Q1 2022 ACADIA Pharmaceuticals Inc Earnings Call

May I have the conference ID number, please?

In regard to the osteoarthritis study, in spite of the headwinds that we all experienced, particularly in these types of studies related to COVID, we continue to expect to complete enrollment around the year end or the beginning of next year with the data, as we said, in the first half, top-line results in the first half of next year.

Good day, ladies and gentlemen, and welcome to Acadia Pharmaceuticals first quarter 2022 financial results Conference call. My name is Crystal and I'll be your coordinator for today.

Hi.

Thank you.

I'm sorry.

Our next question comes from Paul Matthias from Stiefel.

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.

If at any time during the call you require assistance. Please press Star Star followed by zero and a coordinator will be happy to assist you.

The line is really low.

Your line is open.

I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at Acadia. Please proceed.

The conference ID though, it is 698-9476.

Hey, there.

Good afternoon, and thank you for joining us on today's call to discuss the <unk> first quarter 2022 financial results.

Thank you.

Thanks for taking our question.

May I have the spelling of your first and last name?

Joining me on the call today from Acadia are Steve Davis, our Chief Executive Officer, who will provide an overview of our first quarter performance and a review of our business following Steve Brendan T N. Our chief operating officer head of commercial will provide updates on our commercial performance and initiatives Dr. Serge Stankovic, Our President will then discuss our pipeline progress finally, mark.

Schneider, our Chief Financial Officer will discuss our financial results and guidance before turning it back to Steve for final remarks, and opening up the call for your questions.

I would also like to point out that we are using supplement 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. 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 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.

Yes.

This is Alex for Paul.

Thank you Mark good afternoon, everyone and thank you for joining US today, please turn to slide five.

It's Rachel.

Just one more on the, ADP adcom.

R-A-C-H-E-L. Smith.

The foundation of our business rests on three key elements.

First to drive growth of NUPLAZID franchise, where we continued to outperform market competitors.

Second we advanced our three late stage opportunities in Alzheimer's disease, psychosis, Ret syndrome, and the negative symptoms of schizophrenia.

And third to develop the next wave of CNS breakthroughs with our early stage pipeline together with continuing to pursue strategic business development opportunities.

I was wondering maybe, Serge, you could talk a little about the importance of the black box discussion at the adcom.

For the first quarter of 2022, NUPLAZID achieved $115 $5 million in net sales.

I guess, is it your position that there should be no adcom on a potential approved SNDA?

Representing an 8% year over year increase.

Well, Brendan and Mark will go into more detail in a moment I'd like to point out a few key components of our performance during the quarter.

So, Tim is answering, how much evidence do you have outside of PDP to maybe alleviate FDA's concerns around sort of the unknown mortality risk in this class?

Thanks.

First our operational performance in the first quarter was driven by 4% demand growth our level of growth similar to what we experienced through 2021, which is also in line with our assumptions, our net sales guidance of $510 million to $560 million for the full year of 2022.

Alex, I think you meant to say, presume that we would advocate for no black box.

Yeah.

No worries.

Second.

Following the omicron bearing surge as we exited the first quarter and now into the second quarter.

So, Serge, you want to take that question?

Yeah.

Early signs of additional growth in total prescriptions and new patient starts both with NUPLAZID and the overall market as a whole.

Just a bit of context here.

Since the beginning of the pandemic in early 2020, the Parkinson's disease market is growing only 3% cumulatively over this two year period.

In comparison during the two year period prior to the pandemic this market grew 9%.

In addition, as we previously reported in person patient visits to Parkinson's treating physicians are down approximately 20%.

These conditions have resulted in fewer available patients being diagnosed and treated for their Parkinson's and.

And subsequently for Parkinson's disease psychosis, how.

However, as Brendan will speak to in both the community and long term care channels. We've recently seen signs of the overall parkinsons market stabilizing.

Slowly returning to growth.

With mass mandates are lifted and physicians encouraging patients to come back to the office, we're cautiously optimistic that we could see further improvement in these market dynamics.

Throughout the spring and into the summer.

Finally, and most importantly, NUPLAZID has continued to grow year over year outpacing the top brands and medications in the neurology segment, the PD market and in LTC facilities.

We look forward to maintaining that strong performance of delivering on the long term potential of NUPLAZID for PDP.

S-M-I-T-H.

Now, let's turn to our three late stage opportunities on slide seven.

Thank you.

What I will say, without going with all of the details, that the data that we have accumulated, from the previous advisory committee and the previous application and approval with ADP is considerably larger, not only in respect to the control trial data, which we added hundreds and thousands of additional patients in this category of elderly patients, but also with six years of post-marketing surveillance with about 40,000.

First I'd like to start by providing an overview of where we stand with our S NDA resubmission or ADP.

And may I have your company name, please?

And every indication in the data that we see is that we are gradually moving toward, a much better balance and toward the balance in regards to the mortality data compared to previous data reported at a previous submission.

This week, the FDA announced that they had scheduled an advisory committee meeting for June 17 to review our Resubmission.

Ayara.

So from that perspective, we definitely see a favorable trend, and as well as what we, are seeing in some real-life studies based on the Medicare data, and recently reported we had actually two reports where we are also seeing more favorable profile in terms of mortality when compared to other atypical antipsychotics that are used off-label in the Parkinson's disease psychosis.

A-I-E-R-A.

For the meeting were focused on three key messages, which point to the overall positive benefit risk profile for <unk> in this patient population, which include efficacy safety and high unmet need.

I just want to make sure again.

So from that perspective, we are very pleased with the data that we are seeing.

A-I-E-R-A.

For efficacy or package supports our position that Tim advancement provides a consistent and clinically meaningful improvement in the symptoms of psychosis and the reduction of relapsed risks in Alzheimer's disease patients.

That's correct.

Whether this data may be sufficient for removal of box warning is a different question because, we still, as you know, all the analysis of mortality with atypical antipsychotics included thousands of patients from the clinical trial.

On the safety side, we've demonstrated in clinical trials September answering.

Favorable safety and Tolerability profile, and importantly is not associated with worsening either cognition or motor function in Alzheimer's disease patients are particularly challenging issue, which is historically hindered the development of therapies to treat this condition.

Okay.

Thank you.

And from that perspective, the confidence interval is much more narrower than what we, are seeing in the numbers that we have specifically for PMF answering.

And finally with regard to unmet need today, there are approximately 900000 ADP patients being treated in the U S. The majority of which take off label multi receptor acting anti psychotics with marginal efficacy and safety issues.

In the large scale Katie a D study ease off label anti Psychotics were associated with increased impairment of cognition in Alzheimer's patients.

Evelyn two about one year of disease progression.

These medications are also associated with impairment in motor function sedation and increased risk of falls fractures hospitalizations ER visits.

So we are not of an opinion that the total amount of data and evidence because of these, numbers may warrant removal of the box warning.

Today with no FDA approved treatment for Alzheimer's disease psychosis health care providers will continue to prescribe these off label anti psychotics. Despite all of their limitations with families and caregivers. Many times are desperate to treat the debilitating psychosis. These patient center.

But I will just repeat, the trends that we are seeing, the numbers and the data that, we are seeing, we are very confident in the favorable profile of PMF answering in this respect.

I just want to clarify one thing that Serge mentioned.

At the beginning of his answer, he referred to the previous ADP application and what Serge, meant to say was the previous PDP.

We look forward to further making our case to the FDA at the upcoming Advisory Committee meeting that Tim of answer and should be the first FDA approved treatment for Alzheimer's disease psychosis.

And your line will please hold until the conference begins. Thank you.

So he is referring back to our initial approval.

And at that time, there was a very small numerical imbalance in mortality showing, again, very, small numbers, a little bit higher mortality on drugs than placebo. Fast forward, we've now done multiple placebo-controlled studies in elderly patients, and that imbalance has now gone away.

Please turn to slide eight.

Regarding our NDA for Tryphena Todd.

You're welcome.

<unk> NDA meetings are complete and were fully aligned with DFT on the format and content for the upcoming NDA submission for <unk> for the treatment of Ret syndrome.

[music] Good day, ladies and gentlemen, and welcome to ACADIA Pharmaceuticals' first quarter 2022 financial results conference call.

My name is Crystal, and I will be your coordinator, for today.

Our NDA submission will be primarily based on the pivotal phase III Lavender study, which delivered positive topline results in late 2021.

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. If at any time during the call you require assistance, please press star followed by zero, and a coordinator will be happy to assist you.

I would now like to turn the presentation over to Mark Johnson, Vice President of Investor Relations at ACADIA.

These results were recently presented at a late breaker oral presentation at the American Academy of Neurology annual meeting or <unk>.

Please proceed.

Good afternoon, and thank you for joining us on today's call to discuss ACADIA's first, quarter 2022 financial results.

We plan to submit our NDA midyear and expect this to be a priority review with an action date, most likely in the first quarter of 2023.

Joining me on the call today from ACADIA are Steve Davis, our Chief Executive Officer, who will provide an overview of our first quarter performance and a review of our business.

Our commercial team is working hard on launch preparations, which Brendan will speak to in just a few moments.

Following Steve, Brendan Tehan, our Chief Operating Officer, Head of Commercial, will provide updates on our commercial performance and initiatives.

Dr. Serge Stankovich, our President, will then discuss our pipeline progress.

Moving now to our third late stage opportunity Perm advancement for the treatment of negative symptoms in schizophrenia.

As we previously discussed despite decades of attempts today there is no drug approved for the treatment of negative symptoms of schizophrenia.

With him are answering but it's something that is rarely seen.

Positive pivotal study in patients with negative symptoms that is our advanced one study with.

With one positive pivotal study in the bank. We are currently conducting a second pivotal study our advance two study and if this study is successful we will file for approval.

As an important reminder, the advance two study is almost identical to the advance one study with one important modification.

We advanced two we're evaluating the optimal 34 milligram dose, which as you may recall had the most robust efficacy in the previous advanced one study.

We anticipate completing enrollment in this study around year end with top line results in 2023.

Please turn to slide nine.

Beyond our three late stage opportunities. We are also developing several early stage programs, including our ACP Opal for novel non opioid pain program. Currently in early phase two RPM on Pam program with our lead compound <unk> 301, nine currently in phase one testing.

And several earlier stage molecules, including those from our Vanderbilt in Stoke vibrations and additional molecules that build upon our learnings of kind of answering.

And finally, we continue to be highly engaged and focused on potential strategic business development to further expand our pipeline.

Finally, Mark Schneier, our Chief Financial Officer, will discuss our financial results and guidance before turning it back to Steve for final remarks and opening up the call for your questions.

I would now like to turn the call over to Brendan to provide an update on our commercial efforts.

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

Thank you Steve Please turn to slide 11.

Before we proceed, I would first like to remind you that during our call today, we will be making a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.

These forward-looking statements, including goals, expectations, plans, prospects, growth, potential, timing of events, or future results, are based on current information, assumptions, and expectations that are inherently subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially.

I'm pleased with our team's performance this quarter delivering net sales of $115.5 million, representing 8% year over year growth based on 4% year over year demand growth.

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.

Notably this demand growth is in line with our first quarter plan and aligns with our assumptions for our 2022 net sales guidance range.

I'll now turn the call over to Steve.

Thank you, Mark.

As we look ahead, our ongoing HCP and patient caregiver campaigns continue to set us up well, reaching new physicians and patients educating them on the importance of treating PDP early and the potential of NUPLAZID.

Good afternoon, everyone, and thank you for joining us today.

Please, turn to slide five.

The foundation of our business rests on three key elements.

First, to drive growth of the New Plazid franchise, where we continue to outperform market comparators.

As you will note our relative outperformance in the PD in long term care markets reflects our focus on the highest potential prescribers in the community and the top L. T C facilities for treating PDP patients.

Our teams, especially when they are able to have regular in person contact with prescribers a metric that is increasing month over month has made a measurable impact on overall prescribing behavior, leading to more new patient starts.

As Steve mentioned, the pandemic significantly impacted the growth of the overall P. D market. These past two years.

Utilizing data for my Cube, Yeah, we see that the Parkinson's disease market as measured by treated patients grew only 3% since March 2020 base.

Based on pre pandemic growth rates it should've grown three times this rate by 9% over that same timeframe.

The biggest impact was in long term care, especially in the first year of the pandemic. This makes sense as we know many facilities were hard hit by the pandemic with occupancy rates profoundly impacted by the spread of COVID-19, and many potential LTC residents remaining at home as opposed to entering long term care facilities.

The good news is that we have recently started to see not only stabilization, but early signs of a return to growth in the PD market across channels.

The growth of the NUPLAZID brand against this market backdrop gives us great confidence in our ability to accelerate as conditions continue to improve and normalize.

In addition, when comparing our first quarter performance to pre pandemic in the office space setting carbon Hooper and levodopa scripts declined 6% in the top 10, Parkinson's medications were down 12%.

In direct contrast, NUPLAZID grew significantly up 19%, which was roughly four times that of the top 15, neurology brands, which averaged just 5%.

And the long term care channel Carbo to open levodopa declined 9% a reflection of a significantly lower L. T see occupancy rates in the top 15 L. T. C brands were down an average of 13%.

At the same time NUPLAZID maintained growth up 2% over 2019 levels.

This outperformance was fueled by meaningful increases in NUPLAZID market share of new L. T C patients up almost 20% since the beginning of the pandemic.

We are further encouraged that over the past few months, we have seen and heard from our field force early signs of a return to growth in several of the PD market dynamics that have hampered our growth, including a potential increase in physician visits by their PD patients.

As the market normalizes and begins to return to its regular growth dynamics, we plan to further enhance our promotional efforts with more peer to peer life programming speaker programs and potentially broader multichannel physician caregiver and patient engagement efforts to further grow the brand.

Beyond PDP, we have two exciting near term potential commercial opportunities, let's start with a review of team events were in for the treatment of Alzheimers disease psychosis on slide 12.

Second, to advance our three late-stage opportunities in Alzheimer's disease, psychosis, Rett syndrome, and the negative symptoms of schizophrenia.

And third, to develop the next wave of CNS breakthroughs with our early-stage pipeline, together with continuing to pursue strategic business development opportunities.

For the first quarter of 2022, New Plazid achieved $115.5 million in net sales, representing an 8% year-over-year increase. While Brendan and Mark will go into more detail in a moment, I'd like to point out a few key components of our performance during the quarter.

We have a significant potential opportunity ahead of us with team of answering for ADP.

An indication that is approximately seven times the size of our current PDP market.

Our teams are diligently preparing for the upcoming Advisory Committee meeting and subsequent commercial launch if approved.

Key to our commercial messaging at launch for NUPLAZID in ADP will be both the products demonstrated efficacy and of equal importance NUPLAZID demonstrated safety profile. This is especially important for this patient population.

NUPLAZID already has strong brand recognition as the first and only approved drug for PDP and we look forward to potentially expanding this to ADP.

Now, let's turn to slide 13 to discuss our opportunity with tryphena tied in Ret syndrome.

Towards the end of last year, we were very excited to announce positive phase III results for tryphena tied for the treatment of Ret syndrome, a debilitating disease that leads to severe impairments.

<unk> nearly every aspect of life.

The ability to speak walk eat and breathe easily.

This community has waited a long time to see a positive phase III trial in this neurodevelopmental diseases and the results have been met with a lot of excitement.

With the positive readout, we are focused on preparing for approval and the successful commercial launch of the first potential treatments for this disease.

Today, we are laying the foundation for this launch through thoughtful collaboration and engagement with patient advocacy groups within the REIT community centers of excellence and key opinion leaders on the best way to help identify engage and educate ret families. We've made meaningful progress on our commercial infrastructure and our investing.

<unk> throughout the year.

A critical part of our launch preparation includes external stakeholder engagement with caregivers physicians and payers to understand both their particular needs as well as the market opportunity for tryphena tide.

Our market research indicates a very high percentage of health care professionals, who treat <unk> patients today are interested in prescribing tryphena tide when available for their patients.

Many respondents cited tryphena tides potential efficacy in treating the core symptoms of ret syndrome as a significant reason to look forward to prescribing it post approval now.

Not surprisingly caregivers. We're also very excited about <unk> clinical results and expressed a strong interest interested are tied for their loved ones.

This feedback from physicians and caregivers of current rent patients underscore our confidence in this treatment the motivation for obtaining approval and the market opportunity ahead of us as we establish our presence in rare disease.

I would now like to turn it over to Serge to provide an R&D update.

Thank you Brandon and good afternoon, everyone.

I would like to begin on slide 15, taking a deeper dive on our three late stage opportunities.

At this time, we are actively preparing for the upcoming Advisory Committee meeting to review our S. N D. A resubmission.

During the past several months, we have been working closely with the external key opinion leaders in multiple disciplines to help us prepare for the upcoming Advisory Committee meeting.

We continue to refine our presentation to ensure we will be well prepared quarter in active discussion with the committee on the benefit risk profile of the Milan stream corner Alzheimer's disease psychosis.

We see this as an opportunity to make our case that would be my one sitting with its demonstrated efficacy and safety profile should be the first drug approved for Alzheimers disease psychosis.

And finally, I would like to reiterate a critically important point that Steve made earlier.

There are real safety concerns with the off label use of the multiple receptor acting anti psychotics, which remain the current standard of care for ADP patients who are often frail Atlanta.

This significantly increases the risk to these patients in the context of unproven.

And that's best marginal benefit.

Beyond the efficacy we have demonstrated across multiple clinical studies and the endpoints. We also have a tremendous amount of data on cream of answering both in placebo controlled clinical studies and six years of post marketing Pharmacovigilance data, who will support me my answer and well characterized favor.

<unk> safety profile.

<unk> population.

Let's discuss our upcoming NDA submission with the phenotype on slide six feet.

Brett syndrome is a serious and debilitating rare disorder called which we estimate there are between six and 9000 patients in the United States.

There is no FDA approved treatment for this newer developmental disorder, ultimately red syndrome patients lose their ability to maintain independent functioning on a daily basis that require around the clock support.

Our positive results from the pivotal allowed under study demonstrated efficacy across multiple core symptoms of <unk> syndrome, with statistically significant separation from placebo and clinically meaningful benefit on two co primary endpoint.

The Ret syndrome Behavioural questionnaire.

Caregiver assessment tool as well as the clinical global impression of improvement a physician assessment tool.

Fortunately the efficacy results were consistent across all age groups and severity of disease.

We have completed the pre NDA meeting with the FDA and align on the format and content of the upcoming submission.

So when we look at our placebo-controlled studies, mortality on drug and placebo is equivalent in those kinds of populations.

Serge also referred to the fact that we have a lot of pharmacovigilance data now, having been on the market for several years.

And so that data is also continuing to be very, very supportive, and in fact is maybe highlighted by a paper published by two members of FDA, two members of CMS, and two academic members of Stanford University a little over a year ago, demonstrating that Timavanthrin had a statistically significant improvement in mortality rates relative to other antipsychotics used in those populations.

And I think the final point that Serge was making is that this is a class warning.

We plan to submit our NDA mid year and expect a priority review with the Paducah date, most likely in the first quarter of 2023.

So it's not a Timavanthrin box warning.

Now, let's discuss our negative symptoms of schizophrenia program on slide 17.

There are over 700000 patients in the United States, who are currently treated for schizophrenia, but still have persistence and potentially debilitating negative symptoms.

It is a class warning that all antipsychotics have.

It's social withdrawal lack of emotion and bluntly topic among others.

For which there is no FDA approved treatment.

As part of our advanced program, we have one positive pivotal study.

And typically, to remove a class warning from your drug requires a very, very substantial body of evidence, probably larger than the aggregate placebo-controlled data that we have today.

They already are.

<unk> one word.

We have observed statistical separation on the primary endpoint overall and even more robust result in patients receiving 34 milligrams will be my answer.

But despite that, as Serge mentioned, all of the data we have from the time of our PDP approval until today, continues to look more and more favorable as it relates to risk of mortality.

As such we are now evaluating all these the optimal 34 milligram dose of answering in our second pivotal study advance two.

Thank you.

And briefly I wanted to mention that we continue to monitor the ongoing conflict in Ukraine, and Russia and are doing everything we can to minimize any potential impact on the enrolled.

Our next question comes from Jay Olsen from Oppenheimer.

Your line is open.

Oh, hey.

Given the multi region multi country design of the study we believe based on current projection that we can still achieve our enrollment targets.

Thanks for taking the question.

Completion around year end and top line results available in 'twenty three.

Slide 18 highlights our early stage pipeline opportunities.

We are evaluating a C E O 40 core in both acute and chronic pain model.

As previously announced our acute pain phase two study did not achieve statistical significance on the primary endpoint, even though our positive trend was observed in one of the two dose regimen.

As such we are continuing to analyze the data to determine appropriate next step.

Our phase two study in chronic pain model will work their arthritis is ongoing and expected to complete in the first half of 2023.

In addition, we are advancing compounds from our end one Pam program.

The lead compound HCP 319 currently in phase one multiple ascending dose study.

And our corn, we have multiple early stage programs, we are advancing from our collaborations with <unk> therapeutics and internally develop compounds, which build upon the learnings of three months.

With regards to reimbursement, can you talk about where you see the longer-term steady-state cross-net for nuplazid in PDP, and whether or not the mix of 340B pairs has stabilized?

I'll now turn the call over to Mark to discuss our financial results.

And then for trophinazide, any feedback from pair discussions you've had early on would be great.

Thank you Serge today I'll discuss our first quarter 2022 results. Please turn to slide 20 and.

First, our operational performance in the first quarter was driven by 4% demand growth, a level of growth similar to what we experienced through 2021, which is also in line with our assumptions for our net sales guidance of $510 to $560, million for the full year of 2022.

Thank you.

Second, following the Omicron variant surge as we exited the first quarter and now into the second quarter, We're seeing early signs of additional growth in total prescriptions and new patient starts both with Neuplazid and the overall market as a whole.

Great.

Just a bit of context here.

Thanks so much.

In the quarter, we recorded $115 $5 million in net sales an increase of approximately 8% compared to $106 $6 million of net sales in Q1 of 2021.

Since the beginning of the pandemic in early 2020, the Parkinson's disease market has grown only 3% cumulatively over this two-year period. In comparison, during the two-year period prior to the pandemic, this market grew 9%. In addition, as we've previously reported, in-person patient visits to Parkinson's treating physicians are down approximately 20%.

These conditions have resulted in fewer available patients being diagnosed and treated for their Parkinson's and subsequently for Parkinson's disease psychosis.

However, as Brendan will speak to in both the community and long-term care channels, we've recently seen signs of the overall Parkinson's market stabilizing and slowly returning to growth.

Mark Knauer, you want to take the first question, and Brendan the second?

With mask mandates lifted and physicians encouraging patients to come back to the office, we're cautiously optimistic that we could see further improvement in these market dynamics throughout the spring and into the summer.

Yes, sure.

As Stephen Brendan both mentioned our operational performance reflects approximately 4% demand growth year over year. This is consistent with our demand growth during the full year of 2021 and is one of our key assumptions underlining our guidance range for the full year 2022.

Finally and most importantly, Neuplazid has continued to grow year over year, outpacing the top brands and medications in the neurology segment, the PD market, and in LTC facilities.

Thanks for the question.

We look forward to maintaining that strong performance and delivering on the long-term potential of Neuplazid for PDP.

I think I answered the second part first.

Now let's turn to our three late-stage opportunities on slide 7.

So from a 340B standpoint, we still see growth, but that growth is moderating.

First, I'd like to start by providing an overview of where we stand with our SMDA resubmission, or ADP. This week, the FDA announced that they have scheduled an advisory committee meeting for June 17th to review our resubmission.

So I think as we move forward through this year and we continue to moderate for future years, we'll see how that trend continues to evolve.

In regards to revenue recognition, we observe essentially flat selling volume compared to the first quarter of 2021.

For the meeting, we are focused on three key messages, which point to the overall positive benefit-risk profile for Pimivantrin in this patient population, which include efficacy, safety, and high unmet need. For efficacy, our package supports our position that Pimivantrin provides a consistent and clinically meaningful improvement in the symptoms of psychosis and a reduction of relapse risk in Alzheimer's disease patients.

On the safety side, we've demonstrated in clinical trials that Pimivantrin has a favorable safety and tolerability profile and, importantly, is not associated with worsening of either cognition or motor function in Alzheimer's disease patients, a particularly challenging issue which has historically hindered the development of therapies to treat this condition.

And finally, with regard to unmet need, today there are approximately 900,000 ADP patients being treated in the U.S., the majority of which take off-label multireceptor-acting antipsychotics with marginal efficacy and known safety issues. In the large-scale KDAD study, these off-label antipsychotics were associated with increased impairment of cognition in Alzheimer's patients, equivalent to about one year of disease progression. These medications are also associated with impairment in motor function, sedation, and increased risk of falls, fractures, hospitalizations, and ER visits.

Today, with no FDA-approved treatment for Alzheimer's disease psychosis, healthcare providers will continue to prescribe these off-label antipsychotics despite all of their limitations, as families and caregivers many times are desperate to treat the debilitating psychosis these patients endure.

And then as far as long-term growth in that, that's not something that we forecast.

This is the result of two offsetting volume dynamics first as mentioned we grew demand by 4% year over year. However, this was offset by a larger in channel inventory build in Q1 of last year as compared to this year.

As you know in channel inventory will wax and wane from quarter to quarter, but importantly, we achieved growth in Japan, which ultimately drives our future revenue growth.

Moving on our gross to net adjustment for Q1 2022 was 25, 1%.

Year over year gross to net was higher due to the timing of Medicare accruals between the first and second quarter of 2021, and a greater portion of volume coming from $3 40 be institutions in 2022 as compared to 2021 for the full year 2022, we are still projecting gross to net to be between 2022%.

GAAP R&D expenses increased to $128 $9 million in the quarter compared to $57 million in Q1 2021.

The difference was primarily due to the $60 million upfront payment for the stope collaboration meet in January and also from increased clinical spend and CMC costs.

GAAP SG&A expenses decreased to $96 $7 million in the first quarter from $111 $7 million in the first quarter of last year.

The largest factors driving the difference in the prior year period were related to prelaunch expenditures for DRP in Q1 2021.

And finally, our cash balance at the end of the quarter was $446 million.

We give it out on an annual basis and we'll continue to do so.

Now, let's turn to slide 21.

As you can see on this slide for the full year 2022, we are reiterating all of our previously announced guidance ranges and now I'd like to turn the call back to Steve for closing remarks.

Thanks, Mark.

Thank you Mark please turn to slide 23.

Today, we are executing on our promise to deliver NUPLAZID to patients with PDP, where there's a significant long term opportunity to continue to grow the brand.

And Jay, for the second half of your question for trophinazide, obviously we've been excited to jump in with treaters, with the caregiver community, and with payers to talk about the emerging lavender results and their perception of value.

And what we see, and it shouldn't be surprising, is that payers view trophinazide much like they see rare pediatric medications.

There's very little anticipated budget impact given the overall prevalence of the population.

They expect that the product would be priced like other rare disease medications, and you can look at the gamut of rare disease pediatric drugs to get some sense for that.

And they would expect that it would have similar access issues in terms of what was the studied patient population, and potentially looking at sort of the broader Rett treatment community to make certain that access is appropriate based on clinical trial results.

We look forward to further making our case to the FDA at the upcoming Advisory Committee, meeting that Pimivansirin should be the first FDA-approved treatment for Alzheimer's disease psychosis.

Thank you.

In addition, we are focused on the upcoming Advisory Committee meeting with the FDA as they continue their review of our S. N D. A resubmission for ADP.

We're on track with our preparations to submit a new drug application for <unk> for the treatment of Ret syndrome midyear.

And we continue to advance our third late stage opportunity with our ongoing phase III study and the negative central schizophrenia.

With results expected next year.

Please turn to slide 8.

And we have time for one last question.

In closing I would like to thank our employees for their accomplishments and their ongoing commitment and passion as we continue our mission to elevate life.

Regarding our NDA for Trophinatide, the pre-NDA meetings are complete and we are fully aligned, with the FDA on the format and content for the upcoming NDA submission for Trophinatide for the treatment of Rett syndrome. Our NDA submission will be primarily based on the Pivotal Phase III Lavender Study, which, delivered positive top-line results in late 2021. These results were recently presented at a late-breaker oral presentation at the American, Academy of Neurology Annual Meeting, or AAM.

We plan to submit our NDA midyear and expect this to be a priority review with an action, date most likely in the first quarter of 2023.

And our last question comes from Esther Hong from Barenburg.

I'll now open up the call for questions.

Our commercial team is working hard on launch preparations, which Brendan will speak to, in just a few moments.

Operator.

Moving now to our third late-stage opportunity, Pimivansirin for the treatment of negative, symptoms of schizophrenia. As we previously discussed, despite decades of attempts, today there is no drug approved, for the treatment of the negative symptoms of schizophrenia.

With Pimivansirin, we have something that is rarely seen, a positive pivotal study in, patients with negative symptoms. That is our ADVANCE I study.

With one positive pivotal study in the bank, we are currently conducting a second pivotal, study, our ADVANCE II study, and if this study is successful, we will file for approval. As an important reminder, the ADVANCE II study is almost identical to the ADVANCE I study, with one important modification. In ADVANCE II, we are evaluating the optimal 34-milligram dose, which, as you may recall, had the most robust efficacy in the previous ADVANCE I study.

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

We anticipate completing enrollment in this study around year-end with top-line results, in 2023.

If your question has been answered or you wish to withdraw your question press the pound key.

Please limit yourself to one question I repeat please limit yourself to one question Press Star and then one can begin please standby for your first question.

Please turn to slide nine.

Beyond our three late-stage opportunities, we are also developing several early-stage, programs, including our ACP-044 novel non-opioid pain program, currently in early Phase II, our M1-PAM program with our lead compound, ACP-319, currently in Phase I testing, and several earlier-stage molecules, including those from our Vanderbilt and Stoke collaborations, and additional molecules that build upon our learnings of chemoadventuring.

And finally, we continue to be highly engaged and focused on potential strategic business, development to further expand our pipeline.

Thank you, Steve.

I'd now like to turn the call over to Brendan to provide an update on our commercial efforts.

Our first question comes from Charles Duncan from Cantor Fitzgerald. Your line is open.

Please turn to slide 11.

Your line is open.

Esther Hong Hi, thanks for taking my question.

Hi.

I'm pleased with our team's performance this quarter, delivering net sales of $115.5 million, representing 8% year-over-year growth based on 4% year-over-year demand growth.

Notably, this demand growth is in line with our first quarter plan and aligns with our, assumptions for our 2022 net sales guidance range.

Steve and team Thanks for taking our question and congrats on.

As we look ahead, our ongoing HCP and patient caregiver campaigns continue to set us up, well, reaching new physicians and patients, educating them on the importance of treating, PDP early and the potential of nuplazid.

As you will note, our relative outperformance in the PD and long-term care markets reflects, our focus on the highest potential prescribers in the community and the top LTC facilities for treating PDP patients. Our teams, especially when they are able to have regular in-person contact with prescribers, a metric that is increasing month over month, have made a measurable impact on overall prescribing behavior, leading to more new patient starts.

As Steve mentioned, the pandemic significantly impacted the growth of the overall PD market these past two years. Utilizing data from IQVIA, we see that the Parkinson's disease market, as measured by treated patients, grew only 3% since March 2020. Based on pre-pandemic growth rates, it should have grown three times this rate, by 9% over that same timeframe. The biggest impact was in long-term care, especially in the first year of the pandemic. This makes sense, as we know many facilities were hard hit by the pandemic, with occupancy rates profoundly impacted by the spread of COVID-19, and many potential LTC residents remaining at home as opposed to entering long-term care facilities.

The good news is that we have recently started to see not only stabilization, but early signs of a return to growth in the PD market across channels.

It looks like a good quarter despite challenging.

The growth of the Neuplazid brand against this market backdrop gives us great confidence in our ability to accelerate as conditions continue to improve and normalize.

Beyond PDP, we have two exciting near-term potential commercial opportunities.

In addition, when comparing our first quarter performance to pre-pandemic, in the office-based setting, Carbidopa and Levodopa scripts declined 6%, and the top 10 Parkinson's medications were down 12%.

In direct contrast, Neuplazid grew significantly, up 19%, which was roughly four times that of the top 15 neurology brands, which averaged just 5%.

In the long-term care channel, Carbidopa and Levodopa declined 9%, a reflection of a significantly lower LTC occupancy rate, and the top 15 LTC brands were down an average of 13%.

Environment.

At the same time, Neuplazid maintained growth, up 2% over 2019 levels. This outperformance was fueled by meaningful increases in Neuplazid's market share of new LTC patients, up almost 20% since the beginning of the pandemic.

We are further encouraged that over the past few months, we have seen and heard from our field force early signs of a return to growth in several of the PD market dynamics that have hampered our growth, including a potential increase in physician visits by their PD patients.

Mike My question is really related I guess to troponin tied sensing and a whole lot to one and that is.

So just wanted to ask on trophinatide, if you could provide any details on the open, label extension studies that are going on.

As the market normalizes and begins to return to its regular growth dynamics, we plan to further enhance our promotional efforts with more peer-to-peer live programming, speaker programs, and potentially broader multi-channel physician, caregiver, and patient engagement efforts to further grow the brand.

Relative to <unk>.

Upcoming NDA would you anticipate an AD com for that drug given its really first first in class ever and then if approved would you be able to get a P. R V and then perhaps to extend the multipart.

Would that result in changes to the commercial infrastructure should it be approved.

Let's start with a review of Pimavenserine for the treatment of Alzheimer's disease psychosis on slide 12. We have a significant potential opportunity ahead of us with Pimavenserine for ADP, an indication that is approximately seven times the size of our current PDP market. Our teams are diligently preparing for the upcoming advisory committee meeting and subsequent commercial launch, if approved.

And maybe if you can speak about patients who've continued on treatment and what's been, observed.

Great Alright, thanks, much for the question Charles I'm going to ask.

Key to our commercial messaging at launch for Nuplazid and ADP will be both the product's demonstrated efficacy and of equal importance, Nuplazid's demonstrated safety profile. This is especially important for this patient population.

Thanks.

Nuplazid already has strong brand recognition as the first and only approved drug for PDP and we look forward to potentially expanding this to ADP.

Great.

Serge to respond to sub parts, one and two and Brendan part three.

Serge, you want to take that?

Yeah.

Thanks Charles.

Relation to the.

Anticipation of the Advisory Committee of course, we are always thinking of that and preparing for such eventuality.

Charlie historically, though I would say that there is a.

About half top chances in this sort of situation with rare diseases may be even a little bit more on not having the advisory committee.

That.

At least from what we saw on the records that these are all core I would just say we do not see.

Any.

Our priority is substantive controversial issues that would immediately.

<unk> lead us would think that we would have an advisory committee, but I would just say, it's a 50 50 chance.

Thanks, Serge and Charles Thanks for the question.

Yeah.

Just taking us back to when we had.

Brought the program into Acadia, we're very excited about what <unk> means.

Now let's turn to slide 13 to discuss our opportunity with Trophinatide in Rett Syndrome. Towards the end of last year, we were very excited to announce positive phase 3 results for Trophinatide for the treatment of Rett Syndrome, a debilitating disease that leads to severe impairments, affecting nearly every aspect of life, the ability to speak, walk, eat and breathe easily.

Thank you.

As you can imagine, we, as part of our overall data presentation and analysis in the New, Drug Application, we are including the long-term data from the open label studies, particularly from the perspective of the maintenance of effect that we saw in the short-term study in patients on drugs, as well as the changes in the symptoms for patients that are converted from double-blind into open label study, from placebo to active treatment.

In both cases, we are experiencing further improvement or improvement for the former, and improvement for the latter in the open label study that continues over the 40 weeks of treatment and beyond.

To us overall and it fits into our footprint very nicely as you know we already have rare disease experience in house, we expect to leverage synergies from internal operations, but we will also make thoughtful adjustments to address a pediatric neurology.

This community has waited a long time to see a positive phase 3 trial in this neurodevelopmental disease and the results have been met with a lot of excitement.

With the positive readout, we are focused on preparing for approval and the successful commercial launch of the first potential treatment for this disease.

Today we are laying the foundation for this launch through thoughtful collaboration and engagement with patient advocacy groups within the Rett community, centers of excellence and key opinion leaders on the best way to help identify, engage and educate Rett families.

<unk> community for the rare disease and I'm sure will go into further details on the infrastructure of the closer we get.

We've made meaningful progress on our commercial infrastructure and are investing appropriately throughout the year.

A critical part of our launch preparation includes external stakeholder engagement with caregivers, physicians and payers to understand both their particular needs as well as the market opportunity for Trophinatide. Our market research indicates a very high percentage of healthcare professionals who treat Rett patients today are interested in prescribing Trophinatide when available for their patients. Many respondents cited Trophinatide's potential efficacy in treating the core symptoms of Rett syndrome as a significant reason to look forward to prescribing it post-approval. Not surprisingly, caregivers were also very excited about Trophinatide's clinical results and expressed a strong interest in Trophinatide for their loved ones.

This feedback from physicians and caregivers of current Rett patients underscore our confidence in this treatment, the motivation for obtaining approval and the market opportunity ahead of us as we establish our presence in rare disease.

Hey, Charles This is Steve there was the second part.

Second Subpart could you just repeat that for us.

Okay.

Yes, Joe.

Yeah Yeah.

Yeah.

Yeah.

Go ahead Charles.

Yes, I'm sorry.

Is it possible that you would be granted a P. R V F. Carroll finished tightens approved.

Oh.

Yes, sorry about that yeah, yeah, we are.

Having pediatrics.

Orphan designation, we do anticipate that if approved we would have received pediatric voucher.

Got it thank you.

I would now like to turn it over to Serge to provide an R&D update.

Okay.

Thank you. Our next question comes from Neena <unk> Garg from Citi. Your line is open.

Hey, guys. Thank you for taking the question.

I was just wondering about the AD comm for Alzheimer's psychosis coming up in June .

I guess any thoughts that you can share in terms of.

Typical of kind of a PR ad com.

Or do you expect there to be any differences versus the historical panels versus D PDP outcome.

Thank you, Brandon, and good afternoon, everyone.

Yeah. Thanks for the question you said you want to take that.

I would like to begin on slide 15 by taking a deeper dive on our three late-stage opportunities.

Yes. Thanks.

What I would say as we've been saying.

Saying all along.

This is our.

At this time, we are actively preparing for the upcoming advisory committee meeting to review our SMBA resubmission. Over the past several months, we have been working closely with the external key opinion leaders in multiple disciplines to help us prepare for the upcoming advisory committee meeting. We continue to refine our presentation to ensure we will be well-prepared for an active discussion with the committee on the benefit-risk profile of temelanserine for Alzheimer's disease psychosis.

Our.

Response to the complete response letter.

And the Resubmission is not your.

Typical application you know we are making a fairly.

We see this as an opportunity to make our case that pimavenserine, with its demonstrated efficacy and safety profile, should be the first drug approved for Alzheimer's disease psychosis.

Complex case following a very.

Following.

Development that has been having the it's a it's a.

And finally, I would like to reiterate a critically important point that Steve made earlier.

So from that perspective, we are very pleased with that data, and we'll be including that, in our submission.

There are real safety concerns with the off-label use of the multi-receptor acting antipsychotics, which remain the current standard of care for ADP patients who are often frail and elderly. This significantly increases risk to these patients in the context of unproven and, at best, marginal benefits.

In aspect from your second part of the question in terms of the retention of patients, what, we are seeing in the open label study, we are continuing to see relatively good retention of patients with somewhat lesser dropout rates than what we saw in the double-blind period, which is actually expected, even though you have to take into account the double-blind studies 12 weeks long, while open label studies run for many more weeks.

And from that perspective, doing the longer studies eventually results in the people dropping, out to a larger extent.

Courts for poorer for awhile, so from that perspective.

We are making we are trying to really present to the committee.

So from both perspectives, we are very pleased with the data, and that data will be part, of our submission.

Ah pool spectrum, all the historical.

Context, all of our application as well as the data and really the data is the core of what we are trying to present in a comprehensive manner and offered them.

Beyond the efficacy, we have demonstrated across multiple clinical studies and endpoints.

We also have a tremendous amount of data on pimavenserine, both in placebo-controlled clinical studies and six years of post-marketing pharmacovigilance data to support pimavenserine's well-characterized favorable safety profile at this at-risk population.

Uh huh.

Supportive evidence for substantial efficacy and positive benefit risk in Alzheimer's disease, psychosis, but I would say the mechanics and the execution of the advisory committees are fairly typical and I do not expect that in any way this would be outside of <unk>.

Let's discuss our upcoming NDA submission with trophinatide on slide 16.

Rett syndrome is a serious and debilitating rare disorder for which we estimate there are between 6,000 and 9,000 patients in the United States. There is no FDA-approved treatment for this neurodevelopmental disorder. Ultimately, Rett syndrome patients lose their ability to maintain independent functioning on a daily basis and require around-the-clock support.

Usual contacts there'll be advisory committee in a in any.

Significant way.

Our positive results from the pivotal lavender study demonstrated efficacy across multiple core symptoms of Rett syndrome with statistically significant separation from placebo and clinically meaningful benefit on two co-primary endpoints.

Thank you.

We have developed a Rett syndrome behavioral questionnaire, a caregiver assessment tool, as well as the Clinical Global Impression of Improvement, a physician assessment tool.

Importantly, the efficacy results were consistent across all age groups and severity of disease.

Thank you.

Our next question comes from Cory <unk> from JP Morgan Your line is open.

We have completed pre-NDA meetings with the FDA and aligned on the format and context of the upcoming submission.

Mr. Davis, please proceed to closing remarks.

We plan to submit our NDA mid-year and expect a priority review with a FDUFA date, most likely in the first quarter of 2023.

Hey, guys. Thanks for the question. This is kicking on for Corey just one more on NUPLAZID and ADP, but I'm just wondering how the go to market strategy might be different.

Now, let's discuss our negative symptoms of schizophrenia program on slide 17.

Thank you, Operator.

There are over 700,000 patients in the United States who are currently treated for schizophrenia but still have persistent and potentially debilitating negative symptoms, such as social withdrawal, lack of emotion, and blunted affect, among others, and for which there is no FDA-approved treatment.

As part of our ADVANCE program, we have one positive pivotal study already, ADVANCE-1, where we observed statistical separation on the primary endpoint overall and even more robust results in patients receiving 34 mg of pimivanda.

As such, we are now evaluating only the optimal 34 mg dose of Pimavansirin in our second pivotal, study, ADVANCE-2.

And thanks, everyone, for joining us today.

Parkinson's disease psychosis, and if theres any synergies in terms of treatment centers physicians et cetera, I'm, just kind of wanting to get your take on the commercial readiness and launch preparation as it relates to PDP.

And briefly, I wanted to mention that we continue to monitor the ongoing conflict in Ukraine, and Russia and are doing everything we can to minimize any potential impact on enrollment.

We have a pretty full calendar over the course of the next 12 months plus.

We look forward to updating you on our progress.

Given the multi-region, multi-country design of the study, we believe, based on current, projections, that we can still achieve our enrollment targets of completion around year end and top-line results available in 2023.

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

Slide 18 highlights our early-stage pipeline opportunities.

This concludes the presentation.

We are evaluating ACP044 in both acute and chronic pain models.

As previously announced, our acute pain Phase 2 study did not achieve statistical significance, on the primary endpoint, even though a positive trend was observed in one of the two dose regimens evaluated. As such, we are continuing to analyze the data to determine appropriate next steps.

Our Phase 2 study in a chronic pain model of osteoarthritis is ongoing and expected, to complete in the first half of 2023.

In addition, we are advancing compounds from our M1 PAM program with the lead compound, ACP319 currently in Phase 1 multiple ascending dose study.

Thank you, Serge.

You may now disconnect.

Great. Thanks, so much for the question Brendan do you want to take that.

And of course, we have multiple early-stage programs we are advancing from our collaborations, with Stoke Therapeutics and internally developed compounds, which build upon the learnings of Pima Ransom.

Today, I'll discuss our first quarter 2022 results.

I'll now turn the call over to Mark to discuss our financial results.

Sure definitely.

Please turn to slide 20.

Good day.

In the quarter, we recorded $115.5 million in net sales, an increase of approximately, 8% compared to $106.6 million of net sales in Q1 of 2021.

For the question.

As Steve and Brendan both mentioned, our operational performance reflects approximately, 4% demand growth year-over-year. This is consistent with our demand growth during the full year of 2021 and is one of, our key assumptions underlining our guidance range for the full year 2022.

In regards to revenue recognition, we observe essentially flat sell-in volume compared to, the first quarter of 2021. This is the result of two offsetting volume dynamics. First, as mentioned, we grew demand by 4% year-over-year. However, this was offset by a larger in-channel inventory build in Q1 of last year as compared, to this year.

As you undoubtedly know we were getting ready for dementia related psychosis, a year ago and would have been right post launch at this point.

As you know, in-channel inventory will wax and wane from quarter to quarter, but importantly, we achieved growth in demand, which ultimately drives our future revenue growth.

Moving on, our gross to net adjustment for Q1 2022 was 25.1%. Year-over-year, our gross to net was higher due to the timing of Medicare accruals between, the first and second quarter of 2021 and a greater portion of volume coming from 340B institutions in 2022 as compared to 2021.

Now let's turn to slide 21.

For the full year 2022, we are still projecting gross net to be between 20 and 22 percent.

As you can see on this slide, for the full year 2022, we are reiterating all of our previously, announced guidance ranges.

Gap R&D expenses increased to $128.9 million in the quarter compared to $57 million in, Q1 2021. The difference was primarily due to the $60 million upfront payment for the Stoke collaboration, made in January and also from increased clinical spend and CMC costs.

Gap SD&A expenses decreased to $96.7 million in the first quarter from $111.7 million in, the first quarter of last year. The largest factors driving the difference in the prior year period were related to pre-launch, expenditures for DRP in Q1 2021.

And finally, our cash balance at the end of the quarter was $446 million.

And now I'd like to turn the call back to Steve for closing remarks.

The plans were very much already in place both in terms of strategy, our tactical execution targets that we're going for and deployment.

Thank you, Mark.

Please turn to slide 23.

PDP is a subset of the ERP and some of our target physicians for Parkinson's disease psychosis will absolutely be our targets for ADP as well, but we will thoughtfully expand to a broader audience that treats.

Today we are executing on our promise to deliver new plans into patients with PDP where there, is a significant long-term opportunity to continue to grow the brand.

Alzheimer's disease, psychosis, which just as a reminder, 70% of that dementia related psychosis audience, we will expand to cover more psychiatrists and there will be primary care physicians that our sites like in their treatment.

Demonstrating that in their ability to write for Alzheimer's medications, and importantly have demonstrated the ability to prescribe atypical anti psychotics.

In any event, we are prepared to address that Robert Williams.

Okay.

In addition, we are focused on the upcoming advisory committee meeting with the FDA as, they continue their review of our SNDA resubmission for ADP.

Thank you. Our next question comes from Gregory <unk> from RBC capital markets. Your line is open.

We're on track with our preparations to submit a new drug application for Trepidantat for, the treatment of Rett syndrome mid-year.

Great. Thanks, Steve and team for taking the question and congrats on the progress.

And we continue to advance our third late-stage opportunity with our ongoing phase three study, in the negative symptoms of schizophrenia with results expected next year.

Maybe just following up a bit on the AD com in June very helpful to hear about.

In closing, I would like to thank our employees for their accomplishments and their ongoing, commitment and passion as we continue our mission to elevate life.

I'll now open up the call for questions.

Maybe the mechanics and that maybe the technicality of it I'm just curious Steve if you could.

Operator?

Provide some color on how important you think a vote of confidence is from the panel, especially.

In light of that unique situation that you've certainly endured and having the differences in the deal on the initial.

Package that led to the CRM and maybe just.

And also related to just some of the history of that content recommendations and how that leads to approval or not and maybe just on that.

Subpart ill throw one in as well I'm just respect to the potential scenarios of that outcome, maybe providing some color about how you were thinking about scenario planning based on on the boat outcomes. Once you go from.

Ladies and gentlemen, if you wish to ask a question, please press 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.

June until until August thank you very much.

Please limit yourself to one question.

Yes, thanks much for the question Greg.

If you wanted to take the first one regarding the importance of the combo to confidence and I'll take the second part regarding potential scenarios.

I repeat, please limit yourself to one question.

Press star and then one to begin.

Yes. Thank you.

Without a doubt the vote on the advisory community is very important although.

Please stand by for your first question.

This is walt.

It would come with the Advisory Committee is not binding for the FDA.

Our first question comes from Charles Duncan from Cancer Fitzgerald.

Statistics point out that in.

A great majority of deal cases, the FDA, usually go goes along with it.

Your line is open.

Hi.

With the recommendations of the advisory community our own experience from the previous Advisory Committee or Parkinson's disease psychosis, where we received overwhelming support from the Advisory Committee.

And in respect to a positive vote.

<unk> had a significant impact on the ultimate approval of the drug as you know initial reaction then report from the EBITDA was not as favorable so from that perspective, we do.

Certainly.

Believe that it is important that we make a strong case for the advisory committee and obtain or received support from the Advisory Committee for the case, we are making.

Yeah, Steve and team, thanks for taking our question and congrats on what looks like a, good quarter despite challenging environment.

My question is really related, I guess, to Trophinatide since I'm going to hold it to, one.

Yes, thanks Serge.

And Greg in response to the second part of your question.

I think the way we think about it is there are three.

Principal buckets, and maybe a little bit of space between.

The three buckets.

Relative to the upcoming NDA, would you anticipate an adcom for that drug given it's really first, in class ever?

You can come out of an advisory committee meeting with a very significantly.

So cigna opposition so.

You know the math is heavily.

In favor of non approval.

Can come out with the opposite ends of the spectrum, where the math is the boats are heavily in favor of approval and then you can come out with something that's more of a mid.

And then if approved, would you be able to get a PRV and then perhaps to extend the multi-part, would that result in changes to the commercial infrastructure should it be approved?

Great.

The midpoint of that and then of course, some variations in between and so I think for us.

Thanks much for the question, Charles.

And again, we're just reiterating the caveat this surge mentioned that.

I'm going to ask Serge to respond to subparts one and two and Brendan to subpart three.

No.

Ed comes don't approve drugs the FDA does.

But they.

History tells us that they see.

Thanks, Charles.

Significant majority of that bottleneck and so in terms of how we think about that scenario planning impact. It has on us I'll just repeat what Brendan said earlier, we're in the very very fortunate position, we did a lot of work for.

In relation to the anticipation of the advisory committee, of course, we are, always thinking of that and preparing for such eventualities.

Historically, though, I would say that there is about half-half cancers in this sort of situation with rare, diseases, maybe even a little bit more on not having the advisory committee that, at least from what we saw on the records, that this occur.

I would just say we do not see a priori substantive controversial issues that would immediately lead us to think that we would have an advisory committee, but I would just say it's a 50-50 chance.

Thanks, Serge, and Charles, thanks for the question.

Just taking us back to when we had brought the program into ACADIA, we're very excited about what trophinatide means to us overall, and it fits into our footprint very nicely.

As you know, we already have rare disease experience in-house.

We expect to leverage synergies from internal operations, but we will also make thoughtful adjustments to address a pediatric neurology community for the rare disease, and I'm sure we'll go into further details on infrastructure the closer we get.

Charles and Steve, there was a second part, or a second subpart.

<unk> for DRP launch, we've got all that work and the benefits of that on the shelf for ready to pull it off.

And the precise timing of that and how we.

Advance on that will be somewhat a function of.

The AD com in those three buckets and.

And the good news is we have an action date, that's scheduled for August 4th which is not too.

Far down the road after after netcom and so depending on how.

The outcome.

Goes in and kind of where we are in that spectrum of scenarios will be eager to.

To be prepared for launch.

Yeah.

Thank you. Our next question comes from Yadkin Fanega from Guggenheim Partners. Your line is open.

Could you just repeat that for us?

Sorry, Charles.

Yeah, I'm sorry.

Hey, guys. Thank you for taking my question two real quick one for me first one is could you confirm if you requested the outcome as part of the formal dispute resolution or was it proposed by the FDA.

Is it possible that you would be granted a PRV if, trophinatide is approved?

Yeah, sorry about that.

And then the second part is that you know both phase III harmony and zero 109 study had a different study design and endpoints. So I'm just trying to understand.

How can they be supportive of each other when both are trying to answer a different question and the endpoints in studies that are completely different. Thank you.

Yeah, having a pediatric orphan designation, we do anticipate that if approved, we will receive pediatric voucher.

Got it.

Yeah. Thanks, so much for the question I'll take the person is searched and respond to second line.

Thank you.

Thank you.

In terms of requesting an ad com.

Just to level set.

Having that comment out is entirely too.

Discretion of the FDA.

Early in our discussions with FDA after receiving CL.

Did suggest that they consider having an AD com and their response was simply you know it's premature for us to.

Comment I think about that.

Advanced these discussions.

We didn't discuss it any further with them.

And then as we all know now they have.

Permanent they're having an ad com.

Serge you want answered the second question Yeah, Yeah, Let me just make sure I understood. The question that you broke up a little.

Were you asking about the two studies as a part of our.

Our resubmission of <unk>, 19, and <unk> 45, being studies in different patient population than we do different outcomes and how that fits together in this application.

That is correct, yeah, and not maybe the patient population, but just the endpoints are very different for both the studies.

Yeah.

Are there.

Our debt is in that is correct.

But we have been.

<unk> been using in both studies measuring coordination and delusions and the primary symptoms of psychotic.

Break breakdown in one case more in severity defense in another case measuring more in terms of relapse.

Recurrence of symptoms, but in any case, we do have a we can actually.

Fairly reliably compared with data from both studies because we are measuring the same symptoms of the same disorder and from that perspective.

They are I would think of them more as complementary rather than differential in terms of how we see as a matter of fact, if you think about that is in the acute study of about 19, what what we demonstrated is a few of the efficacy of <unk> treatment in patients that are experiencing.

<unk> seen.

A psychotic symptoms in the short term six weeks paradigm on the other hand study all 45.

Within the same symptoms has been evaluated durability of effect in patients that respond to treatment.

Treatment, so from that perspective actually quite upbeat complementarity between the two studies.

Our next question comes from Nina Petrito-Garg from Citi.

Thank you.

Our next question comes from <unk> Richter from Goldman Sachs. Your line is open.

Your line is open.

Hey, guys.

Hey, Thanks, This is Matt on for solving.

Thank you for taking the question.

I was just wondering about the ADCOMM for, Alzheimer's psychosis coming up in June.

First on NUPLAZID could you share how in person office visits and long term care occupancy rates are tracking relative to pre pandemic levels and then on ACP 044.

I guess any thoughts that you can share in terms of how typical of kind of a PADACC ADCOMM you expect this to be, or do you expect there to be any differences versus some of the historical panels or versus the PDP ADCOMM?

Given that you saw a trend in acute pain do you expect better results in chronic or do you view these as unrelated thanks a lot.

Thanks.

Yeah, thanks for the question, Nina.

Yeah. Thanks, so much for the questions.

Serge, do you want to take that?

Brendan you want to take the question on NUPLAZID and surge on the Oklahoma.

Yeah, thanks, Nina.

Sure happy to do that.

What I would say, as we've been saying all along, this is our, response to the complete response letter, and the resubmission is not your typical application.

What we've seen in the first quarter for in person patient visits in the community reflects that there is still about 20% below pre pandemic levels.

We are making a fairly complex case following a development that has been, having its course for a while.

So, from that perspective, the case we are making, we are trying to really present to the committee a full spectrum of the historical context of our application, as well as the data.

With that said I, just want to point out and in visits to see customers. We see that clinicians are beginning to ask their patients to return for inpatient visits and not favor telemedicine over that.

And then for LTC occupancy rates to further answer your question. We have we have two things going on one is there are slight increases in the LTC occupancy rates of late.

From from the base they've returned to about 73% in the most recent data that we're seeing so slightly up from where they were in the fourth quarter and those are being driven by new residents entering long term care facilities, which I think is encouraging for us because we understand if that trend were to continue.

Patients tend to be identified for PDP.

Proximal to there being admitted to a skilled nursing facility.

Yeah.

Yeah.

Mel when in regard to.

A potential read through from our acute.

Model to chronic model of pain and the studies as we have been saying throughout we do not see it'd be Rad direct read through.

From the results of the acute study.

Of course, I would say.

We would love to see.

A very robust positive results of the acute study right.

Rather than a signal that we have observed but there is no direct connection as far as the preclinical data.

And we've reported this previously we see there.

ACP O 44 have been.

Has it positive activity in the animal models of those positive or.

Both acute and the chronic models of pain, so from that perspective, we.

At this point not jumping to any pretty mature conclusions in regard.

To the.

I'll start trying to study and the data will show us the best.

Thank you.

Our next question comes from <unk> Kulkarni from Canaccord. Your line is open.

Good afternoon, Thanks for taking my question.

Comfort and Benson for ADP.

Rather than not having said that because significance specific ADP subgroup and how many what the FDA has already expressed on study one night what are some of the specific mix a key source of the pushback.

Let your external Kilonzo consultants might it might have on the data package will be putting together for the meeting.

Yeah.

Yes. Thanks.

Good question Serge do you want to take that.

Yeah.

No.

Obviously.

We're preparing.

Studiously.

And are looking forward to challenging feedback and questions from our kols to in order to prepare ourselves the best for the Advisory Committee, but I would say that overall.

The feedback we're getting we're getting quite a bit of a support from people in terms of understanding.

Our specific circumstances, and the data and meaningfulness and consistency of the Alzheimer disease psychosis data that we have across the studies across the endpoint and over time, so from that perspective, I think without getting into a.

And really, the data is the core of what we are trying to present in a comprehensive manner and offer them supportive evidence for substantive efficacy and positive benefit-risk in Alzheimer's disease psychosis.

But I would say the mechanics and execution of the advisory committee are fairly typical, and I do not expect that in any way this would be outside of usual context of the advisory committee in any significant way.

Very specific details, which.

You will understand it's not really at the probably the most appropriate.

Situation for us to do that at this point I think that we are.

Preparing.

To meet all of the scientific challenges that can be put in front of us in terms of the data and arguments and analyses that were providing.

Thank you. Our next question comes from David Hung from SMB see your line is open.

Thank you.

Our next question comes from Corey Cosimo from J.P. Morgan.

Hey, thanks, so much for taking the question.

I just wanted to dig a little bit more on the recovery potential recovery of the.

PDT market this year.

Your line is open.

Can you just talk a little bit more and give a little more color in terms of what you're hearing maybe from your.

Salesforce and people in the field that gives you confidence that we.

We should see both LTC and the office channel recover and then you mentioned spring summer as maybe the timeframe in which that happens.

Yeah. It was there is there anything that would potentially allow the recovery happened faster.

Yeah sure let me just.

Reframe your question, a little bit and then I'm going to pass it to Brendan So what we've said is that we're beginning to see some evidence of slow growth. There has been a period of stabilization applebee's see some evidence of of slow growth, we're seeing a little bit.

Hey, guys.

A little bit more in LTC and we are in the office based setting where we're seeing indicators in both sector.

Sections, and what we said is that we're cautiously optimistic that.

That will be able to grow on these and see these build in the course of the spring. So Brendan do you want to.

Answering your question more completely.

Sure. Thanks Steven.

And for the re frame I think that's all very appropriate.

Couple of.

The guide points to us that are encouraging are the new residents entering facilities, we've seen a slow but steady increase.

Over the prior couple of months, that's an encouraging set.

Lee in terms of PD in person patient visits as I said before.

Practices are more open from our experienced two both seeing our representatives, which means we have an opportunity to tell our story face to face to them.

And our Hcp's are really becoming advocates and asking their patients to come in for face to face consultations. This is a movement disorder and the subtleties of changes there coupled with neuro psych neuropsychiatric symptoms.

Make the HCP want to see both the patient and the caregiver face to face where possible. What we saw in the first quarter and what Hep's have told us is <unk>.

For some hesitation in an elderly population to return to those offices that coupled with any parts of the country where winter causes.

Insert for fault also led to hesitation so.

Both of those things.

Prove in the weeks and months ahead.

At least cautious optimism that there will be some return to normalcy and seeing your your clinician face to face. So those are.

Really the key elements.

Thanks for the question.

Thank you. Our next question comes from Marc Goodman from SBB Securities. Your line is open.

This is Tiffany on for Corey.

Okay. Thanks for taking my question.

On the line from Mark So.

So first congrats on the quarter I have a question.

Regarding deposits.

In PDP. So can you talk about the penetration rates so far in the PDP market.

And maybe provide more color on off label use so far in other indications, including ADP. Thanks.

Yeah sure Brendan you want to take those.

Sure. Thanks for the question.

Just one more on, Neuplazid and ADP.

First and foremost I think Steve did a very nice job in prepared remarks talking about the PD market and how it's been impacted over the past couple of years.

We're just wondering how, you know, the go-to market strategy might be different than for Parkinson's disease, psychosis, and if there's any synergies in terms of treatment centers, physicians, et cetera, just kind of wanting to get your take on the commercial readiness and launch preparation as it relates to PDP.

I think what's impressive is despite the fact that there have been fewer inpatient visits fewer prescriptions written for principal motor dysfunction medications carve. It open levodopa, we've seen NUPLAZID continues to grow total prescriptions over pre pandemic levels so that.

Gives us great confidence number one that our message is resonating.

And that we are being chosen more often in the first line position to treat Parkinson's disease psychosis.

Evidenced by what we've seen and increases in share both on the community side and encouragingly in new patient starts on in long term care facilities.

Okay.

Oh I'm sorry in terms of the question on off label use that still continues to be a very very very small number for us as you probably know the vast majority of our prescriptions go through a hub, which requires a treatment form where you indicate specifically why you want to put a pace.

On NUPLAZID.

That has to be indicated as Parkinson's disease psychosis.

And in our environment, where payers are very careful about prior authorizations, we still see very low single digit.

<unk>.

The product essentially used for something other than Parkinson's disease.

Thanks.

Thank you. Our next question comes from Chris Howerton from Jefferies. Your line is open.

Great.

Excellent. Thank you so much for taking the questions.

I guess, what I was wondering about with respect to the advisory committees.

Both for ADP and the potential one for <unk>.

Thanks much for the question.

How important you believe patient advocacy groups to be as part of that conversation and how influential they might be.

And if you would entertain a quick clarification follow up how do you derive the 900000 patients treated with atypical antipsychotics in the ADP population. Thank you.

Brendan, you want to take that?

Yes sure.

Brennan once you take the second question first of all look back to the first one.

Sure. Thanks for the question.

When we speak of 900000 patients being treated for ADP about two thirds of those would be expected to have been off label atypical anti psychotics there.

Also other mood stabilizers and anti depressants used for a similar reason in that patient population, but that is still.

Our consideration of the addressable population for ADP.

And Chris you were breaking up on nine could you repeat the first part of your question around outcomes I didn't hear what you said after that.

Yeah, I'm totally sorry, I guess.

Maybe say more concisely as how important do you think patient advocacy groups are for your advisory committees, either the ADP or the potential one for trophy type.

Sure.

And, Tiffany, thanks for the question.

Got it. Thanks, so much well first let me just say patient advocacy groups.

As you undoubtedly know, we were getting ready, for dementia-related psychosis a year ago and would have been right post-launch at this point. So plans were very much already in place, both in terms of strategy, our tactical execution, the targets that we were going for in deployment.

PDP is a subset of DRP, and some of our target physicians for Parkinson's disease psychosis, will absolutely be our targets for ADP as well.

Advocate for patients right. So they they are.

They are independent device.

But I think in both cases, they are very strong and passion advocacy groups Cushing for therapies.

But we will thoughtfully expand to a broader audience that treats Alzheimer's disease psychosis, which, just as a reminder, is 70% of that dementia-related psychosis audience.

Where there's nothing approved both in ret syndrome, as well as in Alzheimer's disease psychosis.

We will expand to cover more psychiatrists, and there will be primary care physicians that are psych-like in their treatment and have demonstrated that in their ability to write for Alzheimer's medications and, importantly, have demonstrated the ability to prescribe atypical antipsychotics.

And in any event, we are prepared to address that broader audience.

No.

And so I think there.

Thank you.

Very important, particularly in a circumstance, where there is no drug approved.

And that's.

One of the reasons, we see them being very active in this space and making sure that they.

They elevate.

The unmet need that there that they are living with and experiencing everyday in the eyes of the FDA.

Our next question comes from Gregory Renza from RBC Capital Markets.

Thank you.

Next question comes from <unk> Divan from Mizuho Securities. Your line is open.

Your line is open.

Great.

Alright, great. Thanks for taking my questions. Most of mine have been asked but just.

Couple of things just to clarify so.

Thanks, Steve and team, for taking the question, and congrats on the progress.

One on your assumptions around guidance I, just wanted to confirm that you're still not assuming anything on the sales or on the expense side related to ADP.

G&A side, assuming an ADP approval this year and then on the O four for chronic data.

Is that still expected by year end I think he used to be a <unk> 2022 event.

In clinical trials.

December but I'm not seeing it specifically mentioned in your slides so apologies if I missed it in your comments. Thank you.

Maybe just following up a bit on the ADCOMM in June, very helpful to hear about, maybe the mechanics and maybe the typicality of it.

I'm just curious, Steve, if you could provide some color on how important you think a vote of confidence is from the panel, especially in light of that unique situation that you've certainly endured and having the differences in the view on the initial package that led to the CRL, and also related to just some of the history of ADCOMMs and recommendations and how that leads to approvals or not, and maybe just a subpart.

Okay, Let's go to Mark for the first question searches.

Yeah.

Okay.

I'll throw one in as well.

Can you hear us.

We can hear you Mark go ahead.

Just with respect to the potential scenarios of that outcome, it may be providing some color about how you're thinking about scenario planning based on the vote outcomes once you go from June until August.

Okay, Yes, sorry, there's something happening with the phone here so just on the.

Thank you very much.

Guidance question.

As we said previously there is nothing in our revenue or expense guidance related to ADP at this time.

Yeah, thanks much for the question, Rick.

Thanks Serge.

In regard to the all star tried to study.

In spite of the headwinds that we all experience, particularly in the.

These types of studies related to corvid.

We continue to expect to complete enrollment around.

The year end or the beginning of <unk>.

Next year the way the data as we said in the first half topline results in the first half of next year.

Thank you. Our next question comes from Paul Matteis from Stifel. Your line is open.

Hey, there. Thanks for taking our question. This is Alex on for Paul just one more on the ADP AD Com I was wondering maybe you could talk a little about the importance of the black box discussion at the AD Com I guess is it your position that there should be no AD com on a potential approved SBA. So Tim is answering how much evidence you have outside of <unk>.

Serge, you want to take the first one regarding the, importance of the ADCOMM vote of confidence, and I'll take the second part regarding potential scenarios.

Yes, thank you.

P maybe alleviate.

Fda's concerns around sort of the unknown mortality risk in this class.

Yeah, Alex I think you meant to say presume that we would advocate for no black box.

Yes.

Yeah.

So you want to take that question.

Yeah, well, what I will say without going with all of the details that the day that we had in my accumulated from the previous advisory advisory comedian the previous application and approval with ADP is considerably larger.

Without a doubt, the vote on the advisory committee is very important. Although the vote and outcome of the advisory committee is not binding for the FDA, statistics point out that in a great majority of cases, the FDA usually goes along with the recommendations of the advisory committee. Our own experience from the previous advisory committee of Parkinson's disease psychosis, where we received overwhelming support from the advisory committee, and in respect to a positive vote, certainly had a significant impact on the ultimate approval of the drug, as you know, initial reaction and report from the FDA was not as favorable.

Not only in respect to the control trial data, which we added.

Hundreds and thousands of additional patients in this category are frail elderly patients, but also with the six years of post marketing surveillance with about 40000 and every indication in the data that we see.

Is that we are gradually moving towards a much better balance and toward the violence in regards to the mortality data.

Compared to previous data reported at a at a previous submission so from that perspective, we definitely see a favorable.

So from that perspective, we do, we certainly believe that it is important that we make, a strong case to the advisory committee and obtain or receive support from the advisory committee for the case we are making.

Favorable threat.

<unk> trend and as well as what we're seeing in the <unk>.

Yeah.

Some.

A real life studies based on the Medicare data and recently reported we had actually a two reports where we are also seeing.

Thanks, Serge.

More favorable profile in terms of mortality when compare pm of answering to utter.

Two other atypical antipsychotic that are used off label in the Parkinson's disease psychosis. So from that perspective, we are very pleased.

We the data that we see.

What are these data may be sufficient.

For removal of a box warning gets a different question because.

We still as you know the all the analysis or mortality was atypical antipsychotic secluded thousands of patients from the clinical trial and from that perspective.

Concord <unk> third of all these much more narrow word on what we are seeing in the numbers that we have specifically for answering so we are not over an opinion that the.

<unk>.

Total amount of data and evidence because of these numbers may warrant.

All of the.

Box warning.

But I will just repeat the trends that we're seeing the numbers and the data that we are seeing we are very confident in.

Favorable profile on certain industry stuff.

I just wanted to clarify one thing as Serge mentioned at the beginning of this answer he referred to the previous ADP.

Application in data center.

You mentioned it was the previous PDP, so he's referring back to our initial approval.

And at that time, there was a very small.

Numerical imbalance in mortality showing.

Very small numbers, a little bit higher mortality on drug and placebo.

Fast forward, we've now done multiple placebo controlled studies in elderly patients and that imbalance is now gone away. So when we look at our placebo controlled studies mortality on drug and placebo.

Evelyn.

Populations.

Sorry, you also referred to the fact that we have a lot of pharmacovigilance data now having been on the market.

For several years and so so that data is also continuing to be very very supportive and in fact as maybe highlighted by paper published.

Two members of FDA to members of CMS into academic members, San Frans and diversity.

A little over a year ago demonstrating that.

Some of the answer and had a statistically significant improvement in mortality rates relative to other anti psychotics used in those populations. So so.

I think the final point that surge was making is that this is a class one so it's not a timothy answering boxed warning. It is a class one that all anti psychotics.

Typically to remove a class warning from your drug requires a very very substantial body of evidence probably larger than the placebo controlled the aggregate placebo controlled data hasn't yet today.

But despite that.

Serge mentioned all of the data we have from the time of our PDP equivalent till today continues to look more and more favorable as it relates to risk.

Thank you. Our next question comes from Jay Olson from Oppenheimer. Your line is open.

Oh, Hey, thanks for taking the question with.

With regards to reimbursement can you talk about where you see the longer term steady state gross to net for NUPLAZID.

In PDP and whether or not.

The mix of $3 40, B payers has stabilized.

And then.

To finish.

Feedback from payer discussions you've had early on would be great. Thank you.

Great. Thanks, so much Mark Schneider, you want to take the first question and bring in the segment.

And Greg, in response to the second part of your question, I think the way we think about, it is there are three printable buckets and maybe a little bit of space between the three buckets.

Yes sure. Thanks for the question I think from a yeah I answered the second part first.

You know, you can come out of an advisory committee meeting with a very significantly, significant opposition.

So the, you know, the math is heavily in favor of non-approval.

You can come out with the opposite end of the spectrum where the math is, the votes, are heavily in favor of approval, and then you can come out, you know, with something that's more of a midpoint of that, and then, of course, some variations in between.

And so I think, you know, for us, and again, just reiterating the caveat that Serge mentioned, that, you know, ADCOMs don't approve drugs, the FDA does, but the history tells us that a significant majority of the time follow an ADCOM.

And so in terms of how we think about that scenario planning, the impact it has on us, I'll just repeat what Brendan said earlier, we're in a very, very fortunate position.

We did a lot of work preparing for a DRP launch. We've got all that work and the benefits of that on the shelf.

So from a 340 <unk> standpoint, we still see growth, but that growth is moderating.

So I think as we.

<unk> nickel forward for this year and we continue to moderate for future years, we'll see how that trend continues to evolve.

And then as far as long term.

Gross to net.

Something that we forecast we give it out on an annual basis and we'll continue to do so.

Okay.

We're ready to pull it off.

Thanks, Martin for Jay for the second half of your question for Tryphena tied obviously, we've been excited to jump in with Praetors with caregiver community and with payers to talk about the emerging 11 their results and their perception of value and what we see and it shouldnt be.

And you know, the precise timing of that and how we advance on that will be somewhat a, function of the ADCOM and those three buckets.

Surprising.

Is that payers view tryphena that much like they see rare pediatric medications.

Very little anticipated budget impact given the overall prevalence of the population they expect to that the product would be priced like other rare disease medications and you can look at.

The gamut.

Rare disease pediatric drugs to get some sense for that.

And they would expect that it would have similar access issues in terms of what was the studied patient population.

Potentially.

Looking at sort of the broader.

Rhett treatment community to make certain that the excess is appropriate based on clinical trial results.

So the early early findings.

Yes.

Thank you and we have time for one last question and our last question comes from Esther Hong from Baird. Your line is open.

Hi, Thanks for taking my question. So just wanted to ask on Charleston, a tide.

If you could provide any details on the open label extension studies that are going on.

Maybe if you can speak about patient should continue on treatment and what's been observed. Thanks.

Great. So you want to take out.

Yeah.

Thank you as you can imagine we.

Art above our overall day.

Presentation and analysis in the.

Direct application.

We are including the long term data from the open label studies.

Particularly from the perspective.

Uh huh.

Maintaining some effects that we saw in the short term study in patients.

One drug as well as the changes in the symptoms for patients that are converted.

From double blind and two open label study from placebo to active treatment in both cases, we are experiencing.

Further improvement or improvement, Florida reformer and improvement for the ladder in the open label study that continues over the.

40 weeks of treatment and beyond so from that perspective.

We are very pleased with that data.

Sure.

We will be including that in our PMA submission.

And the aspect from the.

Your second part of the question in terms of the.

The retention of patients what we're seeing and you all kind of label study we are.

Continuing to see relatively.

Good retention of patients with <unk>.

<unk>.

Somewhat lesser.

Dropout rates that what we saw in the double blind period, which is actually expected, even though you have to take into account.

Double Blind study is 12 weeks long.

Ill.

Open label studies of around or many more weeks and from that perspective.

Their studies.

Eventually results.

And the people dropping out to a larger extent so from all promote perspective, we are very pleased with the data and that data will be part of our submission.

Thank you Mr. Davis. Please proceed to closing remarks.

Thank you operator, and thanks, everyone for joining us today, we have a pretty full calendar over the course of the next 12 months plus.

And the good news is we have an action date that's scheduled for August 4th, which is, not too far down the road after an ADCOM.

And so depending on how the ADCOM goes and kind of where we are in that spectrum of scenarios, we'll be eager to be prepared for a launch.

Thank you.

Two real quick ones for me.

Our next question comes from Yatin Sanaja from Guggenheim Partners.

First one is, could you confirm if you requested the ADCOM as part of the formal dispute resolution, or was it proposed by the FDA?

Your line is open.

And then the second part is that, you know, both phase three Harmony and 019 study had, a different study design and endpoints.

Hey, guys, thank you for taking my question.

So I'm just trying to understand, you know, how can they be supportive of each other when, both are trying to answer a different question and the endpoints and study design are completely different.

I'll take the first one.

Thank you.

We look forward to updating you on our progress.

Yeah.

Thanks much for the question.

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

That's search to respond.

In terms of requesting an ADCOM, just to level set, having an ADCOM or not is entirely at, the discretion of the FDA.

Early in our discussions with FDA after receiving the CRL, we did suggest that they consider, having an ADCOM.

And their response was simply, you know, it's premature for us to comment or think about, that.

Let's advance these discussions.

There's something happening on the phone here.

We didn't discuss it any further with them.

So, just on the guidance, question, as we said previously, there's nothing in our revenue or expense guidance related to ADP at this time.

Thanks.

And then, as we all know now, they have determined that they're having an ADCOM and released, the Bay Court.

Serge, you want to answer the second question?

[music].

Yeah.

And let me just make sure I understood the question and you broke up a little.

Were you asking about two studies as a part of our resubmission, 019 and 045, being studies, in different patient populations with different outcomes and how that fits together in this application?

That is correct.

Yeah.

And not maybe the patient population, but just the endpoints are very different for both, the studies.

Okay.

There are, that is correct, but we have been using in both studies measuring hallucinations, and delusions and the primary symptoms of psychotic breakdown, in one case more in severity sense, and in another case measuring more in terms of relapse and recurrence of symptoms.

But in any case, we do have, we can actually fairly reliably compare the data from both, studies because we are measuring the same symptoms of the same disorder.

And from that perspective, they are, I would think of them more as a complementary rather, than differential in terms of how we see.

As a matter of fact, if you think about that is in the acute study of O19, what we demonstrated, is acute efficacy of pimobanserine treatment in patients that are experiencing psychotic symptoms in a short-term six-weeks paradigm.

On the other hand, the study of O45, within the same symptoms has been evaluated durability, of effect in patients that respond to treatment. So from that perspective, actually, there is quite a bit of complementarity between, two studies.

Thank you.

Our next question comes from Salveen Richter from Goldman Sachs.

Your line is open.

Hey, thanks.

This is Matt on for Salveen.

First on Nuplazid, could you share how in-person office visits and long-term care occupancy, rates are tracking relative to pre-pandemic levels?

And then on ACP044, given that you saw a trend in acute pain, do you expect better results, in chronic or do you view these as unrelated?

Thanks a lot.

Yeah.

Thanks much for the questions.

Brittany, you want to take the question on Nuplazid and Serge on 044?

Sure.

Happy to do that.

What we've seen in the first quarter for in-person patient visits in the community reflects that, they're still about 20% below pre-pandemic levels.

With that said, I just want to point out in visits to see customers, we see that clinicians, are beginning to ask their patients to return for inpatient visits and not favor telemedicine over that.

And then for LTC occupancy rates, to further answer your question, we have two things going, on. One is there are slight increases in LTC occupancy rates of late. From the base, they've returned to about 73% in the most recent data that we're seeing, so slightly up from where they were in the fourth quarter.

And those are being driven by new residents entering long-term care facilities, which, I think is encouraging for us because we understand if that trend were to continue, that patients tend to be identified for PDP proximal to their being admitted to a skilled nursing facility.

In regard to potential read-through from our acute model to our chronic model of pain and, the studies, as we have been saying throughout, we do not see a direct read-through from the results of the acute study.

Of course, I would say we would love to see very robust positive results of the acute study rather than a signal that we have observed, but there is not a direct connection.

As far as the preclinical data, and we reported this previously, we see that ACP044 has positive activity in the animal models of both acute and the chronic models of pain.

So from that perspective, we are at this point not jumping to any premature conclusions in regard to the osteoarthritis study, and the data will show us the best.

Thank you.

Our next question comes from Sumant Kulkarni from Canaccord.

Your line is open.

Good afternoon.

Thanks for taking my question.

So ahead of the Adcom folks and Vanson for, ADP, other than not having statistical significance for a specific ADP subgroup in Harmony, or what the FDA has already expressed on study 019, what are some of the specific nitpicks or key sources of pushback, if any, that your external KOLs or consultants might have on the data package they have been putting together for the meeting?

Yeah, thanks for the question.

Saurabh, do you want to take that?

You know, actually, obviously, we are preparing studiously and are looking forward to challenging, feedback and questions from our KOLs in order to prepare ourselves the best for the advisory committee.

But I would say that overall, the feedback we're getting, we're getting quite a bit of support from people in terms of understanding specific circumstances and the data and meaningfulness and consistency of the Alzheimer's disease psychosis data that we have across the studies, across the endpoints, and over time.

So from that perspective, I think, without getting into very specific details, which you will understand, it's not really probably the most appropriate situation for us to do that at this point.

I think that we are preparing to meet all of the scientific challenges that can be put in front of us in terms of the data and arguments and analysis that we are providing.

Thank you.

Our next question comes from David Hong from SMBC.

Your line is open.

Hey, thanks so much for taking the question.

I just want to dig a little bit more on the recovery, potential recovery of the, you know, PDT market this year.

Can you just talk a little bit more and give a little more color in terms of, you know, what you're hearing maybe from your sales force and people in the field that gives you confidence that, you know, we should see both LTC and the office channel recover.

And then, you know, you mentioned spring, summer as maybe the timeframe in which that happens.

You know, is there anything that, you know, would potentially allow the recovery to happen faster?

Yeah, sure.

Let me just reframe the question a little bit, and then I'm going to pass it to Brendan.

So what we've said is that we're beginning to see some evidence of slow growth. There's been a period of stabilization now, and we're beginning to see some evidence of slow growth. We're seeing a little bit more in LTC than we are in the office-based setting, but we're seeing indicators in both sections.

And what we said is that we're cautiously optimistic that we'll be able to grow on these and see these build in the course of the spring and summer.

Brendan, you want to answer the question more completely?

Sure.

Thanks, Steve.

And for the reframe, I think that's all very appropriate.

A couple of the guide points to us that are encouraging are the new residents entering facilities.

We've seen a slow but steady increase over the prior couple of months. That's encouraging.

Secondly, in terms of PD in-person patient visits, as I said before, the practices are more open from our experience to both seeing our representatives, which means we have an opportunity to tell our story face-to-face to them, and our HCPs are really becoming advocates in asking their patients to come in for face-to-face consultations.

This is a movement disorder, and the subtleties of changes there coupled with neuropsychiatric symptoms make the HCP want to see both the patient and the caregiver face-to-face where possible.

As both of those things improve in the weeks and months ahead, there's at least cautious optimism that there will be some return to normalcy in seeing your clinician face-to-face.

Those are really the key elements.

Thank you.

Our next question comes from Mark Goodman from SVB Securities.

Your line is open.

Thanks for taking my question.

It's really on the line for Mark.

First, congrats on the quarter.

I have a question regarding the process in PDP.

Can you talk about the penetration rate so far in the PDP market and maybe provide more color on off-label use so far in other indications, including ADP?

Thanks.

Yeah, sure.

Brendan, you want to take those?

Sure.

Thanks for the question.

First and foremost, I think Steve did a very nice job in prepared remarks talking about the PD market and how it's been impacted over the past couple of years.

I think what's impressive is despite the fact that there have been fewer inpatient visits, fewer prescriptions written for the principal motor dysfunction medications, Carbidopa and Levodopa, we have seen New Plazid continue to grow total prescriptions over pre-pandemic levels.

So that gives us great confidence, number one, that our message is resonating and that we're being chosen more often in the first line position to treat Parkinson's disease psychosis.

That's evidenced by what we've seen in increases in share both on the community side and encouragingly in new patient starts in long-term care facilities.

Oh, I'm sorry.

In terms of the question on off-label use, that still continues to be a very, very, very small number for us.

As you probably know, the vast majority of our prescriptions go through a hub, which requires a treatment form where you indicate specifically why you want to put a patient on New Plazid that has to be indicated as Parkinson's disease psychosis.

And in our environment where payers are very careful about prior authorizations, we still see very low single-digit numbers of the product potentially used for something other than Parkinson's disease.

Thank you.

Our next question comes from Chris Howerton from Jeffries.

Your line is open.

Excellent.

Thank you so much for taking the questions.

I guess what I was wondering about with respect to the advisory committees, both for ADP and the potential one for Trofenatide, how important you believe patient advocacy groups to be as part of that conversation and how influential they might be.

And if you would entertain a quick clarification follow-up, how do you derive the 900,000 patients treated with atypical antipsychotics in the ADP population?

Thank you.

Yeah, sure.

Brendan, why don't you take the second question first and we'll go back to the first one.

Sure.

Thanks for the question.

When we speak of 900,000 patients being treated for ADP, about two-thirds of those would be expected to have been off-label atypical antipsychotics. There are also other mood stabilizers and antidepressants used for a similar reason in that patient population, but that is still, in our consideration, the addressable population for ADP.

And, Chris, you were breaking up on mine.

Could you repeat the first part of your question?

I heard ad comms at an interval.

You said after that.

Oh, yeah.

I'm totally sorry.

I guess to maybe say it more concisely is how important do you think patient advocacy groups are for your advisory committees, either the ADP or the potential one for Trofenatide?

Thank you.

Got it.

Yeah, thanks much.

Well, yeah, first, let me just say, patient advocacy groups, advocate for patients, right?

So, I mean, they're independent of us. But I think in both cases, they're very strong and passionate advocacy groups pushing for therapies where there's nothing approved, both in Rett syndrome, as well as in Alzheimer's disease, psychosis. And so I think they're very important, particularly in a circumstance where there's no drug approved.

And that's the, you know, one of the reasons we see them being very active in this space and, making sure that they, they elevate the unmet need that they're that they're living with, and experiencing every day, in the eyes of the FDA.

Thank you.

Our next question comes from Vamal Devan from Mizuho Securities.

Your line is open.

Hi, great.

Thanks for taking my questions.

I mean, most of them might have been asked, but just a couple of things just to clarify.

So, one, on your assumptions around guidance, I just want to confirm that you're still not assuming anything on the sales or on the expense, side related to ADP, I guess, on the SG&A side, assuming an ADP approval this year.

And then on the 044 chronic data, is that still expected sort of by year end?

I think it used to be a 4Q2022 event in clinicaltrials.gov.

It says for December, but I'm not seeing it specifically mentioned in your slides.

So apologies if I missed it in your comments.

Thank you.

Okay, let's go to Mark for the first question, and Serge for the second.

Hey, can you hear us?

We can hear you, Mark.

Go ahead.

Okay.

Yeah, sorry.