Q4 2022 Intra-Cellular Therapies Inc Earnings Call
Speaker 1: meyou.
Speaker 2: The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 11.
Speaker 3: Thank you for standing by and welcome to the Intracellular Therapeutics fourth quarter 2022 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 the session, you'll need to press star 1 1 on your telephone.
Speaker 3: If your question has been answered and you'd like to remove yourself from the queue, simply press star one one again to remove yourself from the queue. As a reminder, today's program is being recorded. And now I'd like to introduce your host for today's program, 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 2022 parents call. Joining me on the call today are Dr. Cheryl Mates, Chairman and Chief Executive Officer.
Speaker 4: Mark Newman, Chief Commercial Officer, Dr. Suresh Drogan, Chief Medical Officer, and Larry Heinlein, 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.
Speaker 4: Those are subject to change and involve a number of risks and uncertainties that might cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our pre-duty filings made with the Securities and Exchange Commission, including our quarterly and annual reports.
Speaker 5: You are questioned not to place a due reliance on these far-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 with you our results for the fourth quarter and the full year 2022. I'm pleased to report that we achieved strong sales growth of CapLIDA and we continue to advance our promising pipeline. 2022 was an exceptional year for the growth of CapLIDA as we successfully launched our new indication for bipolar depression. CapLIDA's prescriptions tripled in 2022 compared to 2021. We have received very positive feedback from physicians and patients on CapLIDA's efficacy, tolerability, and ease of use. We believe CapLIDA is having a positive impact on patient lives.
Speaker 5: For 2022, our total revenues were $250.3 million. Keplida net sales were $249.1 million versus $83.8 million in 2021, representing a 205% increase. Keplida's net sales for the fourth quarter 2022 were $87.4 million, representing a year-over-year increase of 243%. Demand for Keplida has been consistently strong and we are confident of continued growth for Keplida. With this in mind, we are pleased to provide revenue guidance for the first time. In 2023, we expect Keplida net sales to be between $430 and $455 million.
Speaker 5: In 2023, we continue to invest in our near-term and future growth. In the near-term, our commercial team is focused on maximizing the significant potential for Keplida in our current indications of schizophrenia and bipolar depression. Our future growth will be driven by the continued success of Keplida as well as the execution of our clinical programs. Let me elaborate further on our clinical programs. We are excited about the potential for label expansion of Keplida in major depressive disorders and other mood disorders, ITI-1284, our PD-1 inhibitors, ITI-333, and our long-acting injectable program for lumetepron. Beginning with major depressive disorder, which affects about 21 million Americans who experience at least one major depressive disorder.
Speaker 5: episode each year. Many of these patients don't respond or only respond partially to first line treatment. Our global Pivotal Program evaluating Women's TEPRONE as the Junctive Treatment for Major Depressive Disorder in patients who partially respond to any depressances ongoing. Patient enrollment continues and studies 501 and 502. Two global six-week randomized double lines placebo control phase 3 trials to assess efficacy and safety. We expect to file a supplemental new drug application with the FDA for the approval of Women's TEPRONE as an adjunctive therapy to any depressance for the treatment of MDD in 2024. Additionally, we are pleased to announce today we are initiating a third global phase 3 adjunctive MDD study.
Speaker 5: Study 505. This study is similarly designed to our ongoing study and we plan to begin patients enrollment shortly. This approach is consistent with the way we conducted programs for our previous indications and is common strategy and development of mood disorder programs. Let's now move on to our mixed features program. Study 403 is our global clinical trial evaluating women's step-around 42 milligrams in patients with MDD and patients with bipolar depression who exhibit mixed features. This patient population has more severe symptoms, more comorbidities and a higher risk of suicide attempts than patients without mixed features. This results in higher healthcare utilization and associated costs. We anticipate announcing top line results later this quarter. Now let's talk about ITI-1284. This year we are advancing 12 84 programs into phase 2 clinical development in multiple highly prevalent conditions with unmet needs including education and Alzheimer's disease, psychosis and Alzheimer's disease and generalized anxiety disorder or GAD. All-timers disease affects 6.5 million Americans over 865 and will increase in the ageing population. Education is experienced by greater than 50% of Alzheimer's patients and psychosis occurs in 30 to 50% of patients.
Speaker 5: These symptoms are difficult to treat and there's an urgent need for medicines to treat these symptoms. Our other Phase 2 program for ITI-1284 is in GAD. GAD affects approximately 7 million adults in the U.S. each year, with three-quarters of these patients experiencing moderate or severe functional impairment. Lots of patients do not respond to initial therapy. We look forward to updating you on the progress of these studies. We continue to advance the development of our Lumetep-Rome long-acting injectable program. In 2022, we completed a Phase 1 study with our initial formulation. We plan to initiate Phase 1 studies with several LAI formulations in 2023. The goal of this program is the development of LAI formulations that are effective, safe, and well tolerated with treatment durations of one month and longer. Moving to our PDE-1 inhibitor program. PDE-1 is an enzyme highly expressed in certain brain regions.
Speaker 5: Alzheimer's disease.
Speaker 5: For our newest PT1 inhibitor, ITI1020, we recently received a UMAe perceived letter from the FDA and now have an active IND to evaluate this compound as a novel cancer immunotherapy. We plan to start a Phase I study in Healthy Volunteers in the first half of 2023.
Speaker 5: Finally, IGI 3333 has the potential to treat opioid use disorder as well as pain and mood disorders. Opioid use disorder continues to be at epidemic levels. The number of opioid-involved overdose deaths in the U.S. continues to increase, with more than 80,000 deaths reported in 2021, up from 21,000 in 2010. We have completed a Phase 1 single ascending dose study and recently started a multiple ascending dose study. We also have an ongoing neuroimaging study looking at receptor occupancy. We are excited about the potential for our development program as they have the potential to serve patients who currently suffer from serious disorders in areas of unmet need. Our company is in a strong financial position, ending the year with $593.7 million in cash, cash equivalents, and investment securities, and we have no debt. We are very proud of our performance across the company and look forward to continued growth and sharing our progress with you. I'll now turn the call over to Mark.
Speaker 3: to further discuss capillitis performance and commercial opportunity. Mark. Thanks, Sharon, and good morning, everyone. As Sharon noted, 2022 was an exceptionally strong year for capillitis as we successfully launched our new bipolar depression indication. Since launch, total prescriptions have tripled and new patient starts are now at levels five times higher than before the bipolar depression label expansion. For the full year 2022, capillitis total and new prescriptions increased 193% and 220% respectively over the prior year. This growth is being driven by a compelling product profile, broad market access, and strong commercial execution by our experienced sales and marketing team. Capillitis has been well received in the marketplace and we are gratified by the overwhelmingly positive feedback from both prescribers and patients regarding their experience with the product. We continue to see strong underlying demand and prescriber adoption for capillitis as we consistently increase both the breadth and the depth of our prescriber base, adding significant numbers of unique new prescribers and expanding the average number of prescriptions per prescriber. We delivered another great quarter for capillitis. Capillitis prescriptions again significantly outperformed the antipsychotic market. Total capillitis prescriptions grew 21% sequentially versus Q.
Speaker 3: Kaplita has maintained broad coverage in the Medicare Part D and Medicaid channel with more than 98% of lives coverage. We have further expanded coverage in the commercial channel, which is the primary pair for patients living with bipolar disorder. We expect to achieve commercial coverage for approximately 90% of lives by the end of this quarter.
Speaker 3: While we are very pleased with the uptake of caplight at this stage of the launch, we have a strong belief that there remains plenty of room to grow, and we are investing behind the brand accordingly. The bipolar depression market is large and has a significant remaining on met need. Our current label, which includes the use of caplight as both monotherapy and as a jump to treatment in bipolar 1 and bipolar 2 depression, allows us to address large patient populations with tens of thousands of prescribers. As prescribers continue to acquire positive experience with caplight to depth and breadth of utilization increases, this dynamic is building sustained demand for our medicine. This is in line with historical precedence for antipsychotics approved for mood disorders, where branded antipsychotics have long growth trajectories and generates positive volume growth for years.
Speaker 3: We expect the same dynamic for caplida. In summary, 2022 was a tremendous year, and we look forward to another successful year in 2023. Our team has been executing extremely well, and we are building on our growth momentum. I'm confident that we will continue to grow robustly in the coming year as we remain laser focused on executing our commercial plan. We're excited to continue improving the lives of as many patients as possible.
Speaker 3: Now, I'll hand the call over to Larry to detail our financial performance. Larry? you
Speaker 3: Thank you, Mark. I will provide highlights of our financial results for the fourth quarter and year ending December 31, 2022 in our outlook for 2023. Starting with our fourth quarter results, that product sales of capillator worth $87.4 million compared to $25.5 million for the same period in 2021, representing a year-over-year increase of 243% and a 22% increase over the third quarter of 2022. Our gross net percentage remained in the low 30s in the fourth quarter, consisted with our guidance.
Speaker 6: Inventory levels in the trade measured by days on hand of Capelita at the wholesale level remained consistent throughout the quarter. For the full year 2022, total revenues were $250.3 million compared to $83.8 million in 2021. Net product sales of Capelita were $249.1 million for the full year 2022 compared to $81.7 million for 2021, representing an increase of 205 percent. General and administrative SG&A expenses were $94.6 million for the fourth quarter of 2022 compared to $79.7 million for the same period in 2021. For the full year, SG&A expenses were $358.8 million compared to $272.6 million in 2021.
Speaker 6: Research and development are in D expenses for the fourth quarter of 2022 with $33.9 million compared to $29.5 million for the fourth quarter of 2021. R&D expenses for the full year 2022 were $134.7 million compared to $88.8 million in 2021. Cash equivalents and investment securities till the $593.7 million at December 31, 2022 compared to $412.3 million at the summer 31st, 2021. Turning to our outlook for 2023, as Sharon mentioned, we expect capitalite in that fail to be between $430 and $455 million, reflecting continued strong growth. This sales guidance takes into account our expectation that capitalite as gross to net percentage will increase to the mid-30s in 2023. For 2023, we estimate STNA expenses to range between $420.2 million.
Speaker 6: and $450 million, which includes approximately $29 million of non-cash share-based compensation expense. This reflects our commitment to support capillated commercialization through investments in our sales organization and marketing activities. For 2023, we estimate R&D expenses to range between $195 and $220 million, which includes approximately $17 million of non-cash share-based compensation expense. Our R&D guidance reflects investments to support our robust pipeline, including multiple studies in our Luma Tepper Own clinical programs and our three other developmental platforms. In 2023, we anticipate that a substantial portion of our total R&D expenditures will be related to our Luma Tepper Own development programs. This concludes our prepared remarks. Operator, please open the line for questions.
Speaker 3: Certainly, ladies and gentlemen, if you have a question at this time, please press star one one on your telephone. We ask that you please limit yourself to one question each. You may get back in the queue as time allows. One moment for our first question. And our first question comes from the line of Andrew Stice from Jeffries. Your question, please. Thanks. Good morning, and a big congratulations on the great quarter and great guidance. So I'll kick things off and ask about the guidance overall for 2023. Team, what drove your decision to guide on revenue? And secondly, is your revenue guidance provided in such a way that we can expect potentially beaten raises throughout the year? So just trying to gauge whether you're giving a more conservative, more accurate, or more aggressive type of guidance here. Thank you. Thanks, Andrew. And thanks for the kind words. This is Sharon. And I'll start, and then I'll turn it over.
Speaker 3: to Mark. Obviously, we're giving guidance now because we're confidence in our trajectory in what we've seen with our very strong launch for top-lighter. So that's the overall statement and then rather than stealing Mark's thunder, what on my <expletive> part to comment further and then maybe I'll come back if there's anything else to add. Yeah, sure. Sharon, and thanks for your question, Andrew. Yeah, to pick up where Sharon left off, what we've been seeing with Caplighta is we've been consistently increasing both the breadth and the depths of caplighta prescribing month over month and to provide a little context around that date. There've been over 22,000 unique prescribers of caplighta and we're adding over 1200 new first-time prescribers. And in addition to that, the depth of their prescribing is increasing as well. So we're also expanding the average number of prescriptions per prescriber. And while we're really pleased with this update today and it supports the trajectory that you've seen throughout the course of the year, we strongly believe that there's still plenty of room to grow for a lot of the reasons that we talked about in our prepare.
Speaker 3: I guess, a fear towards the low end versus the high end of the range. Thanks. Mark, do you want to take that? Yeah, I think Brian , it's simply looking at the trends that we've had today with the bipolar launch. And an expectation that those trends will continue throughout 2023. We've said before and we continue to believe.
Speaker 3: That the generic entries of lorazadone from latuta should not have a significant impact on capillata. Um, historically in this category, when products go generic. The remaining branded products are not significantly impacted. So, for example, when a billify and Sarah well, when generic. Uh, the growth of Brelar and latuta, uh, was not impacted and they continued their growth trajectory. So we anticipate. A similar dynamic with lorazadone going generic and then I think just the, the belief with the increase investment in our sales force, the continued investment in DTC and across our marketing mix. That we feel that the, the, the trend should continue throughout 2023 and build, especially towards the, the latter part of the year. Got it and in terms of just the variance. Yeah, I think it's just, we don't expect a great deal of variance. We expect the trend to continue and I think.
Speaker 3: you know, specifically with the incremental investments that we're making in the Salesforce as those, and we just recently added them. So they literally are just out in the field this month. As they get more and more comfortable in their territories, that will accelerate the growth or DTC throughout the year should continue to raise awareness among patients, educate them on the benefits of cap light up. And we'll see that continue to go as well as in the market access space. We've always had good broad access, particularly in Medicare and Medicaid with over 98% with commercial. We've been at 85% through the balance of last year. And more recently now have increased that to 90% which we expect to be implemented by the end of the month. So I think all of those things should drive real robust growth throughout the year. And I would just like to remind you, this isn't a variant. It's just telling you that we expect a momentum to build over the course of the year. With growing revenue as we go from quarter to quarter. Obviously, first quarter has some first quarter seasonal dynamics built in. And then less than that. So in the second quarter and then building further into the third quarter and fourth quarter. Thank you. One moment for our next question. And our next question comes from the line of Jessica Faye from JP Morgan Chase. Your question, please.
Speaker 5: Hey guys, this is Natsun on for Jessica. Congratulations on the fantastic guide. Could you provide your latest expectations on when we can hear the top line results from the adjunctive MDD trials and can you talk about, give us a little bit color on the reasonings for starting another adjunctive trial this year? Thank you. Yeah, sure. This is Sharon and I'll start and then I'll ask Suresh if he wants to add. We've guided you to a filing of an SNDA in 2024 for our adjunctive MDD and that's based on studies 501, 502, and 503. We have said that I think was your other question. Just repeat your other question for me please.
Speaker 3: Operator, is anybody there? You may proceed. She may have disconnected, Sharon. Oh, she got disconnected? Okay, well, I think her question was, why are we, does anybody want to paraphrase it or should we just go on to the next question and then we'll come back to it, hopefully she reengages. Certainly one moment for our next question. Our next question comes from the line of Omar Rafat from Evercore ISI. Your question, please. Hi guys, this is Mikey Fiore again for Omar. Thanks so much for taking our questions and congrats on the quarter in progress. Just two for me, one clinical, one commercial. The clinical one, regarding your mixed features trial, I know top line results are due sometime this quarter, but at a recent broker conference, you mentioned that the placebo group, they
Speaker 3: in mixed patients may be very different from what we've seen in depression patients. So how do we think about that? Are depressed patients or patients who are being treated as adjunctive depressed patients since they're already experiencing a partial response? Could we expect a greater placebo response in these patients? Just any thoughts on how to frame that? And the commercial question regarding your guidance, it seems pretty conservative. At the high-pointer guidance that assumes roughly around 80 new prescriptions adds at every week on average. Which seems pretty doable, I think. At the beginning of the year, there's been around an average of 200 prescriptions added weekly. Just any thoughts along those lines. Thanks. So let's start with the commercial question. And I'll ask more questions. Mark, do you want to take that? And then we'll go to Thresh or I'll take the one of us will take the clinical question. Yeah, Mike, I don't know that I have much more to add other than what we've said that we have a high degree of confidence.
Speaker 3: in the continued growth of Capylida, and we set the range at what we thought was the appropriate range, given the growth that we've been seeing. So, overall, I would just say we have a high degree of confidence that we've got the range right. Okay. And also on the clinical question on placebo, I think all studies have placebo effects. I'm really not certain there would be any more or less here than any other study, but I'll ask Suresh if he wants to comment any further. Yes. Good morning. These are different populations. One is the mixed-feature study is a monotherapy study, and the adjunctive treatment study is adjunctive to other antidepressants, and that is patients who have already partially responded to the antidote percent. These are two different populations, and they have several differences within the populations. Also, each individual study comes with its own set of issues. Patti?
Speaker 7: the patients, what kind of patients they are coming from, what concomitant medications they have been on. All these play a role in determining how the study reads out. So you cannot make concretions between one study to another, especially when they are not similar designs when they are two different populations. And that's the reason why you have to look those in two different sets of individual studies. That's it. Thank you. Thank you one moment for our next question.
Speaker 3: And our next question comes to the line of Mark Goodman from SBB Lyric. Here, question please. Here's good morning. Can you give us a little more color on these Phase II programs for 1284, 80 agitation, 86 doses. How are these patients? Different in what endpoints you're looking at that will be different here and the anxiety one. And then just Larry, just quickly, the sales reps that were added, the 50 reps. Are they getting added in 23 or any of them added in the fourth quarter? Thanks. So, rest, you want to take the definitions of agitation versus psychosis.
Speaker 7: And then we'll go to Mark. Yes, so for the 1284 ODT, we are progressing with studies in three different indications. One, the first one is agitation in Alzheimer's disease. This is purely looking at patients who have agitation. It's common for Alzheimer's patients to have behavioral symptoms, both agitation and psychosis, but they are different indications and they have different endpoints. So the first study we would be looking at is the agitation part of the study. And regarding the details of the endpoints and the study designs, as we come closer to starting the trial, we will let you know. In terms of the next indication, that is talking about psychosis in all the emotional disease, in Alzheimer's disease. That endpoints are different from basically looking at psychotic symptoms within the Alzheimer's patients who have Alzheimer's disease. And that study also is going to start this year. And the GAD is a generalized anxiety disorder. And there has been, as we have indicated in our call, that there is a lot of treatment failures and patients only respond partially to some of the drugs.
Speaker 8: for initiating a good adjunctive MDD study and why.
Speaker 8: prior to the readout of the ones that are ongoing.
Speaker 8: And then just with regards to the mixed feature study that's going to read out soon. Help us understand what you think that you need to be able to demonstrate.
Speaker 8: to move ahead and seek sort of registration, on the seek approval in that indication. You're indicating the past that data will drive for the discussion to the FDA. What I'm trying to understand, you think that maybe at least then?
Speaker 8: overhead and seek sort of registration on the seek approval in that indication. You know, you're indicating the past that data will drive for the discussion to the FDA. What I'm trying to understand, you think that maybe at least in the rag one.
The hard run of studies, but then they did not end up getting approval. It appeared to us that the bar was probably high to seek an approval and that patient's upset. So we create to get your thoughts on that. Thanks. Okay. I don't know if the rest do you want to start? And then I can chime in. Regarding the first question you asked about why starting the third study. In deciding when to start the third study, when you look at the landscape including how many studies are being run right now and what countries they are running and what are being conducted, we believe this is appropriate time to initiate the study. And major depressive disorder in objective treatment is a great near term opportunity. Similar to our clinical development strategies followed in our other more disorders program.
For example, the bipolar depression program, it is proven to add additional trials. It's a good decision and it highlights our commitment to expanding a plight in the communication. In terms of the second question about the mixed features, as we have indicated, the readout of the study we were expecting in this quarter.
And the readout will depend on how strong the results are, as we have indicated in the previous times. It depends on what the results show, and we will have to go to the FDA and discuss present data. That's what we have indicated to the FDA. Once we go and discuss based on the results, we will know the next path. I want to also remind that there has not been a path established in the FDA.
And our strategy is mainly to expand across the mood disorder spectrum, both in unipolar and bipolar disorder. I think you had a question about, you know, other than some other company doing this study and not having approval, that I cannot speak to that because I don't know what decisions were made internally. support sometimes. Thank you. Fewer.
Thank you one moment for our next question. And our next question comes in line, Charles Duncan from Canacore. Canter, your question please? Yeah, from Canter. Thanks Sharon and team for taking our question and congratulations on a transformative year last year. I think these are, or this is a commercial question with two parts. One is actually related to last question in terms of the mixed feature readout and strategy.
We recently conducted a KOL call that suggested, the KOL suggested that even a data publication would be picked up by prescribers. And I know that you wouldn't mark it off label, but do you think that the label could encompass prescribing in mixed features patients? And the second part is, what are you doing to prepare for the coming wave of muscarinic modulators as monotherapy in schizophrenia? Or do you think that that's a non-event for your commercial franchise?
Mark, do you want to start or do you want me to? Why don't you go ahead and start and I'll add some color next to the sharing. Okay, I'll start with the label and I think that really what we need to do and you're right, we do not promote anything off label. So what we would do is we're going to wait and we're going to see the data and we are going to go to the FTI with the data and assuming that it's.
very good, which we're, of course, hopeful for, that might guide us towards a particular path. We will publish the results. And, you know, again, we're hopeful that the data is very good and physicians can read the papers. And I guess on, you know, I think it's a little premature to talk about and come to unlabel.
expansion based on these results because we don't know the results. On the muskorenex, I don't think again, no, our first approval was in schizophrenia, our next approval and the direction of the company is schizophrenia is important, but...
move disorders are much larger populations than the indications that we are moving in with our expansion. We do think that, so we do think that anything that's approved for patients with schizophrenia is a good thing. We look for anything that can help patients remember patients cycle through all of these drugs and we would look forward. We don't expect there to be any negative impact on us at all. First of all, they're still in the future, but all I can say is we look forward to having more options to treat patients. Mark, do you want to add anything to that?
No, I think that's great. Thanks Sharon for the color. Thank you one moment for our next question. And our next question comes online. Jason Gerberi from Thank You of America. Your question please. Hey good morning guys. Thanks for taking my question. So just wanted to drill on a little bit more on this, telling a marketing, investment, step up. And really is.
It's a broader trend we see in mood disorder drugs in general. So just wondering if there's a connection at all to this sort of dynamic and in the step up and selling and marketing investment. Yeah, I can take that that Sharon. Yeah, so when we made the decision to expand the sales force, what we were seeing is very strong demand for cap light.
very positive reception in the marketplace. And as we analyzed the data, we saw there was an opportunity to continue to fuel incremental growth. We've been pleased with the growth that we've been seeing, but as we always do with all of our investments, we're good stewards of the investment dollars that we have, and we always look for opportunities that might yield even incremental growth for us. And so in adding the 50 additional neuroscience specialists,
What they will allow us to do is more frequently connect with high volume prescribers and also expand our reach deeper into our target audience. And you mentioned NPs and PAs, and we would agree with you certainly over the last couple of years, NPs and PAs in disease states like schizophrenia, and especially bipolar depression, have become a very important audience for us. They are very much a part of our target audience and will continue to reach out to them, to educate them on the disease and the benefits of cap light up. So I hope that answers your question Jason.
of an LAI form, even the Tupperov, and I guess in the grand scheme of things in your pipeline, how important is it? Thank you. Sure. Thanks for the question. I'll take that. So I think that when we started looking at an LAI, we didn't have all the data that we have now as to apply to safety.
and tolerability profile, and which, as you know, has turned out to be very good. So we are developing an LAI. We don't expect it to take over 50% of the population because of the fact that our oral drug has such a great efficacy and safety and tolerability profile. However, we do think that it's an option for patients and can be an important option for some patients.
who either are not compliant to one-to-day dosing or who simply just don't want to take the drug every day. So we think that it's nice to have. We don't think that, again, that it's going to take over our oral franchise.
compliance to one-to-day dosing or who simply just don't want to take the drug every day. So we think that it's nice to have. We don't think that, again, that it's going to take over our oral franchise.
We are also in our development profile, though, we are seeking not only a one-month delivery, but we're seeking longer period of time, a two-month delivery. So hence we're delivering, we're developing a product that could be useful in both one and two-month deliveries. Okay. Sharon, can you say that the sub-Q or an intramuscular, I don't know if you've ever mentioned that? I have mentioned it. The FaveOne study that we did was a sub-Q. We've been looking at other
ways of administering the drug. So we are looking at both subcue and I am. And so, and it turns out from a patient perspective, it isn't, it really, depending upon your formulation, sometimes they like one over the other, but patients don't seem to mind and I am injection. So we are looking at both subcue and I am.
Thank you. Thank you one moment for our next question. And our next question comes in line. Greg, Senator Nadia from Mizzell. Your question please. Thanks, good morning. Thanks for taking the questions and congrats on the progress. I've got two pipeline questions. My first just has to do with the mixed features study that we're about to get data for.
And my question is just given the trial design where you do have madras as an endpoint and given that it's likely to be mainly MDD patients or many MDD patients in the study, is there a possibility that you could consider or you could propose to the FDA that this perhaps should be counted more as an MDD trial? So just want to get your thoughts around if that's part of the thinking.
And then secondly, I did also want to revisit the new 505 study that you've announced. And I'm curious if the desire to add a study in any way is perhaps hedging against, perhaps a negative result in 501 or 502. Thanks. I'll start with the second part and then I'll turn.
Every sponsor conducts several trials within an indication. So I don't think there's anything, you know, any magic here, anything special here. I think we always think it's prudent to have several shots on goal. And so we thought it prudent to have started another battle. And so we thought it was prudent to have started another battle.
And into the timing of the study, you look around at the different countries, you look at how many other studies are ongoing. And we thought that this is the right time to do this, hence the start of the study. And Sresh, did you want to take the other part of the study?
of the major-diperson population that is a unipolar depression.
So we have approximately, you know, similar patients between each groups. And also, this patient population has been enriched for mixed features. So we use the diagnostic features of DSM-5, specifically enrolled patients only who meet the criteria for mixed features. So it would be difficult and if not, I don't think that it will be...
agreeable but FDA to use that as a MDD study.
No one would we want to be these are patients with mixed features on each of these patients of population. Yeah, in that population.
No one would we want to be these are patients with mixed features in each of these patients population. Yeah, in that population.
And just to tell you, I mean, obviously we don't have any of the results yet, but the way the study was designed, patients were stratified. So we should have roughly equal patient populations in the bipolar and in the MDD patient populations. Thank you. One moment for our next question. And our next question comes from a line of asked from UBS. Your question please.
Thanks for taking my question, congrats on the quarter. I had to first just, can you elaborate on the new DPP campaign that you launched? Since like it is making a recent buzz based on some of the downstream metrics that we track, anything that you can share on how much of the spend is baked in for the DPP in your S-T-N-A guidance for this year. That's first and then the second one. So on the next features, like the feedback that we've heard from physicians indicates that patients are not specifically treated for mixed features, at least not extensively. And this would require some sort of like an indication establishment.
want to understand if you think differently and can you provide any kind of an example of their psychiatric indication went through what's in the path when it was under treated to begin with and became a bigger market eventually. Thanks. We may need for you to I you blanked out on me a couple of times. I couldn't hear what you were saying. I don't know if anybody else could hear at all.
I heard the first part of the question, Sharon, on DTC. I could start there if you'd like. Sure. So, yeah. Hi, Ash. We did recently launch the next iteration of what we call our Let in the Light DTC campaign. This is a broad national campaign that we're implementing. We're implementing it through television ads, digital platforms, social media platforms, all with the intention of seeking to continue to raise awareness of the very significant unmet need.
both in bipolar one and in particular bipolar two depression and educate patients on the potential benefits of catholite. And yes, we agree we're seeing the same positive metrics that you're seeing, which is the reasoning behind continuing the campaign and evolving it and building upon it. Our media is successfully targeting and reaching the bipolar depression audience. We know that from the metrics we're looking at. When we're on air, we drive substantially more visitors to our website, looking for information about papillita and bipolar depression.
the components of our selling and administrative spend. But Larry, I don't know if you have any comments that you'd like to add to that. I have nothing to add to that. Okay, and then Ash, we're going to have to ask you to repeat. I know you had a bunch of questions in there. I'm sorry. We couldn't, I guess none of us could understand what was being asked. So if you could ask again, please. Sure, yeah. So just one mixed feature. This is feedback that you have heard.
I think that many psychiatrists do understand mixed features and citations and treat those patients with whatever they think might be beneficial that's currently available, but you're right, there is no label for it. Until the DSM-5 MDD with mixed features wasn't even specified and...
by polar depression was a much looser definition. The DSM-5 has allowed physicians to see a tighter definition and to be more educated. We agree with you that it is an education process just like by polar 2.
You know, physicians see bipolar 2 patients, they know it when there's nothing to treat patients with. It's more difficult. So having the label for bipolar 2 is very helpful to physicians. And we would look forward to educating on this indication as we go forward. And we would look forward to it.
So we think there's a lot of opportunity here for education and to expand the awareness of the disease. I think, you know, bipolar 2 is a great example where it's now quite well defined with only a few treatments. The tiver but there and there, let's change right? All right, the 300 weeks.
I don't know, Sir Ash, if you have any other examples of the top of your head. Although the example is not exactly the same, but at least something closer to that would be, if you think about the psychosis in Parkinson's disease, remember I think there was nothing approved, but one that is there that took off, similarly, how do you disconnect? I don't ask her an issue, let's maut get that Endura grind has. I'll ask her an issue, let's maut get that Endura grind has.
then extensively well with again they have done a lot of educational campaign to highlight that importance of that. Those are great points, Rosh. Thank you. Okay, operator, I think that time for us to wrap up. One more question. Thank you.
Certainly then, one moment for our final question. And our final question for today comes from a line of Korean Jenkins from Goldman Sachs. Your question, please. Hi, this is Father von Faker and this is a couple of minutes. I believe it by the GPN to the mid 30s range between 90s feet, but would you anticipate and done with cadence over the course of the year?
Yeah, hi, hopefully I heard you it was and you were asking the gross connect for the you know guidance for the year and a cadence for that is that what you said. Yeah Half
Yeah, I think our guidance, you know, the gross penet will fluctuate, you know, as it does throughout the year, but I think you can be, we're comfortable in our mid-30s guidance here. I can't give any more granularity to that.
Got it. Okay. Thanks. And on this the second question was that for MDD data, could it come as early as your end or should we expect that in 2024?
So what we've said on the MDD is that we expect to file in 2024 and that's I think the guidance that we're giving.
Okay. Operator, I think with that. Um, it's-
time for us to wrap up and we thank everybody for joining us today. We think 2022 was a terrific year for us and for the launch of Kaplaita in bipolar depression. We look forward to more progress this year in 2023 and we look forward to update you on a quarterly basis. So thanks everybody for participating and operator you can now disconnect.
Certainly, thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day. Thank you.
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the question during the session, you'll need to press star 11 on your telephone. If your question has been answered, and you'd like to remove yourself from the queue, simply press star 11 again to remove yourself from the queue. As a reminder, today's program is being recorded. And now I'd like to introduce your host for today's program, Dr. Juan Sanchez, Vice President Corporate Communications and Investor Relations. Please go ahead. Good morning and thank you all for joining us on our...
statements are based on current information, assumptions, and expectations.
Those are subject to change and involve a number of risk and uncertainties by my course actual results to differ materially from those contained in the fallal looking statements.
These are not always described in our previous file, may be the securities and exchange commission, including our quarterly and annual report.
You are questioned, not to place on legal lines on these far-looking statements, and the company describes any obligations to such statements. Sharon? Thanks, Ma'am. Good morning, everyone, and welcome to today's call. We are excited to share with you our results for the fourth quarter and the full year 2022. Thank you.
And please to report that we achieved strong sales growth of caplite and we continue to advance our promising pipeline. 2022 was an exceptional year for the growth of caplite as we successfully launched our new indication for bipolar depression. Caplite's prescriptions tripled in 2022 compared to 2021. We have received very positive feedback from physicians and patients on caplite as efficacy, tolerability and ease of use.
We believe Keft Lightest is having a positive impact on patient lives. For 2022, our total revenues were $250.3 million.
Keplite and net sales with $249.1 billion versus $83.8 million in 2021, representing a 205% increase. Keplite has net sales for the fourth quarter 2022 for $87.4 million.
representing a year-over-year increase of 243%. Demands for Kef Leida has been consistently strong, and we are confident of continued growth for Kef Leida.
With this in mind, we are pleased to provide revenue guidance for the first time. In 2023, we expect kept light and net sales to be between $430 and $455 million. In 2023, we continue to invest in our near-term and future growth.
In the near term, our commercial team is focused on maximizing the significant potential for Kaplaita in our current indications of schizophrenia and bipolar depression.
Our future growth will be driven by the continued success of Cathlida as well as the execution of our clinical programs. Let me elaborate further on our clinical program.
We are excited about the potential for a label expansion of cap light up in major depressive disorders and other mood disorders, ITI-1284, our PD1 inhibitors, ITI-330 and our long-acting injectable program for Luma Teppron. Beginning with major depressive disorder, which affects about 21...
treatment for major depressive disorder in patients who partially respond to any depressimances ongoing?
Patient enrollment continues in studies 501 and 502. Two global six-week randomized double blind placebo control phase three trials to assess efficacy and safety.
We expect to file a supplemental new drug application with the FDA for the approval of Luma Teprone as an adjunctive therapy to any depressants for the treatment of MDD in 2024. Additionally, we are pleased to announce today we are initiating a third global phase three adjunctive MDD study study 505.
This study is similarly designed to our ongoing study and we plan to begin patients enrollment This approach is consistent with the way we conducted programs for our previous indications and is common strategy and development of mood disorder programs. Let's now move on to our McFeatures program.
Study 403 is our global clinical trial evaluating on the Tepparone 42 milligrams in patients with MDD and patients with bipolar depression who exhibit mixed features.
This patient population has more severe symptoms, more comorbidities, and a higher risk of suicide attempts than patients without mixed features. This results in higher healthcare utilization and associated costs. We anticipate announcing top line results later this quarter.
Now let's talk about ITI-1284. This year we are advancing 12-A-B4 programs into phase 2 clinical development in multiple highly prevalent conditions with unmet needs, including education in Alzheimer's disease, psychosis in Alzheimer's disease.
and generalized anxiety disorder or GAD. Alzheimer's disease affects 6.5 million Americans over 865 and will increase further with the aging population.
Education is experienced by greater than 50% of Alzheimer's patients and psychosis occurs in 30 to 50% of patients. These symptoms are difficult to treat and there is an urgent need for medicines to treat these symptoms. Our other phase 2 program for ITI-1284 is in GAD.
GAD affects approximately 7 million adults in the U.S. each year with three-quarters of these patients experiencing moderate or severe functional impairment.
Half of patients do not respond to initial therapy. We look forward to updating you on the progress of these studies. We continue to advance the development of our LUMITEP-ROM Long-Acing Injectible Program. In 2022, we completed a Phase I study with our initial formulation.
We plan to initiate Phase One studies with several LAI Formulations in 2023.
The goal of this program is the development of LAI formulations that are effective, safe, and well-tolerated with treatment durations of one month and longer. Moving to our PDE1 inhibitor program.
PD1 is an enzyme highly expressed in certain brain regions, certain cancer cells, and immune cells, including macrophages and microglia.
In disease state, PDE1 becomes highly active and uncontrolled, preventing a cell's ability to respond appropriately to its environment. Inthibition of this enzyme in a pathological state restores normal functions. For example,
In Parkinson's disease, dopamine pathways are affected and PD1 inhibitors restore normal function in these pathways by strengthening dopamine signaling.
PDE1 inhibitors can also function as immunomodulators in neurodegenerative diseases and cancer, where important pathways are compromised in immune cells. We are evaluating our PDE1 inhibitor, Lennonous Posen, and they face two studies in the treatment of motor symptoms and cognitive impairment in Parkinson's disease. We are also evaluating our PDE1 inhibitor, Lennonous Posen, and they face two studies in the treatment of motor symptoms and cognitive impairment in Parkinson's disease.
We expect to begin enrollment later this month. Parkinson's is the second most common neurodegenerative disease after Alzheimer's disease. For our newest PT1 inhibitor, ITI1020, we recently received a UMA-perceived letter from the FDA.
and now have an active IND to evaluate this compound as a novel cancer immunotherapy. We plan to start a Phase I study in healthy volunteers in the first half of 2023. Finally, ITI-TRIPLE-3 has the potential to treat opioid use disorder as well as pain and move disorders.
opioid use disorder continues to be at epidemics levels. The number of opioid involved overdose deaths in the U.S. continues to increase with more than 80,000 deaths reported in 2021, up from 21,020-10. We have completed a phase one single ascending dose study and recently started a multiple ascending dose study.
We also have an ongoing neuroimaging study looking at receptor occupancy. We are excited about the potential for our development programs as they have the potential to serve patients who currently suffer from serious disorders in areas of unmet need. Our company is in a strong financial position.
ending the year with $593.7 million in cash, cash equivalents, and investment securities, and we have no debt. We are very proud of our performance across the company and look forward to continued growth and sharing our progress with you. I'll now turn the call over to Mark to further discuss kept lightest performance and commercial opportunity. Mark.
Thanks, Sharon, and good morning, everyone. As Sharon noted, 2022 was an exceptionally strong year for capillight as we successfully launched our new bipolar depression indication.
Since launch, total prescriptions have tripled, and new patient starts are now at levels five times higher than before the bipolar depression label expansion. For the full year 2022, couple at a total and new prescriptions increased 193% and 220% respectively over the prior year.
This growth is being driven by a compelling product profile, broad market access, and strong commercial execution by our experienced sales and marketing team. Kaplita has been well received in the marketplace and we are gratified by the overwhelmingly positive feedback from both prescribers and patients regarding their experience with the product. We continue to see strong underlying demand and prescriber adoption for Kaplita. Kaplita.
As we consistently increase both the breadth and depth of our prescriber base, adding significant numbers of unique new prescribers and expanding the average number of prescriptions per prescriber.
We delivered another great quarter for caplight. Caplight of prescriptions, again significantly outperformed the anti-psychotic market. Total caplight of prescriptions grew 21% sequentially versus Q3, while the overall anti-psychotic market was essentially flat during that same time.
We have carried this positive momentum into 2023 and the strength of our commercial fundamentals and metrics gives us confidence that Kaplito will achieve sustained growth throughout the year.
We have taken several steps in our prescriber and consumer promotional activities for 2023 to ensure a continuation of the robust growth we have experienced since a launch of bipolar depression. First, commensurate with a strong demand and positive reception of capitalite at the date. We have increased our commercial footprint and recently added 50 highly experienced neuroscience sales representatives to our...
through television, digital, and social media platforms.
to continue to raise awareness about the unmet need in bipolar 1 and bipolar 2 depression and educate potential patients about the benefits of capillight.
All of these efforts are supported by strong market access coverage across all three payer channels. Caplighta has maintained broad coverage in the Medicare Part D and Medicaid channel with more than 98% of lives coverage. We have further expanded coverage in the commercial channel, which is the primary payer for patients living with bi-
the brand accordingly.
The bipolar depression market is large and as a significant remaining on met need.
Our current label, which includes the use of capillita as both monotherapy and as the jumps of treatment in bipolar 1 and bipolar 2 depression.
allows us to address large patient populations with tens of thousands of prescribers. As prescribers continue to acquire positive experience with capillita, the deaths and breath of utilization increases.
This dynamic is building sustained demand for our medicine. This is in line with historical precedence for antipsychotics approved for mood disorders, where branded antipsychotics had long growth trajectories and generate positive volume growth for years. We expect the same dynamic for a cap light up. In summary, 2022 was a tremendous year.
and we look forward to another successful year in 2023. Our team has been executing extremely well, and we are building on our growth momentum. I'm confident that we will continue to grow robustly in the coming year as we remain laser focused on executing our commercial plan.
We're excited to continue improving the lives of as many patients as possible. Now I'll hand the call over to Larry to detail our financial performance. Larry? Thank you, Mark. I will provide highlights of our financial results for the fourth quarter and year ending December 31st, 2022, and our outlook for 2023.
Starting with our fourth quarter results, that product sales of capillator worth $87.4 million compared to $25.5 million for the same period in 2021, representing a year-over-year increase of 243 percent and a 22 percent increase over the third quarter of 2022. Our gross net percentage remained in the low 30s in the fourth quarter, consistent with their guidance.
inventory levels in the trade measured by days on hand of capitalite at the wholesale level remain consistent throughout the quarter. For the full year 2022, total revenues were $250.3 million compared to $83.8 million in 2021.
Net product sales of cap-layed over $249.1 million for the full year 2022, compared to $81.7 million for 2021, representing an increase of 205%.
Selling General and Administrative SGNA expenses were $94.6 million for the fourth quarter of 2022, compared to $79.7 million for the same period in 2021. For the full year, SGNA expenses were $358.8 million, compared to $272.6 million in 2021.
Research and development are in D expenses for the fourth quarter of 2022 with $33.9 million compared to $29.5 million for the fourth quarter of 2021. R&D expenses for the full year 2022 or $134.7 million compared to $88.8 million in 2021. Cash equivalents and investment securities.
Total $593.7 million at December 31, 2022, compared to $412.3 million at December 31, 2021.
Turning to our outlook for 2023, as Sharon mentioned, we expect capillator in that fail to be between $430 and $455 million, reflecting continued strong growth. This sales guidance takes into account our expectation that capillators grossed to net percentage will increase to the mid-30s in 2023. For 2023, we estimate STNA expenses to range between $420 million.
and $450 million, which includes approximately $29 million of non-cash share-based compensation expense. This reflects our commitment to support capillated commercialization, through investments in our sales organization, and marketing activities. For 2023, we estimate R&D expenses to range between $195 and $220 million, which includes approximately $17 million of non-cash share-based compensation expense.
share-based compensation expense. Our R&D guidance reflects investments to support our robust pipeline, including multiple studies in our Lumetepe-Rome clinical programs and our three other developmental platforms. In 2023, we anticipate that a substantial portion of our total R&D expenditures will be related to our Lumetepe-Rome development programs. This concludes our prepared remarks. Operator, please open the line for questions.
Certainly, ladies and gentlemen, if you have a question at this time, please press star 1-1 on your telephone. We ask that you please limit yourself to one question each. You may get back in queue as time allows. One moment for our first question. And our first question comes from the line of Andrew Stuyth from Jeffries. Your question please. Please.
Thanks, good morning and big congratulations on the great quarter and a great guidance. So I'll kick things off and you know, ask about the guidance overall for 2023. Team, what drove your decision to guide on revenue? And secondly, is your revenue guidance provided in such a way that we can expect potentially beaten raises throughout the year?
So just trying to gauge whether you're giving a more conservative, more accurate, or more aggressive type of guidance here. Thank you. Thanks, Andrew, and thanks for the kind words. This is Sharon, and I'll start, and then I'll turn it over to Mark. Obviously, we're giving guidance now because we're confident in our trajectory in what we've seen with our very strong launch for Kaplita.
So that's the overall statement, and then rather than stealing marks under what I asked for to comment further, and then maybe I'll come back if there's anything else to add. Yeah, sure. Sharon, and thanks for your question, Andrew. Yeah, to pick up where Sharon left off, what we've been seeing with caplite is we've been consistently increasing both the breadth and the depth of caplite of prescribing.
with a sub-take today and it supports a trajectory that you've seen throughout the course of the year. We strongly believe that there's still plenty of room to grow for a lot of the reasons that we talked about in our prepare remarks. These are large patient populations. We have a large prescriber base with tens of thousands of prescribers and a significant remaining unmet need. And so we've taken some steps in 2023 that I detailed in the prepared remarks.
to invest behind the brand to really fuel this growth further. And I'd say that we have a strong belief and a high degree of confidence that will continue to experience this robust growth this year. Thank you, one moment for our next question.
And our next question comes to the line, a Brian Abrahams from RBC. Your question, please.
Hey, good morning. Thanks for taking my question and my congrats as well on all the progress. Maybe another question with regards to your cap lighted guidance. Can you talk a little bit more about maybe some of the puts and takes within the guidance and the different ends of the range? You mentioned gross genetic expectations, but also wondering, I guess,
what the guidance contemplates with regards to additional demand growth, any changes in the overall dynamics with additional generic entrance and just I guess curious the scenarios that would steer you that would I guess fear towards the low end versus the high end of the range.
Mark, do you want to take that? Yeah, I think Brian , it's simply looking at the trends that we've had today with the bipolar launch and an expectation that those trends will continue throughout 2023. We've said before and we continue to believe that the generic countries of L'Razadone from Latouda
should not have a significant impact on capillighta. Historically in this category, when products go generic, the remaining branded products are not significantly impacted. So, for example, when a bellify in CERRIC well, when generic, the growth of Braylar and Latuda was not impacted and they continued their growth trajectory. So we anticipate a similar dynamic with Laradadone going generic.
And then I think just the belief with the increased investment in our sales force, the continued investment in DTC and across our marketing mix that we feel that the trends should continue throughout 2023 and build especially towards the latter part of the year. Got it. And in terms of just the variance.
Yeah, I think it's just we don't expect the great deal of variance. We expect the trend to continue. And I think, you know, specifically with the incremental investments that we're making in the Salesforce as those and we just recently added them. So they literally are just out in the field.
And we'll see that continue to go as well as in the market access space. We've always had good broad access, particularly Medicare and Medicaid with over 98% with commercial. We've been at 85% through the balance of last year and more recently now have increased that to 90% which we expect to be implemented.
by the end of the month. So I think all of those things should drive real robust growth throughout the year. And I would just like to remind you, this isn't a variant. It's just telling you that we expect a momentum to build over the course of the year with growing revenue. It has to be built with increasing revenue.
As we go from quarter to quarter, obviously first quarter has some first quarter seasonal dynamics built in and then less so in the second quarter and then building further into the third quarter and fourth quarter.
Thank you. One moment for our next question. And our next question comes from the line of Jessica Faye from JP Morgan Chase. Your question please. Hey guys, this is not Sun on for Jessica. Congratulations on the fantastic guide.
Could you provide your latest expectations on when we can hear the top line results from the adjunctive MDB trials? Can you talk about, give us a little bit color on the reasoning for starting another adjunctive trial this year? Thank you. Thank you.
Yeah, sure. This is Sharon and I'll start in an LF, because we're actually, if you want to add, we guided you to a filing of an S-N-D-A in 2024 for our, a junk of MDD. And that's based on studies 501-502-M503. We have said that I think was your other question.
Just repeat your other question for me, please. Certainly one moment for our next question. Our next question comes from the line of Omar Rafat from Evercore ISI. Your question, please. This is Mike Diffuri and for Omar. Thanks so much for taking our questions and then to grasp on the quarter in progress. Two from a one clinical, one commercial. The clinical one regarding your.
depressed patients since they're already experiencing a partial response. Could we expect a greater placebo response in these patients? Just any thoughts on how to frame that? And the commercial questions regarding your guidance, it seems pretty conservative. At the high point in your guidance that as soon as roughly around 80 new prescriptions adds, added every week on average. Which seems pretty doable, I think. Since the beginning of the year, there's been around.
an average of 200 prescriptions added weekly. Just any thoughts along those lines? Thanks. So let's start with the commercial question. And I'll ask Mark, do you want to take that? And then we'll go to Suresh, or one of us will take the clinical question. Yeah, Mike, I don't know that I have much more to add.
And also on the critical question on placebo, I think all studies have placebo effects. I'm really not certain there would be any more or less here than any other study, but I'll ask the rest if he wants to comment any further.
Yes, good morning. These are different populations. One is the mixed feature study, the monotherapy study and the ageng to treatment study is subject to other anti-depressants.
And that is patients who have already partially responded to 100 percentthese are two different populations and there have several differences within the populations. Also that each individual study has its comes with its own set up issues, that is.
the patients, what kind of patients they are coming from, what concomitant medications they have been on. All these play a role in determining how the study reads out. So you cannot make comparisons between one study to another, especially when they are not similar designs when they are two different populations. And that's the reason why you have to look those in two different.
I said subscribe, individual studies. One moment for our next question. And our next question comes from Mark Goodman from SBB Lyric. Your question, please. Please.
Good morning. Can you give us a little more color on these Phase II programs for 1284, 80 agitation, 80 psychosis? How are these patients? Different in what endpoints you're looking at that will be different here and the anxiety one. And then just, Larry, just quickly, the sales reps that were added to 50 reps, are they getting added in 23 or any of them added in the fourth quarter? Thanks.
in three different indications. One, the first one is agitation in Alzheimer's disease. This is purely looking at patients who have agitation. It's common for Alzheimer's patients to have behavioral symptoms, both agitation and psychosis, but they are...
different indications and they have different endpoints. So the first study we would be looking at is the agitation part of the study and regarding the details of the endpoints and the study designs as we come closer to starting the trial, we will let you know.
In terms of the next indication that is talking about psychosis in Alzheimer's disease, that endpoints are so different from maybe basically looking at psychotic symptoms within the Alzheimer's patients.
who have Alzheimer's disease and that study also is going to start this year and the GAD is generalized anxiety disorder and there has been as we have indicated in our call that there is lot of treatment failures and patients only respond partially to some of the other beiden.
and there is still an unmet need in this population and adding the straw to those populations will help with treating the anxiety symptoms and there is a big unmet need and the details of all of individual designs of the studies will be communicated once the study is closer to start.
Thank you. One more for Mark. Yeah, Mark, I can answer the sales representative timing question. All of the representatives were brought on in 2023, so they had start date in a couple of waves in the latter part of January and pretty much for the month of February have been onboarded and getting trained up and only recently in the last week or two have they been out in the field.
a third adjunctive MDD study and why they should try to read out of the ones that are ongoing.
to move ahead and seek sort of registration on the seek approval in that indication. You're indicating the past that data will drive for the discussions of the FDA. What I'm trying to understand.
You think that maybe at least then the had run of study, but then they did not end up getting approval. It appeared to us that the bar was probably high to seek an approval and that patient subset. So we would be great to get your thoughts on that.
Okay, I don't know if the rest do you want to start and then I can chime in. Yes, regarding the first question you asked about why starting the third study. In deciding when to start the third study.
When you look at the landscape, including how many studies are being run right now and what countries they are running and what are being conducted, we believe this is appropriate time to initiate this study. And major depressive disorder in objective treatment is a great near term opportunity. Similar to our clinical development strategies followed in our other more disorders program, for example, the bipolar depression program, it is proven to add additional trials. It is a good decision and it highlights.
our commitment to expanding apply time in that invitation. In terms of the second question about the mixed features.
As we have indicated, the readout of the study we were expecting in this quarter and the readout will depend on how strong the results are. As we have indicated in the previous times, it depends on what the results show and we will have to go to the FDA and discuss present of data. That's what we have indicated to the FDA. Once we go and discuss based on the results, we will know the next path. I want to also remind that there has not been a path established for approval in mixed speeches.
some other company doing this study and not having an approval, I cannot speak to that because I don't know how many auditions were made internally.
Thank you very much. Thank you one moment for our next question.
And our next question comes to the line of Charles Duncan from Canter. Canter, your question, please? Yeah, from Canter. Thanks, Sharon and team, for taking our question and congratulations on a transformative year last year. I think these are...
or this is a commercial question with two parts. One is actually related to last question in terms of the mixed feature readout and strategy. We recently conducted a KOL call that suggested, the KOL suggested that even a data publication would be picked up by prescribers. And I know that you would market off label, but do you think that the label could
encompass prescribing in mixed features, patients. And the second part is, what are you doing to prepare for the coming wave of muscarinic modulators as monotherapy in schizophrenia? Or do you think that that's a non-event for your commercial franchise?
Mark, do you want to start or do you want me to? What, why don't you go ahead and start and I'll add some color next to your chair. Okay, I'll start with the label and I think that really what we need to do and you're right, we do not promote anything off label. So what we would do is we're going to wait and we're going to see the data.
And we are going to go to the FDA with the data and assuming that it's very good, which we're, of course, hopeful for, that might guide us towards a particular path. We will publish the results. And again, we're hopeful that the data is very good and physicians can read the papers. And I guess on—
I think it's a little premature to talk about and come to on-label expansion based on these results because we don't know the results. On the muscarinics, I don't think, again, our first approval was in schizophrenia. Our next approval and the direction of the company is schizophrenia is important, but mood disorders are much larger populations than the indications that we are moving in with our expansion. We do think that
So we do think that anything that's approved for patients with schizophrenia is a good thing. We look for anything that can help patients. Remember, patients cycle through all of these drugs, and we would look forward. We don't expect there to be any negative impact on us at all. First of all, they're still in the future. But we...
step up and really is sustained sales growth contingent on this sort of level of investment or, you know, is there a possibility as we get into 2024 where you can level off that investment and really kind of leverage this big step up in selling and marketing investment that we've seen in the last two years. And then.
You know, they look at like 2022, half of the script growth came from nurse practitioners, roughly. And so it's a broader trend we see in mood disorder drugs in general. So just wondering if there's a connection at all to this sort of dynamic and in the step up and selling and marketing investment. Yeah, I can take that, that Sharon. Yeah, so when we made the decision to expand the sales force, what we were seeing is very strong demand for capillight a very positive reception in the marketplace. And as we analyze the data, we saw there was an opportunity to continue to fuel incremental growth. We've been pleased with the growth that we've been seeing.
But as we always do with all of our investments, we are good stewards of the investment dollars that we have, and we always look for opportunities that might yield even incremental growth for us. And so, in adding these 50 additional neuroscience specialists, what it will allow us to do is more frequently connect with high-volume prescribers and also expand our reach deeper into our target audience. And you mentioned NPs and PAs, and we would agree with you, certainly over the last couple of years.
Question?
And our next question comes from a line of David Anceland from Piper Sandler. Your question, please.
Hey, thanks. So I wanted to ask you about LAI, Lumetepyrone, and get your thoughts behind the rationale there. My understanding is that the LAIs are primarily in the schizophrenia and bipolar, more mania populations.
As you're leaning more and more into depression, by forward depression and then MDD, how do you think about the significance of an LAI form, even the tepora, and I guess in the grand scheme of things in your pipeline, how important is it? Thank you. Sure. Thanks for the question. I'll take that. So I think that when we started looking at an LAI, we didn't have all the data that we have now as to...
kept light of safety and tolerability profile and which as you know has turned out to be very good. So we are developing an LAI. We don't expect it to take over 50% of the population because of the fact that our oral drug is
has such a great efficacy and safety and tolerability profile. However, we do think that it's an option for patients and can be an important option for some patients who either are not compliant to once-a-day dosing or who simply just don't want to take the drug.
So we think that it's nice to have. We don't think that, again, that it's going to take over our oral franchise. We are also in our development profile, though we are seeking not only a one-month delivery, but we're seeking longer period of time, a two-month delivery. So hence, we're delivering where.
developing a product that could be useful in both one and two months delivery. Okay, Sharon, can you say if it's a sub-Q or an intramuscular? I don't know if you've ever mentioned that. I have mentioned it. The phase one study that we did was a sub-Q. We've been looking at other ways of administering the drugs, so we are looking at both sub-Q and I am.
And so, and it turns out from a patient perspective, it isn't, it really depending upon your formulation. Sometimes they like one over the other, but patients don't seem to mind and I am injection, so we're looking at both sub Q and I am.
Thank you. Thank you one moment for our next question. And our next question comes to the line of Greg Cendronavia from Mizzou. Your question please.
Thanks, good morning. Thanks for taking the questions and congrats on the progress. I've got two pipeline questions. My first just has to do with the mixed features study that we're about to get data for. And my question is just given the trial design where you do have madras as an endpoint, and given that it's likely to be mainly MDD patients or many MDD patients in the study, is there a possibility that you could consider or you could propose to the FDA at this?
and I'll turn it over to Suresh. So the start of a new study is prudent. It is simply the way the CNS trials are run. It's the way we've conducted our other programs. We did this in bipolar. We did it in schizophrenia. You see every sponsor.
conduct several trials within an indication. So I don't think there's anything, you know, any magic here, anything special here. I think we always think it's prudent to have several shots on goal. And so we thought it prudent to start another battle. And into the timing of the study, you look around at the different countries you look at, you know, how many other studies are ongoing.
And we thought that this is the right time to do this, hence the start of the study. And Sresh, did you want to take the other part of the question? Yes. Question. I think the first question was about the mixed features can that be used as a MDD study? So the mixed suite of study is designed, especially.
with two populations. We have the bipolar depression population and we also have the major depression population that is the unipolar depression. So we have approximately, you know, similar patients between each group and also this patient population has been enriched for mixed features. So we use the diagnostic features of DSM-5 specifically endowed patients only who meet the criteria for mixed features. So it would be difficult and if not, I don't think that it will be...
agreeable, but they have to use that as a MDD study. No, I would we want to. These are patients with mixed features in each of these patients' populations. Yeah, in the population. Right. And just to tell you, I mean, obviously we don't have any of the results yet, but the way the study was designed patients were stratified so we should have roughly equal patient populations in the bipolar and in the MDD patient populations.
indicates that patients are not specifically treated for mixed features, at least not extensively. And this would require some sort of like indication establishment. I want to understand if you think differently and can you provide any kind of an example of their psychiatric indication went through what's in the path when it was under treated to begin with and became a bigger market eventually. Thanks.
We may need for you to I, you blanked out on me a couple of times. I couldn't hear what you were saying. I don't know if anybody else could hear at all. I heard the first part of the question sharing on DTC. I could start there if you'd like. Sure.
So, yeah, hi, we did recently launch the next iteration of what we call our lead in the light. ETC campaign. This is a broad national campaign that we're implementing. We're implementing it through television ads, digital platforms, social media platforms.
All with the intention of seeking to continue to raise awareness of the very significant unmet need, both in bipolar 1 and in particular bipolar 2 depression and educate patients on the potential benefits of catholite. And yes, we agree. We're seeing the same positive metrics that you're seeing, which is the reasoning behind continuing the campaign and evolving it and building upon it our media.
is successfully targeting and reaching the bipolar depression audience. We know that from the metrics we're looking at. When we're on air, we drive substantially more visitors to our website looking for information about capillaria and bipolar depression. And also on the back end, when we survey physicians, an increasing number of physicians are reporting an increasing number of patient requests for capillaria. And we would expect this to increase as our ad continues to air. So yes, we've been pleased with the campaign. We're seeing the positive metrics.
And that led to the decision to continue it. I don't know. I can turn it over to Larry. I don't know if Larry has a comment on the spend. We don't typically specifically talk about the components of our selling and administrative spend. But Larry, I don't know if you have any comments that you'd like to add to that. Have nothing to add to that. Okay. And then Ash, we're going to have to ask you to repeat. I know you had a bunch of questions in there. I'm sorry. I guess none of us could understand what was being asked. So if you could ask it again, please.
So, yeah, just on mixed features, this is feedback that you've heard from physicians that patients are not specifically treated for this indication, at least not extensively. Do you agree or disagree to that and any example that you can give on other psychiatric indications that went through a path of being under-treated to becoming a bigger market? Sure. So, I would agree with you that I do think that many psychiatrists do understand mixed features and see patients and treat those patients with, you know, whatever they think might be beneficial that's currently available. But you're right, there is no label for it.
Until the DSM-5, MDD with mixed features wasn't even specified, and bipolar depression was a much looser definition. So DSM-5 has allowed physicians to see a tighter definition and to be...
more educated. We agree with you that it is an education process just like bipolar 2. You know, physicians see bipolar 2 patients. They know it when there's nothing to treat patients with. It's more difficult. So having the label for bipolar 2 is very helpful to physicians. And we would look forward to educating on this.
indication as we go forward. So we think there's a lot of opportunity here for education and to expand the awareness of the disease. I think Bipolar II is a great example where it's now quite well defined with only a few treatments.
I don't know, Suresh, if you have any other examples off the top of your head. Other examples, not exactly the same, but at least something closer to that would be if you think about psychosis in Parkinson's disease, there was nothing approved, but one study there that took off. Similarly, how did this Kinesia, the market that, you know, inure kind has done extensively well with, again, they have done a lot of.
educational campaign to highlight that importance of that. Those are great points, Erash. Thank you. Okay, operator, I think that it's time for us to wrap up. One more question? Certainly, then, one moment for our final question. And our final question for today comes from Alina, Korean Jenkins from Goldman Sachs. Your question, please. I will put a one for current. This is a couple for us. I believe it by the dream to the miss 30 range between my needs fee, but was.
I can't give any more granularity to that. Got it. Okay. Thanks. And on this second question was that for MBD data could it come as early as your end or should we expect that in 2024? So what we've said on the MDD is that we expect to file in 2024. And that's I think the guidance that we're giving. Thank you.
Go ahead, okay, thank you. Okay, operator, I think with that, it's time for us to wrap up. And we thank everybody for joining us today. We think 2022 was a terrific year for us and for the launch of Camp Leida in bipolar depression. We look forward to more progress this year in 2023 and we look forward to update you on a quarterly basis.
So thanks everybody for participating and operator you can now disconnect. Certainly thank you ladies and gentlemen for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.