Intra-Cellular Therapies Inc (ITCI) 2023 Q4 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to Intra-Cellular Therapies fourth-quarter and year end financial results conference Call. (Operator Instructions) Please note that today's conference is being recorded.

I would now like to turn the conference over to Dr. Juan Sanchez, Vice President Corporate Communications and Investor Relations. Please go ahead.

Good morning, and thank you all for joining us on our fourth-quarter and full year 2023 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 Laurie Hineline, Chief Financial Officer.

As a reminder, during today's call, we will be making certain forward looking statements. These forward-looking statements are based on current information, assumptions and expectations. These 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.

There is another risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements and the company disclaims any obligations to update such statements, Sharon?

Thanks, Juan. Good morning, everyone, and welcome to today's call. We are excited to share our results for the fourth quarter and the full year 2023. This past year was defined by strong and consistent growth throughout our company. We achieved major milestones as we establish CAPLYTA as a key treatment option for broad patient populations with bipolar depression and schizophrenia. We also advanced our pipeline programs and look forward to announcing top line results in our major depressive disorder study, Study 501 and Study 502.

Our full year 2023, total revenues were $464 million. CAPLYTA net sales in 2023 were $462 million compared to $249 million in 2022, representing an 86% increase. Similarly, total scripts grew by 85% in 2023 compared to 2022. Demand for CAPLYTA remains strong. Our well executed commercial efforts continue to drive prescription growth from both new and existing prescribers.

We anticipate continuing strong demand for CAPLYTA. Based on positive momentum, I am pleased to report that we expect full year 2024 CAPLYTA net product sales to be in the range of $645 to $675 million. Mark will elaborate on our commercial performance and plans for this year in a moment, and then Larry will share additional details regarding our financials. We continue to strategically invest in our pipeline, and we anticipate further advancements in several of our late mid and early stage clinical programs in 2024.

I'd like to share more specifics regarding our plans for expanding CAPLYTA beyond its current indications. We have two upcoming Phase 3 top line readouts for the use of Lumateperone as an adjunctive treatment in major depressive disorder or MDD. Our 501 study is fully enrolled and most patients have completed treatment.

We allowed the small number of patients who are in screening when we reached our previously determined enrollment targets to continue and be randomized to the double-blind treatment phase of the study. The rationale for allowing these patients to continue to participate in the double-blind treatment is that we believe that ethically, if the patient has participate in the screening process and qualify for enrollment, they should be allowed the possibility of receiving treatment.

As a result, we expect to report top line results from Study 501 in April of this year rather than late March. We remain on track to report top line results from Study 502 late in the second quarter of this year. Subject to those results, we continue to anticipate filing a supplemental new drug application with the FDA in the second half of this year.

We have a high degree of confidence in our MDD program, as we have previously shared multiple lines of evidence support this confidence starting with [LeuTech] loans mechanism of action simultaneously modulating serotonin, dopamine and glutamate systems. Importantly, we have significant clinical evidence in several patient populations, including patients with schizophrenia with comorbid depression, patients with bipolar depression and patients with MDD exhibiting mixed features. Of note, CAPLYTA is the only antipsychotic approved for both bipolar I and bipolar II depression, both as monotherapy and as adjunctive therapy.

We remain very excited by the possibility of helping millions of patients with MDD. The significant uptake of the last two antipsychotics approved for adjunctive treatment in MDD underscores the continued unmet need and large opportunity in this market. Given the efficacy and safety profile to date, we are confident in CAPLYTAs future potential in this patient population.

As we mentioned to you previously, we were expecting to have a meeting with the FDA to discuss the results of Study 403, particularly with respect to the MDD patient population with mixed features. I'm pleased to report that we recently had a constructive meeting, and as you know, we wait for minutes prior to making any statements regarding our interactions with the FDA. We expect to receive the minutes from this meeting later this quarter and plan to update you regarding the outcome and next steps at that time.

Beyond our MDD program, we continue to invest in our lumateperone R&D program. Accordingly, we have initiated our lumateperone pediatric program, which includes an open-label safety study in schizophrenia and bipolar disorder. A double-blind placebo-controlled study in bipolar depression, and two double-blind placebo-controlled studies in irritability associated with autism spectrum disorder.

Approximately 2.8% of children in the United States have autism spectrum disorder. Irritability is a common system that appears their daily activities with prevalence estimates ranging from about 25% to 45% of those patients.

There are only two antipsychotic approved for the treatment of irritability associated with autism spectrum disorder and two antipsychotics approved for the treatment of bipolar depression in the pediatric population. We believe lumateperone with its efficacy and favorable safety profile, if approved, can address important medical needs for these younger patients and their families, especially given the heightened concern regarding metabolic and motor issues in these patient population.

Additionally, in the first half of 2024, we will continue to advance our long-acting injectable lumateperone programs studying four different formulations. In summary, we continue the very successful launch of CAPLYTA and are confident in the continued robust growth throughout 2024. CAPLYTA is an important treatment option for patients with bipolar disorder and schizophrenia.

These conditions account for about 50% of the US anti-psychotic markets, nearly 68 million scripts each year. With the potential addition of MDD, our total addressable market would expand to cover nearly 80% of the market prescriptions. In addition, we expect our development programs among younger patient populations, and I'll work with long-acting injectables to further maximize the value of our lumateperone portfolio.

Outside of lumateperone, our pipeline continues to move forward with several clinical trials underway and others commencing soon. ITI-1284 is an important product candidate in our neuropsychiatry portfolio. In the first half of 2024, we plan to initiate patient enrollment in Phase two clinical trial.

Starting with our generalized anxiety disorder program, our first study will evaluate 1284 as adjunctive treatment to SSRIs and SNRIs. Also in the first half of 2024, we'll begin clinical conduct to evaluate ITI-1284 for the treatment of psychosis in Alzheimer's disease and agitation in Alzheimer's disease. In our phosphodiesterase one inhibitor program, our Lendlease potent Phase two clinical trial in Parkinson's disease is ongoing, and we expect to complete enrollment in late 2024 with top line results expected in the first half of 2025.

With respect to our ITI-1020 oncology program, our Phase one single-ascending dose study in healthy volunteers is progressing. Our earlier stage development programs include ITI-333 for Opioid Use Disorder and pain for which a multiple ascending dose study and a positron emission tomography study are both ongoing. Also in development is our(inaudible) and Agennix psychedelic program. This past December at the American College of neuro psychopharmacology, we presented the preclinical data from our lead compound ITI-1549.

We are very encouraged by the positive reception our presentation received from the scientific and medical community, and we look forward to advancing ITI-1549 into human testing in late 2024 or early 2025. In 2023, we presented new CAPLYTA data regarding our development programs at several medical and scientific meetings. We also published results in various medical journals, demonstrating our progress throughout the course of the year.

Looking ahead to 2024, we are starting off operationally and financially strong. As of December 31st, 2023, we had approximately $500 million in cash, cash equivalents and investment security, and we have no debt. I'm incredibly proud of our team and our accomplishments, and I'm excited to embark on our next phase of growth in 2024.

I will now turn the call over to Mark to further discuss CAPLYTA's performance and our plans for 2024. Mark?

Thanks, Sharon. Good morning, everyone. It's great to be with you today. 2023 was a year of tremendous progress in establishing CAPLYTA as a leading treatment option for patients with bipolar depression and schizophrenia, setting the stage for continued robust growth in 2024 and beyond.

We continue to work our way up the physician adoption curve adding more than 15,000 new first-time prescribers of CAP LYTA during the year and growing the breadth of our cumulative physician prescriber base since launch to over 36,000 by the end of the year.

We also saw consistent quarter-over-quarter increases in the depth of prescribing, as existing prescribers identified more and more patients who are appropriate for CAPLYTA treatments. This progress was driven by our comprehensive promotional activities, including the expansion of our sales force executed in Q2 of 2023, extensive peer-to-peer medical education programming and robust digital advertising.

Complementing our professional promotion was a comprehensive consumer and patient campaign featuring broad national advertising through television and social media to enhance awareness among the 11 million adults with bipolar disorder, and to communicate the potential benefits of CAPLYTA for these patients.

For the year, CAPLYTA posted strong growth, increasing total prescriptions by 85% in 2023 versus 2022 and finishing the year with significant momentum, accelerating growth in total prescriptions to 10% sequentially in Q4 versus Q3. We are well positioned to drive continued robust growth throughout 2024. CAPLYTA has a very compelling product profile that features strong efficacy and a favorable safety and tolerability profile.

In our clinical studies, CAPLYTA's metabolic parameters, which include changes in weight, cholesterol and glucose are all similar to placebo. Equally important movement disorders like EPS and Akathisia are also similar to placebo. CAPLYTA's favorable profile is very important as these side effects can often lead to poor patient compliance and drug discontinuation.

Another real benefit we hear from physicians is that they can start their patients at the effective dose without having to titrate, instead of waiting days or weeks to complete that process. Physicians also appreciate the convenience of CAPLYTA's one daily dose.

In 2024, we will continue to invest in optimizing the growth of CAPLYTA with several enhancements to our comprehensive promotional plan. As I mentioned previously, we added approximately 50 additional sales representatives late in Q1 of 2023, and those representatives are now firmly established and contributing significantly to our growth. We've also had consistently favorable results from our comprehensive direct-to-consumer platform, and we will continue these efforts throughout 2024 with a new creative campaign being introduced in Q2.

Finally, we continue to enjoy a strong market access position with over 99% of Medicare and Medicaid lives covered and about 90% covered commercial lives. As I mentioned in our last call from the end of Q3 2023 and the beginning of the fourth quarter, we negotiated an improvement in the utilization criteria for CAPLYTA with two of the largest Medicare Part B payers.

We were able to move CAPLYTA from a prior authorization and two generic steps to unrestricted status with these plans. We've already seen some initial benefits from this in the fourth quarter, and we expect to see the full impact of these changes this year.

In summary, we made tremendous progress with CAPLYTA in 2023. And we are confident that CAPLYTA's favorable product profile and our incremental promotional investment behind the brand will result in a robust year of CAPLYTA growth in 2024.

And I'll now turn the call to Lawry to discuss our financial performance. Lawry?

Thank you, Mark. I will provide highlights of our financial results for the fourth quarter and year ending December 31st, 2023, and our outlook for 2024. In the fourth quarter, net product sales of CAPLYTA were $131.5 million compared to $87.4 million for the same period in 2022, representing a year-over-year increase of 50.4%. Our increase in net product sales was primarily driven by strong underlying prescription growth, a 55% increase versus the same quarter in 2022, and a 10% sequential increase over the third quarter of 2023.

This increase was partially offset by a higher gross to net percentage in the fourth quarter, that was at the high end of the low 30s, still in line with our prior guidance. For 2024, we expect CAPLYTA's gross to net percentage to be in the mid 30s throughout the year. Q4 inventory levels in the trade measured by days on hand of CAPLYTA at the wholesale level remain consistent relative to the prior quarter. For the full year 2023, total revenues were $464.4 million compared to $250.3 million in 2022.

Net product sales of CAPLYTA were $462.2 million for the full year 2023, in line with our guidance. This represents an increase of 85.5% compared to 2022. SG&A expenses were $409.9 million for the year ended December 31st, 2023, compared to $358.8 million for the year ended December 31st, 2022. R&D expenses were $180.1 million for the year ended December 31st, 2023, compared to $134.7 million for the year ended December 31st, 2022.

Turning to our outlook for 2024. As Sharon mentioned, we expect CAPLYTA net product sales to be between $645 and $675 million, reflecting continued strong demand. For 2024, we estimate SG&A expenses to range between $450 and $480 million, which includes approximately $38.6 million of non-cash share-based compensation expense. This reflects our commitment to continue to effectively and efficiently support CAPLYTA commercialization through investments in our sales organization and marketing activities.

For 2024, we estimate R&D expenses to range between $215 and $240 million, which includes approximately $22.5 million of noncash share-based compensation expenses. Our R&D guidance reflects investments to support our broad pipeline. In 2024, we anticipate that a large portion of our total R&D expenditures will be related to our lumateperone development programs, as we continue to explore the use of lumateperone in additional patient populations.

Our financial position remains strong. Cash, cash equivalents, investment securities and restricted cash totaled $499.7 million at December 31st, 2023. This concludes our prepared remarks.

Operator, please open the line for questions.

Thank you. (Operator Instructions)

Andrew Tsai, Jefferies.

Hey, thanks, good morning. Congrats on the strong execution and the continued progress. So, for me, I wanted to ask on MDD today, what is your guys' latest thinking in terms of what we can expect to see in the top line release in April?

And then on understanding as a two point placebo adjusted change should be a good efficacy result. But is there anything else you would encourage the street to also look for as we think about CAPLYTA's potential differentiation in adjunctive MDD such as response rates, remission rates, safety profile, anything else? Thank you.

Thanks so much for the question, Andrew and for the kind words. This is Sharon, and I'll start off and then I'll ask Suresh has anything he wants to add. So, typically in our top line data, what we do, put out is all of the information that we have at that point. As you know, these are large studies that we do. And so we don't get all of the top line data, all of the data at one moment in time and since we know how anxious both we and the Street are. We put the data out when we get it. So, we certainly expect the primary endpoint, which is change from baseline on [matters]. And we'll also put out any other data that we have at that point.

And you're right, that typically in these studies, you expect to see a two to four point change on the (inaudible). But on an adjunctive study, you expect to be at the lower end, whereas the monotherapy studies you expect to be at the higher end. So, that's what we're expecting. We power our studies to approximately 90%. And so, and we obviously, as I said in our prepared remarks, we have confidence both in our program in the studies and on lumateperone performance in these studies.

So with that, I don't know, Suresh, do you have anything you want to add?

Not at this time. You have covered.

Thank you.

Thank you.

Brian Abrahams, RBC Capital Markets.

Hey, congrats as well from my end on all the continued progress. Maybe continuing on MDD. Can you talk, maybe give us a little bit more of a sense of the degree of, I guess of over enrollment you may have in the study, how that might impact powering. And then I guess, how you're thinking about, as these results come out of it during the second quarter, where the most differentiation potential that could be here in terms of positioning relative to some of the other adjunctive typicals in this space? Thanks.

Thanks. So, this is Sharon, again. And I'll start with regards to, yes, as we've said, patients come into screening and we did believe that patients who are in screening who passed through successfully, through the screening process should be allowed to enter. Typically you plan your studies, so that you will have at least the number of patients whenever you put a protocol in place, you say approximately like we had approximately 470 patients. We screen appropriately for that and we had patients come through. So, it's a small number of patients.

It's typically under 5% that you over involved and that is what fits the bill here that we allowed to come in that you hold the screen and if they pass, you ate allowed to go in. So, that is what we have, but of course, you do need to wait for them to complete. So, it's just a couple of weeks later that they are coming through finishing up the study. And that's why the study will read out in April rather than in March.

So, I think, I don't know, Suresh did you want to add anything to that?

Yes. I think they were asking about the powering. For this, I'm not going to be any powering applications because, the number is still small. So, I would not expect any powering implications.

Right. And on differentiation, you also asked about that, and I think that CAPLYTA has demonstrated its efficacy and favorable safety and tolerability profile. And with that, we think that there is a real need in the marketplace for additional agents and that CAPLYTA can perform well in this marketplace.

Thanks, Sharon, Thanks, Suresh.

Jessica Fye, JP Morgan.

Hey, guys. This is Nelson for Jess. Congratulations on the strong guidance for CAPLYTA in 2024. Can you walk us through some of the assumptions that's underlie the guidance? What does it mean in terms of patient penetration? And then how do we think about the gross-to-net dynamics in 2024?

So, maybe I'll ask Mark, if you want to talk to the first part. And then Lawry, if you want to talk to the gross to net.

Yes, sure, Sharon. So, the guidance that we put out, the main driver of that guidance is the underlying strong demand trend that we see in the business and the continued demand for CAPLYTA. So, any variation around that trend is really where you get the range in the guidance. We expect to continue to penetrate both the schizophrenia and bipolar depression market, where we focus both on increasing the breadth of prescribing, our prescriber base as I mentioned in my prepared prepared remarks.

Last year, we added over 15,000 new first-time prescribers of CAPLYTA. We expect to see that continue in 2024, as well as at the same time across the entire prescriber base of what is now over 36,000. We expect to continue to see increased depth of writing, as these existing prescribers get more experience and they find more and more patients that are appropriate for CAPLYTA. So, those are the main factors that go into the guidance range that we provide. And I think you also had a question on how to think about gross to nets for 2024. So, for that, I'll turn it over to Lawry.

Yes, thanks, Mark. Yes, the gross to net in 2024 is going to be and we project to be in the mid 30s. And that's compared to the low 30s that we saw in 2023. Now there are several primary drivers for this increase, where we have increases in volume going through the commercial channel as a result of the strong uptake in the bipolar program, plus there are also been recent improvements in Medicare Part D coverage. So, those two are the main drivers for the increase from the low 30s to the mid 30s.

Alright. Does that answer the question?

Yes. Operator, why don't you go ahead with that next call, please.

Jeff Hung, Morgan Stanley.

Hi, this is Michael Riyadh on for Jeff Hung. Thank you for taking our question. For adjunctive MDD, to what extent is the background ADT influence the placebo effect? And how should we be thinking about placebo response variability between Study 501, 502 and 505. Are the three studies balanced in terms of the background regimen? Thanks so much.

Suresh, would you like to answer to that?

Yes. So yes, so in this program for MDD with adjunctive treatment for MDD, we have allowed SSRIs, SNRIs and other antipsychotics to be the background, and all that are approved are allowed into this. So, the background in terms of you're talking about the placebo response. Again in all CNS trials and MDD trials, in particular, placebo response, we tried to mitigate it by taking several measures. So, this is no different than this study also that we are taking measures allowing for proper delegates of patients, making sure that they have a right severity that are coming in.

So, we have taken those measures in terms of the placebo response. In terms of individual mitigations, we group them based on SSRIs and SNRIs. Individual medications will not be taken into account and just be taking into account from a class platforms.

And all of the the whole program has been done the same way. (multiple speakers)

Umer Raffat, Evercore.

Hi, guys, this is (inaudible) for Umer Raffat. Thanks a lot for taking my question and congrats on all the progress in 2023. Two from me, one is a variation of the question just asked Study 501 for the adjunct of MDD trials seem to have a little bit more diverse set of ex US countries participating compared to study 502.

And my question is, could there be any local regional differences in the way medicine is practiced that makes you more or less confident that the study 502 would be successful, given that both trials are designed exactly the same and I have a follow-up.

Yes. So this is Sharon. Thanks for the question, Mike. And I'll start and I'll ask Suresh if he wants to fill in. We plan all of our studies the same way that our late-stage global studies. And that is, you look at the different countries and we plan for the US to have a proportion of patients and for ex US have a proportion of patients. And that proportion of patients is typically around 30% US and then ex US fills in. And this is no different.

So, 501 and 502 are the same as I don't, I didn't quite get your part of the question where you seem to think there's a difference because, there isn't any difference. Some of the countries are different, but it's ex US and US patient populations as per what is common practice and what in discussions with the FDA, what they like to say.

Got it, that's helpful. I'm sorry, do you have anything more to add?

I don't know, Suresh, did you have anything to add?

in terms of again, that's true, you know, we have got 30% coming from US and ex US. And the question about different countries, but these are all standard practice guidelines. So, that's pretty much absorbed throughout the world. So, in terms of the practice guidances and other factors, we look into that and we select countries that have similar patterns.

I couldn't hear what Suresh said, just to make clear, we aim for around 30%, give or take a percent or two on either side.

Got it, that's helpful. And my follow-up question is and forgive me if I missed this. Have you met with the FDA to discuss the mixed features data in context of the broader adjunctive MDD indication as? And if so, would you be able to offer any commentary or color there? Thank you.

Yes, thanks, Mike. Yes, in our prepared remarks, I did say that we did recently have a meeting with the FDA and that it was a constructive meeting. And that, as is our practice, we always wait for the FDA minutes before we say anything and so once we have the minutes, we will further update you on the program and on the meeting. So, we are good.

Thank you.

Marc Goodman, Leerink Partners.

Thanks for taking my question. It's really on (inaudible) Mark. Congrats on the quarter. So, could you, maybe talk about a CAPLYTA's growth trajectory moving into first quarter '24? How should we think about a sequential growth versus fourth quarter, given the seasonality and maybe additional color on the DTC campaign, you're plan in 2024? Thanks.

Thanks, Mark, you want to take that, please?

Yes, sure. Thanks for the question. So, we had very strong fourth quarter, accelerating our total prescription growth at the 10%. So, we come into the year in 2024 with some significant momentum in that regard. Typically, as you allude to in the first quarter, you see some typical headwinds associated with patients switching market access plans.

When you have a product like ours with an increasing portion of the business coming through the commercial channel. You also have increased co-pay assistance required as patient deductibles reset for the year. And then typically that decreases over the course of the year.

So, we feel very good about the momentum we have, the underlying business, the demand in the business, the reception that physicians have had to the product and the feedback that they provide to us on their experience and the patients' experience. But yes, typically in the first quarter, you do see some headwinds. And then in the second quarter, you see a reacceleration in growth. So, that's in general how I would, how I think about the upcoming quarters.

Joseph Thome, TD Cowen.

Good morning. Thank you for taking my question and congrats on the quarter. Maybe just if you could talk a little bit on the expected size of the sales force expansion that will be necessary, if the MDD indication is allowed to move forward under the label. I know we've heard some success in MDD in the primary care setting. So, would you look to expand a little bit more there. Is any of your expense guidance for 2024 earmarked for an expansion for MDD deal, would that be more of a 2025 move? Thank you.

Mark. Would you like to take that?

Yes, sure. Thank. Thanks, Joseph, for the question. Yes, so to answer the second part of the question first, our SG&A guidance for the year for 2024 does not contemplate any material expansion in our sales force. We continually evaluate our marketing activities and our sales force sizing, and we take advantage of any opportunities that we see to fuel additional growth.

But in terms of any major expansion, we don't contemplate that in 2024. Once we have the data and we understand that we're on the track for a filing and approval, we do expect to increase the size of our sales force to ensure that we're optimizing CAPLYTA and the growth opportunity we would see in MDD, which is a very significant market.

To give you a little bit of background for bipolar depression and schizophrenia. We currently target about 43,000 physicians that are primarily psychiatrists and the nurse practitioners that support them and a smaller segment of primary care physicians, who do treat a lot of bipolar depression and our high-volume prescribers of antipsychotics. They are included in our current 43,000 physician target list.

As we contemplate an approval in MDD, that target list will increase significantly and it will increase mostly in the area of primary care because, there are many more primary care physicians who are comfortable treating MDD with adjunctive antipsychotics who aren't very high-volume prescribers for bipolar depression and certainly not for schizophrenia, and it would be for that group of physicians that we would look to expand our sales force.

Now the 43,000 physicians that we currently call on, we'll be able to leverage them because, virtually all of the 43,000, who are high-volume prescribers for bipolar depression will also be high-volume prescribers for MDD, and they'll have about four or five years of experience with the brand. So, we think we'll be able to have a really good jumping off point with that group of physicians and the extent to which we expand our sales force will be determined by how far and how quickly we want to go into primary care.

And those are the things that we have been working on, and as we get a little bit closer to the talking about our launch plans, we'll come back to you with more specifics about that. So, hopefully that background is helpful for you, and I'll leave it at that for now.

Great, thank you.

David Amsellem, Piper Sandler.

Thanks. So, just two quick ones. One is with the MDD label expansion, can you talk to payer access and particularly how we should think about rebating with commercial plans and the gross-to-net over time with MDD in the mix. So, that's number one.

And number two regarding deuterated lumateperone, wanted to get your early thoughts on how you're thinking about the value proposition here in terms of differentiation from the legacy product, particularly on tolerability and safety, given that the current form of lumateperone was extensively pretty well tolerated and seen widely seen as pretty safe within the category. So, just wanted to get your thoughts on that. Thank you.

Great. Hi, David. Thank you for the question and maybe I'll ask Mark to start out and then I'll take the 1284 and they need to ask you to repeat it, if I can't remember by them, but let's start with Mark.

Yes, sure. Thanks for the question, David. Yes, for the potential label expansion into MDD. We would expect a pretty seamless process as to the addition of MDD to the label when it comes to payer access. In general with the antipsychotic category, the payers manage these products at the brand level, not at the indication level, meaning that whatever your coverage is for the existing indication, that coverage gets carried over to the new indication as well.

That's what we experienced. When we moved from schizophrenia to the label expansion for bipolar depression, and we've seen similar dynamics with competitive products who have added MDD to an already existing schizophrenia and bipolar depression label. So, we would expect that to be a fairly similar process. And it's another reason why we expect to be able to get off to a quick start with that potential approval in MDD.

So, with that, maybe I'll turn it back over to Sharon for the second question that you had around 1284.

Great, thanks. Let's for those listening who may not be familiar with 1284. Let me just remind everyone that 1284 is a deuterated form of lumateperone, where the carbon deuterium bonds are strategically replaced with carbon hydrogen bonds. So, it is a new molecular entity and it's formulated as an ODTSL to be delivered once-a-day sublingually. And we have done a Phase one program that found that 1284 ODTSL was very rapidly absorbed into the systemic circulation was metabolically stable and resulted in high systemic exposure just on that activity, sorry.

So, we have and you are right to point out that lumateperone has a very good safety and tolerability profile. What we have seen with 1284 is that we have seen some things in a PK profile that we think may be even more advantageous, especially as we studied it in a small population of the elderly and other populations based on PK characteristics that we think make it amenable.

And that is so in the elderly populations with Alzheimer's disease and the general population with GAD. So, we think and that's why we're doing these studies. So, we do believe that there are some advantages to 1284 over lumateperone, and we are doing the studies to confirm that, and we'll keep you apprised of these studies and other results as we move forward. So, thanks a lot for your question.

Okay, thanks, Sharon.

Jason Gerberry, Bank of America.

Hey, good morning. Thanks for taking my question. First to share, I wanted to clarify, so is the thinking that you only need one of these three MDD trials coupled with your mix feature positive trial to satisfy the FDA's requirement for the and MDD filing?

I just wanted to get your sense of the confidence around that. And then for Mark, just your current kind of understanding of what's going on in the adjunctive landscape for MDD for these atypical antipsychotics. Is the (inaudible) launch kind of lifting all boats, so to speak with the different atypicals or is this a market share grab game? I'm just wondering how much of a switch dynamic is involved here with some of the agent? Thanks.

Great, maybe I'll ask Mark to start and then I'll come in.

Yes, sure, Jason. The dynamics that we're seeing in the MDD space for adjunctive antipsychotics is very encouraging to us in terms of the potential opportunity for CAPLYTA in the future. And by that I mean, (inaudible) has had a very successful launch in MDD significantly growing that market, which is not a surprise to us, but rather is confirmation of what we believe to be a very significant unmet medical need in MDD for an adjunctive antipsychotic with a good efficacy and safety profile.

So, we don't believe it's a share grab Rexulti's business does not seem to have been impacted significantly by the launch in (inaudible). So, we think we're seeing a lot of market growth there. And with successful studies and a successful filing and approval when we get to the market, we see that as a very, very robust opportunity for CAPLYTA.

And to continue on that and to answer your first question. Our MDD platform is composed of two studies for the treatment for adjunctive treatment in MDD. Having said that, we'll see the readouts on these studies and hopefully they're both positives. If one is positive and one misses, it depends on why it missed and how it missed and the FDA looks at the totality of your evidence, and that's where you asked about the mixed features, and mixed features is not part of the adjunctive MDD program.

However, what happens is the FDA does take into account the totality of your evidence. And so an example of that is Rexulti, where they had two studies, one hit, one missed, but the FDA looks at the totality of your evidence and they then [Alpine]. And so I think that's where all of our data, any data you have that we have an MDD will be looked at in our submission. So, I think the very, very strong positive data that we had in our mixed future studies can only help us. And I'll leave it at that.

Okay, got it, thank you.

Ash Verma, UBS.

Hi, thanks for taking my questions. So, maybe just a couple on pipeline. For the LAI, I think the press release mentioned that there was some sad data that you had generated. Just wonder what did that show and what are these four different formulations that you're going after in this new study that you're starting and then for a lender [Sporlan], so Parkinson can be a big market with different segmentation. Are you trying to position this as a monotherapy or adjunctive or is it going after the early or the day state disease? Thanks.

Okay. Maybe Suresh do you want to start or actually I can start with the LAI and then turn it over to you for the lenders potent. I'm sorry, guys, I appear to be losing my voice you. So, we did a Phase one study and what study showed was in fact what we're looking for is a formulation that is good for both the one month and longer duration. The first study so first of all, we can administer, this was a subcu formulation, but it would not be an ideal formulation to go forward with certainly for greater than nine month.

So, we went back to the drawing board and based on what we heard about a subcu formulation versus other types of formulations like I am also based on site of injection. And so the four formulations that we have prepared look at both subcu versus Iams and site of administration and looking at the ability to deliver the molecule over both one month and longer duration. So, that's the answer your first question and maybe Suresh, do you want to talk about our Parkinson's study and the(inaudible)

Yes. So, the Parkinson's(inaudible) study is a study in Parkinson's disease. We are looking at populations where the primer objective is to look at efficacy (inaudible)administered once daily as an adjunctive treatment to existing levodopa therapy. So, the patients must be on stable doses of existing levodopa therapy. And our primary endpoint there is looking at the Hauser diary, that is increase in on-time without troublesome dyskinesia.

We also are looking at the motor aspects, MDS-UPDRS part two of activities of daily living. In that study, we are also measuring other multiple things. One, looking at measurements and cognition, but also looking at several biomarkers of inflammation. This is important for both Parkinson's and also looking at programs outside of the CNS. And once we look at the data based on the moment measurements, cognition and inflammation, our next studies will look into defining what the path forward will be for this program.

Okay, thank you.

Sumant Kulkarni, Canaccord Genuity

Good morning, great to see all the progress, and thanks for taking my question. I'm going to ask a bigger picture one. On your MDD program, you're clearly putting a lot of resources behind it. So, for the benefit of investors, what would be the latest and most accurate characterization from within the company on whether you view the addition of the MDD indication as a nice to have lumateperone given the size of the market and unmet needs? Or is it more a strategic imperative for the company?

Hi, Sumant. That's an interesting question. Maybe I don't know, Mark, would you like to start from a commercial perspective and then we can chime in.

Yes, sure. That is a very interesting. Interestingly phrased question, Sumant and I would guess what I would say is, we believe with our current business in schizophrenia and bipolar depression. We are still in the early innings of tapping into the opportunity for CAPLYTA and we see tremendous opportunities for continued growth in bipolar depression as we continue to penetrate that market.

Certainly, MDD is equally a large opportunity with significant opportunities for growth as I just mentioned in answering one of the previous questions, and we would certainly be excited to add that to our label and have the opportunity to bring CAPLYTA to physicians and patients in the area of MDD as well.

I have nothing to add. I think well stated well stated position of the company.

Thanks.

Ami Fadia, Needham & Company.

Good morning. Thanks for taking my question and congrats on all the progress. My question is more of a clarification question on your comments on the MDD regulatory plan. Would you say that if one study hits and the other misses you would still go in for a regulatory submission without waiting for the third one to read out?

And then also just going back and thinking about mixed features, what's your latest thinking about the regulatory path forward? And could you use some of the data from the MDD studies that are going to be reading out to pursue a specific label in mixed features? Thank you.

Hi, Ami, thanks for the question. I think it's a little too early to comment on how we're going to proceed until we know what the data is, okay. I will tell you that obviously, two positive studies we proceed as planned. One positive study and one negative study. Again, it really really depends on it really depends on what happened and why you missed whether or not and we would we always submit all of our data to the FDA as soon as we can.

So, I think it's a little bit too soon to answer your questions on what happens just because, it depends on what the data says, and I think we can leave it at that.

There may have been was there another question in there or we are good?

My question was also regarding mixed features and what your latest thinking there is.

As we said in our prepared remarks that we did have a very constructive meeting with the FDA and as always, we wait for our minutes. And once we have our minutes, we'll come back to you..

Operator, I think may be other question.

Charles Duncan, Cantor Fitzgerald.

Hey, good morning, Sharon and team. Congrats on a good year and thanks for taking our questions. I'm hopping between calls. So, sorry if this has already been addressed, but I wondered what your perspectives were with regard to the possibility of muscarinic agonists being approved for monotherapy in schizophrenia later on this year.

And I guess I'm wondering, if you could provide us a little bit of color on your preparation in terms of differentiation of CAPLYTA relative to those candidates and how you're, you know, addressing the prescriber base at this point?

Mark, do you want to take that?

Yes, sure, Charles. So, we have a great deal of confidence in the product that we have in CAPLYTA. We feel across both schizophrenia and bipolar depression. We see very strong efficacy, a very favorable safety and tolerability profile and the dosing regimen that physicians and patients really like and our focus is on educating physicians and patients to make sure that they're aware of CAPLYTA, they understand the potential benefits of CAPLYTA for their patients.

And so that's where we put our energy. New products potentially being added to the mix for physicians is always a good thing for patients, as you know, in this category there's a tremendous amount of churn, what we call churn, meaning patients try one therapy often prior to CAPLYTA, they would experience side effects either on the movement disorder side or on the metabolic side. And so they cycle through multiple different products, so for them to have another option to choose from is always a good thing for patients.

I would say for us and more and more of our business, as we've talked about in the past is coming from bipolar depression and in the future with the successful MDD study, as we just talked about would be coming from that area as well. So, we don't see a significant impact on the CAPLYTA business of any new entrants coming into the market. So, I hope that addresses your question, Charles.

I'll just add to that we agreed and we as the company can any new product that can help patients. It's great for patients. And as Mark said, especially in schizophrenia, these patients cycle through these product, but as part of the disease state. So, we think it can be a benefit to patients and that's terrific. Now having said that, there are 2.4 million patients with on schizophrenia.

There's four to five times that patients size in bipolar depression, and there are even more patients with MDD and our business is growing in the bipolar space, and we expect that to continue. So, as Mark said as the summary statements, we really do not expect this to really impact our business at all.

That makes sense, Sharon and Mark, and it doesn't appear that those agents impact depression at all. So, clear differentiation. One quick point of clarification, though, given what's going on with regard to acquisitions. Could I think I know the answer to this question, but the small royalty that you pay to Bristol-Myers that is paid to gas company without any input on their part you just send them a check. They have no role in marketing CAPLYTA at this point.

They have no role in marketing CAPLYTA .

Okay, thanks.

Thank you. And with that, ladies and gentlemen, we conclude the Q&A answer period. I will turn to Dr. Sharon Mates for final comments.

Thank you, everyone for joining us(inaudible). I know that we're a little bit over in time. So, I'll make it very brief. I think we are very proud of our performance during 2023 and we're really looking forward to 2024 and look forward to updating everybody as we go forward. So, thanks again for joining the call. And with that, operator, you can disconnect.

Thank you, everybody, for joining our call today. You may now disconnect.