays, but COEs are operating at the same cadence, and we would expect that we will, as families come back from vacations and get into the regular preparation for the upcoming school year, that we would expect to see our new patient starts continue to progress as we get into August and September. The second question was around discontinuations. There are really two different types that we've described.

Brendan: So I would say that the summer it looks like the summer.

Brendan: In terms of what we see for just patient cycling.

Brendan: July there are patients that are taking holidays are also hcp's taking holidays.

Speaker Change: Coes are operating at the same cadence.

Speaker Change: And we would expect that we will as as families come back from vacations and get into the regular preparation for the upcoming school year that we would expect to see our new patient starts continue to progress.

Speaker Change: As we as we get into August.

Speaker Change: September.

Speaker Change: The second question was around discontinuation there really.

Speaker Change: Two different types that we've described but one is the discontinuation where our family has told us and as you know.

Brendan Teehan: One is a discontinuation where a family has told us, and as you know, we have really excellent relationships with our patients and families. We have our FAM team that's out in the field with them, as well as our clinical nurse coordinators that speak with them on a regular basis. So we know a patient has been discontinued. But there are also those who may just be taking a pause, maybe having a medical procedure, and may just have a lapse in treatment.

Speaker Change: Really exquisite relationships with our with our.

Speaker Change: Patients and families. We have our fam team that's out in the field with them as well as our clinical nurse coordinators that speak with them on a regular basis. So we know a patient as discontinued but theyre also those who may just be taking a pause maybe having a medical procedure.

Speaker Change: And may just have a lapse in treatment.

Brendan Teehan: What we've seen over time is if you have, if you've gone out past 60 days, there's still about 20% of those patients that will come back to refill. That gives you some sense for it. In terms of actual discontinued patients, fewer patients that have discontinued have at least to date returned to debut treatment.

Speaker Change: What we've seen over time is if you have if you've gone out past 60 days.

Speaker Change: Still about 20% of those patients that will come back to refill that gives you some sense for it in terms of actual discontinued patients fewer patients that discontinued have at least to date returned to debut treatment.

Operator: Thank you. Our next question comes from Joel Beatty with Baird. Your line is open.

Speaker Change: Thank you. Our next question comes from Joel Beatty with Baird. Your line is open.

Joel Beatty: Hi, congrats on the progress and thanks for the detailed update. For the 70% of diagnosed patients who have not initiated on Debut, are you able to break that group down into any market segments that might be helpful for thinking about that opportunity? So just perhaps, you know, what percent have heard of Debut, or what percent have discussed it with a physician? And then, as a second part, you mentioned a survey that said that over the next 24 months, health care professionals expect to increase their prescriptions of Debut by more than 70% for their patients. Anything about what percent of that surveyed population they were currently at at that point in time of the survey? Thanks.

Joel Beatty: Hi, Congrats on the progress and thanks for the detailed update.

Speaker Change: 70% of diagnosed patients who have not initiated on debut are you able to break that down into any market segments that might be helpful for thinking about that opportunity. So just perhaps what percent have awareness debut of Barclays. You have discussed it with a physician.

As a second part.

Speaker Change: You mentioned a survey that mentioned that over the next 24 months healthcare professionals are expect to increase the prescriptions that debut two more than 70%.

Speaker Change: So their patients.

Speaker Change: Anything about what percent of that survey population. They were currently at that point in time for the survey.

Steve Davis: Yeah, thanks much for the question, Brendan.

Speaker Change: Yes, thanks, so much for the question Brandon.

Brendan Teehan: Thanks. I may ask you to repeat the second question you trailed off at the end. I wasn't sure what that was, but I can answer the first one. So, in terms of the 70% of the population that remains, first, I would remind everyone that Debut has a very broad label. It is for ages two and up.

Brandon: I may ask you to repeat the second question you had.

Speaker Change: Railed off at the end of wasn't sure what that was but I can I can answer the first one for sure. So in terms of the 70% of the population that remains first I would remind everyone that debut has a very broad label. It as for ages, two and up we see both male and female patients being treated and thus far.

Brendan Teehan: We see both male and female patients being treated, and thus far, the patient population is very much reflective of the prevalent population. So we see a wide range of ages and disease severities treated. In terms of the remaining 70%, unsurprisingly, the highest penetration that's expected is in the two to 20-year-old range. It's slightly lower in the 21 plus percent range, but it's still substantially higher than what physicians have been treating to date. And then for the second question, I didn't hear precisely how it was stated.

Speaker Change: The patient population is very much reflective of the prevalent population. So we see a wide range of ages and disease severity is treated in.

Speaker Change: In terms of the remaining 70% unsurprisingly the the highest penetration that's expected is in the 2% to 20 year old range, it's slightly lower than the 21 plus percent range, but it's still substantially higher than what physicians have been treating to date and then for the second question.

Speaker Change: I didn't hear precisely how it was stated.

Operator: If the docs are expected to be treating 70% of their patients in the future, what percent of their patients are they currently treating today, according to that survey? Sorry, good. Thanks for that.

Speaker Change: If the tax are expected to be treating 70% of their patients in the future what percentage of their patients are they currently treating today according to that survey.

Brendan Teehan: Sorry, good. Thanks for the repetition. Yes, no problem.

Speaker Change: Alright, good thanks for the repetition, yes, no problem. So we know that we have prescriptions. We've started 30% of patients we have prescriptions for more than that and the physicians that responded felt that they their patient population. They are treated about 40%. So when I say, 70% in aggregate.

Brendan Teehan: So we know that we have prescriptions. We've started 30% of patients. We have prescriptions for more than that. And the physicians that responded felt that their patient population had been treated about 40%. So when I say 70% in aggregate, that's stating that they would increase from their 40% to a total of their total addressable population of approximately 70%, which varies by age category. Great. Thank you. Thank you. Our next question.

Speaker Change: That's stating that they would increase from their 40% to a total of their total addressable population of approximately 70% which varies by age category.

Speaker Change: Great. Thank you.

Speaker Change: Yes.

Operator: Thank you. Our next question comes from Mark Goodman with WeRink. Your line is open.

Speaker Change: Thank you. Our next question comes from Marc Goodman with <unk>.

Speaker Change: Your line is open.

Marc Goodman: Yeah, we've talked a lot about <unk>, but can you talk about new Clos it a little bit just the rest of the year the puts and pulls on.

Marc Goodman: On making the high end and low end of the numbers. Thanks.

Mark Goodman: Yeah, thanks much for the question, Mark. Mark Schneyer, do you want to take that? Yeah, thanks, Mark.

Speaker Change: Yeah. Thanks, so much for the question Mark.

Speaker Change: Mark do you want to take that.

Steve Davis: Yeah, thanks, Mark. On Neuplazid, yes, sir, we're certainly pleased with our performance to date and have increased our range, as we talked about in the prepared remarks. You know, for Neuplazid, you know, in the metrics we are, where we are today, you know, we're tracking around the midpoint of the guidance. So, you know, kind of high and low from there, you know, outperformance, you know, we'll, you know, we'll have new patient starts kind of beyond where we're tracking towards today and potential, you know, early positive benefits beyond our timing expectations for the DTC campaign. The lower end would just be us, you know, falling a little behind our performance where we are today.

Mark: Yes, thanks Mark.

Plaza: Plaza, Yes, we're certainly pleased with our performance to date and have increased our range as we talked about on the prepared remarks.

Speaker Change: For NUPLAZID and the metrics, we are where we are today, we're tracking around the midpoint of the guidance.

Speaker Change: So kind of high and low from their outperformance.

Speaker Change: We will have new patient starts kind of beyond where we're tracking towards today and potential.

Mark: Early positive benefits beyond our timing expectations for the DTC campaign lower end.

Mark: B us falling a little behind our performance are where our where we are today and then of course.

Mark: With the brand and NUPLAZID small fluctuations of gross to net or in channel inventory can impact where our final results will be for the year.

Mark Schneyer: Thank you. Our next question comes from Jeff Hung with Morgan Stanley. Your line is open.

Steve Davis: And then, of course, you know, with the brand and Neuplazid, small fluctuations of gross to net or in channel inventory can impact where our final results will be. Thank you. Our next question comes from Jeff Hung with Morgan.

Speaker Change: Thank you. Our next question comes from Jeff Hung with Morgan Stanley. Your line is open.

Speaker Change: Thanks for taking my question for <unk> hundred one in <unk> can you just talk about your confidence in your approach versus what.

Speaker Change: Give me what competitors are doing it what is your current thinking about potentially expanding development into other indications with hyperphagia obesity.

Mark: Okay.

Operator: Yeah, thanks much for the question. I'm going to ask Kimberly Manhard to take that.

Mark: Yes. Thanks, so much for the question I'm going to ask Kimberly Manhart icebreaker.

Kimberly Manhard: Yes, so with respect to Prader-Willi, you're probably aware of Seleno's compound, GCCR, which is diazoxide, diazoxide-choline controlled release. Diazoxide actually was originally approved for hypoglycemia, so it's been out in the market for some time, but this is a different form, a covalent diazoxide-choline.

Mark: Yes.

Kimberly Manhart: Spectra, <unk>, Willi and Youre, probably <unk> compound <unk> oxide.

Mark: At dice onsite choline controlled lease.

Speaker Change: Douglas connections are originally approved for hypoglycemia and so it's been out in the market for some time, but this is a different platform currently I apologize I think Helene.

Kimberly Manhard: And they have indicated back in late June that they filed their NDA, and so they had a randomized controlled trial that was not positive for the overall data set. But when they looked at inpatients and data up through the start of COVID, they were able to see statistically significant differences between the placebo and active. And then they conducted an open label extension, and from that extension, they gained agreement to do a randomized withdrawal period of the open label extension and saw positive benefits.

Mark: And they add.

Mark: Have.

Mark: Indicated back in late June that they filed their NDA and so they had a.

Mark: Randomized controlled trial.

Mark: It was not positive for the overall dataset, but when they looked at in patient data through starting to Covid and we're able to see.

Mark: Particularly significant difference between the placebo and active and then they conducted an open label extension in that open label extension integrating that changeover randomized it's Carl here yet on the open network entered and saw a positive benefit.

Mark: But we think that there are lot of opportunities for treatment of hyperplasia and product release, and John that's a very devastating disease, and we mentioned a need it.

Kimberly Manhard: So, but you know, we think that there are a lot of opportunities for treatment of hyperphagia and Prader-Willi syndrome. It's a very devastating disease, and new treatments are needed. If the product is approved, then we've done an analysis to show that they should be able to be given together since they have very different mechanisms of action, and also there's no PK, or PK interaction or any overlapping toxicities. Their main toxicities were hypertrichosis, pulmonary edema, and hyperglycemia. But we don't see those in our trials.

John: If the product is approved and we've done an analysis to show that they should be able to be given together.

John: Since there are very different mechanisms of action.

John: And also there is no PK and PK interaction no overlapping toxicity.

Speaker Change: Main toxicities were.

John: Hypertrichosis and.

John: Pulmonary edema and hyperglycemia, so we don't see that in our trials.

Steve Davis: And Jeff, maybe just to annotate that a little bit, I think that, you know, the confidence in our making an investment here and in running a phase 3 study really comes from the data. It comes from the phase 2 data, where we see a nominally significant reduction in hyperphagia associated with Parder-Willi Syndrome at the dose that we're testing. It's the same primary endpoint in the phase 3 study as in the phase 2. And so, there are lots of things that go into these assessments, but the principal data that we're resting on is that phase 2.

Mark: Hey, Jeff maybe just to annotate that a little bit I think that the confidence in.

Mark: Our.

Jeff Hung: Making an investment here and in running a phase III study really comes from the data becomes from the phase II data, where we see a nominally significant.

Jeff Hung: Reduction in hyperphagia associated with partly Willi syndrome at the dose that we're testing as the same primary endpoint in the phase III studies phase II and so.

Mark: There are lots of things that go into these assessments, but the principle.

Mark: The data that were resting on it is that phase two data.

Keith Taffer: Thank you. Our next question comes from Keith Taffer with BMO Capital Markets. Your line is open.

Operator: Thank you. Our next question comes from Keith Taffer with BMO Capital Markets. Your line is open. Hi team, congratulations on the quarter and thanks for taking my questions. Congratulations to Liz on the transition to ACADIA. First, a question on

Mark: Thank you. Our next question comes from Keith Tapper with BMO capital markets. Your line is open.

Keith Tapper: Hi team congrats on the quarter and thanks for taking my questions and congratulations to lose on the transition to Acadia.

Keith Tapper: First question on debut.

Keith Tapper: Would be helpful to understand the impact of the community engagement and how that's underway to address discontinuation I was wondering on the <unk>.

Speaker Change: Effort or the impact of GI management efforts on patient dynamics could you provide color on when the efforts began to reach the community and when the impact should be fully realized and is there an effort to drive restart maybe through patient claims surveillance or revisiting providers. Thanks.

Operator: Yeah, thanks much for the question. I'm going to ask Parag Meswani to address those questions. Yeah, thanks.

Speaker Change: Yes. Thanks, so much for the question I'm going to ask <unk> to address.

Speaker Change: Address those questions.

Parag Meswani: Yeah, thanks for the question. So as a reminder, on our last call, we talked a lot about the consistent application of GI management and GI mitigation strategies. That's an ongoing effort, right? We do that with physicians on a regular basis, and we do that with caregivers on a regular basis as well. So, you know, ensuring consistent implementation of simple things like stopping constipation medications, adding fiber to your diet, hydration, and usable paramide. Dose modification is a new part of the algorithm that's now being utilized more and more often as well. We're starting to see the impact of that. You saw that in the second quarter, right?

Speaker Change: Yes. Thanks, Thanks for the question so as a reminder.

Speaker Change: Last call, we talked a lot about the consistent application of GI management Gi mitigation strategy. That's an ongoing effort right. We do that with physicians on a regular basis and we're doing that with rent provider caregivers on a regular basis as well so.

Speaker Change: Ensuring consistent limitation of simple things like stopping constipation medication, adding fiber to your diet hydration and use of loperamide Joseph modification as there is a new part of the algorithm that is now being utilized more and more often as well we're starting to see the impact of that you saw that in the second quarter, we have begun to implement a more consistent.

Parag Meswani: We've begun to implement a more consistent message to providers and caregivers on that, and we're starting to see some of the benefits of that, just in terms of the total active patients on therapy and the decline in numerical discontinuations that we saw in the past quarter. And we'll continue to reinforce that for the remainder of this year. On restarts, we're beginning to see some patients begin to come back on therapy, but our focus has been on ensuring a very positive treatment initiation and supporting those patients that have been on therapy for the longest time.

Speaker Change: Message to provider than a caregiver crews on them, we are starting to see some of the benefits of that in terms of the total active patients on therapy and the decline in numerical discontinuation that we saw in the past quarter.

Speaker Change: And we will continue to reinforce that for the remainder of this year on restarts, we're beginning to see some some patients begin to come back onto therapy, but our focus has been on ensuring a very positive treatment initiation and it's important to those patients that had been on therapy.

Speaker Change: The long term.

Parag Meswani: Thank you. Our next question comes from David Hoang with Citigroup. Your line is open. Hi there. Thanks for taking my question. So I wanted to ask about patients on debut long term. Do you have any data points?

David Hoang: Thank you. Our next question comes from David Hoang with Citigroup. Your line is open.

Speaker Change: Thank you. Our next question comes from David Wong with Citigroup. Your line is open.

Operator: Or maybe

David Wong: Hi, there thanks for taking my questions.

David Wong: I wanted to ask about patients on gave you long term do you have any data points.

David Wong: Or maybe kind of the earliest patients that initiated therapy of any reached a year or more and do we have.

Speaker Change: Any visibility on I guess 12 month persistency rate.

Speaker Change: Compared to nine months and then.

Speaker Change: Just one follow up would be on ACP 204, if I heard correctly. It sounded like <unk> did not agree to a seamless phase III protocol and so I'm just curious kind of why that might be what was the pushback and how that how might that impact the regulatory path in Europe. Thank you.

Steve Davis: Yeah, thanks a lot, David. Brendan, do you want to take the first question? And then Liz, do you want to take the second?

Brendan: Yes. Thanks, so much David Brendan you want to take the first question and then second for sure. Thanks, David for the question.

Brendan Teehan: For sure. Thanks, David, for the question. And as I said in my prepared remarks, we actually have a number of patients that are out past two or three years that are on debut. And actually, in some of our programming, we have caregivers of those loved ones that speak about the benefits they're seeing at six months, at a year, and two years, often providing really the marker for other families on what they might hope to see in the future.

Brendan: As I said in my prepared remarks, we actually have a number of patients that are out.

Speaker Change: Past two or three years that are on on debut and actually in some of our programming we have caregivers of those loved ones that speak about the benefits. They are seeing at six months at a year and two years, often providing really the marker for other families on what they might hope to see.

Brendan Teehan: What they might hope to see with longer-term treatment. You also asked about the persistency curve. So the LILAC-1 study, the placebo rollovers, are the ones that we're using to look at our performance in the real world, as opposed to that study, where we tracked 10 or more percentage points above that, out to nine months. And at 12 months, we don't have a comparator to give you, but we are still seeing excellent persistency rates, well above 50%, that give us that confidence in the longer-term persistency we're expecting to see in the real world with the support we're able to give.

David Wong: With with longer term treatment you also asked about persistency curves so the.

Speaker Change: The lilac one study the placebo rollovers or the ones that we're using to look at our performance in the real world as opposed to that study, where we track more 10 or more percentage points above that out to nine months.

David Wong: And at 12 months, we don't have a comparator to give you but are still seeing excellent persistency rates well above 50%.

David Wong: Give us that confidence in the longer term persistency, we're expecting to see in the real world with the support we are able to give.

Brendan Teehan: And just one additional point there, of all the patients that started on debut in our Phase 3 program, 40% of them are still on debut. So again, they've been on therapy for three plus years. And of all of those patients that rolled over to the commercial drug, they've all stayed on therapy during the 15 months that we've been on the market with the exception of one patient.

David Wong: And just one additional point there.

Speaker Change: Of all the patients they started debut.

Speaker Change: Our phase III program, 40% of them are still in beta.

Dave: And Dave you today, so again thats had been on therapy.

Dave: <unk> therapy for three plus years.

Dave: And of all of those patients that rolled over on the commercial drug.

Dave: They've all stayed on therapy during the <unk> months that we're going to market with except for one patient that has continued.

Liz Thompson: And for the 204 point, just to clarify, so how we were doing this was running it under a master protocol, and it was really just the master protocol concept that the EU had an issue with at this point. So we fully anticipate running phase two, and then running a separate, rolling them into phase three at a later time. So Europe will participate in phase three, and we anticipate that this is going to be acceptable for regulatory purposes. But it's really just that they can't go straight through with seamless enrollment under a master protocol right now.

Speaker Change: And so the 204 point just to clarify so how long we're doing this is putting it under a master protocol and it was really just the Master protocol concept that you had an issue with at this point until we fully anticipate running phase II and then running a separate.

Dave: Rolling them into phase III at a later time to Europe will participate in the phase III. We anticipate that this is going to be acceptable for regulatory purposes, but it's really just that they can't come straight through with the seamless enrollment under a master protocol right now.

Paul Manis: Thank you. Our next question comes from Paul Manis with Stiefel. Your line is open.

Operator: Thank you. Our next question comes from Paul Maness with Stiefel. Your line is open. Hey, this is James. I'm for Paul. Thanks for taking our question. Maybe one on Neuplazid and you know, you mentioned

Speaker Change: Thank you.

Paul <unk>: Our next question comes from Paul <unk> with Stifel. Your line is open.

Speaker Change: Hey, this is James on for Paul Thanks for taking our question.

James: Maybe one on NUPLAZID and you mentioned the DTC and you don't expect the effect to kind of really take.

James: To take effect until 2025, and 2026 I guess.

Brendan: What are your expectations in terms of like what growth can look like in <unk>.

Speaker Change: Your ROI on DTC could look like for NUPLAZID, and then could you just remind us on how gross and that's going to evolve for NUPLAZID overtime.

Speaker Change: Missed it a little bit I, just wanted to make sure. Thanks.

Operator: Yeah, I'll take the first question, Mark, and I'll ask you to answer the second. We've run DTC campaigns previously in the New Plaza franchise. It's an important part of The communication, The, this patient population. As we mentioned in our remarks, it turns over pretty quickly.

Speaker Change: Yeah I'll take the first question Mark I'll ask you to answer the second.

Mark: We've run DTC campaigns previously.

Speaker Change: NUPLAZID franchise.

Speaker Change: It's an important part of.

Mark: The communications.

Speaker Change: The patient population.

Speaker Change: As we mentioned in our remarks turns over pretty quickly and so there is a kind of a continual feet of new patients that have not heard messaging before and based upon the previous DTC campaigns. We've done we've seen they had very positive rois and we've seen a meaningful impact on being able to grow this franchise.

Steve Davis: And so there's a kind of continual feed of new patients that have not heard messaging before. And we, based on the previous DTC campaigns we've done, we've seen very positive ROIs, and we've seen a meaningful impact on being able to grow this franchise. We're now eight years in. We paused DTC during the pandemic and in the few years since because the market was pretty turbulent. And it just wasn't an ideal environment for making these investments.

Steve Davis: We indicated at the time that if market conditions change, and we see an opportunity to make these investments, we would. The opportunities that we have today, I think are really as well as, as Brendan described in his remarks, the awareness of hallucinations and delusions is down dramatically. That's important because when patients are diagnosed with delusions, Parkinson's disease, many times their physicians don't talk about hallucinations and delusions because they don't come up until years later, and they only impact about half the population.

Brendan: We're now eight years in we paused DTC during the pandemic and the two year sense, because the market was pretty turbulent and it just wasn't an ideal environment for making these investments we indicated at the time that if market conditions change and we see an opportunity to make these investments we will the opportunities that we have.

Brendan: Today, I think is really as well.

Brendan: As an attractive is set up is it could be as Brendan described in his remarks, the awareness of hallucinations and delusions was down dramatically that's important because when patients are diagnosed with <unk>.

Steve Davis: So when they happen, these patients just don't connect the dots. They just don't associate them with Parkinson's. So many times, they go untreated for a very long period of time. And so it's really important to get this messaging out there. I think we have a very, very fertile environment to make this investment. And we're very excited.

Speaker Change: Parkinson's disease, many times their physicians don't talk about hallucinations and delusions, because they don't come up until years later.

Speaker Change: The only impact about half the population so when they happen. These patients just don't make connect the dots. They just don't associate them with Parkinson's as so many times. They go untreated for very long period of time, and so it's really important to get this messaging out there I think we have a very very fertile environment to make this investment.

Speaker Change: Very excited about making.

Mark Schneyer: And I can jump in to address the question on gross to net. So, you know, for next year, starting 2025, we expect the Medicare Part D redesigned to take place.

Speaker Change: And I can jump into the to address the question on gross to net so for next year, starting 2025, we expect.

Speaker Change: The Medicare part D redesigned to take place and as part of that we will qualify for the specified small manufacturer phased in as I mentioned in the prepared remarks. So as we look from gross to net for this year from this year to next year for NUPLAZID, We expect our gross debt go down by about 300 basis points.

Operator: And as part of that, we will qualify for the specified small manufacturer phase in, as I mentioned in the prepared remarks. So as we look from gross to net for this from this year to next year for New Plazid, we expect our gross net to go down by about 300 basis points as well as that small manufacturer phase in starts. And then from there, you know, the gross net will likely gradually increase as that small manufacturer phase in unwinds over the coming year. Thank you. Our next question comes from Yatin Suneja with Guggenheim Securities. Your line is open.

Speaker Change: As well as got small manufacturer fees and starts and then from there it will.

Speaker Change: <unk> will likely gradually increase as that small manufacturer phasing unwind over the coming years.

Speaker Change: Thank you. Our next question comes from <unk> with Guggenheim Securities. Your line is open.

Speaker Change: Great. Thanks for taking my question. This is Eddie on for Alan.

Eddie: Debut, where there any gross to net differences from <unk>, how much of that revenue growth came from an increase in net price versus patient growth and then on the patient number you told US there was 900 as of August one or you are you able to give us a sense of how many of those came in July. Thank you.

Steve Davis: Yeah, I'm gonna ask Mark to take the first question, and Brendan to take the second.

Speaker Change: Yes, im going to ask Mark to take the first question Brendan the second.

Speaker Change: Yeah.

Mark Schneyer: Yes, so, as we said in the prepared remarks, you know, our volume and price split sequentially for debut was 7% follow-on growth, so essentially volume and patient growth, and 4% net benefit from price as we took a price increase midway through the second quarter.

Mark: Yes, so so as we said in the prepared remarks.

Speaker Change: Our.

Speaker Change: <unk> and price split.

Mark: Sequentially for debut was 7% followed growth, so essentially volume and patient growth and 4%.

Speaker Change: Net benefit from price as we took a price increase midway through the second quarter.

Brendan Teehan: And for the second question about the 900 patients, just a couple of things. Um, there's, there's, uh, as a reminder, it was towards the end of the first quarter that we hit sort of our low point for patients, active patients on treatment. Throughout that time period moving forward, we've seen nice incremental month over month growth in active patients. So, you know, 900 wasn't a sudden overnight thing. This was a fairly steady progression of those 66 patients added over a 90 plus day period.

Speaker Change: And for the second question around the 900 patients just a couple of things.

Speaker Change: There is there is.

Speaker Change: As a reminder, it was towards the end of the first quarter that we hit our low point for patients active patients on treatment.

Speaker Change: Throughout the throughout that time period, moving forward, we've seen nice incremental month over month growth in active patients. So 900 wasn't.

Speaker Change: A sudden overnight, saying this was a fairly steady progression of those 66 patients added over 890 plus day period.

Steve Davis: Yeah, and I might just add to that that when you start looking at things on a daily or weekly basis, which we do every day, things, you know, move around a little bit, you know, last week was one of the best weeks we've had in a couple of quarters. So, we're hesitant to try to break things down into two. This is a shorter period, but as Brendan mentioned, the trend that we've seen has been a consistent trend throughout the country.

Speaker Change: Okay, and I might just add to that.

Speaker Change: You start looking at things on a daily or weekly basis, which we do every day.

Speaker Change: Yes of course things move around a little bit.

Speaker Change: Last week was one of the best which we've had in a couple of quarters. So.

Speaker Change: We're hesitant to try to break things down in two.

Brendan: Shorter period, but as Brendan mentioned the trend that we've seen has been a consistent trend throughout the quarter.

Operator: Thank you. Our next question comes from Tess Romero with J.P. Morgan. Your line is up. Hi, good afternoon, Stephen team. Specifically, where are you most focused with respect?

Tess Romero: Thank you. Our next question comes from Tess Romero with J.P. Morgan. Your line is up.

Speaker Change: Thank you. Our next question comes from Tessa Romero with Jpmorgan. Your line is open.

Speaker Change: Hi, good afternoon, Stephen Kim.

Tessa Romero: Specifically where are you most.

Stephen Kim: Back to your commercial strategy for the second half here, particularly salary.

Tessa Romero: And for DBS and have you thought about all green or changing your sales infrastructure target key providers new providers.

Speaker Change: And can you also just remind us what is your current prescriber base number and where that city, including Britain overall target.

Steve Davis: Thanks much, Tess. Keep us honest here. Make sure we answer. I think it was a three-part question. I'm going to ask Rob to start.

Speaker Change: Thanks, so much guys.

Speaker Change: As honest here to make sure we answer I think it was a three part question I'm going to have some broad just hard.

Unknown Executive: Yeah, so I'll start with the first question, which I think was, where are we going to source growth from here from an ACB perspective? One thing I'll say at the outset is there are still plenty of opportunities at the Centers of Excellence, right? They are still a core constituent in driving prescriptions and patient ads. But we have been pivoting our business and our priorities outside of the Centers of Excellence for all the reasons that we've talked about before. Three out of four patients are being seen outside of COEs. They are getting more and more comfortable with this new tool in their toolkit.

Speaker Change: Yes.

Speaker Change: Start with the first question, which I think was where are we going to source growth from here from from an ACB perspective, one thing I'll say at the outset as there is still plenty of opportunities at the centers of excellence or they are still a core constituent and driving prescriptions and patient add but we have been inhibiting our business and our priorities outside of et cetera.

Speaker Change: Pipelines for all the reasons that we've talked about before.

Speaker Change: Three out of four patients are being seen outside of <unk>.

Speaker Change: They are getting more and more comfortable with this new tool in their toolkit and at this stage, we're seeing a very even distribution of where our prescriptions are coming from about a third from Coa is about a third from that middle bucket of high volume institution and a third from the community and if we're going to continue to fish, where the majority of patients are being seen and so our priority has been.

Unknown Executive: And at this stage, we're seeing a very even distribution of where our prescriptions are coming from, about a third from COEs, about a third from that middle bucket of high-volume institutions, and a third from the community. And we're going to continue to fish where the majority of patients are being seen. And so, our priority has been and will continue to be for the remainder of Q3 and into Q4, growing our business and getting our fair share of business from the RET population that is being treated outside of the RET Centers of Excellence.

Speaker Change: And we continue to be for the remainder of Q3 into Q4 growing our business and getting our fair share of business from the population that is being treated outside of the centers of excellence.

Unknown Executive: And we expect to see continued breadth of prescribing in those account settings but also depth of prescribing. We have well over 700 unique prescribers at this point, some of whom have just prescribed AB to a single patient. And our goal is to continue to get more physicians to prescribe AB, and for those that have more than one patient, to have them prescribe it to more of the patients that they are prescribing to.

Speaker Change: But to see continued.

Speaker Change: Breadth of prescribing and those account settings, but also depth of prescribing.

Speaker Change: Have well over 700 unique prescribers at this point I would love just prescribed gave you to a single patient.

Speaker Change: Our goal is to continue to get more physicians to prescribe it for those that have more than a patient that is prescribed to more of the patient that they are currently treated.

Operator: Thank you. Yes, did we catch all, all aspects of your question? I think Brendan maybe has something to add. I can speak. Yeah, I think Tess, you spoke a little bit about structure and prerogative. If I missed anything, feel free to add to it.

Speaker Change: Thank you guys did we catch every.

Speaker Change: All aspects of your question I think Brendan maybe.

Brendan: I think you spoke a little bit to structure and parag, if I Miss anything feel free to add to it but yes, I think 16 months in we've seen a couple of great opportunities that have emerged.

Brendan Teehan: But yes, I think 16 months in, we've seen a couple of great opportunities that have emerged. We've put a team out there called the PACE team. That's the Patient and Community Education Team. It's for families that have expressed a lot of interest in DayView and more information but have not yet signed up for a prescription. Unsurprisingly, as people learn more and more, they have a lot of questions, some of which clinicians can clearly answer.

Speaker Change: We've put a team out there that's called the pace team, that's a patient and community education team. This is for families that have expressed a lot of interest in debut in more information, but have not yet signed up for a prescription.

Speaker Change: Unsurprisingly as people learn more and more they have a lot of questions some of which clinicians can clearly answer but others. They just want to know about.

Brendan Teehan: But others, they just want to know about the access and reimbursement process. They want to know what support they're going to be able to get from ACADIA along the journey, which gives us a chance to talk about our FAM team and others. So we've already had successes of families meeting with our PACE team members and then deciding to get started on a prescription. We have them all placed regionally so that they can be face-to-face with families either individually or at RET community gatherings.

Speaker Change: <unk> access and reimbursement process, they want to know what support they're going to be able to get from the from from Acadia, along the journey, which gives us a chance to talk about our fam team and others. So we've had already successes of families meeting with our Pes team members and then deciding to get started on a prescription.

Speaker Change: We have them all placed regionally so that they can be face to face with families either individually or at <unk>.

Speaker Change: Community.

Brendan Teehan: And as you know, we're heading into RET Awareness Month, or really what I would call more like RET Awareness Quarter because it happens between September and November, really, when we'll have lots of opportunities to engage those families. Then we also have TLLs, or Thought Leader Liaisons, that are engaging with thought leaders in RET but also thought leaders that have a lot of experience with DayVu to help just better describe the treatment journey, the do's and don'ts, and how to be successful in starting patients on therapy. So a couple of enhancements to our promotional field footprint. Yeah,

Speaker Change: Gatherings and as you know, we're heading into red awareness month, or really what I would call more like awareness quarter, because it happens between September and November really where we'll have lots of opportunities to engage those families. Then we also have tll's. Our thought leader liaisons that are engaging with thought leaders in rent, but also thought leaders that have a lot of experience.

Speaker Change: Debuted to help.

Speaker Change: Better describe the treatment journey, the do's and don'ts and how to be successful and starting patients on therapy. So.

Speaker Change: Couple of enhancements to our promotional field footprint.

Unknown Executive: Yeah, the only thing I'll add, Tess, to what Brendan said is that we currently have 100% coverage with our field sales footprint. So with the 5,000-plus patients that are out there, we have 100% coverage of the treating physician for all of those with the field footprint that we have. And we continue to fine-tune that model, and Brendan mentioned a couple of fine-tune adjustments to that, which is the addition of new roles that give us greater opportunities to engage with the prescriber base on the keeping it leader side, but also to have a new resource that can engage directly with recreational caregivers and help them better understand JV's product profile and whether it's right for their loved ones.

Speaker Change: Yes, the only thing I'll add to that.

Speaker Change: Brendan said is we currently have with our field sales footprint, 100% coverage.

Speaker Change: The 5000, plus patients that are out there.

Brendan: We have 100% coverage of the treating physician for all of those with the footprint that we have and we continue to fine tune that model and Brendan mentioned, a couple of fine tune adjustments to that which is the addition of new role that give us great opportunity to engage with the prescriber base on the keeping a liter side, but also on Avenue resource that can engage directly with caregivers and health.

Brendan: Them better understand gave you is product profile and whether it's right for them.

Operator: Thank you. This concludes the question and answer session for today's call. Mr. Davis, please proceed to your closing remarks.

Speaker Change: Thank you. This concludes our question and answer session for today's call. Mr. Davis. Please proceed to closing remarks.

Steve Davis: Great, thank you, operator. Thanks again, everyone, for joining us today. We look forward to updating you on our progress next quarter.

Mr. Davis: Great. Thank you operator, thanks again, everyone for joining US today, we look forward to updating you on our progress next quarter.

Operator: Thank you for your participation in today's conference call. This concludes the presentation. You may now disconnect. Good day.

Speaker Change: Thank you for your participation in today's conference call.

Speaker Change: This concludes the presentation you may now disconnect good day.

Speaker Change: Okay.

Speaker Change: [music].