Intra-Cellular Therapies - Q2 2024
August 7, 2024
Executive Summary
- Q2 2024 total revenues were $161.4M, with CAPLYTA net product sales of $161.3M (+46% YoY), and net loss of $16.2M ($0.16 EPS); management raised FY2024 CAPLYTA sales guidance to $650–$680M, increased SG&A guidance to $480–$510M, and lowered R&D guidance to $210–$230M.
- CAPLYTA prescriptions grew 36% YoY and 10% sequentially; the company is adding ~150 sales reps in Q3 to expand reach in primary care, with most impact expected in 2025.
- Positive Phase 3 results in MDD (Studies 501 and 502) underpin plans to submit an sNDA in 2H 2024; management emphasized robust efficacy, favorable safety, and early-onset benefit.
- CMS Specified Small Manufacturer Exception status implies minimal Part D phase‑in rebates near term; CFO transition announced with Sanjeev Narula joining Aug 12, 2024.
What Went Well and What Went Wrong
What Went Well
- CAPLYTA continued strong uptake: net product sales reached $161.3M (+46% YoY); “We are very pleased with the strong performance of CAPLYTA during the second quarter” — Sharon Mates (CEO).
- MDD Phase 3 success: Lumateperone met MADRS primary endpoint with LS mean differences of −4.9 and −4.5 vs placebo, p<0.0001; key secondary endpoints (CGI‑S, QIDS‑SR) also positive; safety/metabolic changes similar to placebo.
- Raised FY 2024 CAPLYTA sales guidance to $650–$680M; management highlighted durable demand and expanded primary care reach driving growth.
What Went Wrong
- Profitability still negative: net loss was $16.2M and EPS $(0.16), reflecting continued investment and higher SG&A; loss from operations was $(27.7)M.
- Operating expenses increased YoY: SG&A $121.6M and R&D $56.2M vs $101.0M and $49.8M in Q2 2023, tied to commercialization and pipeline progress; SG&A will rise further with sales force expansion.
- Seasonality likely to temper Q3 momentum: management flagged typical summer seasonality with stronger Q4, guiding expectations accordingly.
Transcript
Operator (participant)
Good morning, ladies and gentlemen, and welcome to Intra-Cellular Therapies' second quarter 2024 earnings conference call. At this time, all participants are in a listen-only mode. A slide deck that you may find helpful while you listen to this call is available on the Investor Relations section of the company's website. After the speaker's presentation, there will be a question-and-answer session. To ask the question during this session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to turn the call over to Dr. Juan Sanchez, Vice President, Corporate Communications and Investor Relations. Sir, you may begin.
Juan Sanchez (VP of Corporate Communications and Head of Investor Relations)
Good morning, and thank you all for joining us on our second quarter 2024 earnings call. Joining me on the call today are Dr. Sharon Mates, Chairman and Chief Executive Officer. Mark Neumann, Chief Commercial Officer. Dr. Suresh Durgam, Chief Medical Officer. And Larry Hineline, Chief Financial Officer. During today's call, we will be making certain forward-looking statements. These forward-looking statements are based on current information, assumptions, and expectations. Those statements are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. We caution not to place undue reliance on these forward-looking statements.
These statements are made only as of the date of this conference call, and the company disclaims any obligations to update such statements. I will now turn the call over to Sharon.
Sharon Mates (Chairman and CEO)
Thanks, Juan. Good morning, and thank you for joining us today. We are pleased to report our strong progress in Q2. In addition to Caplyta's impressive growth trajectory, during the quarter, we announced robust positive results from our two phase III clinical trials in major depressive disorder, or MDD. These results form the basis for an expanded label for Caplyta, and we are on track to submit a supplemental NDA for Caplyta for the adjunctive treatment of MDD later this year. In addition, we continue to advance our broad development pipeline, which I will discuss later. We are very pleased with the company's progress. Our vision has been to establish Caplyta as a first choice treatment across multiple depressive disorders, and we are well on our way to achieving this goal.
Caplyta has already become an important treatment option for schizophrenia and bipolar depression, and we now have generated strong efficacy data and favorable safety and tolerability data in our phase III studies in MDD. Pending FDA approval, we are confident in Caplyta's potential to become a leading medication for the treatment of MDD and a commercial success in this large market. This confidence is bolstered by our proven commercial capabilities and our strong financial position. Before discussing progress with our pipeline, let me list highlights of our second quarter financial performance. In the second quarter, Caplyta net product sales increased to $161.3 million, representing 46% growth versus the same period in 2023. The uptake of Caplyta remains strong, and we look forward to continued growth.
Consequently, we are increasing our Caplyta net product sales guidance range for the full year 2024 to $650 million-$680 million. As we continue to maximize Caplyta's opportunity in bipolar depression, we plan to expand our reach in primary care during this quarter. Mark and Larry will provide further details on our expansion plans during their remarks. I would now like to further discuss our adjunctive MDD program. Last quarter, we announced robust positive top-line results from studies 501 and 502. These studies evaluated lumateperone 42 milligrams as an adjunctive treatment to antidepressants in patients with MDD. We are particularly proud to have two global phase 3 studies with robust and consistent positive results.
Both studies demonstrated robust efficacy of lumateperone added to an antidepressant for the treatment of MDD in the primary endpoint, the MADRS total score, with a large separation versus placebo of 4.9 points in study 501 and 4.5 points in study 502, and a robust effect size of 0.61 in study 501 and 0.56 in study 502. In both studies, symptom improvement occurred as early as one week. Both studies also met the key secondary endpoint, CGI-S, and showed statistically significant efficacy in the patient's self-reported measure of symptom severity of depression, or the QIDS score. The favorable safety and tolerability profile for lumateperone in these studies was consistent with our other Caplyta studies. We previously described the metabolic profile of lumateperone in study 501.
We are now pleased to share the lumateperone metabolic profile in Study 502. Similar to Study 501, mean changes in key metabolic parameters, including glucose, insulin, triglycerides, and total cholesterol, including LDL and HDL cholesterol, were similar between lumateperone and placebo. Importantly, mean changes in weight were also similar to placebo. Our team is currently preparing our supplemental NDA submission, which we expect to file with the FDA later this year. We look forward to sharing additional results from Study 501 and 502 with the medical community this fall at upcoming conferences, including ECNP and Psych Congress. The opportunity for Caplyta in MDD is sizable. Current antidepressant therapies do not adequately address depressive symptoms in more than half of patients receiving treatment. We believe these patients deserve new treatment options.
Depression now represents about 30% of all antipsychotic prescriptions in the U.S., similar to the percentage of antipsychotic prescriptions generated for bipolar disorder. We are very excited about the possibility of bringing Caplyta to patients with MDD and believe its efficacy, tolerability, and safety profile, coupled with its convenient dosing, have the potential to make it a first choice for adjunctive treatment of MDD. We continue to invest in lumateperone's development with the objective of helping a greater number of patients. To that end, our pediatric program is underway. This pediatric program 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. Currently, pediatric patients have limited treatment options.
There are only two antipsychotics 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. These treatments are associated with treatment-limiting side effects. Given the characteristics of this patient population and Caplyta's favorable profile, we believe Caplyta may play an important role for this patient population. In addition, we have initiated two phase 3 studies evaluating lumateperone for the acute treatment of manic or mixed episodes associated with bipolar one disorder, commonly known as bipolar mania. Our adult bipolar mania program is the result of an agreement with the FDA in connection with our lumateperone pediatric exclusivity program. This agreement provides that pharmacokinetic studies in adolescents and children, together with bipolar mania studies in adults, would be sufficient to satisfy our obligations with respect to obtaining pediatric exclusivity.
Completing the overview of our lumateperone programs, we continue to advance our long-acting injectable lumateperone program and expect to initiate phase 1 studies with several formulations shortly. I also want to share updates on other candidates in our pipeline. ITI-1284 represents the most advanced product candidate in our pipeline. I am pleased to point out that we recently initiated patient enrollment in our phase 2 clinical trial evaluating ITI-1284 for generalized anxiety disorder, or GAD, as adjunctive therapy to generalized anxiety medications. We also initiated patient enrollment in our phase 2 clinical study, evaluating 1284 as monotherapy for psychosis associated with Alzheimer's disease. We also anticipate commencing patient enrollment in our phase 2 program with 1284 for agitation in Alzheimer's disease shortly. These studies are large and designed as potential registration studies.
In our GAD study, we expect to enroll approximately 705 patients randomized to three arms, placebo and two doses of ITI-1284. The primary endpoint of the study is the improvement of anxiety symptoms versus placebo at week 6, as measured by the Hamilton Anxiety Rating Scale, or HAM-A. The key secondary endpoint is the CGI-S. We expect to initiate a second GAD study evaluating ITI-1284 as monotherapy later this year. In our Alzheimer's disease psychosis study, we expect to enroll approximately 370 patients randomized to two arms, placebo and a flexible dose of ITI-1284. The primary endpoint is to evaluate the efficacy of ITI-1284 versus placebo, as measured by change from baseline to the end of week 6 in the Behavioral Pathology in Alzheimer's Disease Rating Scale, or BEHAVE-AD, psychosis subscale score.
The key secondary endpoint is the CGI-S. Continuing with our pipeline, next year, we expect to report top-line results from our ongoing phase 2 study with lenraspodin in Parkinson's disease. The primary endpoint of the study relates to motor symptom improvements, and we are also exploring the effects of lenraspodin in cognition, a key non-motor manifestation of the disease, and measuring biomarkers of neuroinflammation to help inform next steps. ITI-1020, our second PDE1 inhibitor, is being developed for oncology indications and continues in a phase 1 single ascending dose study in healthy volunteers. Regarding ITI-333, our multiple ascending dose study and a positron emission tomography study are both ongoing. ITI-1549 continues to advance in preclinical development, and we expect to begin clinical testing in 2025.
ITI-1549 is a non-hallucinogenic psychedelic, which we now refer to as a neuroplastogen, that we believe lacks hallucinogenic and cardiovascular side effects associated with psychedelics. Certain neuropsychiatric diseases, including MDD and anxiety, are associated with loss of synaptic connectivity, primarily in prefrontal cortical regions of the brain. These drugs have the potential to restore lost functional activity. Therefore, ITI-1549 has the potential to be a safe, effective medicine with a novel mechanism of action that can be safely and conveniently administered to patients for the treatment of these disorders. In summary, we are thrilled with our second quarter results and progress with our pipeline. We are in a strong financial position, ending the second quarter with approximately $1.025 billion in cash, cash equivalents, and investment securities, and we have no debt.
Lastly, we are excited to welcome Sanjeev Narula as our Chief Financial Officer later this month. Sanjeev is a finance leader with extensive experience in the pharmaceutical industry, and I look forward to working with him as we continue to build on ITCI's success. You can read more about Sanjeev's background in the press release we issued earlier this morning. I also want to thank Larry for his significant contributions and wish him all the best in his well-deserved retirement. I'll now turn the call over to Mark to provide details on Caplyta's performance and our expansion plans. Mark?
Mark Neumann (Chief Commercial Officer)
Thanks, Sharon. Good morning, everyone. It's great to be with you today. Caplyta's strong performance continued in Q2 with robust year-over-year growth in total prescriptions of 36% and an acceleration in quarter-over-quarter sequential growth of 10%. Once again, Caplyta's quarterly prescription growth outpaced both the branded and overall antipsychotic market, reflecting its continued strong uptake and market share gains in bipolar depression. We have also seen significant strength in new-to-brand prescription, hitting new all-time highs several times during the quarter, which is a leading indicator of robust future growth.
This growth is being driven by increases in both the breadth of our prescriber base, which now stands at nearly 43,000 unique healthcare providers since launch, having added more than 3,600 new first-time prescribers in Q2, as well as an increase in the average depth of prescribing as healthcare providers continue to identify more and more patients who are appropriate for Caplyta treatment. The commercial opportunity for Caplyta within its current indications of schizophrenia and bipolar depression is large, with those two indications representing nearly 50% of the approximately 68 million annual antipsychotic market prescriptions in the U.S. An important dynamic in the bipolar market has been the increasing role of primary care in treating bipolar depression. Caplyta's broad label, which includes both bipolar one and bipolar two depression, provides us with an opportunity to expand our reach and educational activities with primary care physicians.
We believe Caplyta's clinical profile, including strong efficacy and a very favorable metabolic weight and movement disorder profile, coupled with once-daily dosing with no titration, will be beneficial attributes for these providers in treating patients with bipolar depression. To capitalize on this opportunity and optimize the growth of Caplyta in our base business, we are expanding our sales force by approximately 150 representatives during the third quarter of this year. Through this sales force expansion, we will be increasing our reach into this increasingly important prescriber segment and expanding our overall target audience to over 70,000. Once our new sales representatives are onboarded and trained by the end of the third quarter, they will promote Caplyta for bipolar depression in primary care offices.
It will take some time for these representatives to be fully optimized in their territories, so while we expect some positive effect in the fourth quarter this year, most of the impact will be seen in 2025. We have also made substantial progress in our commercialization planning for a potential label expansion in MDD, which would increase our total addressable market for Caplyta from nearly 50% of antipsychotic prescriptions for schizophrenia and bipolar depression to nearly 80% with the addition of MDD. To fully optimize the launch in MDD, we expect to further expand our sales team next year, and we will share more details of those plans with you as we get closer to potential approval by the FDA. In summary, we are very pleased with the continued adoption of Caplyta and are highly confident in continued growth in both the short and longer term.
I'll now turn the call over to Larry to further discuss our financial performance. Larry?
Larry Hineline (CFO)
Thank you, Mark. I will provide highlights of our financial results for the second quarter ending June 30, 2024. In the second quarter, net product sales of Caplyta were $161.3 million, compared to $110.1 million for the same period in 2023, representing a year-over-year increase of 46%. Our net sales grew 11% sequentially versus Q1 2024, primarily driven by increased prescription demand. Our gross to net percentage in the second quarter was in the mid-thirties and consistent with our guidance for the full year. We expect our gross to net percentage to be in the mid-thirties for the remainder of the year.
We believe underlying demand for Caplyta will remain strong, and thus we are re-raising our Caplyta full-year 2024 net product sales guidance range to $650 million-$680 million. Selling, general, and administrative expenses were $121.6 million for the second quarter of 2024, compared to $101 million for the same period in 2023. Research and development expenses for the second quarter of 2024 were $56.2 million, compared to $49.8 million for the same period in 2023. As Sharon and Mark described, we expect to increase our sales force during the third quarter to continue to maximize Caplyta's opportunity in bipolar depression, and as a result, we are increasing our full-year SG&A expense guidance range to $480 million-$510 million.
This increase is primarily the result of sales, marketing, and other expenses associated with our sales force expansion in the primary care segment in the second half of 2024. We are also reducing our full-year R&D expense guidance range to $210 million-$230 million. Our financial position remains strong. Cash, cash equivalents, investment securities, and restricted cash totaled $1.025 billion at June 30, 2024, compared to $499.7 million at December 31, 2023. This concludes our prepared remarks. Operator, please open the line for questions.
Operator (participant)
Thank you. Ladies and gentlemen, as a reminder to ask the question, please press star one one on your telephone and then wait to hear your name announced. To withdraw your question, please press star one one again. We ask that you limit yourself to one question and one follow-up. Please stand by while we compile the Q&A roster. Our first question comes from the line of Andrew Tsai with Jefferies. Your line is open.
Andrew Tsai (Analyst)
Hi. Good morning. Congrats on the strong quarter. Thanks for taking my question. So the first one is, as we think about your revised guidance range, do you expect scripts in Q3 to grow at a similar pace or even a stronger pace than what you saw in Q2? Or are you factoring in some potential slowdown due to summer seasonality, holidays, and vacations? And then secondly, for MDD, it's very clear you're preparing for that, potential approval and launch. So, the question would be: Would you expect the potential script inflection in MDD to be larger than what you saw in the bipolar depression launch, say, within the first 6-12 months? Thank you.
Sharon Mates (Chairman and CEO)
Great. Thanks, Andrew. Maybe Mark, do you want to take the first question and then you can also take the second, and then I'll chime in?
Mark Neumann (Chief Commercial Officer)
Yeah, sure, Sharon. So, Andrew, thanks for the question. As you know, our guidance has been increased for 2024, and we're confident in that guidance and in both the near-term and the long-term growth prospects for Caplyta. As you know from past years, typically, we see some summer seasonality during the third quarter, and then we have a stronger fourth quarter. So I would say that that's all factored into the guidance that we've provided for the year. And then in terms of our preparations for MDD, they are well underway. We do expect, if and when we get approved for MDD, that we will see a significant increase in the trajectory of prescriptions, similar to what we saw with bipolar depression.
I think if you look back at some of the recent launches in MDD, the kind of uplift that you get from a new indication in MDD is quite significant, and we would expect to see another inflection upon approval with MDD as well.
Sharon Mates (Chairman and CEO)
I think that covers both-
Mark Neumann (Chief Commercial Officer)
Sharon, was there anything you wanted to add to that? Yep. Okay.
Sharon Mates (Chairman and CEO)
No, I think that covers both of your questions, Andrew. So operator-
Mark Neumann (Chief Commercial Officer)
Yep.
Sharon Mates (Chairman and CEO)
Then we can move to the next question, please.
Operator (participant)
Thank you.
Andrew Tsai (Analyst)
Yep. Thank you.
Operator (participant)
Please stand by for our next question. Our next question comes from the line of Jessica Fye with J.P. Morgan. Your line is open.
Jessica Fye (Analyst)
Hey, guys. Good morning. Congrats on the results, and thanks for taking my question. First, with respect to the sales force expansion, can you just confirm what that will bring your total sales force size to? And what's the right way to think about the additional sales force expansion plan for next year? Could that be similar in size to this increase, larger, smaller? And then separately, the press release mentions that you received notice from CMS that Caplyta qualified for the specified small manufacturer exception under the IRA. Can you confirm what you expect that to mean for the product? Thank you.
Sharon Mates (Chairman and CEO)
Mark, I think this goes to you as well.
Mark Neumann (Chief Commercial Officer)
Yeah, sure. Thanks for the questions, Jess. Yes, in terms of the size of the sales force, we'll be adding approximately 150 sales representatives, so that will take us north of 500 representatives out in the field for us. Could you just repeat your second question on MDD, Jess?
Jessica Fye (Analyst)
Next, next year's expansion that you alluded to-
Mark Neumann (Chief Commercial Officer)
Yeah.
Jessica Fye (Analyst)
Should we think about it as similar in size, larger, smaller?
Mark Neumann (Chief Commercial Officer)
Yep. So, what I would say is we're excited about the commercial opportunity of a potential label expansion in MDD, and we will be looking to invest behind the brand at a level that we feel optimizes the launch and the growth prospects for the brand. As we've done in the past, we'll share more details of those efforts with you as we get closer to potential approval by the FDA.
Sharon Mates (Chairman and CEO)
And then you asked about what we put in the press release about being a specified small manufacturer and having that exemption. So we have that status. So, what it means is that we would be assessed minimal safe harbor in rebates, so we don't expect to have a big impact on the company, at all, at least until the end of the decade into the next decade.
Jessica Fye (Analyst)
Thank you.
Operator (participant)
Thank you. Please stand by for our next question. Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is open.
Brian Abrahams (Analyst)
Hey, guys. Congrats on the quarter. Thanks for taking my question, and congrats and best of luck to Larry as well. So I guess I'm curious, as we look to the presentations of the MDD data this fall, I'm curious the key things that you're looking to highlight to the community, and how we should be thinking about potential for an inflection once those data are in the scientific literature versus potential label expansion. And then I guess, as a follow-up on the label expansion, I'm curious, the key elements kind of that you're thinking about, as you build out commercial infrastructure, and what are the key elements towards achieving comparable share of voice to competitors?
Is it all about boots on the ground, or are there other important elements as well that you're considering strategically as you look towards next year? Thanks.
Sharon Mates (Chairman and CEO)
Great. Thanks, Brian. That's a lot of questions, so hopefully, we remember all of them. We'll try and take them one by one. Maybe, Suresh, would you like to start, talking about what we're going to be highlighting, to the medical and scientific community as we go forward?
Suresh Durgam (Chief Medical Officer)
Yes. In terms of the data from the two studies, we will be presenting at different conferences, starting, you know, this second half of this year, right now. And then we also have going to highlight the robust efficacy of the study, both studies, we have seen. In terms of what we have seen in an adjunctive setting, these are unprecedented results we have seen, and we'll be highlighting those. And also, the safety profile that we have seen, which was similar to placebo in key aspects for antipsychotics, mainly the cardiometabolic side effects, the prolactin issues, weight gain, all these things will be highlighted at conferences.
Sharon Mates (Chairman and CEO)
As well as what will be highlighted is the lack of movement disturbances as well-
Suresh Durgam (Chief Medical Officer)
Yes.
Sharon Mates (Chairman and CEO)
such as akathisia, parkinsonism, et cetera. And then, I guess, going to the label expansion, talking to what we'll be looking at in terms of sales force and how we will maintain our equal share of voice. Mark, would you like to address that?
Mark Neumann (Chief Commercial Officer)
Yeah, sure, Brian. When we think about achieving a comparable share of voice in an area, it's really across the whole promotional mix that we have, with the main elements being some of the ones that you cited. Certainly, the size and the activities of our sales force is an important one. Our activities around medical education and educating physicians on the profile of Caplyta. And then on the consumer side, maintaining a comparable share of voice in our DTC efforts and our digital presence. I think those are the three that are probably the main ones that we look at, but it really is across the whole promotional mix that we have.
Brian Abrahams (Analyst)
That's really helpful. Thanks so much.
Operator (participant)
Thank you. Please stand by for our next question. Our next question comes from the line of Jason Gerberry with Bank of America. Your line is open.
Dina El-Rayes (Analyst)
Hi, good morning. This is Dina El-Rayes on for Jason Gerberry. Congrats on the quarter, and thank you so much for taking our questions. We just had a couple on ITI-1284. Do you view the Rexulti launch as a representative comp for an atypical launching into the Alzheimer's disease neuropsych space? And be curious what your thoughts are on the challenges in displacing generics and the resistance to prescribing atypicals in a nursing home setting. And just, you know, how do you think lumateperone could win in a market with these barriers? Thank you.
Sharon Mates (Chairman and CEO)
So I'll start, and I'll then ask, Mark and/or Suresh if they wanna chime in. First, on the Rexulti launch, I think it's early days, and so I think what we're only seeing is exactly that. Sometimes these markets take time to develop, and there is a great medical need in these patient populations. I think that there is a large opportunity for a product with the right profile. I'd like to emphasize again, the safety and tolerability profile of lumateperone across every area where we have been investigating the use of lumateperone. So I think that we will see in larger studies whether the side effect profile we've seen in our early studies, whether this in elderly patients, that this again holds true as we are in larger patient populations.
I think then, maybe Mark, did you wanna add anything to that?
Mark Neumann (Chief Commercial Officer)
Yeah, I think you're exactly right, Sharon, and this is a launch that we're watching carefully and seeing how the market there evolves. I would reemphasize the point that Sharon made, that we believe it is still in the early innings for the use of antipsychotics in a chronic sense for agitation. And it takes some time for treatment paradigms like this to develop. So, I think the story still needs to be told there, and we're watching that very carefully.
Dina El-Rayes (Analyst)
Thank you.
Operator (participant)
Thank you. Please stand by for our next question. Our next question comes from the line of Charles Duncan with Cantor. Your line is open.
Charles Duncan (Analyst)
Hey, morning, Sharon and team. First of all, congratulations on a really nice quarter, and thanks for taking our questions. I had a question on regulatory strategy in adjunctive MDD. You may not answer it, but I was curious as to what indications you'll be seeking. Will it be adjunctive MDD alone, or would you include mixed features, or would you seek to just have that data in the label? And then I did have a question on 1284.
Sharon Mates (Chairman and CEO)
So I'm going to take that, and then I'll ask Suresh if he wants to add anything. So just to remind you, the clinical studies, the phase three program, was in adjunctive treatment of MDD. So you can assume that that is the label that we are going for. I think it's a little bit early for us to discuss any more about about the label other than that it's for the adjunctive treatment of MDD. Suresh, did you wanna add anything?
Suresh Durgam (Chief Medical Officer)
No. That's good.
Sharon Mates (Chairman and CEO)
Okay.
Charles Duncan (Analyst)
Got it. Then I did have a question on 1284, and it kind of dovetails into your lumateperone expansion. On 1284, use or study in generalized anxiety disorder, it seems to me that given that, that's often a comorbidity of depression, I'm wondering why you're not looking at lumateperone in that indication, and what it is about 1284 that you think suits it well for generalized anxiety disorder. And then on lumateperone, in terms of pediatric data, do you think that we could see some pediatric information in 2024 or in 2025?
Sharon Mates (Chairman and CEO)
Suresh, did you wanna take that, or would you like me to?
Suresh Durgam (Chief Medical Officer)
Yes. In terms of the last question about the pediatric indications you're talking about, so we have posted on ClinicalTrials.gov. These are pediatric studies. It takes little longer time than adults, so we will not be seeing the results in 2025, a little bit later than that. In terms of your question on looking at other indications for 1284, we are going to be looking at, we are constantly reevaluating new indications. Right now, our first indication, as we said, we started the GAD program in adjunctive program in GAD. We have also started the psychosis in Alzheimer's patients. We have indicated that we have announced that we are going to start soon the agitation program as well as the monotherapy in GAD. Other indications, stay tuned. We will, as we reevaluate, we will keep updating.
Sharon Mates (Chairman and CEO)
As we go forward, we will be announcing new studies, other studies that we'll be doing with 1284. So as Suresh said, just stay tuned. Have a little bit of patience. We'll tell you as soon as we get very close to or start enrolling those patient populations.
Charles Duncan (Analyst)
Absolutely. Thanks for taking the question.
Operator (participant)
Thank you. Please stand by for our next question. Our next question comes from the line of Marc Goodman with Leerink. Your line is open.
Marc Goodman (Analyst)
Morning, Sharon. Can you talk about how you're thinking about business development these days? And obviously, a massive sales force you'll have in a year with one product. Just curious how you're thinking about leveraging that sales force. And then just secondly, how are you thinking about Caplyta ex-US, and if there's any partnership arrangements that you're thinking about, and thanks.
Sharon Mates (Chairman and CEO)
Sure. So, we do look at BD opportunities constantly. And obviously, what would be terrific would be if we are able to find a product that fits into the present sales force. We continue to look for that. And then we have also moved to adjacencies. So far we haven't found sound products that we think fit the bill there, but we do continue to look. In addition, we look earlier, as you heard on this call today, we have a very, very robust internal pipeline. And while we progress that internal pipeline, we do also look to supplement it with external opportunities. So we look at all opportunities. Our head of external innovation is in charge of doing that, and we will keep you informed on our progress there.
Additionally, ex US, we continue to evaluate that. It is a landscape that has been rapidly changing, and so, we will keep you updated as we go forward in the ex US landscape as well. Thanks.
Operator (participant)
Thank you. Please stand by for our next question. Our next question comes from the line of Michael DiFiore with Evercore ISI. Your line is open.
Michael DiFiore (Analyst)
Hi, guys. Thanks so much for taking my question, and congrats on all the progress this quarter. Two questions from me. Number one, with regards to the MDD trial study 505, any plan to shut this trial down? And if so, how should we think about R&D spend throughout the balance of the year? And my second question is on ITI-1284, specifically the phase 2 anxiety trial. What's your powering and expectations for placebo response here, and how you're controlling for it, especially since the trial has two active arms? Thank you.
Sharon Mates (Chairman and CEO)
Maybe we wanna go in reverse, since that's top of our mind. Suresh, you wanna talk about the powering that we do? I can give you a very broad summary, and that's we always power our studies. Well, why don't I let Suresh take it?
Suresh Durgam (Chief Medical Officer)
Yeah. So these studies are powered, you know, as registration studies, so all of them are powered at 90% power. That's what we typically do. And in terms of controlling for placebo response, as we adjudicate every patient that goes into the trial to make sure that they actually meet the criteria, and there is different levels of that. And we do adjudicate each patient that is coming into the trial so that they have the correct symptomatology. And also, the severity also is there. And throughout the study, we monitor for, you know, any inconsistencies across different scales and things like that. So that we have done in other trials, and we'll continue to do that in this upcoming studies also.
Sharon Mates (Chairman and CEO)
I'll address the study 505. We are coming down the home stretch in our evaluation of what will happen, what will be the fate there. But why don't you just give us just a little bit more time, and we'll update you on the fate of 505. Then I think you had another question in there, but I'm not sure I remember it.
Michael DiFiore (Analyst)
No, that's it. Thank you very much.
Sharon Mates (Chairman and CEO)
Okay, great. Thanks.
Operator (participant)
Thank you. Ladies and gentlemen, in the interest of time, we ask that you limit yourself to one question only. Please stand by for our next question. Our next question comes from the line of Jeff Hung with Morgan Stanley. Your line is open.
Jeff Hung (Analyst)
Thanks for taking my questions. I guess for 1284 and Alzheimer's disease psychosis, can you just talk about your approach versus what others are doing for the indication, and then just your confidence in 1284 for, for AD psychosis? Thank you.
Sharon Mates (Chairman and CEO)
So, thanks for the question, Jeff. Maybe I take it you're referring to the scale that we're using. Is that correct?
Jeff Hung (Analyst)
I mean, partially, but then also just in terms of the, you know, candidate itself, you know, your confidence in that versus, you know, other competing approaches for treating AD psychosis.
Sharon Mates (Chairman and CEO)
Okay. Maybe, Suresh, would you like to-
Suresh Durgam (Chief Medical Officer)
Yeah.
Sharon Mates (Chairman and CEO)
Give just an overview.
Suresh Durgam (Chief Medical Officer)
Sure.
Sharon Mates (Chairman and CEO)
on what we're doing? That would be great. Thanks.
Suresh Durgam (Chief Medical Officer)
Yeah. So for psychosis in Alzheimer's, first point, based on the mechanism of action of the drug, we believe that based on its influence, its effect on the dopamine system, serotonin, and glutamate system, we believe that this will be effective in psychosis of Alzheimer's disease. In terms of the study itself, we have. This is a 6-week study that is going to be a 4 weeks of screening period, followed by 6 weeks of double-blind treatment and a follow-up period of 30 days. In terms of the study scales, we have picked the BEHAVE-AD psychosis subscale, which focuses mainly on the psychosis element of the disease, and it has 15, sorry, it says 12 items.
Seven items from the paranoid and delusional ideation domain, five items from the hallucination domain, and then we have a total score of 36. We also have a key secondary is CGI-S. That is the Global Severity Improvement in patients with psychosis in Alzheimer's dementia. All these are the design elements, and in terms of, again, I have indicated that in terms of the patients that get into the trial, we ensure that patients have the right diagnosis and also the right severity. And that is very key to the success of any clinical trial, to make sure that the patients have enough severity so that we can detect the change at the end of the study.
Operator (participant)
Thank you. Please stand by for our next question. Our next question comes from the line of Amy Fadia with Needham & Company. Your line is open.
Amy Fadia (Analyst)
Hi, good morning. Thanks for taking my question. Maybe just with, with regards to ITI-1284, what doses will you be evaluating across the three indications? And what's your rationale for evaluating two doses, as well as a mono and adjunctive treatment in GAD? And maybe just to follow up to the previous question on Alzheimer's disease psychosis. You explained the endpoint that you're using, but why do you believe that that is the appropriate one for ITI-1284 versus what some of the other companies are using? Thank you.
Sharon Mates (Chairman and CEO)
So I'm gonna start because I need, and this goes to Jeff's question as well. I need to understand a little bit better. There are a few different studies, but very few. So I think we have chosen our parameters after interactions with the FDA, and conclusions about the best study, the best design for our studies, in which includes the best scales to use, or the appropriate scales to use, as well as the different doses that we're doing. So that's why we say we think we have early evidence of safety, of efficacy with different doses, and so now we're testing them. You get a lower range, you get an upper range, and that's the reason for choosing two doses. I don't know.
Suresh, do you want to add anything?
Suresh Durgam (Chief Medical Officer)
No. And yeah, the scales, you know, definitely this scale, as we have, you know, you have indicated that this was based on discussions we had with the agencies.
Sharon Mates (Chairman and CEO)
If there's another question about the trials that we're missing, maybe you could let us know, and we can try and address it.
Amy Fadia (Analyst)
Just with regards to GAD, the thought process behind evaluating it both as a mono and adjunctive therapy. Thank you.
Sharon Mates (Chairman and CEO)
We think it's appropriate. As you know, there are very few drugs that are approved for GAD, and there are a few clinical studies ongoing. And we think that there's an opportunity for a drug with a good tolerability and safety profile, as well as demonstrated efficacy. So I think that's why both a monotherapy and an adjunctive therapy.
Amy Fadia (Analyst)
Thank you.
Operator (participant)
Thank you. Please stand by for our next question. Our next question comes from the line of Joseph Thome with TD Cowen. Your line is open.
Joseph Thome (Analyst)
Hi there. Good morning, and thank you for taking my question. Maybe on the, what proportion of bipolar depression patients are treated by primary care physicians, just to get a little bit of an idea of, what growth you could see from this expanded sales force? And was the expansion related to something that you're seeing, in the field specifically, or was this, because of the MDD trial or just a normal cadence of launch? Thank you.
Sharon Mates (Chairman and CEO)
Mark?
Mark Neumann (Chief Commercial Officer)
Yeah, yeah, I can take that, Sharon. Thanks, Joseph, for your questions. So the primary care, as you said, is playing an increasingly important role in the treatment of bipolar depression, and we believe that they account for about 25% of all the prescriptions written for bipolar depression. So they play an important role. Psychiatry is still the main treater of the disease, but they play an important role, and that role has been increasing over time. And so for us, this was a couple things. Up until this point, our primary promotional efforts have been concentrated on psychiatrists and the nurse practitioners that support them. However, we've also been targeting a smaller segment of primary care that represents the highest volume prescribers in primary care, and we've actually had good success with the primary care physicians.
We've seen that Caplyta's broad label, including both bipolar one and bipolar two depression, coupled with the strong efficacy and favorable safety and tolerability, and the convenient once daily dosing with no titration is a very compelling profile for primary care treating patients with bipolar depression. So to fully leverage that growing opportunity, this expansion is allowing us to go deeper into primary care and extend our reach and frequency in this setting. And to your other point, yes, the robust results that we've seen in the two phase 3 MDD studies gives us a high degree of confidence in the long-term growth prospects of Caplyta and gives us increased confidence to invest in the brand today at an even higher extent for our base business in bipolar depression.
So for all those reasons, we believe now is the right time to be extending our reach into primary care.
Joseph Thome (Analyst)
Thank you.
Operator (participant)
Thank you. Please stand by for our next question. Our next question comes from the line of Graig Suvannavejh with Mizuho Securities. Your line is open.
Graig Suvannavejh (Analyst)
Thank you very much. Thanks, and congrats on the progress in the quarter, and congrats, Larry, on your retirement. Maybe, Sharon, this question is for you. It's a bigger picture strategy question. As you think about the pipeline that you have, which is, you know, quite extensive, and with increased investment in either additional studies with lumateperone or 1281, I'm sorry, 1284. I'm just trying to think about how you're thinking about some of the other programs, whether it be the 333 program or 1020 or the Parkinson's program, and kind of the interest in getting the data, but then either investing further in those assets or perhaps using those assets as opportunities to perhaps find a partner to offload some of the R&D spend in order to advance those programs.
Just philosophically, how you're thinking about the pipeline?
Sharon Mates (Chairman and CEO)
So first, thank you for acknowledging that we have a very robust pipeline, and we are very data-driven. So the first thing to do is get the data. And these early studies with ITI-1020 with ITI-333, which you didn't mention, but a program we're extremely excited about, ITI-1549. While they will generate extremely valuable data, they're your earlier phase studies, and they are less costly than your later stage programs. So I think the first thing for us to do is get the data and see if the data looks robust and is both in efficacy and also what the safety and tolerability profile looks like.
And we might, we'll make our decisions as to do we move it along alone, or do we move it along with partner, or do we not move it along based on data. This, this company was founded on data-driven events, and we continue to look at the science and drive our decisions based on data that we get.
Graig Suvannavejh (Analyst)
Okay, thank you.
Operator (participant)
Please stand by for our next question. Our next question comes from the line of Corinne Jenkins with Goldman Sachs. Your line is open.
Corinne Jenkins (Analyst)
Hi, this is Corinne Jenkins. Just one question from us. How are you thinking about the path to profitability from here as you sort of balance building out a commercial infrastructure and your R&D efforts against the backdrop of continued revenue growth?
Sharon Mates (Chairman and CEO)
Wait, I'm sorry. You came through very muffled. I could not understand any-
Corinne Jenkins (Analyst)
I, yeah, I couldn't either.
Sharon Mates (Chairman and CEO)
Can you repeat, please?
Corinne Jenkins (Analyst)
Sure, sure, I can go again. Is this, is this better?
Sharon Mates (Chairman and CEO)
Much better. Thank you.
Corinne Jenkins (Analyst)
Awesome. Yeah, I was just asking, how are you thinking about the path to profitability from here as you sort of balance building out a commercial infrastructure and R&D efforts against the backdrop of continued revenue growth?
Sharon Mates (Chairman and CEO)
I think we're asking if you're asking about our path to profitability and balancing it-
Corinne Jenkins (Analyst)
Mm-hmm.
Sharon Mates (Chairman and CEO)
-against R&D and our continued growth. Larry, do you want to take that?
Larry Hineline (CFO)
Yeah, sure. We haven't given any guidance as far as profitability. I mean, we feel, you know, we're very excited about the growth in scripts and the path that that's taking. We've given you guidance on R&D spend for the rest of this year. We intend to, you know, finance these R&D projects to the best of our ability. And so, having said that, we are focused on becoming profitable, but at this point, we can't give you any guidance. We'll keep you updated on the components of that as we go further.
Corinne Jenkins (Analyst)
Understood. Thank you.
Operator (participant)
Please stand by for our next question. Our next question comes from the line of Joel Beatty with Baird. Your line is open.
Joel Beatty (Analyst)
Thanks. For the next sales force expansion, is that something you're looking to do early in 2025 or later around the time of MDD approval?
Sharon Mates (Chairman and CEO)
Mark?
Mark Neumann (Chief Commercial Officer)
Yeah, so as I mentioned in my prepared remarks, we're very excited about the commercial opportunity of this potential label expansion in MDD for Caplyta, and we intend to invest behind the brand at a level that will help us optimize the launch and our longer-term growth prospects. As we've done in the past, we'll share more of those details, both in terms of the magnitude of the expansion and the timing of the expansion, as we get closer to potential approval by the FDA. So hang in there for a little while and we'll come back to you as we get closer to that launch.
Joel Beatty (Analyst)
Thanks.
Operator (participant)
Thank you.
Sharon Mates (Chairman and CEO)
I think we have time for one more question if there is one.
Operator (participant)
Our final question will come from the line of David Amsellem with Piper Sandler. Piper Sandler. David, your line is open.
David Amsellem (Analyst)
Hey, thanks.
Operator (participant)
Uh-
David Amsellem (Analyst)
Just a quick one from me on the bipolar mania program. Can you talk about how additive you think it is to the overall sales potential of Caplyta? Or maybe put it differently, I mean, what's the extent to which you're getting usage in patients who are manic? And just help us understand your rationale for doing that program and getting that into the label. Thanks.
Sharon Mates (Chairman and CEO)
Suresh, do you want to start and I'll chime in?
Suresh Durgam (Chief Medical Officer)
Yes, I can. We are looking at adults and pediatrics for any unmet needs that we have for drugs, for looking for any drugs with efficacy, safety, and tolerability needs. Coming specifically to your question on bipolar mania, we have an agreement with the FDA in connection with our pediatric exclusivity program. This agreement provides that the PK studies in adolescent and children, together with the bipolar mania studies in adults, would be sufficient to satisfy the obligations with respect to obtaining pediatric exclusivity. That is the reason we were planning and conducting these studies.
Operator (participant)
Thank you. At this time, I would like to turn the call back over to Sharon for closing remarks.
Sharon Mates (Chairman and CEO)
Great. Thanks, everybody. As you can see, I think we had a great quarter, and we're moving forward. We really look forward to an approval and a launch in adjunctive treatment in MDD, and to advancing all of our other programs. We thank you for your support and for listening, and we have great opportunities ahead of us, and we look forward to informing you of yet more progress from ITCI as we move forward. With that, operator, you can disconnect.
Operator (participant)
Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.