Q1 2021 ACADIA Pharmaceuticals Inc Earnings Call

[music].

Okay.

Mary: Good day, ladies and gentlemen, and welcome to ACADIA Pharmaceuticals' first quarter 2021 financial results conference call. My name is Mary, and I will be your coordinator for today. At this time, all participants are in a listen-only mode.

Good day, ladies and gentlemen, and welcome to Acadia Pharmaceuticals first quarter 2021 financial results Conference call. My name is Mary and I will be your coordinator for today at this time all participants are in a listen only mode. We will be facilitating a question and answer session towards the end of today's call.

Mary: We will be facilitating a question and answer session towards the end of today's call. If at any time during the call you require assistance, please press star followed by zero, and a coordinator will be happy to assist. I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at ACADIA. Please proceed. Thank you, Mary.

If at any time, if you're going to call you require assistance. Please press star followed by zero and a coordinator will be of she will be happy to let's say for you I would now like the turn the presentation over to Mark Johnson, Vice President of Investor Relations at Acadia. Please proceed.

Thank you Mary.

Mark C. Johnson: Good afternoon, and thank you for joining us on today's call to discuss ACADIA's first quarter 2021 financial results. Joining me on the call today from ACADIA are Steve Davis, our Chief Executive Officer, who will provide an overview of our Q1 2021 financial performance and a review of our business operations. Also joining us on today's call is Amanda Morgan, our Chief Revenue and Customer Officer, and Charmaine Likens, Global Product Planning and Chief Marketing Officer, who will provide updates on our commercial performance.

Good afternoon, and thank you for joining us on today's call to discuss the Acadia is first quarter 2021 financial results.

Joining me on the call today from Acadia are Steve Davis, our Chief Executive Officer will provide an overview of our Q1 2021 financial performance and a review of our business operations also joining us on today's call is Amanda Morgan, our chief revenue and customer officer, and chairman like in global product planning and Chief marketing Officer, who will provide updates.

Of our commercial performance Dr.

Mark C. Johnson: Dr. Serge Sankovich, our President, will discuss our pipeline progress, and our Chief Financial Officer, Alaina Ridloff, will then discuss our financial results in more detail, before turning it back to Steve for final remarks and opening the call up for your questions. I would also like to point out that we are using supplementary slides, which are available on the events and presentation section of our website. Before we proceed, I would first like to remind you that during our call today, we will be making a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.

Doctor search stankiewicz, our president will discuss our pipeline progress and our Chief Financial Officer of Atlanta, Red Lobster will then discuss our financial results in more detail before turning it back to Steve for final remarks, and opening the call up for your questions.

I would also like to point out that we were using supplement slides, which are available on the events and presentations section of our website.

Before we proceed I would first like to remind you that during our call today, we will be making a number of forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995. These forward looking statements, including goals expectations plans prospects growth potential timing of events or future results are based on current information assumptions and expectations.

Mark C. Johnson: These forward-looking statements, including goals, expectations, plans, prospects, growth potential, timing of events, or future results, are based on current information, assumptions, and expectations that are inherently subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially. These factors and other risks associated with our business can be found in our filings made with the SEC.

Currently subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially the.

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.

Mark C. Johnson: You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of today's date. I'll now turn the call over to Steve. Thank you, Mark. Good afternoon, everyone.

Now I'll turn the call over to Steve.

Thank you Martin good afternoon, everyone and thank you for joining us today.

Stephen R. Davis: And thank you for joining us. Please turn to slide four. We remain steadfast in our commitment to our mission and to executing on our three strategic pillars to create long-term growth. First, driving continued growth of nucleoside for patients with Parkinson's disease psychosis or PDP.

Please turn to slide four.

We remain steadfast in our commitment to our mission and to executing on our three strategic pillars to create long term growth.

First driving continued growth of NUPLAZID for patients with Parkinson's disease psychosis or PDP.

Stephen R. Davis: Second, delivering on the Dementia-Related Stochosis, or DRP, opportunity. And third, developing the next wave of breakthrough therapies by advancing our development pipeline and acquiring new assets. Let's review our Q1 results in greater detail, starting on slide 5. For the first quarter of 2021, New Plaza achieved $106.6 million in net sales. This represents an 18% year-over-year increase driven by strong year-over-year performance in the office space setting. However, during the first quarter, sales of new appliances were negatively impacted by the post-holiday spike of COVID-19 and ongoing conditions relating to the pandemic.

The second delivering on the dementia related psychosis for DRP opportunity.

And third developing the next wave of breakthrough therapies by advancing our development pipeline and acquiring new assets.

Let's review, our Q1 results in greater detail starting on slide five.

For the first quarter of 2021, NUPLAZID achieved $106 $6 million in net sales.

This represents an 18% year over year increase driven by strong year over year performance in the office based setting.

During the first quarter sales for NUPLAZID for negatively impacted by the post holiday Spike of.

Of COVID-19, and ongoing conditions relating to the pandemic.

Stephen R. Davis: As we look ahead, we observed improvements related to the pandemic in the latter part of the first quarter and into the beginning of the second quarter. And based on these indicators, we are projecting continued growth throughout the year and reiterating our net sales guidance for fiscal year 2021 at $510 to $550 million. Let's move to an update on our DRP program on slide six. We remain committed to bringing Pimivansir into the DRP patient community.

As we look ahead, we observed improvements related to the pandemic in the latter part of the first quarter and into the beginning of the second quarter.

Based on these indicators, we are projecting continued growth throughout the year and reiterating our net sales guidance for fiscal year, 'twenty, 'twenty, one and $510 million to $550 million.

Let's move to an update on our D. R. P program on slide six.

We remain committed to bringing him advance for into the DRP patient community.

In April we announced that the FDA issued of complete response letter or C O L.

Regarding our supplemental new drug application for dementia related psychosis.

We look forward to a constructive dialogue with the FDA and our type a meeting where we plan to discuss the cereal and the potential path.

Stephen R. Davis: In April, we announced that the FDA issued a complete response letter, or CRL, regarding our supplemental new drug application for dementia-related psychosis. We look forward to a constructive dialogue with the FDA at our Top A meeting, where we plan to discuss the CRL and a potential path to approval for Pimlivans.

Ruble path for kind of answering.

We are prudently planning and preparing for multiple scenarios based on what we learned at this meeting.

I want to remind you of the significant unmet need that remains in this disease.

Current treatment of the ERP involves the use of off label anti Psychotics, which carries significant risks for this often frail and elderly patient population, including worsening of cognition and impairment of motor symptoms.

We've heard both publicly and privately for many physicians caregivers and concerned family members, who have made their voices heard on this critically important matter.

Stephen R. Davis: We're prudently planning and preparing for multiple scenarios based on what we learned at this meeting. I want to remind you of the significant unmet need that remains in this disease. Current treatment of DRP involves the use of off-label antipsychotics, which carry significant risks for this often frail and elderly patient population, including worsening of cognition and impairment of motor symptoms.

We're further encouraged by the public statements made by patient advocacy groups, such as us against all timers, the Lewy body Dementia Association and the Alzheimer's Association.

We all recognize debt without an FDA approved treatment the burden of DRP remains significant.

In addition to D. R. P. We're focused on developing and expanding our pipeline of innovative new programs across multiple therapeutic areas as shown here on slide seven.

Our phase III program for true from the Dod remains on track to deliver top line results by the end of the year and our phase III program for payment of answering for the negative symptoms of schizophrenia continues to enroll well.

Stephen R. Davis: We've heard both publicly and privately from many physicians, caregivers, and concerned family members who have made their voices heard on this critically important matter. We are further encouraged by the public statements made by patient advocacy groups such as Us Against Alzheimer's, the Lewy Body Dementia Association, and the Alzheimer's Association. We all recognize that without an FDA-approved treatment, the burden of DRP remains significant. In addition to DRP, we're focused on developing and expanding our pipeline of innovative new programs across multiple therapeutic areas, as shown here on slide seven. Our Phase III program for Trifinitide remains on track to deliver top-line results by the end of the year.

We recently initiated the phase II study evaluating ACP Oh for for <unk>.

Software the pain following bunionectomy surgery.

And expect topline results by year end.

In the second quarter, we plan to initiate an additional phase II study evaluating a C. P O four for in pain associated with osteoarthritis.

This is the development continues to be a key priority of our strategy to expand our pipeline fuel long term growth and bring new therapies to patients with high unmet needs.

I would now like to turn the call over to Amanda and for our main to discuss our first quarter commercial performance and growth initiatives.

Thank you.

Today, we'd like to review, our first quarter performance and our long term expectations for NUPLAZID.

Okay.

The strong base of PDP patients continuing on NUPLAZID.

Nathan the conditions related to the pandemic I spoke.

Stephen R. Davis: And our Phase III program for Pimivansir and for the negative symptoms of schizophrenia continues to enroll well. We recently initiated a Phase II study evaluating ACP-044, the post-operative pain following bunionectomy surgery, and expect top-line results by year end. In the second quarter, we plan to initiate an additional Phase 2 study evaluating ACP-044 in pain associated with osteoarthritis. Business development continues to be a key priority of our strategy to expand our pipeline, fuel long-term growth, and bring new therapies to patients with high unmet needs. I would now like to turn the call over to Amanda and Charmaine to discuss our first quarter commercial performance and growth initiatives. Thank you, Steve.

Based on growth initiatives will enable us to deliver double digit revenue growth.

On the one.

Please turn to slide nine.

NUPLAZID continues to transform the standard of care for patients of PDP.

In the first quarter, we delivered net sales of $106 $6 million, representing an 18% year over year increase.

Performance in the quarter was driven largely by new patient starts and growth of our prescriber.

Prescriber base with any of the state.

The channel.

As Steve mentioned NUPLAZID for bookings in Q1 was negatively impacted the results.

The COVID-19 cases.

The thing and a decline of.

Yeah.

However.

In the quarter.

Sure.

Thank you for returning to traditional levels, including an increase in face to face.

The interaction.

All of which the related.

Of the pandemic and then increase vaccination rates.

While continuing patients on NUPLAZID remains high we think the unique kept for all dynamics in the first quarter per.

Pre pandemic guidance of <unk>.

Amanda Morgan: Today, we'd like to review our first quarter performance and our long-term expectations for Neuplazid in Parkinson's disease psychosis, a strong base of PDP patients continuing on Neuplazid in 2021. Please turn to slide 9.

30 day refill versus the ability to obtain a 90 day Phil.

The policy reversal temporarily interrupted our average style per continuing patient and impacted our Q1 net sales.

Within the long term care channel at the show several months of stability in the.

The first quarter, we observed an additional of decline in census, however.

However, we are now starting to see census, and more importantly admission improve in March and into April.

Amanda Morgan: We proudly continue to transform the standard of care. In the first quarter, we delivered net sales of $106.6 million, representing an 18% year-over-year increase. Performance in the quarter was driven largely by new patient starts and growth of our prescriber base within the office-based channel. As Steve mentioned, Neuplaza's performance in Q1 was negatively impacted as a result of the post-holiday spike in COVID-19 cases.

For both the office based setting and the long term care channel are leading indicators.

Market conditions are steadily improving.

As we come out of the pandemic, the timing and pace of recovery and face to face interaction PD patient office visits and LTC, new admissions will be key drivers for our 2021 for performance and where we land in our reiterated fiscal year 2021, net sales guidance of 510.

$550 million.

Please turn to slide 10.

We have recently started to see early indicators pointing towards a return to growth from the LTC channel include.

Amanda Morgan: However, as we exited the quarter, we observed overall visits returning to traditional levels, including an increase in face-to-face interaction, all of which are related to improving conditions of the pandemic and an increase in vaccination rates. While continuing patience on these flags has remained high, we face a unique temporal dynamic in the first quarter as payers reverted to pre-pandemic guidance of 30-day refills versus the ability to obtain a 90-day fill. This policy reversal temporarily interrupted our average bottle per continuing patient and impacted our Q1 net sales. Within the long-term care channel, after showing several months of stability, in the first quarter, we observed an additional decline in sensitivity.

Including an increase of new long term care admissions and modest growth in sensors.

The following key points highlight this observation.

First more of facilities are allowing the family members to visit loved one which previously was the major impediments for new resident in medicine.

And second in the first quarter, both large and small LTC provider groups share the rapid vaccination of.

All residents with prioritized for other areas of care.

There are now high vaccination rates from our residents and staff, which has led to a greater than 90 per cent drop in COVID-19 cases since December 2020.

And finally, our data shows that new revenue.

Highly correlated leading indicator of new patient starts within the long term care channel.

We are encouraged by these improving market conditions within the long term care market that support a return to growth.

I'll now turn it over to share may to discuss our focus on sustainable growth for the overall PDP business.

Amanda Morgan: However, we are now starting to see census and, more importantly, admissions improve in March and into April. For both the office-based setting and the long-term care channel, our leading indicators and overall market conditions are steadily improving. As we come out of the pandemic, the timing and pace of recovery and face-to-face interaction, T.D. Patient Office Visits, and LTC New Admissions will be key drivers to our 2021 performance and where we land in our reiterated Fiscal Year 2021 Net Sales Guidance of $510-550 million. Please turn to slide 10.

Sure I mean, I believe you are on mute.

Thank you. Thanks, Amanda please turn to slide 11.

Tailor, our marketing channel mix to maximize response of the underlying market condition as we begin to emerge from the pandemic.

It continues to amplifier of health care professional and consumer campaigns, both digitally and in person and we expect that these initiatives will drive growth throughout the remainder of the year.

This means strong engagement with virtual CME and speaker programs and leveraging virtual promotional booth at several key medical crosses the Congress is across the country.

In April our virtual NUPLAZID product theaters at the American Academy of Neurology and the American College of physicians were very well attended and we will continue to leverage our virtual Congress presence throughout the rest of this year.

Amanda Morgan: We have recently started to see early indicators pointing towards a return to growth in the LTC channel, including an increase in new, long-term care admissions and modest growth in... The following key points highlight this observation. First, more facilities are allowing family members to visit loved ones, which previously was a major impediment to new resident admissions.

In addition to that we are executing and on air DTC and online campaign to support that DTC campaign in order to activate patients and caregivers to request NUPLAZID specifically.

Our current DTC campaign is exceeding our targets and working synergistically with social media and other digital tactics that we have out there to grow the breadth and depth of the prescriber base.

Amanda Morgan: Second, in the first quarter, both large and small LTC provider groups shared that rapid vaccination of all residents was prioritized over other areas of care. There are now high vaccination rates among residents and staff, which has led to a greater than 90% drop in COVID-19. December 2020.

The market opportunity for NUPLAZID remains large most patients today are prescribed off label antipsychotic, which curious significant safety risks, including the potential for a worsening of motor symptoms for.

Focused on growing our share of the PDP market and our new patient share continues to exceed our overall share. This is a key indicator of future growth and penetration.

Amanda Morgan: And finally, our data shows that new resident admissions is a highly correlated leading indicator of new patient starts within the long-term care channel. We are encouraged by these improving market conditions within the long-term care market that support a return to growth. I'll now turn it over to Charmaine to discuss our focus on sustainable growth for the overall PDP business. Charmaine, I believe you are on mute.

In recent week, you're starting to see growth across our business, which is supported by the improving market conditions and importantly, as we exited the quarter and into April it started to observe a recovery in face to face interactions.

In office patient visits.

Long term care of new admissions.

Our commercial teams expertise has positioned us well for strong performance during the pandemic and the ability to grow future business as we emerge from it.

We are well positioned to drive long term prescription growth of NUPLAZID in PDP.

Charmaine Likens: Thank you. Thanks, Amanda. Please turn to slide 11. We've tailored our marketing channel mix to maximize response to the underlying market conditions as we begin to emerge from the pandemic. We continue to amplify our healthcare professional and consumer campaigns, both digitally and in person, and we expect that these initiatives will drive growth throughout the remainder of the year. This means strong engagement with virtual CME and speaker programs and leveraging virtual promotional booths at several key medical congresses across the country.

And now I'll turn it over to Serge to discuss our pipeline progress.

Thank you sort of made good afternoon, everyone. Please turn to slide 13.

In regards to DRP, our team has been diligently preparing a briefing package, which outlines our perspective on F N da the.

Positive phase III Harmony study the results and provides a template for discussion in the future interactions with the FDA.

This document is almost complete now and will be included in the request for the type a meeting.

Our objectives for the type a meeting to discuss the CRM.

Charmaine Likens: In April, our virtual New Plasley Project Theaters at the American Academy of Neurology and the American College of Physicians were very well attended, and we will continue to leverage our virtual Congress presence throughout the rest of this year. In addition to that, we are executing an on-air DTC and online campaign to support that DTC campaign in order to activate patients and caregivers to request duplazid specifically. Our current DTC campaign is exceeding our reach targets and working synergistically with social media and other digital tactics that we have out there to grow the breadth and depth of the prescriber base. The market opportunity for Neuplaza remains large. Most patients today are prescribed off-label antipsychotics, which carry significant safety risks, including the potential for worsening of motor symptoms.

And identify a mutually agreeable path towards approval with the FDA.

We are confident in the science, the data and benefit risk profile of the momentum sitting in DRP described in our S. M B a.

We're committed to achieving FDA approval and make NUPLAZID available to patients caregivers and their families who suffer from DRP.

As we've said before we believe that the perspective of the agreed development program and the design of the pivotal Harmony study is scientifically the most appropriate way to evaluate the efficacy and safety of the Melbourne.

<unk> as a treatment for DRP.

Our position is informed by the following.

For the pivotal harmony study met its net.

The specified primary and key secondary endpoints with highly statistically significant and clinically meaningful results.

Consistent with the results in the double blind portion of the study.

Charmaine Likens: We're focused on growing our share of the PDP market, and our new patient share continues to exceed our overall share. This is a key indicator of future growth and penetration. In recent weeks, we've started to see growth across our business, which is supported by improving market conditions. And importantly, as we exited the quarter and into April, we started to observe a recovery in face-to-face interactions, in-office patient visits, and long-term care and new admissions. Our commercial team's expertise has a position as well, the strong performance during the pandemic and the ability to grow future business as we emerge from it.

<unk> demonstrated meaningful separation from placebo on the measures of severity of psychotic symptoms such as Carlos the nations and delusions or on the global clinical assessments.

And all of this with the notable effect size for.

Are there more in the open label portion of the study over 60% of patient Smith very rigorous treatment response criteria, while on the theme of answering demonstrated meaningful and sustained reduction in the symptoms of psychosis consistent across patient subgroups.

The consistency of the above described the results in our people go Harmony study further informs our view on the benefit risk profile of the mob answered for DRP.

Charmaine Likens: We are well-positioned to drive long-term prescription growth for Nupava and PDP. And now I'll turn it over to Serge to discuss our pipeline progress. Thank you, Charmaine. Good afternoon, everyone.

We would like to better understand the division's position in hopes that we can align on the inefficient plan towards the resubmission.

We look forward to keeping you updated on our progress.

Serge Sankovich: Please turn to slide 13. In regards to DRP, our team has been diligently preparing a briefing package that outlines our perspective on SNDA, the positive Phase III Harmony Study results, and provides a template for discussion and future interactions with the FDA. This document is almost complete now and will be included in the request for a Type A meeting. Our objectives for the Taipei meeting are to discuss the CRL and identify a mutually agreeable path toward approval with the FDA. We're confident in the science.

Beyond the ERP, we are advancing our pipeline on all of the knowledge of treatments for areas of high unmet need with ongoing clinical trials across five disease areas.

Let's briefly review of the rest of our pipeline starting on slide 14 with Ret syndrome.

Ret syndrome is a rare neurological disorder with debilitating symptoms, including severe cognitive emotional sensory and motor impairment.

It's all sort of lose spoken communication and purposeful hand use leading to a loss of independence.

Serge Sankovich: The data and benefit risk profile of Pimavansirin in DRP described in our SNDA, and we are committed to achieving FDA approval and making Nuplazid available to patients, caregivers, and their families who suffer from DRP. As we've said before, we believe that the perspectively agreed development program and the design of the Pivotal Harmony Study is scientifically the most appropriate way to evaluate the efficacy and safety of Pi Our position is informed by the following.

Our phase III program continues to progress well with top line results expected from our allowed under study in the fourth quarter of this year.

Please recall that the law of under study uses the same validated endpoints as the positive phase two study, which are designed to show improvements from the core symptoms of <unk> syndrome.

Turning to slide 15.

There are over 700000 patients in the United States, who are receiving treatment for schizophrenia, but still experienced the debilitating magnitude of symptoms, including social withdrawal lack of emotion, the restricted speech and blend to the Africa.

Serge Sankovich: The Pivotal Harmony Study met its pre-specified primary and key secondary endpoints with highly statistically significant and clinically meaningful results. Consistent with these results, in the double-blind portion of the study, timovansirine demonstrated meaningful separation from placebo on the measures of severity of psychotic symptoms, such as hallucinations and delusions, or on a global clinical assessment, and all this with a notable effect charge.

These symptoms can lead to long term disability and significant caregiver burden.

As a reminder, our phase III program evaluating the Melbourne Sydney for the treatment of negative symptoms of schizophrenia includes two pivotal study our positive other brands, one study and advance to which we initiated in the third quarter of last year and is currently enrolling patients.

Serge Sankovich: Furthermore, in the open-label portion of the study, over 60% of patients met very rigorous treatment response criteria while on Pimavansirin and demonstrated meaningful and sustained reduction in the symptoms of psychosis consistent across patient subgroups. The consistency of the above-described results in our Pivotal Harmony Study further informs our view on the benefit-risk profile of pimavanserine for DRP. We would like to better understand the division's position in hopes that we can align on an efficient plan toward resubmission.

Please turn to slide 16 for an update on our HCP all 40 for program.

The ACP of 44 is a novel first in class orally administered non opioid analgesic that is being studied for both acute and chronic pain.

I am pleased to announce the three recently initiated the phase two study of evaluating ACP of 44 for the treatment of postoperative pain following bunionectomy surgery.

The studies of randomized double blind placebo controlled study enrolling approximately 240 subjects and evaluating the efficacy and safety of ACP of 44.

Serge Sankovich: We look forward to keeping you updated on our progress. Beyond DRP, we are advancing our pipeline of innovative treatments for areas of high unmet need with ongoing clinical trials across five disease areas. Let's briefly review the rest of our pipeline, starting on slide 14 with RETCIM. Rett syndrome is a rare neurological disorder with debilitating symptoms including severe cognitive, emotional, sensory, and motor impairment.

The primary endpoint of the studies average pain intensity score measured by a numeric rating scale from first dose on the day of surgery through 24 hours, we anticipate top line results from the study before the end of the year.

Furthermore, we plan to initiate an additional phase two study for patients suffering from pain associated with the all star dry days later this quarter.

Slide 17 highlights a brief summary of our HCP $3 19 program for the potential treatment of cognition in schizophrenia.

Serge Sankovich: Patients often lose spoken communication and purposeful hand use, leading to a loss of independence. Our Phase 3 program continues to progress well, with top-line results expected from our Lavender Study in the fourth quarter of this year. Please recall that the LAVENDER study uses the same validated endpoints as the positive phase 2 study, which are designed to show improvements in the core symptoms of Rett syndrome. Turning to slide 15. There are over 700,000 patients in the United States who are receiving treatment for schizophrenia but still experience debilitating negative symptoms, including social withdrawal, lack of emotion, restricted speech, and blunted. These symptoms can lead to long-term disability and significant caregiver burden.

Zeeshan and continuation of the Phase one program is progressing well and we look forward to providing more detailed updates on this program in the future.

Slide 18 summarizes our ongoing development timelines in the first quarter, we initiated phase two study for ACP old 44 for postoperative pain.

In the second quarter, we plan to initiate the phase two study of HCP, all 44 for pain associated with the start writers.

And in the fourth quarter, we expect to announce top line results from our phase III <unk> started the ret syndrome.

Yeah.

We look forward to keeping you updated as we advance our pipeline.

And with that I'll turn the call over to Atlanta.

Thank you Serge sales discuss our first quarter 2021 results and our updated 2021 financial outlook. Please turn to slide 20.

Serge Sankovich: As a reminder, our Phase III program, Evaluating Pimavansirin for the Treatment of Negative Symptoms of Schizophrenia, includes two pivotal studies, our positive ADVANCE I study and ADVANCE II, which we initiated in the third quarter of last year and is currently enrolling patients. Please turn to slide 16 for an update on our ACPO 44 program. ACPO 44 is a novel, first-in-class, orally-administered, non-opioid analgesic that is being studied for both acute and chronic pain.

In the first quarter of 2021, the recorded $106 $6 million in net sales.

An increase of approximately 18% compared to $91 million of net sales in Q1 of 2020 the.

This is driven by 4% volume growth year over year.

Importantly, this comparison is challenging because last year's first quarter with pre pandemic. Despite the suite delivered increased demand year over year.

Our performance was led by the office based channel with year over year growth impacted by fewer patient office visits and the decline in average of bottles per patient in the quarter as Amanda described.

Serge Sankovich: I am pleased to announce that we recently initiated a Phase II study evaluating ACP-044 for the treatment of postoperative pain following bunionectomy surgery. The study is a randomized, double-blind, placebo-controlled study enrolling approximately 240 subjects and evaluating the efficacy and safety of ACPO44. The primary endpoint of the study is the average pain intensity score measured by a numeric rating scale from the first dose on the day of surgery

In the long term care channel demand declined year over year, driven by a further decline in census levels in LTC facilities in the first quarter of 2021 following several months of stabilization in the second half of last year.

However, we started to see patient office visits and the office based channel increase and census levels in our demand and proven L. P. C. As the exited the first quarter and into April.

Of course with Tonight adjustment for Q1, 2021, with $22 3 million a 22, 3% as a reminder growth Tonight is typically highest in the first quarter two of the annual reset of the donut hole for Medicare part D patients.

Serge Sankovich: We anticipate top-line results from this study before the end of the year. Furthermore, we plan to initiate an additional Phase 2 study for patients suffering from pain associated with osteoarthritis later this quarter. Slide 17 highlights a brief summary of our ACP 319 program for the potential treatment of cognition and schizophrenia.

Weeks of inventory in the channel at the end of the first quarter were slightly higher than year end.

Moving down the P&L GAAP R&D expenses decreased to $57 million in the quarter compared to $72 6 million in Q1 2020.

Serge Sankovich: Transition and continuation of the Phase 1 program is progressing well, and we look forward to providing more detailed updates on this program in the future. Slide 18 summarizes our ongoing development timeline. In the first quarter, we initiated a Phase 2 study for ACPO44 for postoperative pain.

GAAP SG&A expenses increased to $111 $7 million from the first quarter from 102 million in the first quarter of last year non.

Noncash stock based compensation expense during the quarter with $13 $2 million compared to $22 $3 million for the same period in 2020.

Serge Sankovich: In the second quarter, we plan to initiate a Phase 2 study of ACP-044 for pain associated with osteoarthritis, and in the fourth quarter, we expect to announce top-line results from our Phase III tropinatide study in RefSyndrome. We look forward to keeping you updated as we advance our pipeline. And with that, I'll turn the call over to Elena. Thank you, Serge.

Our cash balance at the end of the quarter with $577 $8 million per.

Please turn to slide 21 for.

For the full year 2021, we are reiterating our NUPLAZID revenue guidance of $510 million to $550 million.

Given the impact of the pandemic, we observed in the first quarter, we could land in the lower end of the guidance range, just where we finish will be a function of the timing and pace of recovery in face to face field interactions patient office visits and L. P C new admissions.

Tessa Thomas Romero: Today I'll discuss our first quarter 2021 results and our updated 2021 financial outlook. Please turn to slide 20. In the first quarter of 2021, we recorded $106.6 million in net sales, an increase of approximately 18% compared to $90.1 million in net sales in Q1 of 2020. This was driven by 4% volume growth year over year. Importantly, this comparison is challenging because last year's first quarter was pre-pandemic.

On the expense side for 2021, we now expect GAAP R&D to be between 280 and $300 million for the full year from our previous range of $300 million to $320 million. This reflects some optimization of our development expenses and includes approximately $25 million and stock based compensation.

Matt.

We are reducing our SG&A guidance to reflect the reduction of expenses associated with the delay in the potential DRP launch, we now expect GAAP SG&A to be between 385 and $415 million for the full year from our previous range of $560 million to $590 million to revive.

Tessa Thomas Romero: Despite this, we delivered increased demand year over year. Our performance was led by the office-based channel, with year-over-year growth impacted by fewer patient office visits and a decline in average bottles per patient in the quarter, as Amanda described. In the long-term care channel, demand declined year over year, driven by a further decline in census levels in LPC facilities in the first quarter of 2021, following several months of stabilization in the second half of last year.

The guidance range includes approximately $50 million the stock based compensation expense.

That I will turn the call back over to Steve.

Thank you Elena please turn to slide 23.

In closing we are confident in our long term commercial outlook for PDP.

We are committed to bringing the advanced through end of patients and caregivers struggling with the ERP and we are focused on investing in our clinical programs and business development opportunities.

I would like to thank our employees for their unwavering passion for our mission to elevate line.

Tessa Thomas Romero: However, we started to see patient office visits in the office-based channel increase and census levels, and our demand improve in LPC as we exited the first quarter and into April. The growth to net adjustment for Q1 2021 was 22.3 million, 22.3%. As a reminder, growth to net is typically highest in the first quarter due to the annual reset of the donor hole for Medicare Part D patients. However, weeks of inventory in the channel at the end of the first quarter were slightly higher than year-end.

I'll now open up the call for questions operator.

Thank you, ladies and gentlemen, if you wish to ask the question. Please press star followed by one on your Touchstone telephone you for your question has been answered or you wish do we tell your question press the pound key please limit yourself to one question I repeat please limit yourself to one question.

Star one to begin please standby for your first question.

Your first question comes from the line of beat the barrel from Cowen. Your line is now open.

Tessa Thomas Romero: Moving down the P&L, GAAP R&D expenses decreased to $57 million in the quarter compared to $72.6 million in Q1 2020. GAAP ST&A expenses increased to $111.7 million in the first quarter from $102 million in the first quarter of last year.

Hi, guys. Thanks for taking the question I wanted to ask about the path forward for DRP I guess first very quick housekeeping question have you formally requested the type a meeting at this point.

Then to the.

The the broader question here is I guess.

Tessa Thomas Romero: Non-cash, stock-based compensation expense during the quarter was $13.2 million compared to $22.3 million for the same period in 2020. Our cash balance at the end of the quarter was $577.8 million. Please turn to slide 21. For the full year 2021, we are reiterating our new Plazid revenue guidance of $510 to $550 million. Given the impact of the pandemic we observed in the first quarter, we could land in the lower end of the guidance range.

If the main issue has to do with the <unk>.

The one one study and potentially records kept around that is there any way to sort of address those record keeping quality issues.

With those clinical trial records that are worth discussing at the type a or beyond.

Yeah. Thanks, so much for the question for you too I'm going to answer the first part of your question I'll, let al lot of search to answer the second part. So the answer is we have not yet submitted the request. So in order to request the type a meeting the first half to prepare a briefing document which outlines your position.

Provide the template for discussion and it's important to get this right and lay the right Foundation and tin plate for the benefit of the future interactions.

Tessa Thomas Romero: Just where we finish will be a function of the timing and pace of recovery in face-to-face field interactions, patient office visits, and new LTC admissions. On the expense side, for 2021, we now expect GAAP R&D to be between $280 and $300 million for the full year, from a previous range of $300 to $320 million. This reflects some optimization in our development expenses and includes approximately $25 million in staff-based compensation expense. Additionally, we are reducing our SG&A guidance to reflect the reduction of expenses associated with the delay in a potential DRP line. We now expect GAAP SG&A to be between $385 and $415 million for the full year from a previous range of $560 to $590 million. The revised guidance range includes approximately $50 million in stock-based compensation expense.

We believe we have very strong arguments to discuss with the FDA and want to be diligent in preparation before submitting the formal request and this includes.

The input from expert counsel and outside advisors.

The documents also.

Almost complete and will be included in our official request for the type a meeting again very soon.

And as a reminder of the type a meeting.

It will be scheduled by the FDA.

Within 30 days of our request.

So do you want to take the second part of <unk>.

The question.

Yes.

Redo I I'll, just reiterate first what Steve mentioned earlier and that is the.

Our principal objective in this meeting is really to understand the.

On the <unk>.

And issues raised by the division in the company.

For the response letter.

Considering the part of those issues were related to the study all of the 19 that you mentioned, we certainly in our briefing document will be addressing all of the issues point by point debt were raised in the in the complete response letter in.

Tessa Thomas Romero: And with that, I'll turn the call back over to Elena. Please turn to slide 22. In closing, we are confident in our long-term commercial outlook for PPP. We are committed to bringing PIMM Advantage to patients and caregivers struggling with DRP, and we are focused on investing in our clinical programs and business development opportunities. I would like to thank our employees for their unwavering passion for our mission to elevate lives. I'll now open up the call to questions. Operator.

The detailed and extensive manner in the hope that we can provide.

Additional information that will be helpful to the division to understand the context of.

Those concerns and issues and to address that.

Got it thanks.

Next question comes from the line of Charles Duncan from Cantor Fitzgerald. Your line is now open.

Yeah, Hi, guys. Thanks for taking the question the good quarter on the top line.

Operator: Thank you. Ladies and gentlemen, if you wish to ask a question, please press the star followed by one on your touchtone telephone. If your question has been answered or you wish to withdraw your question, press the pound key.

Had a follow up question on the DRP indication I guess I'm wondering if.

And maybe this is jumping the gun, but are you willing to pursue of dispute resolution or do you need to learn more information before you determine strategy and could you imagine.

Operator: Please limit yourself to one question. I repeat, please limit yourself to one question. Press star one to begin.

Refiling with a more limited label based on some diagnostic criteria.

Operator: Please stand by for your first question. Your first question comes from the line of Ritu Baral from Cowen. Your line is now open. Hi guys, thanks for taking the question. I wanted to ask about the path forward for DRP. I guess first, a very quick housekeeping question.

So.

The.

The following.

Following the type a meeting we can't agree on the appropriate path towards a resubmission there is baked into the FDA process and the visual appeal.

The process.

Stephen R. Davis: Have you formally requested the type A meeting at this point? And then two, the broader question here is, I guess, If the main issue has to do with the 011 study and potentially records kept around that, is there any way to sort of address those record-keeping quality issues with those clinical trial records that are worth discussing at the Type A meeting or beyond? Yeah, thanks much for the question, Ritu. I'm going to answer the first part of your question.

Could be pursuit at this time, we don't think it's productive to speculate on that.

Appeal process until we've actually had the meeting with FDA and any other.

Since for and gather information of that so that's the next step for them.

The focus on that.

And I'm sorry, Charles the was the second part of your question. It's escaping me now.

Yeah that makes sense, thanks, Steve regarding a limited label based on some diagnostic criteria.

Yes.

Remember now.

You know look there too we need to have the stop a meeting we need to learn what we can learn there and I don't want to speculate about.

Stephen R. Davis: I'll allow Serge to answer the second part. So the answer is that we have not yet submitted the request. So in order to request a Type A meeting, you first have to prepare a briefing document which outlines your position and provides a template for discussion.

The potential avenues beyond the type a meeting we've obviously done a lot of scenario planning, but we just need to have the meeting first.

Okay. Thanks for taking the question.

The.

Our next question comes from the line of Karri CASM of from Jpmorgan. Your line is now open.

Stephen R. Davis: And it's important to get this right and lay the right foundation and template for the benefit of future interactions. We believe we have very strong arguments to discuss with the FDA and want to be diligent in preparation before submitting the formal request, which includes input from expert counsel and outside advisors. The document is almost complete and will be included in our official request for the Type A meeting again very soon. And as a reminder, the Type A meeting will be scheduled by the FDA within 30 days of our request. Sir, do you want to take the second part of Ritu's question? Um, yes.

This is turner on for Cory. Thank you for taking my question I'm. Just curious what are your latest thoughts on your European strategy does the.

The ERP delay in the U S impact how you think about Europe and is it possible to potentially take this package the European regulators along with PDP. Thanks.

Yes. Thanks, so much for the question so as we previously indicated.

Frame shifted.

Our European filing strategy and this is really.

A just a reflection of the very very dramatic difference in pricing that drugs. Like this this is not unique to Tim of answering the drugs like this get in <unk>.

Europe versus in the United States. So in other words the.

The.

The vast majority of the value pie for <unk>.

Serge Sankovich: Ritu, I'll just reiterate first what Steve mentioned earlier, and that is that our principal objective in this meeting is really to understand the concerns and issues raised by the division in the complete response letter. Considering that a part of those issues were related to the study O19 that you mentioned, we certainly in our briefing document will be addressing all of the issues point by point that were raised in the complete response letter in detail and extensively in the hope that we can provide additional information that will be helpful to the division to understand the context of those concerns and issues and to address them. I got it. Thanks. The next question comes from the line of Charles Duncan from Cantor 50.

Drug like this is in the United States.

And because the pricing is so dramatically different.

We felt it was important to play out.

The.

The work that we're doing in other indications.

To try to get multiple indications into a common senior data exclusivity group. So we're not of anything more to say on that at this juncture, but we'll continue to assess as we go forward.

But just wanted from items.

For the valley buys of the Pis there isn't outside of the U S. We certainly want to make sure we secure every.

Every bit of of value with whom of answering but at this juncture.

We don't have anything more to say about the timing.

Timing of filing in other jurisdictions.

Thanks, that's helpful.

Next question comes from the line of Jason Butler from JMP Securities. Your line is now open.

Operator: Your line is now open. Hi guys, thanks for taking the question. Good quarter on the top line.

Hi, Thanks for taking the question just had one on the the thinking about the PDP opportunity moving forward.

Operator: I had a follow-up question on the DRP indication. I guess I'm wondering if, maybe this is jumping the gun, but are you willing to pursue dispute resolution or do you need to learn more information before you determine strategy and could you imagine refiling with a more limited label based on some diagnostic criteria? Yeah, thanks much for the question, Charles. So, the answer is...

Just looking a little into the future midterm as we exit the the COVID-19 headwinds how do you see the opportunity for growth in the office based channel versus long term care, which one has the the larger opportunity for growth and if you could just remind us of your views on the market size in each channel how deeply penetrated in each you are.

For today in that context. Thanks.

Yes. Thanks, so much for the question Sherman I'm going to ask you to answer that.

Stephen R. Davis: If following the type A media... We can't agree on the appropriate path towards a resubmission. There is baked into the FDA process an official appeal process that could be pursued. At this time, we don't think it's productive to speculate on that appeal process until we've actually had the meeting with FDA and have a sense for and gather information about meetings.

Yeah sure. Thanks, Steve well first of all when you look overall about our opportunity for growth in PDP, we're committed to accelerating growth across all of the channels, both office space and long term care and we're going to do this through several means.

Namely our commercial initiatives have demonstrated the positive effects across both channels over time, and we're going to continue to provide resources to deliver information to the patients and caregivers to activate that caregiver and that patient to request NUPLAZID and also of establishing NUPLAZID as the only FDA approved treatment out there for parking.

Stephen R. Davis: So that's the next step, and we'll be focused on that. And I'm sorry, Charles, there was a second part to your question. It's escaping me. Yeah, that makes sense. Thanks, Steve, regarding a limited label based on some diagnostic criteria. Yeah, I remember now.

And the disease psychosis the.

And that we're educating the medical community, which has an impact both in the office based business and the long term care setting an important data on can the of answering the benefits of NUPLAZID through virtual promotional booth of several congresses debt.

Stephen R. Davis: I, you know, look, I'm there too. We need to have this type of meeting; we need to learn what we can learn there. And I don't want to speculate about potential avenues beyond the type A meeting. We've obviously done a lot of scenario planning, but we just need to have the meeting first. Okay, thanks for taking the question. The next question comes from the line of Kari Kazimov from JP Morgan. Your line is now open. Hey, this is Turner on behalf of Corey.

Of that we've already actually participated in and virtual Speaker Bureau of throughout the year and.

In addition to that we set of fully integrated consumer awareness program with.

Which is executing the social media both on the HCP side and on the consumer side and we continue to see strong results coming from our digital platform across both HCP and consumer regardless of the setting I think I would say overall, we continue to perform.

Operator: Thank you for taking my question. Just curious, what are your latest thoughts on your European strategy? Does the DRP delay in the US impact how you think about Europe? And is it possible to potentially take this package to European regulators along with PDP? Thanks.

Outperform actually the market basket and long term care the market basket of products that we benchmark ourselves against which I think further underscores the effectiveness of these tactics that we're executing on today. So we're very optimistic of our growth prospects not only in the long term care channel, but also in the offices channel.

Okay, great. Thanks.

Stephen R. Davis: Yeah, thanks so much for the question. So, as we previously indicated, we've frame shifted our European filing strategy. And this is really just a reflection of the very, very dramatic difference in pricing that drugs like this are not unique to the answer to drugs like this yet in Europe versus in the United States. So in other words, the vast majority of the pie for drugs like this is in the United States.

Thanks for taking the question.

Okay. Next question comes from Gregory of Enzo.

From RBC capital markets. Your line is now open.

Okay.

Hey, Stephen and team. Thank you for the update and thanks for taking my question.

Steve I, just wanted to focus a bit on the near term outlook for PDP and it sounds like you had an encouraging exit.

<unk> first quarter metrics and the the the reiteration of the full year guidance I was just curious if you could just touch a little bit more on those factors.

Stephen R. Davis: And because the pricing is so dramatically different, we felt it was important to play out the work that we're doing in other indications in an attempt to try to get multiple indications into a common 10-year data exclusivity period. So we don't have anything more to say on that at this juncture. We'll continue to assess as we go forward, but I just want to remind you that the value pie is, There are a few outside of the U.S., and we certainly want to make sure we secure every bit of value with PIMA Vanturin, but at this juncture, we don't have anything more to say about timing of filing in other jurisdictions. Thanks a couple. The next question comes from the line of Jason Butler from KMP Securities. Your line is now open.

For the Atlanta correctly, I think she indicated that maybe the lower end of of the range. So just curious if you could maybe unpack.

That a bit.

Maintaining that guidance versus perhaps.

Narrowing net or lowering of just in light of the commentary you added and then just lastly related to that of just curious to what degree if any was the DRP opportunity this year of potential potentiate or for for that for PDP penetration in the market. Thank you very much.

Yeah. Thanks, so much for the question I'm going to answer the second question first and I'm going to escalate. It answered the first question. So.

Operator: Hi, thanks for taking the question. I just had one on the thinking about the PDP opportunity moving forward. I guess just looking a little into the future midterm as we exit the COVID headwinds. How do you see the opportunity for growth in the office-based channel versus long-term care? Which one has the larger opportunity for growth? And if you could just remind us of the market size for each channel, and how deeply penetrated you are today in each, in that context, thank you. Yeah, thanks so much for the question. Charmaine, I'm going to ask you to answer that. Yeah, sure. Thanks, Steve.

We.

From the time, we launch this drug we've had very very low off label use we.

We can't see every bottle.

In all channels, but.

The significant majority of <unk>.

Scripts come through our hub and we know exactly.

The percentage of scripts that are on label and it's always been in the high 90% range, then that hasn't deviated so I don't see any.

In the impact on first quarter from.

From from.

The changes in off label.

Charmaine Likens: Well, first of all, when you look overall at our opportunity for growth in PDP, we're committed to accelerating growth across all the channels, both office space and long-term care. And we're going to do this through several means. Namely, our commercial initiatives have demonstrated positive effects across both channels over time, and we're going to continue to provide resources to deliver information to patients and caregivers to activate that caregiver and that patient to request Neuplazid. And also establishing Neuplazid as the only FDA-approved treatment out there for Parkinson's disease psychosis.

For example off label use.

In PDP. In addition, just as a reminder, you know obviously as you know.

Our overall results in DRP were very very compelling.

And of course, the the results in <unk>.

PDD patients or Parkinson's disease dementia.

For the end psychosis.

We're also super compelling so I, just don't see any connectivity between the ERP and <unk>.

The PDP first quarter of bottles when do you want to take the the first question.

Sure so.

We are confident in our guidance range.

I did comment with.

With regards to the low end of the range just to remind you and I and folks that when you look.

Charmaine Likens: Beyond that, we're educating the medical community, which has an impact both in the office-based business and the long-term care setting, on important data on Pima Vancerin and the benefits of Nuplazib through virtual promotional booths at several congresses that we've already actually participated in, and virtual speaker bureaus throughout the year. In addition to that, we've got a fully integrated consumer awareness program, which is being executed with social media, both on the HCP side and on the consumer side.

The.

From the first quarter have fewer new patient starts the unexpected that has an impact on the continuing bottles for those patients for the remainder of the year.

As we talked about the in both March and April have seen improved trends in both the office based setting in the long term care channel and we expect to see continued continued growth.

And both of those channels.

So we are confident in the guidance range that we reiterated today.

That's great. Thank you very much guys.

The next question comes from Nina.

Charmaine Likens: And we continue to see strong results coming from our digital platform across both HCP and consumers, regardless of setting. I think I would say, overall, we continue to perform, or actually outperform, the market basket in long-term care, the market basket of products that we benchmark ourselves against, which I think further underscores the effectiveness of these tactics that we're executing on today. So we're very optimistic about our growth prospects, not only in the long-term care channel but also in the office-based channel.

Credo Garg from Citi. Your line is now open.

Hey, guys. Thanks for taking my question.

So I guess just another question on kind of the next steps and in DRP I guess could you elaborate a little bit more on I guess, what's the timeline to us kind of hearing the outcome of the type a meeting and is that something that you do plan to communicate.

Or right after the meeting or would you wait until after you minutes from that meeting of could you just talk a little bit more about that that'd be great.

Yeah. Thanks, so much for the question so.

The meeting on the on the.

Charmaine Likens: Okay, great. Thanks for taking the question.

Under the Fda's structure.

Should happen within 30 days of the request and they usually are right at 30 days.

Operator: The next question comes from Gregory Renza of RBC Capital Markets. Your line is now open.

Once we have the meeting.

As we would do and most meetings of the sort of whether it's in the end of phase two meeting of previous NDA meeting.

Operator: Hey, Steve, and team. Thank you for the update. And thanks for taking my question. Steve, I just wanted to focus a bit on the near-term outlook for

Or in this case of the type a meeting on the CRM.

We would typically wait until we get minutes from the meeting.

Speaking of public granted that's airplane in the space as well.

Great. Thank you.

Operator: https://www.pdp.org

The next question comes from Jeff Hung of Morgan Stanley. Your line is now open.

Operator: I'm curious if you could just touch on a little bit more on those factors.

Hey, everyone. Thanks for taking the question for DRP should you go down the path of the Appeals I know, it's really early but are there any precedent cases, you can highlight where companies went through the appeals process and the <unk> was overturned in any similarities or differences that you would highlight from those cases, depending of answering the DRP.

Stephen R. Davis: If I heard Alana correctly, I think she indicated maybe a lower end of the range, so just curious if you could maybe unpack that a bit, maintaining that guidance versus, you know, perhaps narrowing that or lowering it just in light of the commentary you added. And then, just lastly, related to that, just curious, to what degree, if any, was the DRP opportunity this year a potential potentiator for PDP penetration in the market? Yeah, thanks so much for the question. I'm going to answer the second question first, and I'm going to ask Delaney to answer the first question.

Yeah.

Well.

First just wanted to kind of just to make sure. We're all level set.

Theres no overturning of the CRA all per se because once you get the cereal you have to resubmit. So the question always is what do you need to do to resubmit.

And in some cases, you can resubmit without doing additional clinical work and the other cases, you need to do additional clinical work.

The the.

This was the.

The S NDA of supplemental new drug application. So the the the decision on issue can you see Earl was made by the Psychiatry Division and that is the division with whom we will have the the.

Operator: So, from the time we launched this drug, we've had very, very low off-label use. We can't see every bottle in all channels, but the significant majority of scripts come through our hub, and we know exactly the percent of scripts that are on label, and it's always been in the high 90% range. That hasn't deviated. So, I don't see any..., www.pdpharm.com. Our overall results in DRP were very, very compelling. And of course, the results in PDD patients, or Parkinson's disease dementia patients that have psychosis, were also super compelling. So I just don't see any connectivity between DRP and PDP first-quarter models. Lenny, do you want to take the first question? Sure.

Type of meeting and so as we are.

Once we had that meeting will be in a position as indicated earlier to comment further about claims board and of course it will then.

The inform our view of of.

What the next steps will be.

Okay. Thanks for the clarification.

The next question comes from Sullivan Richter of Goldman of Goldman Sachs. Your line is now open.

Thanks for taking the question for Andrew on for Celgene.

Maybe some questions on the pipeline of search maybe if you could speak a bit more on the mechanism of action for ACP zero for for and if Theres any reason to believe the draws maybe more effective than acute versus chronic pain.

And as you look at those two opportunities of one is more of a low hanging fruit and then I have a second really.

Yes.

Hum.

The.

Operator: So, Greg, we are confident in our guidance range. I did comment with regard to the low end of the range, just to remind you and folks that when you lose patients in the first quarter or have fewer new patient starts than expected, that has an impact on the continuing bottles for those patients for the remainder of the year. As we talked about, in both March and April, we saw improved trends in both the office-based setting and the long-term care channel, and we expect to see continued growth in both those channels. So, we are confident in the guidance range that we reiterated today.

Very interesting mechanism of action first of all we are particularly.

Excited about having the non all period mechanism of action day.

Yes.

One pound has.

A deal it is too.

Accelerate the elimination of the paradox of nitride, which is.

Yes.

In the in the development of the pain, it's the underlined.

The upstream mechanisms for sensitization of multiples paid mechanisms and that's really what what is the particularly.

Operator: That's great. Thank you very much, guys.

Particularly attractive this is also.

Operator: The next question comes from Neena Bitritto Garg from Citi. Your line is now open.

There is early the restricted compound so the.

Operator: Hey guys, thanks for taking my question. So I guess just another question on kind of the next steps in DRP. Can you elaborate a little bit more on, I guess, just the timeline for us kind of hearing the outcome of the type A meeting? And is that something that you do plan to communicate? Or, you know, right after the meeting? Or would you wait until after a few minutes from that meeting?

The risks of any potential.

The.

Dependence of abuse of liabilities is not the present so from that perspective, we are very excited about the drug.

In regards to the question, whether we anticipate.

Better benefits.

In the acute versus chronic pain models.

Stephen R. Davis: If you could just talk a little bit more about that, that'd be great. Yeah, thanks so much for the question. So, um, the meeting on the FDA's Once we have the meeting, as we would do in most meetings of this sort, whether it's an interface 2 meeting, a pre-SMV meeting, or, in this case, a top 8 meeting following the CRL, we would typically wait until we get minutes from the meeting before speaking publicly on it, and that's our plan in this case. Great, thank you. The next question comes from Jeff Hung of Morgan Stanley. Your line is now open. Hey, everyone.

So far we have all the indications we have are the from the preclinical data that we have.

And those mechanisms.

Quite a bit of an efficacy displayed in the variety of deeper in the pain models central pain models, whether acute or chronic and in some extent we saw in efficacy that is quite on par or better with the opioids so from that perspective.

We are a quite bullish in terms of our anticipation of possible ability to demonstrate the benefits both in the acute models of pain as well as.

As of colony models, and that's why in the phase two trial, we are pursuing both models, obviously looking forward to the clinical data for the confirmation.

Operator: Thanks for taking the question. For DRP, should you go down the path of appeals? I know it's really early, but are there any precedent cases you can highlight where companies went through the appeals process, and the CRL was overturned, and any similarities or differences that you would highlight from those cases to Pimavazarin and DRP? Well, first, just one kind of, just to make sure we're all level set. There's no overturning of a CRL per se because once you get a CRL, you have to resubmit.

Got it and then with your and one Pam maybe you could just speak on what what's the status right now of that phase one of the nature of that and when we could start to see some of the data emerge.

Would be helpful. Thank you.

Yes, as I said, we have.

Okay.

Hum.

We are quite up quite progress in the process of transitioning the.

Stephen R. Davis: So the question always is, what do you need to do to resubmit? And in some cases, you can resubmit without doing additional clinical work. And in other cases, you need to do additional clinical work. And so, once we've had that meeting, we'll be in a position, as was indicated earlier, to comment further about the plans for moving forward. And, of course, it will then inform our view of what the next steps will be. Thanks for the clarification.

And kantar.

Continuing the phase one work.

This is.

This compound.

Already is in the phase one we need to continue through the <unk>.

Expanding the.

Exposures.

As as we move forward and that's actually the stage, where we are right now both from the perspective of.

Operator: The next question comes from Salvin Richter of Goldman Sachs. Your line is now open. Thanks for taking the question. This is Andrea on behalf of Salveen.

Providing.

Appropriate.

Toxicology covering so that we can be increasing debt those exposures in humans as well as doing the.

Operator: Maybe some questions on the pipeline surge. Maybe if you could speak a bit more on the mechanism of action for ACP 044 and if there's any reason to believe the drug may be more effective in acute versus chronic pain. And as you look at those two opportunities, if one is more of a low-hanging fruit, and then I have a second.

The human work, but we are.

In the phase one right now and as we as we complete this work we will be of reporting obviously and updating you on the future plants.

Moving forward.

Serge Sankovich: Yes, a very interesting mechanism of action. First of all, we are particularly excited about having a non-opioid mechanism of action. This compound has the ability to accelerate elimination of paroxynitrite, which is, in the development of pain, an underlying upstream mechanism for sensitization of multiple pain mechanisms. And that's really what is particularly attractive.

Great. Thanks, so much cash.

Sure. Nick next question comes from Paul <unk> of Stifel Financial Your line is now open.

Hey, Thanks for taking my question.

I know, there's a lot of moving parts of the <unk> and we just heard from.

About changes in compliance and repo rates.

I wanted to try to simplify it did you exit the first quarter with more patients on drug than you had at the end of last year and I guess, what do you kind of see now that think the reopening in terms of the cadence of the patient add rate for the rest of the first half.

Serge Sankovich: This is also a peripherally restricted compound, so the risks of any potential dependence or abuse liabilities are not present. So from that perspective, we are very excited about the drug. In regard to the question whether we anticipate a better benefit in the acute versus chronic pain models, so far, all the indications we have are from the preclinical data that we have. And in those mechanisms, we saw quite a bit of efficacy displayed in a variety of different pain models, whether acute or chronic.

Yes. Thanks, so much for the question Elena you want to take that.

Yeah. Thanks for the question as we talked about ending Q1, we are.

We did see growth in both the office based setting and the long term care channel. So we are exiting Q1 and the good and a good place outside of just Wanna comment on the continuing bottles.

We had a strong continuing.

<unk> bottles.

For the majority of our patients.

There was a small portion where.

Serge Sankovich: And to some extent, we saw an efficacy that was quite on par or better with opioids. So from that perspective, we are quite bullish in terms of our anticipation of the possible ability to demonstrate benefit both in the acute models of pain as well as in the chronic models. And that's why in the Phase II trial, we are pursuing both models, obviously looking forward to the clinical data for confirmation. And then with your M1 PAM, if you could just speak about what the status right now is in phase one, the nature of that, and when we could start to see some of the data emerge. That would be helpful.

The single digit percentage of patients that are started to receive 90 day sales, which Amanda spoke about in her prepared remarks.

That historically.

The pre pandemic was about five percentage rate of about 8% in the pandemic.

And in.

In Q1, we saw that reverse to 6% and now in April at the back to 5%. So we expect starting in Q2, which is the more normal trend as far as average bottles are continuing patients.

Okay. Thanks, so much.

Next question comes from Brian <unk> of Jefferies. Your line is now open.

Hi, everyone. Thanks for taking my questions.

So maybe a few follow ups on O for for an acute post operative pain.

Serge Sankovich: Thank you. Yes, as I said, we have, you know, we are quite, quite progressed in the process of transitioning and continuing the phase one work. We, you know, this compound is already in phase one; we need to continue through expanding the exposures as we move forward. And that's actually the stage where we are right now, both from the perspective of providing appropriate toxicology guidance so that we can be increasing those exposures in humans, as well as doing the human work. But we are in phase one right now. And as we complete this work, we will be reporting, obviously, and updating you on the future plan. Moving forward. Thanks so much.

Also can you speak to the PK profile, maybe its estimated half life and onset of action and then as a follow up can you outline of the dosing strategy I know, there's a high end of low dose, but if its once a day daily or as needed.

And then finally, maybe you could talk about what rescue medications are allowed and how that's going to be handled in the primary endpoint.

Sure do you want to take those questions.

Yes.

As a matter of fact.

There is.

The study that we're conducting the right now one of the important questions that we want the answer is.

What is the optimal dose in the range of regiment.

For the drug so we are essentially testing the same daily dose, but in the two different dosing regimens.

The trial has.

Three arms to walk the of arms and one placebo and the.

That's essentially one of the objective for us because we would definitely want to better understand.

Operator: The next question comes from Paul Mathias, Upstable Financial. Your line is now open. Hey, thanks a lot for taking my question. I know there are a lot of moving parts in OneQ and, you know, we've heard from Nir about changes in compliance and refill rates. I guess I wanted to try to simplify it.

The votes from the pharmacokinetic, but also pharmacodynamic perspective.

Uh huh of behavior of the drug.

So for analgesic coverage in that respect.

Yes.

Okay.

I'm not sure that I addressed your second part of your question if you're one of them just about rescue medications.

How they'll be handle for the primary and with the.

There are allowed.

Operator: Did you exit the first quarter with more patients on drugs than you had at the end of last year? And I guess what do you kind of see now that things are reopening in terms of the cadence of the patient at rate for the rest of the first half? Yeah, thanks so much for the question. Elena, do you want to take that?

Yes, we are.

We don't go into the debt.

Debt level of details of the protocols and all of that but obviously the.

The design of this trial is very very.

It's a classical opioid pain design and of course, we do make records there are certain medications that are prohibited debt.

Tessa Thomas Romero: Yeah, thanks for the question. As we talked about ending Q1, we did see growth in both the office-based setting and the long-term care channel. So we are exiting Q1 in a good place. I also just want to comment on the continuing bottles. We had strong continued bottles for the majority of our patients. There was a small portion where a single-digit percentage of patients that started to receive 90-day fills, which Amanda spoke about in her prepared remarks, which historically pre-pandemic was about 5%. It grew to about 8% during the pandemic, and in Q1, we saw that reverse to 6%. And now, in April, it's back to 5%.

Interfere with the is but we are.

No.

There is there is in the in terms of the primary measure we are measuring pain intensity.

The.

There are of certain restrictions in terms of the rescues.

Okay. Thank you.

Next question comes from the <unk> of Guggenheim. Your line is now open.

Hi, everyone. This is Eddie on for you on the thanks for taking my questions. So on the Lavender study given the face given the phase two is only six weeks and youre up against the 12 weeks.

In the phase II of the drug arm was still decreasing when that study stopped how much additional benefit do you think you can get.

Those clinical endpoints without out of time.

And then in the phase III of ear enrolling slightly older patients.

Is there any age or severity of disease related differences in that phase II data that led you to to add order growth for the study. Thanks.

Yes.

Tessa Thomas Romero: So we expect, starting in Q2, to see a more normal trend as far as average bottles per continuing patient goes. Okay, thanks so much. The next question comes from Brian Mullis of Cafres. Your line is now open. Hi, everyone.

Yes.

The our view on the data and discussion with the experts that we had as well as vis vis the mechanism of action of the the phenotype.

Led us to come.

Conclusion that actually the.

Operator: Thanks for taking my questions. So maybe a few follow-ups on 044 in acute postoperative pain. So if possible, can you speak to the PK profile?

Sure the trial.

Did not provide the pool of opportunity to display the benefit and the the additional benefit basis based on the <unk>.

Symptom.

Operator: Maybe it's estimated half-life and onset of action. And then, as a follow-up, can you outline the dosing strategy? I know there is a high and a low dose, but is this once daily or as needed? And then, finally, maybe you could talk about what rescue medications are allowed and how that's going to be handled in the primary endpoint. Thanks.

Changing the symptoms over time.

Would have been.

Potentially obtain so therefore.

We have decided to design the trial and the way how it is design and we do expect that of educational benefits will be very volume of course, we did not want to go with the.

With the.

Overly extended.

Period for the trial, but we believe that we are in the.

Serge Sankovich: Sure, do you want to take those questions? Uh, yeah.

Right.

Serge Sankovich: Yes, you know, as a matter of fact, this study that we are conducting right now, one of the important questions that we want to answer is what is the optimal dosing regimen for the drug. So we are essentially testing the same daily dose, but in two different dosing regimens. So the trial has three arms, two active arms and one placebo, and that's essentially one of the objectives for us because we would definitely want to better understand, both from the pharmacokinetic but also pharmacodynamic perspective, the behavior of the drug and potential for analgesic coverage in that respect. I'm, And I'm not sure that I addressed the second part of your question, if you want to.

Right timing for the duration of this trial in terms of the.

The specific all the characteristics I mean.

The.

The important point with this particular patient population is the.

We have a patient population that is within the span of the.

The school age.

Where the patients are receiving also a number of.

Number of.

Rehabilitations measures that are up.

<unk> in DS the pace.

Things that are older than that may have a different.

Disease course, or maybe more stagnating from the from that perspective. So similarly, we did not include in the us.

Serge Sankovich: Yeah, just about rescue medications, how they'll be handled for the primary and... if they're allowed. Yeah, we don't go into that level of detail in the protocols and all that, but obviously, the design of this trial is very, very, it's a classical acute pain design, and of course, we do make records. There are certain medications that are prohibited that interfere with this, but we are, you know, there is, in terms of the primary measure, we are measuring pain intensity, and there are certain restrictions in terms of the rescues. Okay, thank you. The next question comes from Yatin Suneja of Guggenheim. Your line is now open. Hi everyone, this is Eddie on behalf of Yatin.

The trial are very young patients we are doing that in the separate.

Separates the clinical trial, but for the group that is including in this trial, we do not anticipate that there will be significant variability in terms of the symptoms.

Across the group I mean, some variability is always present, but we do not expect it.

Expect it to be of significant and subset of there.

Thanks for your question comes from Jay Olson from Oppenheimer. Your line is now open.

Oh, Hey, thanks for taking the question, maybe just to follow up on two of affinity side.

Can you talk about the the target product profile for retrofit of the tide and any any work that youre doing to prepare for the launch and how you're thinking about the ultimate market potential for attrition of time. Thank you.

So do you want to take the target product profile.

Operator: Thanks for taking my question. So on the Lavender study, given that the Phase 2 study was only 6 weeks, and you're upping it to 12 weeks, and in the Phase 2 study, the drug arm was still decreasing when that study stopped, how much additional benefit do you think you can get on those clinical endpoints with that added time? And then in Phase 3, you're enrolling slightly older patients. Was there any age or severity of disease-related differences in that Phase 2 data that led you to add older girls to the study? Uh, yes, um, the...

In Germany, and you want to take the.

A question regarding the preparation for launch.

Yes.

I think that the.

The important point I would like to underscore here, we're talking about the phenotype is debt.

The sorafenib wide target of core symptoms over Ed disease, meaning.

Multiple as we know of multiple symptoms as we know Red. This is manifest itself in the variety of different system as they mentioned cognition matzo communication.

Serge Sankovich: The, our view of the data and discussion with the experts that we had, as well as vis-a-vis the mechanism of action of trophinatide, led us to a conclusion that the shorter trial did not actually provide a full opportunity to display the benefit and that the additional benefit based on the changing symptoms over time would have been potentially obtained. So therefore, we have decided to design the trial in the way it is designed, and we do expect that the additional benefit will be verified.

Neurological symptoms, including Caesars and.

So far our data suggest that the benefits seen with surfing the died.

Sure.

As seen across the deeper in the symptoms clusters and that is something that is relatively unique so far from the perspective of the treatments that have been tested or applied in this patient population as you know we have some development programs where people.

Serge Sankovich: Of course, we did not want to go with an overly extended period for the trial, but we believe that we are at the right time for the duration of this trial. In terms of the specific characteristics, I mean, the important point with this particular patient population is that we have a patient population that is within the span of school age, where the patients are receiving a number of rehabilitation measures that are applied in this, and patients that are older than that may have a different disease course or may be more stagnant from that perspective.

Or more mostly targeting the respiratory symptoms others, we're targeting seizures and so on so I think that's the one distinguished characteristics out there at this point of at least that.

But we're not aware of all the programs that are targeting a broad array of the core symptoms of <unk> syndrome as total phenotype. The nice thing that's that's where.

Obviously, there is nothing else available for treatment and there is broad.

The target of symptoms is certainly.

Serge Sankovich: So similarly, we did not include very young patients in this trial. We are doing that in a separate clinical trial, but for the group that is included in this trial, we do not anticipate that there will be significant variability in terms of the symptoms across the group. I mean, some variability is always present, but we do not expect it to be significant and substantial variability. The next question comes from Jay Olson from Oppenheimer. Your line is now open.

The most sealy and the characteristics of the characteristic of the phenotype.

And from the commercialization perspective, as we look to prepare for launch.

The thing is this is a rare disease of.

Of course, the caregiver is very very important and of high touch relationship with those caregivers in those patients is also going to be very important for lines. Some of the things that we're working on our strong relationships with advocacy, particularly ret syndrome foundation of that work of Ret syndrome that word as well as looking to understand the patient journey and the di.

Operator: Well, thanks for taking the question. Maybe just to follow up on trophinatide, can you talk about the target product profile for trophinatide and any work that you're doing to prepare for the launch and how you're thinking about the ultimate market potential for trophinatide? Thank you.

There's two routes to rat initially and then how that patient is managed throughout the course of their disease, and where we might find an opportunity for a true veneti at launch to Hell.

Those patients manage their disease. So it's a lot of the early core foundational brand strategy types of deliverables that we're working on with an extra emphasis on the caregiver and the patient knowing that this is a rare disease.

Serge Sankovich: Sir, do you want to take the target product profile, and Chairman, do you want to take the question regarding preparation for launch? Yeah, I think that the important point I would like to emphasize here talking about trophinotide is that trophinotide targets core symptoms of rare diseases, meaning multiple. As we know, this rare disease manifests itself in a variety of different systems, as I mentioned, cognition, motor, communication, neurological symptoms, including seizures.

Great. Thanks for taking the question.

The next question comes from the meal demand of Mizuho Securities. Your line is now open.

Hi, great. Thanks for taking my question. So I guess this was for Stephen I asked this question do you previously but.

Just curious given the sort of delay here of DRP, how that maybe impacting your thoughts around the overall corporate strategy I'm sure you want to get through the type a meeting and kind of really get more clarity on some of the outlook there, but just as you think about business development of other steps you could take.

Charmaine Likens: And so far, our data suggests that the benefits seen with trophinotide are seen across different symptom clusters, and that is something that is relatively unique so far from the perspective of the treatments that have been tested or applied in this patient population. As you know, we had some development programs where people were mostly targeting respiratory symptoms, others were targeting seizures, and so on. So I think that's one distinguishing characteristic out there at this point, at least that we're not aware of programs that are targeting a broad array of the core symptoms of Rett syndrome as trophinotide.

Diversify the story of what is has anything sort of evolved in your thinking over the last couple of months.

Since you first got the notification debt there was some deficiencies at any of it.

For your thoughts would be helpful. Thanks.

Yes, thanks, so much for the question.

Look we're obviously very disappointed in.

In in Uh Huh.

Moving the setback here and the ERP it doesn't change the strategy.

We are equally committed to.

The capitalizing on the opportunities we have of <unk>.

Very attractive revenue growth going forward in PDP.

Were determined.

To meet the unmet need in DRP patients and we will continue.

Charmaine Likens: And I think that's where, obviously, there is nothing else available for treatment. And this broad target of symptoms is certainly the most salient characteristic of trophinotide. And from a commercialization perspective, as we look to prepare for launch, the thing is, this is a rare disease. Of course, the caregiver is very, very important, and a high-touch relationship with those caregivers and those patients is also going to be very important for launch. Some of the things that we're working on are strong relationships with advocacy, particularly RettSyndromeFoundation.org or RettSyndrome.org, as well as looking to understand the patient journey and the diagnosis of Rett initially, and then how that patient is managed throughout the course of their disease, and where we might find an opportunity for trifenatide at launch to help those patients manage their disease.

Business development be a key pillar of our strategy as it relates to business development.

I've said previously and this continues to be the case of just want to make sure of reiterate it.

You will see more deals.

Second we have a strong foothold both the neurology and psychiatry today, we have a presence both in.

The chronic indications with significant unmet need as well as rare disease. As we go forward you will likely see the shift on the <unk>.

Types of deals that we do.

Uh huh.

The evolve and more neurology in rare disease and.

And more on the.

Specialty front.

That doesn't just mean.

Clearly there is still very very interesting opportunities in.

In psychiatry, and neurology, there interesting opportunities abroad.

Charmaine Likens: So, it's a lot of the early, core, foundational, grand strategy types of deliverables that we're working on with an extra emphasis on the caregiver and the patient knowing that this is a rare disease. Great, thanks for taking the question. The next question comes from Vamil Devan of Mizuho Securities. Your line is open.

The symptomatic relief chronic therapy.

Therapies as well as in rare disease that you'll see.

Things evolve in that direction. So again business development will continue to be of very very important part of our business.

And as I've said before you'll see more news from us.

Okay. Thank you.

Next question comes from Daniel <unk> of Raymond James Your line is now open.

Operator: Hi, great, thanks for taking my question. So I guess this one's for Steve.

Yeah.

Hi, I've got another tryphena tied the question.

Could you remind us what we should be looking for in the laboratory of datasets. Later this year with respect to what do you consider to be a clinically meaningful outcome for the two co primary at the behavioral endpoints of the RSP Q and the CGI. Thanks.

Operator: I asked this question to you previously, but I'm just curious, you know, given the delay here with DRP, how that may be impacting your thoughts around the overall corporate strategy. I'm sure you want to get through the Type A meeting and kind of really get more clarity on the outlook there. But just as you think about business development or other steps you could take, whether it's to diversify the story or what, has anything sort of evolved in your thinking over the last couple months since you first got that notification that there are some deficiencies? Any up-to-date thoughts would be helpful. Thanks. Yeah, thanks.

Yeah.

Yeah.

It's a little bit.

Sort of difficult to.

Describe that in the context of two co primary measures as you.

<unk> mentioned, we have.

The red behavior of old symptom questionnaire, which is a pair of SaaS.

<unk>.

Outcome, and then clinical global assessment, which all of the improvement which is the clinician assessment of the changes we obviously.

Stephen R. Davis: Yeah, thanks much for the question. Look, we're obviously very disappointed in having the setback here in DRP, but it doesn't change the strategy.

Being of pulp primary we have two separate statistically on both of these measures in order to declare the trial's positive and I think in itself.

Stephen R. Davis: We're equally committed to capitalizing on the opportunities we have for very attractive revenue growth going forward in PDP. We're determined to meet the unmet need in DRP patients, and we will continue to have business development be a key pillar of our strategy. As it relates to business development, what I've said previously, and this continues to be the case, I just want to make sure I reiterate it, you will see more deals.

A high threshold, but achievable threshold because both of these measures.

Separated significantly in our smaller phase two trial, so we have.

A reasonable reasonable expectations that we will be able to replicate these are of difficult trial I will say in absence of.

Stephen R. Davis: Second, we have a strong foothold both in neurology and psychiatry today. We have a presence in chronic indications with significant unmet need, as well as rare diseases. As we go forward, you will likely see the shift on the types of deals that we do evolve in more neurology and rare disease and more on the specialty front. But to be completely clear, there are still very, very interesting opportunities in psychiatry and neurology, very interesting opportunities in broad symptomatic relief, chronic therapies, as well as in rare diseases.

The substantive really beneficial treatments out there the.

The improvements that we would see on both of the scales.

Even on the.

Even if on a lower end of the.

Effect size would be tremendously valuable to patients and the families and that debt that is although we expect.

To repeat the relatively robust the results that we have in phase two we would not be disappointed with the.

Stephen R. Davis: You'll see things evolve in that direction. Again, business development will continue to be a very, very important part of our business. As I've said before, you'll see more deals. Okay, thank you. The next question comes from Daniel Beale of Rema James Urlani. Hi, I've got another Tricinitide question. Could you remind us what we should be looking for in the Lavender dataset later this year with respect to what you consider?

A win on both the primary measures for primary measures.

Great. Thanks.

The next question comes from David Wong of S. M. D. C. Your line is now open.

Hi team thanks for taking the question.

So Mike I just had a couple of so first of all one.

Could you talk to how you talked the much kols following fda's issue of issuance of the CRM and ERP and just the kind of wanted to get a sense of our prescribers are still excited too.

Operator: to be a clinically meaningful outcome for the two co-primary behavioral endpoints, the RSB-Q.

Two of the answer in DRP is there any.

Operator: Behavioral Endpoint, the RSBQ, and the CGI. Thanks.

Concern or hesitancy on their part in terms of willingness to prescribe after the the agency's decision.

Serge Sankovich: Yeah, it's a little bit difficult to describe that in the context of two co-primary measures. As you mentioned, we have the Red Behavioral Symptom Questionnaire, which is a parent-assessed outcome, and then the Clinical Global Assessment of Improvement, which is the clinician assessment of the changes. Obviously, being a co-primary, we have to separate statistically on both of these measures in order to declare the trial positive. And I think, in itself, that's a high threshold, but an achievable threshold, because both of these measures separated significantly in our smaller Phase II trial.

Yeah, So all of it.

Take that sort of if you want it.

Any additional color please feel free to.

So I.

The answer is yes, we continue to talk to Kols, even after the seawell tissue I wanted to just take a little bit of running started this in the.

Describe kind of what the those interactions have been line from the time, we initially announced the results of the Harmony study. So when we announced those results we convened a panel of 15 kols.

Around the time to see debt meeting and went through all of the data with them and they were extraordinarily excited about the date of that.

Serge Sankovich: So, we have reasonable expectations that we will be able to replicate, although this is a difficult trial. I will say, in the absence of substantively beneficial treatments out there, the improvements that we would see on both of these scales, even if on the lower end of the effect size, would be tremendously valuable to patients and their families. And that is, although we expect to repeat the relatively robust results that we have in Phase II, we would not be disappointed with a win on both primary measures. Great, thanks. The next question comes from David Hoang of SMBC. Your line is now open.

It has not changed so we've we've had regular dialogue with a broad array of kols in this space.

We've gone through all of the data.

And they continue to be very impressed with both the efficacy that we observed in the study.

We get strong support in the medical community that they believe this is the right way to study this population.

The subtypes of <unk> are very tricky to diagnose theres often mixed etiology, it's very frequently misdiagnosed and about 40% of dementia patients don't get a subtype of diagnosis because of the challenges associated with debt.

Operator: Hi, team. Thanks for taking the questions. So, I just had a couple. So, first one, have you talked to many KOLs following FDA's issuance of the CRL and DRP and just kind of wanted to get a sense, are prescribers still excited? Transcription by Transcription Outsourcing, LLC.

On the safety side of the equation the.

The.

Net.

The Kols and I would say the medical community in general that we consulted with along the way have been very excited about the fact that this drug is.

We observed clinically.

Does not impair cognition and that's not what you see with the dopaminergic anti Psychotics you see that day.

Stephen R. Davis: Yeah, so I'll take that, Serge, if you want to add any additional color, please feel free to. So the answer is yes, we continued to talk to KOLs even after the CRL was issued. I want to just take a little bit of a running start on this. So, we've had regular dialogue with a broad array of KOLs in this space. We've gone through all of the data, and they continue to be very impressed with both the efficacy that we observed in this study. We get strong support in the medical community that they believe this is the right way to study this population.

The very large study very well established that the impair cognition, it's not insignificant it's equivalent to about one year of disease progression. So of the very unfortunate situation and using those drugs is that when you use them. In this patient population you actually make you may help on the psychosis, although it's very debatable, whether they are even get any EBITDA.

There.

But you certainly.

Have to compromise because they make the cognitive impairments of these patients have worse.

Stephen R. Davis: The subtypes are very tricky to diagnose, and there's often mixed etiology. It's very, they're frequently misdiagnosed. And about 40% of dementia patients don't get a subtype diagnosis because of the challenges associated with that. On the safety side of the equation, the KOLs, and I would say the medical community in general that we've consulted with along the way, have been very excited about the fact that this drug, as we've observed clinically, does not impair cognition. And that's not what you see with the dopaminergic antipsychotics. You see that they, in a very large study, very well established, they impair cognition. It's not insignificant. It's equivalent to about one year of disease progression.

So as we continue to.

The advanced toward our type a meeting with continued NAV.

Dialogue with the broad array of of.

Of medical and scientific experts and continue to feel very very confident in our data.

Got it thanks for sharing day.

Just one quick follow up.

Okay.

I'm sorry your line.

Yeah, I think we lost you.

The operating maybe maybe you can get back in the queue I think we lost the connection there.

Sorry, David Wang Yu. Your line is now open again.

You think of the Hi, how are you able to hear me.

Yeah. We can go ahead, okay, great. Thanks.

Just the second quick question in terms of the Phase III Harmony study can you just remind us which subgroup sold the of the great magnitude of benefit there.

Yeah sure sort of do you want take that.

Stephen R. Davis: So the very unfortunate situation with using those drugs is that when you use them in this patient population, you actually make, you may help with the psychosis, although it's very debatable whether they're even getting any benefit there, but you certainly have to compromise because they make the cognitive impairment that these patients have worse. So as we've continued to advance toward our type A meeting, we've continued to have dialogue with a broad array of medical and scientific experts and continue to feel very, very confident in our. I got it. Thanks for sharing that!

Yes, the greatest magnitude of debt that was observed was the parkinsons disease dementia patients with psychosis.

The following of course debt if you abstract.

The dementia with lewy body of patients because the.

We just simply could not calculated they're small numbers, but it was also.

<unk>.

Notable difference or actually there was one relapsed.

In the.

In the placebo, while no relapses on drug.

The next in line with the.

Operator: And maybe just one quick follow-up. I'm sorry we lost you. Yeah, I think we lost you. Operator, maybe we can get back in the queue. I think we've lost the connection. Sorry, David Hoang, your line is now open.

Is some sense of the number of patients who has all the current alzheimers disease.

Psychosis subgroup.

In that subgroup, we observed the.

Approximately 40% reduction in the risk of relapse, which is.

The clinically very meaningful.

Operator: You can go ahead. Hi.

Notable and in line with all of the data that we are aware of the clinically meaningful results and statistically significant results from differ in randomized withdrawal of trials.

Operator: Yeah, we can do it. Yeah, go ahead.

Operator: Okay, great, thanks. Just a second quick question. In terms of the Phase III Harmony Study, can you just remind me?

Operator: Unknown Attendee Can you just remind us which subgroup sold the greatest magnitude of benefits there? Alright, sure.

Okay I appreciate the interest.

As there are no further question at this time Mr. Davis you May proceed on your closing remarks.

Serge Sankovich: So do you want to take that? Yeah, the greatest magnitude that this was observed was in Parkinson's disease dementia patients with psychosis. Following, of course, that if you abstracted the dementia Lewy body patient, because we just simply could not calculate there due to small numbers, but it was also a notable difference. Actually, there was one relapse in placebo, while no relapses occurred on the drug. Next in line with the substantive number of patients is the Alzheimer's disease psychosis subgroup, and in that subgroup, we observed, So, approximately a 40% reduction in risk of relapse, which is clinically very meaningful and notable and in line with all of the data that we are aware of, the clinically meaningful results and statistically significant results from different randomized withdrawal trials.

Great. Thanks, much operator index each of you for joining US today, we look forward to updating you on our progress.

Thank you for your participation in today's conference call of this concludes the presentation. You may now disconnect good day.

Okay.

[music].

Operator: Okay, I appreciate the input.

Operator: There are no further questions at this time. Mr. Davis, you may proceed with your closing remarks. Great.

The dividend payment.

Sure.

The growth.

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Of course.

Income.

[music].

Yes.

[music].

Stephen R. Davis: Thanks much, operator. Thanks to each of you for joining us today. We look forward to updating you on our progress. Thank you for your participation in today's conference call. This concludes the presentation. You may now disconnect. Good day.

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