Intra-Cellular Therapies - Q3 2024

Executive Summary

• Q3 revenue rose 39% year-over-year to $175.4M, driven by CAPLYTA net product sales of $175.2M (+39% YoY), while net loss was $26.3M; management raised 2024 CAPLYTA sales guidance to $665–$685M and narrowed OpEx ranges.
• Prescriptions stayed strong: CAPLYTA total Rx +38% YoY and +9% QoQ; the company added ~150 primary care reps in Q3 to expand reach, with a second primary care expansion planned in 2025 to support a potential MDD indication.
• Management characterized CAPLYTA as an at least $5B sales opportunity over the next 10 years across mood disorders, supported by robust Phase 3 adjunctive MDD data and a planned sNDA filing in Q4 2024; cash and investments were ~$1.0B at quarter-end, providing ample flexibility.
• Key stock drivers: raised FY24 sales guidance, accelerating primary care build-out, imminent MDD sNDA, and management’s $5B long-term revenue framework; watch OpEx ramps (SG&A, R&D) as the pipeline and commercial footprint scale.

What Went Well and What Went Wrong

What Went Well

• CAPLYTA demand remained robust: Q3 net product sales were $175.2M (+39% YoY) as total revenues reached $175.4M; total prescriptions rose 38% YoY and 9% QoQ, outpacing branded and overall antipsychotic markets.
• FY24 outlook improved: CAPLYTA sales guidance raised to $665–$685M; SG&A and R&D ranges narrowed, reflecting visibility into spending as the sales force and pipeline scale.
• Clear strategic ambition and confidence: “CAPLYTA represents at least a $5 billion opportunity within the next 10 years,” underpinned by mood disorder breadth and potential MDD label expansion; “we are on track to submit our sNDA…for MDD later this year”.

What Went Wrong

• Loss widened YoY: Net loss was $26.3M vs. $24.3M a year ago as SG&A ($132.1M) and R&D ($66.8M) rose with sales force expansion and multiple late-stage studies (bipolar mania, pediatric, ITI-1284).
• Gross margin moderated sequentially: cost of product sales increased to $15.3M vs. $11.4M in Q2; calculated CAPLYTA gross margin dipped QoQ (see table).
• Consensus benchmarking unavailable: S&P Global consensus data could not be retrieved in our system for Q3, limiting formal beat/miss framing (see Estimates Context) [GetEstimates error noted].

Transcript

Operator (participant)

Good day, and thank you for standing by. Welcome to the Intra-Cellular Therapies 3Q 2024 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star one one on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the call over to Juan Sanchez, Head of Investor Relations. Please go ahead.

Juan Sanchez (Head of Investor Relations)

Good morning, and thank you all for joining us on our third quarter 2024 earnings call. Joining me on the call today are Dr. Sharon Mates, Chairman and Chief Executive Officer, Mark Neumann, Chief Commercial Officer, Dr. Suresh Durgam, Chief Medical Officer, and Sanjeev Narula, Chief Financial Officer. A slide deck to complement today's call is available under the Investors Events section of our corporate website. During today's call, we will be making certain forward-looking statements.

These forward-looking statements are based on current information, assumptions, and expectations. The statements are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. We caution you not to place undue reliance on these forward-looking statements. These statements are made only as of the date of this conference call, and the company disclaims any obligation to update such statements. I will now turn the call over to Sharon.

Sharon Mates (Founder, Chairman, and CEO)

Thanks, Juan. Good morning, and welcome to our third quarter earnings call. We are pleased to share our Q3 results and to describe the exciting progress we have made across the company. Caplyta's growth trajectory continues to reflect a compelling product profile and our successful commercial execution, with net sales of $175.2 million in the third quarter, representing a 39% increase over the third quarter of 2023.

Based on this continued strong performance, we are raising our 2024 full-year net sales guidance range to $665 million-$685 million. We look forward to building on our positive momentum for the rest of 2024 and beyond. In addition, we continue to advance our broad pipeline, and we are on track to submit our supplemental NDA for the adjunctive treatment of major depressive disorder, or MDD, this quarter.

Looking at the big picture, our objective has always been to help the greatest number of patients. We believe that the recent unprecedented efficacy and safety data for Caplyta in our MDD phase III studies profoundly expands the impact Caplyta will have in the treatment of mood disorders. As we approach this major MDD approval milestone, we wanted to give you our perspective on the tremendous market opportunity that we see for Caplyta across the mood disorder spectrum and provide the rationale for our confidence.

First, as I noted, Caplyta's efficacy results in Studies 501 and 502 for the adjunctive treatment of MDD are truly exceptional. This efficacy was confirmed in both studies, not only by the primary endpoint, the MADRS total score, but also by the strong results in the clinician-rated CGI-S scale and the patient-reported QLS scale.

This data further builds on the consistently strong efficacy data we have seen in our pivotal studies throughout our Caplyta development programs. Caplyta's robust efficacy is complemented with a favorable safety and tolerability profile, including a favorable metabolic, weight, and movement disorder profile. Metabolic disturbances, weight gain, and motor adverse events are major reasons why patients discontinue their treatment and often result in poor clinical outcomes.

Another important feature of Caplyta is its convenient dosing. Caplyta is dosed once a day with no need for titration, with or without food, making it an attractive option for prescribers and patients. These are important attributes that become more critical as the medicine is used by broader patient populations. With this compelling profile, we are excited about Caplyta's potential for the treatment of MDD, a large market with unmet medical needs.

There are over 21 million patients with MDD, and current antidepressant therapies do not adequately address depressive symptoms, and more than half the patients are currently using them. There are a few drugs approved for the adjunctive treatment of MDD, and there is still a significant unmet need for efficacious, safe, and well-tolerated medicines for these patients.

As a result, we believe Caplyta is well-positioned to become a drug of choice across the spectrum of major mood disorders. Starting with bipolar depression, Caplyta has the broadest label in this indication, which includes bipolar I and bipolar II patients, and as monotherapy and as adjunctive therapy. In patients with mixed features and anxious distress, difficult-to-treat patient phenotypes, we have also reported robust positive clinical results.

The potential addition of the adjunctive MDD indication not only adds a large patient population that can benefit from Caplyta, but also gives prescribers additional confidence about the efficacy, safety, and tolerability of the drug across multiple patient populations. In our view, this positions Caplyta as a top-of-mind choice for prescribers when treating a broad spectrum of patients, including patients with a diagnosis of Bipolar I or Bipolar II disorder or MDD.

We have demonstrated our commercial expertise and have the financial resources we anticipate will be necessary to maximize Caplyta's full potential. Taking all this together, we believe Caplyta represents at least a $5 billion opportunity within the next 10 years. This reflects our expectation that Caplyta will become a leading treatment across the spectrum of mood disorders and is primarily driven by contributions from bipolar depression and MDD, and to a lesser extent, schizophrenia.

In addition to Caplyta, we have a very rich pipeline, which includes additional lumateperone programs as well as other novel programs. This will result in significant clinical milestones in the near and medium term. In terms of our lumateperone long-acting injectable program, we commenced clinical conduct in our phase I single-ascending dose study evaluating four different formulations.

Our objective is to develop formulations with treatment durations of one month or longer, and over the next year, we will be prioritizing the formulations with the best profile as we proceed with this phase I study. Let me now touch on our ITI-1284 development programs, which we are very excited about. Patient enrollment is ongoing in our phase II clinical trial evaluating ITI-1284 in patients with Generalized Anxiety Disorder, or GAD, as an adjunctive therapy to generalized anxiety medications.

We believe GAD represents at least a $1 billion opportunity for ITI-1284. Currently, there are only five drugs approved for the treatment of GAD and only as a monotherapy. Anxiety prevalence and severity is on the rise, and recent reports suggest a prevalence of 20 million patients in the U.S., with 13 million patients being treated.

About half of patients who receive treatment do not respond adequately to initial therapy. If approved, ITI-1284 would represent a new mechanism of action in the treatment of GAD and be the only drug approved for patients who have failed prior medications. We believe ITI-1284 is well-suited for this patient population and may offer an effective, safe, and well-tolerated treatment. Patient enrollment is ongoing in our ITI-1284 phase II clinical study evaluating patients with psychosis associated with Alzheimer's disease.

We are pleased to announce that we recently commenced patient enrollment in our phase II program in patients with agitation and Alzheimer's disease. All of our ongoing phase II studies with ITI-1284 are large and designed as potential registration studies. Continuing with our pipeline, our lenrispodun phase II clinical trial in Parkinson's disease is progressing, and we expect to complete this study by the end of 2025.

ITI-1020, our second molecule in our PDE1 platform, is being developed for certain cancers and cancer-related comorbidities. ITI-1020 is currently advancing through a phase I single-ascending dose study. Lastly, we are very excited about our 1500 program, exemplified by ITI-1549, a non-hallucinogenic neuroplastogen. We believe that ITI-1549 holds great promise as a treatment of mood, anxiety, and other disorders.

ITI-1549 may offer a safe, effective medicine with a novel mechanism of action that can be conveniently administered without the risks associated with psychedelic hallucinogens. Earlier this year, at the Society of Biological Psychiatry annual meeting and the recent Society for Neuroscience meeting, we presented results from our clinical work showing that ITI-1549 is non-hallucinogenic, provides improved social interactions, reverses anhedonia, and decreases anxiety-like behaviors in animal models.

Preclinically, ITI-1549 has also been shown to enhance neuroplasticity by stimulating the mTOR signaling pathway in the prefrontal cortex and to increase neurite growth and complexity. ITI-1549 is completing IND-enabling studies and expected to enter human testing in 2025. In summary, we are very excited about our bright future. We are confident in our ability to capitalize on the substantial growth opportunities ahead.

We have experienced high-performing teams, and we are in a strong financial position. I am proud of our accomplishments and look forward to building on this success. I'll now turn the call over to Mark to provide details on Caplyta's performance and commercial plans. Mark.

Mark Neumann (EVP and Chief Commercial Officer)

Thanks, Sharon, and good morning, everyone. Caplyta registered another strong performance in Q3 with robust year-over-year growth in total prescriptions of 38% and a sequential quarter-over-quarter growth rate of approximately 9%, demonstrating strong commercial execution as we overcame a traditionally slower quarter for the antipsychotic market due to summer seasonality factors.

Caplyta's growth again outpaced both the branded antipsychotic market, which grew at 4% this quarter, as well as the overall antipsychotic market, which grew at only 1%. Caplyta's market-leading growth is being driven by its continued strong uptake in bipolar depression and is being sourced by significant increases in both the breadth of our prescriber base as well as an increase in the average depth of prescribing. During Q3, we added 4,000 new first-time prescribers of Caplyta, having now increased that cumulative total since launch to over 49,000 unique prescribers.

We expect this strong growth trajectory to continue in the fourth quarter and throughout 2025 as we continue to invest to optimize the growth of Caplyta in bipolar depression. To this end, we recently completed an expansion of our sales force during Q3, adding 150 new sales representatives to leverage the growing opportunity with primary care physicians in Caplyta's current indication.

This new sales team is now in the field promoting Caplyta for bipolar depression in primary care offices. Caplyta's broad label, which includes both Bipolar I and Bipolar II depression, provides us with an opportunity to expand our reach and educational activities with primary care physicians as we have seen an increasing role of primary care in treating bipolar depression.

Early feedback to the messaging has been highly positive as primary care physicians value Caplyta's compelling clinical profile of strong efficacy and favorable metabolic weight and movement disorder profile, coupled with convenient once-daily dosing with no titration. Primary care physicians view all of these product attributes to be beneficial in treating their patients with bipolar depression. It will take some time for this new sales team to be fully optimized in their territories, so while we expect to see some positive effect in the fourth quarter this year, we believe most of the impact will be realized in 2025 and beyond.

We also continue to make substantial progress in our commercialization planning for a potential label expansion in major depressive disorder, which would increase our total addressable market for Caplyta from nearly 50% of antipsychotic prescriptions for schizophrenia and bipolar depression to nearly 80% with the addition of an MDD indication.

We believe the robust results in studies 501 and 502 will position Caplyta as a leading option in the adjunctive treatment of MDD, and coupled with our existing data in bipolar depression, we will look to establish Caplyta as a first-choice treatment across mood disorders. There are more than 30 million adult patients in the U.S. with either bipolar depression or major depressive disorder representing large medical conditions.

The substantial growth in the bipolar depression market and the strong uptake of recent new drug launches in MDD both speak to the important unmet medical needs for efficacious, safe, and well-tolerated treatment in both patient populations. We believe Caplyta will play a leading role in addressing these needs. Our recently completed expansion provides the opportunity to promote Caplyta in bipolar depression to primary care physicians and allows these prescribers to gain familiarity with Caplyta use and enhance brand awareness ahead of a potential label expansion in MDD.

To fully optimize the launch in MDD, a second primary care sales force expansion is planned for 2025 in connection with the potential approval of Caplyta for the adjunctive treatment of MDD. We will share more details of those plans at the appropriate time next year. In summary, we believe we are well-positioned to drive consistent growth of Caplyta and to maximize the significant opportunities ahead of us in the coming years. I look forward to continuing to update you on the successful launch of Caplyta. I'll now turn the call over to Sanjeev to further discuss our financial performance. Sanjeev.

Sanjeev Narula (CFO)

Thank you, Mark, and good morning, everyone. Great to be with you today to share my thoughts on the recent quarter and our full-year expectations. First, I'd like to start off by saying how honored I am to have joined the Intra-Cellular Therapies leadership team as Chief Financial Officer. I'm thrilled to be part of the company during this exciting time of growth.

Since I began in August, I've been meeting with colleagues across the company, and I'm impressed with the high caliber of our talent. I believe we have the right strategy to grow Caplyta in its approved indications and look forward to the potential launch in MDD next year, as well as advancing our robust pipeline. I'm confident in our strong fundamentals and the company's growth potential.

I consider it a privilege to partner with Sharon and the rest of our management team to continue to create significant shareholder value. Our third-quarter results represent another strong quarter in Caplyta's growth trajectory. As Sharon mentioned, Caplyta's net product sales increased to $175.2 million, representing 39% growth versus the same period in 2023.

Our net sales grew 9% sequentially versus Q2 2024, primarily driven by increased prescription demand. Our gross-to-net percentage in the quarter was in the mid-30s, consistent with our expectations. Selling general and administrative expenses for the third quarter were $132.1 million, compared to $105.2 million for the same period in 2023. The increase was mainly a result of the primary care sales force expansion, as well as an increase in the marketing, advertising, and general administrative expenses to support the company's growth.

Our R&D expenses for Q3 were $66.8 million, compared to $41.6 million for the same period in 2023. Our pipeline continues to advance. In the third quarter, R&D expenses increased primarily due to activities associated with lumateperone and other clinical programs. Specifically, the initiation of our phase III bipolar mania studies, our phase III pediatric program, as well as our ITI-1284 phase II studies in GAD and psychosis and agitation studies in Alzheimer's disease.

Now, let me say a few words on Q4 and full-year guidance ranges. We expect net product sales momentum to continue, driven by strong prescription demand. We expect our gross-to-net percentage to remain in the mid-30s% for the fourth quarter. As a result, we're raising our Caplyta net product sales guidance range to $665 million-$685 million for 2024.

Given the year-to-date spend at this time, we're narrowing our full-year SG&A expense guidance range to $490 million-$510 million and our full-year R&D guidance range to $220 million-$230 million. Finally, our financial position remains strong. Cash and investment totaled $1 billion on September 30, 2024, compared to $499.7 million on December 31, 2023.

To recap, our business fundamentals are sound. We're ending the year with a positive momentum. With a strong balance sheet, we believe we are well-positioned to maximize Caplyta's potential and continue to invest in our pipeline program. This concludes our prepared remark. I'd like to hand it back to the operator to open the line for your questions.

Operator (participant)

Certainly. As a reminder, to ask a question, please press star one one and wait for your name to be announced. To withdraw your question, please press star one one again. Please limit yourself to one question, and one moment for our first question. Our first question will be coming from Andrew Tsai of Jefferies. Your line is open.

Andrew Tsai (SVP)

Hey, good morning. Thanks for taking my questions. Congrats on the quarter and the strong execution. My question is around your sales opportunity comment for Caplyta, $5 billion over the next 10 years. So are you thinking a fairly equal sales mix between MDD and bipolar, or are you expecting MDD sales to be meaningfully larger than bipolar? And then just bigger picture, is it fair to assume you're expecting Caplyta ultimately to be prescribed more than the rest of these other antipsychotics out there, the branded ones at least? Thanks.

Sharon Mates (Founder, Chairman, and CEO)

So thanks for the question, Andrew. And thanks for the kind words in the intro to your question. Maybe Mark, would you like to address the question?

Mark Neumann (EVP and Chief Commercial Officer)

Yeah, sure. Thanks for the question, Andrew. To reiterate, at least at a high level, Sharon's comments and her prepared remarks, what the forecast reflects is really our confidence that Caplyta will become a leading treatment option across the mood disorders, across Bipolar I, Bipolar II, and MDD. And the forecast is primarily driven by bipolar depression and MDD, and to a much lesser extent, schizophrenia, which continues to grow nicely but is the least of the three indications.

To give you a little additional color, for bipolar depression, we see Caplyta continuing on its current growth trajectory, which leads to significant market share gains over time. And Caplyta becomes one of the leading treatments in bipolar depression. For MDD, we recently conducted some rigorous quantitative market research, which confirms our belief that studies 501 and 502 represent a best-in-class profile for Caplyta, and we believe that'll lead to a market-leading share among the branded antipsychotics, so to your question, Andrew, both bipolar depression and MDD contribute very significantly to the overall estimate that we have of achieving $5 billion within 10 years.

Andrew Tsai (SVP)

Thanks. Very helpful. Congrats again.

Sharon Mates (Founder, Chairman, and CEO)

Thank you.

Operator (participant)

One moment for our next question. Our next question will be coming from Jessica Fye of JPMorgan. Your line is open.

Jessica Fye (Managing Director and Equity Research Analyst)

Hey, guys. Thanks for taking my question. Just following up on the prior question, can you just touch on what prompted you to unveil this $5 billion long-term target for Caplyta now? And then I have a follow-on.

Sharon Mates (Founder, Chairman, and CEO)

Thanks for the question, Jessica. I'll start, and then I'll ask Mark or Sanjeev if they want to chime in. As you know, we are continuously being asked by the Street what the market opportunity is for both Caplyta and drugs in our pipeline. Just as early on, we did not give you revenue guidance. We think as we mature, it is time for us to be giving you our internal forecasts as we refine them too and as we get the confidence in the potential for what we've been finding in all of our market research and all of our internal forecasting. Mark, do you want to add anything to that?

Mark Neumann (EVP and Chief Commercial Officer)

No, I think that's exactly it, Sharon. I think we've always believed in the potential for Caplyta in certainly the near term, but also the long term. I think when we saw the results of Studies 501 and 502, we were certainly impressed by the very robust efficacy and favorable safety and tolerability profile in MDD, and now we've had a chance to do some rigorous quantitative market research, which confirmed our impressions of what that profile represented, and I think it just all of that added to the confidence that we have about the long-term potential of Caplyta.

Sharon Mates (Founder, Chairman, and CEO)

I think also with the increase now with the launch of our primary care dedicated sales force, I think gives us even further confidence. These drugs are being prescribed more and more in the primary care setting, as well as not only by physicians, but by nurse practitioners and PAs, et cetera, in the mood disorders. We think that all of this builds on the confidence to support these numbers.

Jessica Fye (Managing Director and Equity Research Analyst)

Okay. And then just one quick follow-up on the pipeline. Curious if you could just speak to how enrollment is going in the phase II GAD studies for 1284. Is there any chance we could see the anxiety data for 1284 next year?

Sharon Mates (Founder, Chairman, and CEO)

Well, I'd never say never, but typically, one doesn't do their projections based on enrollment speeding up. You do your projections based on enrollment either being status quo or slowing down. So I think that we stick by the guidance we've given to date. And if next year something changes, we can let you know about that.

Andrew Tsai (SVP)

Great. Thank you.

Operator (participant)

And one moment for our next question. Our next question will be coming from Charles Duncan of Cantor Fitzgerald. Your line is open.

Charles Duncan (Managing Director)

Super. Thanks for taking the questions. Congrats on the quarter. Very nice performance. And I'd like hearing the substance behind the $5 billion vision. I had a question really on pipeline. When you consider LAI and what other companies are being challenged with LAI, how important is that for the Luma franchise versus, say, 1284, et cetera, in terms of the vision longer term? And then you have a lot of pipeline candidates. Could you tell us what you're most excited about? It's a little simplistic, but let me know what your thoughts are.

Sharon Mates (Founder, Chairman, and CEO)

Okay. Hi, Charles. And thanks for the kind words. I'll start, and then I'll ask if Suresh wants to chime in. On the LAI, we started the development of LAIs for patients to have another option. As you know, we're now testing four different formulations. And as I mentioned in our prepared remarks, that study is ongoing.

And throughout next year, we will have further data as we're basically pitting these different formulations against each other. And we'll be looking at the safety, the tolerability, at the PK values. And certain ones will drop out, we anticipate. I think that it is separate and apart from our Caplyta franchise, which we continue to see as growing very substantially over time. And we're very excited about it. As for 1284, that again is a separate pipeline right now. And I think that we're very excited about GAD as a huge opportunity.

We think that we would really be paving the way for drugs with new mechanisms in GAD. Really, we look forward to seeing that data. As to what do I like best or what do we like best, it's really, really hard to say. In one-on-one meetings, I say that's like asking you which child of yours do you like the best. I think we'll continue to look.

We're a science-driven company, and we'll continue to look at the science, and we'll continue to look at the data. Assuming the data is good for each clinical trial, they'll continue to progress. If there's some hiccups in data as we go forward, those programs may get called. We'll let the science drive us. The data is always the most important thing to help guide you in your development of these programs.

Suresh, do you want to add anything? I guess not. Okay.

Operator (participant)

One moment for our next question. Our next question will be coming from Jason Gerberry of Bank of America Securities. Your line is open.

Jason Gerberry (Managing Director and Equity Research Analyst)

Hey, guys. Thank you for taking my question. Mine is around the guide. If I look at the midpoint, it implies that the annual growth rate steps up in fourth quarter, close to, I think, high 40% versus 39% growth rate year-on-year in 3Q. So as I think about that acceleration in growth, I'm wondering if you can kind of just flag the tailwinds there. Is this sales force expansion? Is this getting some uptake in unipolar MDD or mixed features or just something else? Appreciate it. Thanks.

Sharon Mates (Founder, Chairman, and CEO)

Andy?

Andrew Satlin (Company Representative)

Yeah. Yeah. So Jason, thank you for the question. So Jason, we had, as you saw, a strong quarter, right? 9% quarter-over-quarter growth on a quarter which typically has seasonality of summer. And then we outperformed the market in general, as Mark pointed out. If you look at the antipsychotic market on the branded antipsychotic, which grew 4%, and the overall antipsychotic market grew 1%, and we grew 9%.

So that momentum continues with us. So what we expect Q4 generally stronger, and that's why we expect that. And then also, even though primary field forces are just being operational in the field, probably we'll see most impact in 2025, but we do expect some impact of that in the fourth quarter. So if you take the midpoint, Jason, we expect to grow a little. If you take the midpoint, we expect to grow sequentially 11%. So from 9%-11%, I think it's pretty reasonable. And we're confident about our guide from that perspective.

Jason Gerberry (Managing Director and Equity Research Analyst)

Okay. Thank you.

Operator (participant)

One moment for our next question. Our next question will be coming from Jeff Hung of Morgan Stanley. Your line's open.

Jeff Hung (Biotechnology Equity Research Analyst)

Thanks for taking my question and congratulations on the progress. Following up on the LAI program, what are your expectations on demand for that formulation? And what proportion of patients might be interested in long-acting lumateperone versus the current dosing? And then I have a follow-up.

Sharon Mates (Founder, Chairman, and CEO)

Yeah. This is Sharon. Thanks for the question. I think it's a little too soon to tell. Again, we're going to be driven by the data. We do not expect the LAI to have a huge impact. And presently, depending on whose numbers you want to look at in schizophrenia, the percent penetration is anywhere from 5% to the highest number I've ever seen is 10%, but usually it's about 8% as the highest number. So I think that we don't really expect there to be any impact on our oral franchise.

I would like to just remind you that given the safety and tolerability of Caplyta, we really think that patients like taking an oral compound very much. And so we really don't see much impact there. We will be updating you as we go forward on what we see with these different formulations, and we'll let you know.

Jeff Hung (Biotechnology Equity Research Analyst)

Great. Thanks. That's very helpful. And then maybe quickly, you indicated that additional results from the phase III MDD studies will be shared at upcoming conferences. Are you presenting data at ACNP? And if so, what new aspects of the 501, 502 data might you be sharing with the medical community? Thanks.

Sharon Mates (Founder, Chairman, and CEO)

Suresh, do you want to take that?

Suresh Durgam (EVP and Chief Medical Officer)

Yes. Yes. We are going to be presenting at ACNP different aspects of the studies, both the 501, 502, and also the open-label study, the 503, so all that will be included, and also the data that was not released, only we talked about the top-line results. We'll be talking about the secondary endpoints. Additional post-hoc analysis will be presented at the meeting.

Jeff Hung (Biotechnology Equity Research Analyst)

Great. Thank you.

Operator (participant)

And one moment for our next question. Our next question will be coming from Brian Abrahams of RBC Capital Markets. Your line is open.

Hi everyone. This is Nevin on for Brian. Congrats on a great quarter. Just had a couple of questions on the peak sales guide that you provided. So in regards to that, how are you kind of thinking about what the shape of the MDD expansion could look like post-approval there?

And would the Vraylar launch into MDD be perhaps a good comparison, or do you believe you could potentially bend the curve even more given the efficacy and safety profile of Caplyta that's been shown? And then are you also seeing any early effects of the recent KarXT launch into schizophrenia? And do you anticipate that there might be any share erosion that could occur as that launch progresses?

Sharon Mates (Founder, Chairman, and CEO)

Mark? You want to take that?

Mark Neumann (EVP and Chief Commercial Officer)

Yeah. Sure, Nevin. Let me start with your second question. With the launch of the KarXT product, we haven't seen a lot out there yet. It's too early to see the prescription data coming through. Our understanding is that they're launching this week. We don't expect a significant impact on Caplyta of that launch. Certainly, it's good for patients.

Any new launches are good for patients, especially in schizophrenia, but schizophrenia is a market that has this switching dynamic where patients are really dissatisfied with existing antipsychotics, typically on the safety and tolerability side, which is where Caplyta has really had its gains in schizophrenia, so we don't see any one product dominating that schizophrenia market, and secondly, as we've talked about in our prepared remarks and some of the questions, the long-term potential for Caplyta is really in the mood disorders.

That's where we're going to see the real significant potential across bipolar I, bipolar II, and MDD. And we don't see the KarXT product competing there. So we don't see a big impact there. As far as the shape of the MDD curve, yeah, again, with the market research that we did, we do expect a rapid uptake in MDD.

If you look at the analogs in the past, both our own and the sort of the hockey stick inflection that we saw when we got the bipolar depression indication, we would expect at least a similar type of uptake in MDD given the profile that came out of 501, 502. And this is consistent with other antipsychotics that have added mood disorder indications like bipolar depression and, more recently, MDD with Vraylar.

We think that the success that Vraylar has had in the marketplace with MDD really reflects what was our belief all along, that there still remains a very significant unmet medical need for a product with robust efficacy, which was delivered in 501 and 502 with a favorable safety and tolerability profile, which we replicated in MDD, a similar profile that we saw in bipolar depression and saw in schizophrenia.

With the addition of a convenient dosing regimen once a day without regard to food, and the physician can start the patient at the effective dose and not have to titrate them up. All of those things taken together, we think, will lead to a rapid uptake in MDD and supports the overall guidance that we've provided on the $5 billion opportunity.

Great. Thank you so much.

Operator (participant)

One moment for our next question. Our next question will be coming from Michael DiFiore of Evercore ISI. Your line is open.

Michael DiFiore (Managing Director)

Hey, Guy. Thanks so much for taking my question and congrats on such great progress during the quarter. Two quick ones from me. Number one, are there any incremental updates regarding your plans for pursuing anxious distress indication separately? And I know you can only offer limited comments now, but regarding the planned primary care force expansion in 2025, could you share whether it'll match or exceed the recent 150 representative increase? And additionally, are there any specific geographic regions targeted for this expansion? Thank you.

Sharon Mates (Founder, Chairman, and CEO)

Great. Thanks. So I'll ask Suresh to address the anxious distress. And maybe what you can do is define anxious distress and talk about how the DSM addresses anxious distress. And then, Mark, if you could address the question on the sales force expansion.

Suresh Durgam (EVP and Chief Medical Officer)

Yes. In terms of the anxious distress, that is a specifier that was added into the DSM-5, and we have looked at anxious distress as patients within slightly different having who has MDD, major depressive disorder, or bipolar disorder in the mood disorder space, have symptoms of anxiety. And there are five symptoms they have classified.

Of those five symptoms, if they have at least two symptoms of anxiety, that is considered anxious distress. And also, there is a rating for severity, having three, four, or five, the severity increases. We have looked at these patients in our studies, both in our bipolar mixed feature study, the 403 study, where we have looked at patients with bipolar depression with mixed features and anxious distress. We also looked at the MDD population in that also having mixed features and anxious distress.

We have shared the data earlier that it was robust in both these populations of MDD with anxious distress as well as bipolar with anxious distress. We also looked at further in our augmentation MDD program, and we have seen good results in that. We'll be presenting that data in our next conferences. This is also important because anxious distress patients are difficult to treat.

They have higher comorbidities and also have higher suicidality both in terms of thoughts and suicidal ideations. This is also important in terms of treating the patient, knowing that the patients who are in the clinicians' offices, if they have anxious distress comorbid with MDD, that the option for lumateperone is able to help those patients. This is in terms of what anxious distress is.

Sharon Mates (Founder, Chairman, and CEO)

So I'll update you on this program further as we get further along and as we start presenting all of this data. So then if we could go to the second part of your question on sales force expansion, Mark.

Mark Neumann (EVP and Chief Commercial Officer)

Yeah. Sure. Mike, regarding further sales force expansion next year, we will provide you more details in later calls. What I would say is our current sales force stands at about 530, and we will be expanding that further. And I will say the early feedback on the messaging to primary care physicians in bipolar depression with Caplyta is really resonating.

The profile of strong efficacy, favorable safety and tolerability, and especially the single dose, once-daily dosing that the primary care physician can start the patient at the effective dose and not have to titrate up is something that they really see as beneficial in treating their patients. So the early feedback on our expansion into primary care is that the message is resonating very well. Now, looking to the future, we're also very excited, as we said, about the commercial opportunity of the potential label expansion in MDD.

And we will look to invest behind the brand at a level that will optimize that launch and the growth prospects that we have for the brand. So as we've done in the past, we'll share more details of those efforts and that expansion at the appropriate time next year.

Michael DiFiore (Managing Director)

Got it. Thanks so much.

Operator (participant)

And as a friendly reminder, please limit yourself to one question. Our next question will come from Marc Goodman of Leerink Partners. Your line is open. Again, Marc, your line is open.

Basma Radwan (VP)

Hi. Yeah. Hi. Good morning. This is Basma up for Marc. Thank you for taking our question. We have a question regarding the 1284. Can you elaborate a little bit more on the differentiation of 1284 from Caplyta? We were actually wondering whether the deuterated formulation yielded further improvement on the safety profile, especially with regard to the somnolence rate. Thank you.

Sharon Mates (Founder, Chairman, and CEO)

Especially what? I'm sorry. I missed the last part of your question.

Basma Radwan (VP)

With regards to somnolence rate?

Sharon Mates (Founder, Chairman, and CEO)

Yes. Okay. Thank you. I'll start and then ask Suresh if he has anything. So yes, we are very excited about the 1284 program and several different indications. And we will have even further indications as we progress with these programs. We did phase I studies in normal healthy volunteers and in one cohort of elderly volunteers. And we did see the safety profile is very good.

In fact, you hit on what we saw in the elderly population, especially is a decrease in the somnolence. Now, it's a small patient population, and we're looking at whether that continues in these larger studies. We're very excited about that. To remind you, the deuterated form expresses more of the parent than lumateperone. So we are looking to explore the meaning of that in terms of both, really in terms of efficacy, in terms of where we go with that, if it's in the dosing or whether it's in the indication that are extremely difficult to treat patients, etc. We're looking at all of that. Suresh, did you want to add anything?

Suresh Durgam (EVP and Chief Medical Officer)

No. Nothing further to share.

Basma Radwan (VP)

Okay. Thank you.

Operator (participant)

Thank you. One moment for our next question. Our next question will be coming from David Amsellem of Piper Sandler. Your line is open.

David Amsellem (Senior Research Analyst)

Hey, thanks. So another question on 1284, specifically on your GAD program. Wondering what kind of market research you've done on the extent to which atypical antipsychotics are used specifically for GAD. What is the level of prescriptions that we generally see for atypicals in this setting, whether it's monotherapy or adjunctive therapy? And as you look at that opportunity, is your goal here essentially to expand the overall antipsychotic footprint by offering a product with a differentiated profile? I guess, how are you thinking about this in terms of share gains versus market expansion? Thanks.

Sharon Mates (Founder, Chairman, and CEO)

Thanks for the question. Mark, do you want to start? And then either Suresh or I will chime in afterwards.

Mark Neumann (EVP and Chief Commercial Officer)

Yeah. Sure, David. In the research that we've been doing and as we've been looking at the GAD market, we actually see a lot of similarities with how the antipsychotic market evolved in MDD. You have a condition that's highly prevalent, about 20 million patients a year. Most of them get first-line therapy that does not adequately treat their disease. And even though there are no antipsychotics currently approved in GAD, there is some off-label use.

What you tend to see is GAD many times is comorbid with other mental health conditions like depression, like bipolar depression, and other things. And so you're dealing with a patient that has both a depressive disorder as well as an anxiety disorder. And so adjunctive use of an antipsychotic is something that I think physicians probably see as similar to how they would use an antipsychotic in treating MDD adjunctively.

Now, certainly, there are also patients with GAD as their only condition. The penetration of antipsychotics into that segment is less because there's no antipsychotics currently approved for that. So I think we believe that with good clinical results in GAD for 1284, this is a large market. It's a market that we think we could penetrate well, both in the patient with comorbid conditions but also in the patient that is suffering from GAD alone. So maybe I'll stop there and ask if Suresh or Sharon, you have any further comments on that.

Sharon Mates (Founder, Chairman, and CEO)

I don't, but maybe Suresh, do you have any comments on the drugs that are being used now and what our opportunity is?

Suresh Durgam (EVP and Chief Medical Officer)

Yes. In terms of the GAD, the current drugs that are approved are very limited in terms of mainly SSRIs and SNRIs. There are only five drugs that are approved for long-term use. That is duloxetine, that is Cymbalta, Effexor, Paxil, and Lexapro, and also we have the Buspar, another medication that was approved, and you have benzos for short-term, but you cannot use them for long-term.

All these are approved as first-line therapies, so we see an unmet need in patients who do not respond to these medications, and similar as Mark was mentioning, that prescribers are prescribing antipsychotics for patients who do not respond, and this will be similar to what we have seen with MDD, where initial days of MDD, adjunctive treatment was added on, so we see similarities there.

Also, from the mechanism of the 1284 and the safety profile, we believe that this will be a good opportunity to pursue this indication and also help the patients who do not respond to initial therapies.

Sharon Mates (Founder, Chairman, and CEO)

As in our bipolar program, where we had a study that was a monotherapy program and another clinical study program that was adjunctive use, we're following a similar pattern in GAD. So right now, we have ongoing the adjunctive treatment. And very shortly, we will begin study therapy.

David Amsellem (Senior Research Analyst)

Okay. Thanks again.

Operator (participant)

One moment for our next question, and our next question will be coming from Joel Beatty of Baird. Your line is open.

Joel Beatty (Senior Research Analyst)

Hi. Thanks. On the expectation of Caplyta reaching $5 billion in sales, what kind of changes in pricing over time are built into that projection?

Sharon Mates (Founder, Chairman, and CEO)

Mark, do you want to address that or Sanjeev? I'm not sure who's addressing it.

Mark Neumann (EVP and Chief Commercial Officer)

Yeah. I can start, and Sanjeev, if he has anything he'd like to add. We've assumed moderate improvements in net selling price over time, which incorporates our expectations of the potential impact of our IRA over time. So that's how I would characterize the pricing assumptions that we've used for that forecast.

Joel Beatty (Senior Research Analyst)

Thank you.

Sharon Mates (Founder, Chairman, and CEO)

Okay. I think that's what we have. Do we have any more questions?

Operator (participant)

We do have additional questions.

Sharon Mates (Founder, Chairman, and CEO)

We have time for one. Oh, okay. I think we have time for one or two more.

Operator (participant)

Certainly.

Sharon Mates (Founder, Chairman, and CEO)

I think one more.

Operator (participant)

Our next question will come from Corinne Jenkins of Goldman Sachs. Your line is open, Corinne.

Corinne Jenkins (VP of Equity Research)

Great. Thanks, guys, for squeezing me in here. Maybe from us, can you just talk a little bit about the sales force expansion kind of post-next year? Do you think you'll be pretty right-sized for MDD at that point, or should we anticipate kind of continued sales force expansion over the coming years? Maybe you could just talk a little bit about your philosophy around how you think about the sales force size relative to the market opportunity things.

Sharon Mates (Founder, Chairman, and CEO)

Mark?

Mark Neumann (EVP and Chief Commercial Officer)

Yeah. Corinne, our expectation is once we complete the expansion next year, which will take us further into primary care predominantly, we will be right-sized to optimize the launch and the growth prospects that we have for Caplyta.

Over time, you always reevaluate that. And any market conditions that might change, we'll constantly reevaluate that. But we expect that the expansion next year will get us where we need to be, which is highly competitive with a product profile that the market research suggests is a best-in-class profile. And we think that'll be a combination that will allow us to maximize the opportunity that we have in MDD.

Corinne Jenkins (VP of Equity Research)

Thank you.

Operator (participant)

One moment for our next question. Our last question will be coming from Graig Suvannavejh of Mizuho Securities. Your line is open.

Graig Suvannavejh (Biotech and Biopharma Analyst)

Thanks so much for taking my question. Congrats on the quarter. I was just very curious about the 1284 program and your comments around the phase II studies as you've designed them as being registrational. And so the question is, assuming positive data in one or all, perhaps even of those studies, what are you currently contemplating for the regulatory strategy and next steps in order to secure approval? In other words, are there more trials that are likely, or could these be the trials that support an sNDA or, I'm sorry, an NDA? Thanks.

Sharon Mates (Founder, Chairman, and CEO)

Yeah, so I think that the one that is where the regulatory pathway is extremely clear is in GAD, or at least the clearest, I should say, and so assuming that the two studies are positive, we would go and discuss with the FDA, them being the efficacy studies that are required for our filing. And then, of course, we'll have rollover safety, long-term safety studies as well. And so I think that program is very clear. On the other indications, I think it's a little too early. On the Alzheimer's indications, it's a little too early to say anything. But we will update you on that as we get further into next year.

Graig Suvannavejh (Biotech and Biopharma Analyst)

Thank you.

Operator (participant)

I would now like to turn the call back to Sharon Mates for closing remarks.

Sharon Mates (Founder, Chairman, and CEO)

So thanks, everybody, for joining today. As you can see, I think we're very pleased with the progress we've made. We're very pleased with the performance of Caplyta and our ability to help patients. I want to just remind everybody that's how we started this journey, is to help patients and to expand the population of patients that we can help. So I think that we are advancing on our mission, and we look forward to continuing to do that and to updating you on our progress. With that, operator, you can disconnect the call.

Operator (participant)

This concludes today's conference call. Thank you for participating. You may now disconnect.