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spk45: Good morning, ladies and gentlemen, and welcome to Intracellular Therapy's first quarter 2024 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you would need to press star 11 on your telephone. You would then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to your speaker today, Dr. Juan Sanchez, Vice President, Corporate Communication and Investor Relations. Please go ahead.
spk53: Good morning and thank you all for joining us on our first quarter 2024 earnings call.
spk54: Joining me today on the call are Dr. Sharon Nates, Chairman and Chief Executive Officer, Mark Newman, Chief Commercial Officer, Dr. Suresh Dorgam, Chief Medical Officer, and Larry Heinlein, Chief Financial Officer. The slides to help guide today's call are available on the Investor Events section of our corporate website. I'm on slide number two. 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. You are cautioned not to place on due reliance on these forward-looking statements. These statements are made only as the date of this conference call, and the company claims any obligation to update such statements. I will now turn the call over to Sharon. Sharon will begin on slide four. Sharon?
spk16: Thanks, Juan. Good morning, everyone, and welcome to today's call. We are pleased to share our results for the first quarter of 2024 and to provide updates on our clinical studies. Our team continued to deliver strong growth for Keplida in our current indications of bipolar depression and schizophrenia. With the overwhelmingly positive top line results from study 501, we achieved a major milestone as we worked to expand Keplida's label into major depressive disorder and establish Keplida as a drug of choice for broad patient populations with mood disorders. I'll talk more about this in a moment, but first, let's start with our commercial performance. Our strong growth continued. First quarter total revenues increased to $144.9 million. As we preannounced, Cap Lida net sales increased to $144.8 million, representing a 53% growth versus the same period in 2023. We are pleased with our performance, and we are confident in the continued growth of Keplida. Consequently, we are reiterating our guidance for full-year Keplida net sales between $645 and $675 million. Mark and Larry will provide a more detailed picture of our performance later in the call. Let me highlight our most recent clinical development news. Last month, we announced robust, positive top-line results from Study 501, evaluating Lumetepirone as an adjunctive treatment to any depressants in patients with MDD. These results are shown in slides 7 through 10. In this adjunctive study, Lumetepirone met the primary endpoint of change from baseline at week 6 on the Madras total score versus placebo with an impressive 4.9 point reduction. The p-value was less than 0.00 0.01, with a robust Cones V effect size of 0.61. As you can see, statistically significant reductions in depressive symptoms as measured by the madras were seen at the earliest time point tested, week one, and these improvements continued throughout the course of the trial. Lumotepirone also met the key secondary endpoint of change from baseline on the clinician-rated CGIS with a p-value of less than 0.0001 and a robust effect size of 0.67. The CGIS also statistically significantly improved at the earliest time point tested, week one. In this study, we also included a measure of the patient's voice to complement the clinician-rated scales. On a patient-reported measure, the Quick Inventory of Depressive Symptomatology Self-Report Scale, or QIDS, patients reported robust reduction in their depressive symptoms. There was a robust reduction in symptoms with a p-value of less than 0.0001. We are very pleased that the patient reported improvements in depressive symptoms support the clinician-rated endpoints in this study. We continue to see a favorable safety and tolerability profile. Adverse events were similar to those seen in prior studies of Lumetepirone as a treatment for bipolar depression and schizophrenia. Today, we are pleased to report the results of additional safety information demonstrating that mean changes in key metabolic parameters, including glucose, insulin, triglycerides, and total LDL and HDL cholesterol were similar between Lumetepirone and placebo. Importantly, mean changes in weight were also similar to placebo. These strong results from study 501 underscore the potential for Lumetepirone to treat a broad spectrum of mood disorders. We have now shown Lumetepirone's strong antidepressant activity in patients with MDD as an adjunctive therapy, in patients with bipolar I and bipolar II both as a monotherapy and as adjunctive therapy, in patients with MDD and bipolar depression, exhibiting mixed features, and in patients with comorbid depression in our schizophrenia program. The results of Study 501, coupled with Lumetepirone's distinct pharmacology, reinforce our label expansion strategy and the long-term prospects for Lumetepirone across mood disorders. Our second Phase III trial in MDD, Study 502, has recently completed clinical conduct. We expect to report top line results from study 502 later this quarter. Subject to the results, we anticipate filing a supplemental new drug application with the FDA in the second half of 2024. MDD is a highly prevalent disorder with approximately 21 million adults affected every year thus presenting a large opportunity to expand on our already approved indications of schizophrenia and bipolar disorder. MDD accounts for 30% of the approximately 68 million annual antipsychotic market prescriptions. Therefore, as seen on slide 12, the total addressable market for Kaplida increases to approximately 80% of the annual antipsychotic market prescriptions with the addition of an MDD indication from nearly 50% with bipolar and schizophrenia indications. We are very excited about the possibility of providing a new treatment option for these patients. Let me now provide an update on our pipeline, starting with other Lumateparone programs. Our Lumateparone 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. Patient enrollment is ongoing in the open-label safety study, as well as in the double-blind placebo-controlled bipolar depression study. We anticipate beginning patient enrollment in the autism spectrum disorder studies in the third quarter of this year. Additionally, we continue to advance our long-acting injectable Lumetepirone with the initiation of Phase I studies with additional formulations later this year. We continue to advance our other pipeline programs, including 1284. ITI-1284 is a deuterated Lumetepirone and is an important drug candidate as we continue to build our neuropsychiatry franchise. This quarter, we expect to initiate patient enrollment in our Phase II clinical trial, evaluating ITI1284 as adjunctive therapy to anti-anxiety medications in patients with generalized anxiety disorder, or GAD. There are approximately 10 million diagnosed adults in the U.S. with GAD. It is important to note that about half of patients who receive treatment do not respond adequately to initial therapy. We believe ITI-1284 is well-suited for this patient population and could offer an effective, safe, and well-tolerated treatment. Also later this quarter, we plan to initiate patient enrollment in Phase II clinical study in psychosis associated with Alzheimer's disease, as well as a Phase II study in agitation associated with Alzheimer's disease. Our phosphodiesterase-1 inhibitor program includes lenrispotin and ITI-1020. Our Phase II study with lenrispotin in Parkinson's disease is ongoing, and top-line results are expected in 2025. Besides motor symptom improvement, we are exploring the effects of lenrispotin in cognition, a key non-motor manifestation of the disease, and measuring biomarkers of neuroinflammation to help inform next steps. Our second PDE1 product candidate, ITI1020, is being developed for oncology indications. We are currently conducting a phase one single ascending dose study with ITI1020 and healthy volunteers. I'd also like to give a quick update on our earlier stage programs. We're exploring ITI333 to treat opioid use disorder and pain. Our multiple ascending dose study and a positron emission tomography study are both ongoing. Finally, last year we introduced a portfolio of non-hallucinogenic psychedelics for the treatment of mood, anxiety, and other neuropsychiatric disorders. ITI 1549, the lead candidate, is advancing preclinical development, and we expect to begin clinical testing in 2025. A scientific poster describing the preclinical advancement of ITI 1549 will be presented next week at the Society of Biological Psychiatry annual meeting. In this poster, we further describe the novel mechanism of action of ITI 1549. We also demonstrate improvement in preclinical models of anhedonia and a reduction in symptoms of anxiety. We look forward to sharing this information following our poster presentation. We are in a strong financial position to maximize the opportunities ahead of us with CapLida, and we continue to build our robust pipeline. We ended the first quarter with approximately $477.4 million in cash, cash equivalents, and investment securities. In April of 2024, we received approximately $575 million in gross proceeds from our public offering of common stock. Additionally, we have no debt. I'll now turn the call over to Mark to further discuss this quarter's Kaplida performance. Mark?
spk47: Thanks, Sharon, and good morning, everyone. Kaplida's strong performance continued in Q1 of 2024 with robust year-over-year growth in total prescriptions of 39%, despite typical first quarter seasonal dynamics, as well as the industry disruption caused by the Change Health cyberattack that occurred during the quarter. Capillitis growth continues to be driven by a strong uptake in bipolar depression, where it has solidified its position as the first and only treatment option indicated for patients with bipolar I and bipolar II depression as monotherapy and as adjunctive therapy with lithium or valproate. We also continue to see steady growth in schizophrenia. We continue to expand our prescriber base, which now stands at more than 39,000 healthcare providers since launch. Physicians appreciate Capilet's proven efficacy, favorable safety and tolerability profile, and convenient once-daily dosing with no titration required. Beyond a compelling product profile, the team's commercial execution continues to be very strong. Our sales team is currently educating our prescriber base, which includes psychiatrists, nurse practitioners, and primary care physicians. Our sales efforts are complemented by a comprehensive marketing program, including extensive peer-to-peer medical education programming, digital promotion, and a broad national consumer advertising campaign delivered through television and social media. We're very pleased to have just launched a new consumer TV advertisement, which depicts the experience of people living with bipolar depression and the benefits Capuleta may provide them. We also continue to enjoy a strong market access position with broad access with over 99% of lives covered in Medicare and Medicaid and about 90% of lives covered in commercial. In early Q4 2023, Capilita gained unrestricted status on two of the largest Medicare Part D plans. We are pleased with the initial results of these changes and expect to see the full impact of these changes throughout 2024. As Sharon mentioned, the commercial opportunity for Capilita within its current indications is large and represents nearly half of the approximately 68 million annual antipsychotic prescriptions in the U.S. We will continue to invest behind the brand, build on our strong momentum, and fully optimize the current opportunity as we further penetrate the bipolar depression and schizophrenia markets. In closing, we are pleased with Capilita's strong performance. Keplida has a very compelling product profile, and we are well positioned for continued growth, both in the short term and the long term, as we work to establish Keplida as a first-choice treatment across mood disorders. We look forward to continuing to update you on the success of Keplida. I'll now turn the call over to Larry to further discuss our financial performance. Larry?
spk24: Thank you, Mark. I will provide highlights of our financial results for the first quarter ending March 31, 2024. In the first quarter, net product sales of Capilito were $144.8 million, compared to $94.7 million for the same period in 2023, representing a year-over-year increase of 53%. Our net sales growth in the first quarter was primarily driven by increased prescription demand and, to a lesser extent, higher inventory levels. Our gross net percentage in the first quarter increased to the mid-30s, consistent with our guidance. We expect our gross net percentage to remain in the mid-30s for the remainder of the year. We believe underlying demand for Capilata will remain strong, and we are reiterating our full-year 2024 Capilata net sales guidance of $645 to $675 million. Selling general and administrative expenses were $113.1 million for the first quarter of 2024, compared to $98.9 million for the same period in 2023. Research and development expenses for the first quarter of 2024 were $42.8 million, compared to $38 million for the same period in 2023. Our financial position remains strong. Cash, cash equivalents and investment securities totaled $477.4 million at March 31, 2024, compared to $499.7 million at December 31, 2023. In April 2024, we completed a public offering of our common stock, in which we sold approximately 7.9 million shares for aggregate gross proceeds of $575 million and net proceeds of approximately $543 million. This concludes our prepared remarks. Operator, please open the line for questions.
spk45: Thank you. As a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please limit to one question each. Please stand by while we compile the Q&A roster. The first question comes from Jessica Phi with JP Morgan. Your line is open.
spk07: Hey, guys. Good morning. Thanks for taking my question. So I was wondering, with the Demonstrated commercial track record and a robust balance sheet. I'm curious how you think about the possibility of adding another product to the bag and how you think about the right time to do that, i.e., if it's something you wouldn't want to do simultaneous with the MDD launch, for example, or if you think there is the organizational capacity to do both at the same time. Thank you.
spk16: Hi, Jessica. This is Sharon. Thanks for the question. So, yes, we're always looking for new opportunities. And as you said, with our robust balance sheet, that certainly allows us to contemplate opportunities that are marketed products. As to, I'll let Mark speak, but I know what he's going to tell you about. You probably don't want to launch simultaneously two new products. However, we do certainly have the bandwidth that we could stagger these and have two products in their launch phases simultaneously. Mark, did you want to add anything to that? And we're very excited to do that, and we keep looking for new products to add.
spk47: Yeah, no, Sharon. Yep, I think you've got it right. Certainly, we have the capacity and the capability of doing it. I think when you have a product as strong as Capilita, you want to make sure that the focus stays there and we continue to execute well. So, as we look at these opportunities, we look for strategic fits. We look for products that have compelling product profiles. and would be a good fit with the call points that our Salesforce currently has in their call universe. So we look at all those things and up until this point, we haven't found the right fit, but as Sharon said, we would certainly welcome another product into the portfolio and certainly have the capacity and the capability to do that.
spk45: One moment for the next question. The next question comes from Brian Abrahams with RBC Capital Markets. Your line is open.
spk36: Hi there. Good morning. Thanks for taking my question. I'm curious if you could talk about any initial KOL feedback that you received on the MDD data and where CapLIDA could potentially fit in. And I guess along those lines, I'm also curious how the top line MDD data may have impacted or may be impacting uptake in bipolar depression, if you're seeing any pull-throughs or sort of early shifts in use patterns there. Thanks.
spk16: Great. Hi, Brian. Thanks for the questions. And maybe, Suresh, would you like to start? I'll just give you an overall on the KOLs. It's been very gratifying to hear their responses and their enthusiasm. Suresh is at APA. I think he's sitting in some room off to the side right now. So maybe, Suresh, do you want to say whether you've had any further feedback and what your conversations with KOLs are like?
spk19: Yes. In terms of the conversations with KOLs, I have met several KOLs here at the APA, and the feedback on our data on 501 study is very, very positive. and also with the robustness of the data showing in all endpoints, both the primary and key secondary endpoints, and also the self-rated, patient-rated scale. So they were very happy to see the results and are looking forward for the second study.
spk16: And as to the uptake on if there's any pull-through, I think I'm not sure. Mark, are you comfortable speaking to that?
spk47: Yeah, sure, Brian. I think it's far too early to see an impact of the most recent results on prescribing, as you say, within bipolar depression. Typically, any kind of lift that you might get on your current indications usually comes after data is presented in the scientific literature. And I know Suresh and his team are working hard on that for future presentations of the data. But at this point, I don't think we've seen any kind of material lift in our existing indications from presentation of the data.
spk35: Got it. That's all really helpful. Thanks so much.
spk16: And just to say that we hope to be presenting the 501 data at medical meetings later this year.
spk45: One moment for the next question. The next question comes from Andrew Tsai with Jefferies. Your line is open.
spk38: Hey, good morning. Thanks for taking my question. Maybe on MDD, since we're one to two months away from second half 2024, is a Q3 filing a possibility after the second data set reads out or should the street be thinking Q4? at this juncture, and then in the scenario in which the second data set did look different, would you still look to file in second half, or is there a scenario in which you waited for the third data set later in 2025 before filing the SNDA? Thank you.
spk16: Thanks. I didn't write down your question, so I hope I remember all of them. So first, I think on our potential filing, later this year in the second half, what that would be. So we've said that our readout of 502 was going to be late in the second quarter. So you can anticipate that that most likely means June. So then you have to drop everything into shells that are being created and put all the data together. So when we say a filing in the second half, I would tell you Q3, is aggressive, not doable, but aggressive. So that's the answer to that question. And then you asked, oh, about what is our filing strategy. And I think, first of all, we need to see the data, which we will do soon. We do believe in the very robustness of our package as it exists now. So I think we are working very hard on timeline of we will be submitting our application in the second half of this year.
spk33: Great. Thank you. Thank you.
spk45: One moment for the next question. The next question comes from Charles Duncan with Cantor. Your line is open.
spk06: Morning, Sharon and team. Congrats on a strong commercial performance in the quarter as well as recent data. I had a two-part question. One is if CapLida is approved as adjunctive therapy in MDD, can you provide us a little color on what you would anticipate Salesforce sizing to be and if eventual demand for the product in that market could drive the franchise to profitability. And then with regard to 502, could you remind us of the sample in terms of it being comprised of number of patients from clinical sites other than from 501? Thanks.
spk16: Mark, do you want to take the first part and then Suresh the second part? Sure.
spk47: Yeah, sure. Hi, Charles. Yes, what we said in the past about Salesforce size with an eventual approval in MVD is that we certainly would expect to significantly increase the size of our Salesforce. As you know, currently, our Salesforce has a target audience of about 43,000 physicians, the vast majority of them being psychiatrists and the nurse practitioners that support them. So We have very good coverage of the psychiatry community. We do have a segment of primary care that we currently call on. Those are primary care physicians who are comfortable treating bipolar depression and are high-volume prescribers of antipsychotics for that condition. But as we contemplate an approval in MDD, the expansion would come by a much larger target audience within the primary care community. There aren't many more psychiatrists that we don't already call on for our current indications, but it would be for an expansion into primary care. As we get closer to the timing of a potential approval, we'll come back to you with more details about the specific size and timing that we would be executing against.
spk11: Okay.
spk47: And Suresh, I think there's a second part. Yeah.
spk19: Yes. In terms of the sample size, it's a very similar sample size for 502 compared to 501. And in terms of the clinical sites, there is no overlap of sites. But, however, we tend to include about 30% of patients coming from U.S. and about remaining coming from ex-U.S. sites.
spk15: So there's some contact overlap, but site overlap.
spk02: Yes.
spk16: Because you don't want to be competing with yourself when you're enrolling patients.
spk05: Got it. Makes sense. Thank you.
spk45: One moment for the next question. The next question comes from Mark Goodman with Learing Partners. Your line is open.
spk41: Yes, on ITI 214, can you remind us of the differentiation in this product and how you look to kind of break into the Parkinson's market, which is a tough market over the past decade for new products? And, Larry, could you also just tell us what the inventory change was in the quarter? Thanks.
spk16: Okay. Suresh, do you want to start with talking about 214?
spk19: Yes, 214, that is the hindospodin. We have an ongoing study in Parkinson's disease, and that is a proof-of-concept study. In that study, we are evaluating several things. One, evaluating the motor symptom improvement. We are also evaluating cognition measures as well as biomarkers for inflammation. So based on the data from that, we will decide on the next steps looking at the data we read from that. That study is a four-week study. The primary endpoint is the Hauser diary. We're looking for increase in on-time without troublesome dyskinesia. And the key secondary is the MDS-UPDR as part two, which measures motor aspects of experiences of daily living. And we also, as I indicated earlier, One of the things we're looking at is looking for biomarkers for inflammation in that study.
spk16: And to the second part on inventory, Larry, do you want to take that?
spk24: Yeah, sure. During this quarter, we experienced strong prescription growth that's continued over the last several quarters. And in this quarter, this prescription demand was the primary driver for revenue. There was, to a lesser extent, an inventory increase for this quarter, but the primary driver was Scripps.
spk42: Can you quantify the inventory change?
spk24: No, we've not given that sort of granular detail before, and it's difficult to do. Okay.
spk45: One moment for the next question. The next question comes from Umar Rafat with Evercore. Your line is open.
spk27: Hi, guys. This is Mike DeFiori in for Umar. Thanks so much for taking my question and congrats on all the success. Just two quick ones from me. Any updated thoughts on pursuing a monotherapy indication for MDD given Capilates' improved safety profile compared to second-generation atypical antipsychotics? I'm asking because Seroquel pursued this in the path and although it was efficacious, The FDA didn't approve the monotherapy indication for MDD due to CH concerns. And my follow-up is on the, I guess, separate follow-up is on the PDE1 program. Just a quick observation. Last quarter, they said the top line was expected in one-half-25. Now, this quarter, it's just 20-25. I was wondering if there's any sort of recruiting or trial delays on that front. Thank you.
spk16: Okay. Suresh, do you want to take that?
spk19: In terms of the... Yeah, you can start, Sharon, and I can... Go ahead. Okay. In terms of the study itself, the recruitment is slower, and we are... Wait a minute.
spk16: Wait, wait, wait. The 214, the first part of the question... was an update on monotherapy for MDD and that Seroquel did try for monotherapy. And as you correctly pointed out, Mike, that the FDA was concerned about their metabolic consequences, et cetera. I think that we're evaluating all of this and Obviously, as you know, there isn't the safety concerns that one sees with Seroquel with Lumetepirone. So we're looking at that. There are a lot of things to look at. It's also different times than when Seroquel was first approved. On the PDE program, recruitment has gone slower than we originally expected. thought that could be because of studies that are ongoing. It could also be because we try to ensure that we get in appropriate patients, et cetera. But we still are in 2025 in our timeline. So we've just left out saying first half, second half, or anything, which I don't think we had said before either. Maybe we did. I can't remember. So I think it is 2025 and also you're correct that or actually I think the speaker before you was correct in talking about that Parkinson's is a crowded market. But we think that we're getting or we should be getting some very good data on the use of these PDE1 inhibitors in neuro inflammation. And that should help inform us both on taking forward 214 and Parkinson's disease and in taking forward other molecules within the PDE1 space into several different arenas. With that Suresh, did you want to add anything else? I'm sorry, I didn't mean to cut you off.
spk19: No, in terms of the 501 study, yeah, the MDD program, that's true. That, again, we'll be looking at the data, and then we'll figure it out what to do next steps for the monotherapy.
spk28: Very helpful. Thanks so much.
spk45: Please stand by for the next question. The next question comes from Jason Gerbery with Bank of America. Your line is open.
spk50: Hey, guys. Good morning, and thank you for taking my question. On ITI1284, I'm not seeing this on ct.gov yet, but maybe I'm missing something, but just generally trying to get a sense, you know, how big are these trials, how many dose arms, are these going to be like 12-week treatment periods to get to proof of concept and figure out dose, and just trying to get a rough sense of timeline here ultimately. And then just as my follow-up, if I can squeeze it in, I didn't hear an update on mixed features. I think you guys were waiting for the minutes which tend to come like I think 30 days after the meeting. So just curious if there's a mixed features update. Thanks.
spk16: I'll start with the second part and then I'll ask Suresh to chime in on the first part. So we did update you on the mixed features and said that we would come back to you after our readout of 502. and as we continue to put together our strategy for mixed features in MDD. So stay tuned. Hopefully in the near future we'll have some updates for you on the mixed features. And I'll give you the short answer on 1284 is we will be posting these studies, we said, before the end of this quarter. And I'll leave it to Suresh to talk to you about the design and powering of these studies.
spk19: Yes. Regarding the 1284 studies, we have three programs right now. That is the GAD program, the psychosis in Alzheimer's disease, and agitation in Alzheimer's disease. The first study we will be starting is the GAD program. That is a fully powered study as a registration study. It's as an adjunctive treatment and it is sample size would be somewhere in the range of about 600 patients. It's going to be three arms placebo versus two doses. Again, the details once we start the trial soon in the next few we will be posting that online for the clintiles.gov. Similarly for the agitation and psychosis and Alzheimer's, those are Phase II studies but are powered as registrational studies. Those details also will be posted as soon as we start the studies. And they are intended to start in the second quarter. Thank you.
spk45: Please stand by for the next question. The next question comes from Sumant Kulkarni with Canaccord. Your line is open.
spk18: Thanks for taking my question. Sorry about the two-parter. So on the last MDD data-focused call, I know you requested me to hold off on this question until this update, so I'll ask it now. 1284, are you planning to specifically develop that product in the various subindications of depression? And on Lumetapirone for autism spectrum disorder, I'm asking because unmet need is high, how is the company thinking about dosing for pediatric patients? Is there a weight-based dosing paradigm, or will it be as simple as the product that's out there on the market right now in terms of logistics around dosing?
spk16: Thanks. Suresh, you want to take the second part, and then I'll need you to repeat the first part. Yes.
spk19: Regarding the second part about the autism for Lumotepirone, we are going to be starting those studies for irritability in autism. And regarding the dosing, we are looking at we have to first finish the PK studies for the lower age group between 5 to 10 years old based on the PK exposure levels that comes from that study, we will be deciding on the dosing for those patients. For patients in the upper age group, it will be similar to what it is in adults, for example. From 13 to 17, it will be similar to 42 milligrams. So the lower age groups we have to figure out by the PK studies.
spk18: Got it. And the first part was on 1284. We know you're developing it for Alzheimer's disease, psychosis, and agitation, and generalized anxiety disorder, but are there any specific plans to develop that within the depression context?
spk16: Yeah. Well, we are contemplating other indications within 1284, but let us get these studies started first, and then we'll come back to you with the other studies that we'll be doing. Thank you.
spk55: One moment for the next question.
spk45: The next question comes from Jeffrey Hung with Morgan Stanley. Your line is open.
spk48: Hi, this is Michael Rion for Jeff Hung. Thank you for taking our question. Thinking more generally about the results from study 501 versus 403, how important is it to get DSM-5 classifiers
spk16: into the label versus a more broad label like adjunct mdd i guess i'm just trying to ask what happens more regularly in standard clinical practice and to what extent do classifiers influence treatment decisions thanks so much so i think our broad label um is obviously what we always aim for and what we're doing is exploring um value of having anything you know, specific in any label that we have. And again, as we get the 502 readout, we'll come back to you with further updates on exactly what it is that our strategy is now and will be. Mark, did you want to add anything to that?
spk43: No, I think that's good.
spk16: Okay.
spk45: One moment for the next question. The next question comes from Greg Suvanavage with Mizuho. Your line is open.
spk37: Good morning, everyone. This is Charles Wayne, author of Greg. Thanks for taking our question. Given study 501 indicated a very strong placebo-adjusted effect size of 4.9, does the company expect to see similar efficacy in study 502?
spk16: Yeah, that was a point change. That wasn't the effect size. But the effect size was very strong as well. And I think what you're looking for, the studies are powered to show, actually this study was powered to show a two-point change. Because in adjunctive studies, typically you are at the lower end of the two to four point change in the madras that you're seeing. So I think we're very close to the data. We hope very much that we have as strong a readout as we saw in 501, but no two studies are alike. And you can, as you know, if you look at precedents at other studies, no two studies are exactly the same, even within a program. So we look forward to seeing the data, and we'll update you as soon as we get it. Suresh, did you want to? Are you okay?
spk19: No, that's correct. Yeah, I would agree with that.
spk45: One moment for the next question. The next question comes from Troy Langford with TV Cohen. Your line is open.
spk39: Hi, congrats on all the progress this quarter, and thanks for taking our questions. Just on the capitalized commercial performance, Do you think we've already seen the majority of the impact of the expanded Salesforce, or do you think we could see this impact play out gradually over the course of the rest of this year? And how long do you think it will take for us to see the impact of the new TV app on the Capilitis sales trajectory?
spk47: Yeah, sure, Sharon, I could take that. Yeah, I think we are, we've been very pleased with the impact that the additional 50 representatives that we brought on a little over a year ago typically it takes up to six months for representatives to see an optimized performance in their territory so I think they're they're hitting on all cylinders now and I think you can expect a continued impact from them as you can with all of our representatives and all of our territories and in terms of the DTC impact we've been continuously running our DTC with the lead in the light campaign as I mentioned in the prepared remarks we're very pleased to have just very recently launched a new campaign that builds on the Lead in the Light campaign. And we would expect to see the impact of that over the course of the year as well. We've been pleased with the response that we've seen in all of the metrics that we track for our DTC programs. And we're very pleased to be able to refresh the creative campaign So keep an eye out for that in the coming weeks and months. Great.
spk33: Thanks for the call.
spk45: One moment for the next question. The next question comes from Ash Verma with UBS. Your line is open.
spk34: Hi. Good morning. Thanks for taking our question. Just quickly on the pipeline, IDI 1500D psychedelic, Just wanted to understand, like, what's the base molecule you're pursuing here? What is the target that it is hitting? Just mechanistically, if you can talk about, like, what is the value proposition? That would be great. Thanks.
spk16: Yeah, thanks. The first part of your question got a little muffled, so I may need to ask you to repeat it. But I think you were asking about the mechanism of the 1500 series and where it comes from. It is the entire program has been developed in-house, has been discovered, the scaffolds have been discovered and worked on internally going based off of our many years of knowledge in serotonin biology and in particular in 5HT2 biology. So that's what these molecules have been molded around. And we are very excited because they are agonists, but they do not have the hallucinogenic activity in animals. And also they do not have the cardiovascular side effects that you see. with 5-HTPA agonists in general. So we're very pleased with that.
spk45: As a reminder, please limit to one question. Please stand by for the next question. The next question comes from Ami Fadia with Needham. Your line is now open.
spk04: Hi, good morning. Thanks for my question. I had a quick follow-up on ITI 214. You mentioned you're going to collect some biomarker data on inflammation. Could you elaborate a little bit more about how that could translate into differentiation versus existing treatment options within Parkinson's? And also in the past, you've talked about potentially looking at impact on movement and cognition. Could you sort of remind us if there are ways in which you're going to be measuring that in the four-week study? Thanks. Juresh?
spk19: Yes. In terms of the 2 and 4 Parkinson's study, that is a proof of concept study, As indicated, we are looking at the moment scales, cognition, and inflammatory biomarkers. Your question specifically regarding the cognition, we are measuring what is called symbol digit modalities test. This measures the processing speed with a simple substitution task that is sensitive to detect cognitive dysfunction. this scale is similar to the DSST version, but for Parkinson's patients, this is a better version of that for Parkinson's patients. In terms of the biomarkers, we are testing biomarkers for inflammation. IL-6, IL-18, CCL are being tested and other biomarkers are tested to see if the effect on these biomarkers. And in terms of the utility of that, that will help for us in our other indications we are pursuing in inflammation. That will help us figure out what other things we can do with that.
spk55: One moment for the next question.
spk45: Our next question comes from Corinne Johnson with Goldman Sachs. Your line is open.
spk09: Good morning, everyone. I wanted to circle back to your answer to Jessica's question earlier around potential interest in asset acquisition. And I guess as you think about and evaluate the assets that are out there, what sort of parameters do you have in mind as you evaluate these opportunities? And how do you think about that? development or business development in the context of not just the commercial priorities, but also your other pipeline products.
spk16: Right. I'll start and I'll ask Mark if he wants to add anything. So hi, Corinne, and thanks for the question. So obviously, the best case scenario would be the addition of a marketed product that our present sales force can add to their bag, so to speak. so that as they're out there, they can be speaking about both Kaplanida and another product. Going down the wrong one step, if we are not successful there, which we do look, and to date we haven't brought in anything there, we go to adjacencies.
spk03: So
spk16: marketed products that may require adding another sales force, but it really depends on the product and the size of the sales force that you would need. And then we also look at late-stage development assets, and we've been moving earlier and earlier. And you're absolutely right in implying or suggesting or asking a question of How do you then prioritize bringing in an early stage product to our own pipeline? And I have to tell you, every time we evaluate something that's early stage, that's exactly what happens. We need to weigh it against what we already have. And you can't just keep adding early stage programs. So it would probably displace one of our own early stage programs. So you're always weighing these things. You know, we do look across the spectrum now from the marketed products that I gave you the order that we look at these all the way down to early stage programs. Thanks. That's super helpful. Appreciate that.
spk45: One moment for the next question. The next question comes from David Amselem with Piper Sandler. Your line is open.
spk31: Hey, thanks. So I wanted to drill down a little more deeply on the deuterated lumetepirone program. I'm particularly interested in your thoughts on the path forward in Alzheimer's agitation with one product already approved for the setting and axon's ability in late stage development. But I'm just wondering out loud, You've got a couple of randomized withdrawal studies that Axome's running on or has run on Avelity, but then you also have more regular way randomized studies. And I'm just trying to get a sense from you of how you're thinking about what you're going to need to do to move AD agitation through, just given that it's not exactly a well-worn regulatory pathway. Thank you.
spk16: Sure. Thanks for the question. I'll start and then I'll ask Suresh if he wants to add anything. You're correct. It's not a well-worn regulatory pathway, but the pathway is becoming clearer and clearer. With the approval of Rick Salty in Alzheimer's agitation, we know what are allowed. We also, you know, the FDA has been refining their requirements, et cetera. So I think that the study that we're doing that Suresh told you about, it is a phase two study powered as a phase three study. So we look forward to that data. And by the way, the study has been, we've gone back and forth with the FDA. They are completely apprised and have had input into how you do these studies and what you do and what scales you use in these studies, how you use them. So I think that, and the randomized withdrawal is something that is oftentimes used. And again, that would be with discussion with the FDA as we go forward, should we choose to want to use that paradigm. Suresh, did you want to add anything?
spk19: Just again, to reiterate that the path, as you said, you know, while it is not fully there, but at least with the breakfast proposal, there is a path forward from that angle. We have to see if other designs would be okay with FDA at this point.
spk29: Okay. Helpful. Thank you.
spk45: And our last question will come from Joel. Your line is now open.
spk32: Thanks for taking the question. For capillitis sales, how much growth is coming from new first-time prescribers versus greater depth from existing prescribers?
spk13: Mark, do you want to take that?
spk47: Yeah, Sharon, I can take that. So, we're seeing a nice balanced contribution both of increasing new prescribers as well as depth of prescribing. Over time, as I mentioned in my prepared remarks, we now have over 39,000 unique prescribers of CapLida. That continues to grow at a strong rate each quarter. We're adding 3,000 to 4,000 new first-time prescribers every quarter, and we really haven't seen that slow down. over the quarters. So, we look at our depth and our breadth metrics for the launch, and we're very encouraged by what we're seeing there. So, we continue to put effort toward both getting new prescribers of Capilita as well as increasing the depth of prescribing for each of those prescribers.
spk12: Thank you.
spk45: At this time, I would now like to turn the call back over to Sharon for closing remarks.
spk16: Well, thanks everyone for participating on today's call and thanks for all of your questions as well. We look forward to updating you on our MDD studies as well as on our other studies. We think it's a very exciting time. for ITCI and we look forward to continuing to help patients and to develop new medicines to treat patients. With that, I can ask the operator to please disconnect. Thanks very much. Bye-bye.
spk45: This concludes today's conference call. Thank you for your participation. You may now disconnect. Music playing. Bye. Thank you.
spk01: Thank you. Bye. Thank you.
spk45: Good morning, ladies and gentlemen, and welcome to Intracellular Therapy's first quarter 2024 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you would need to press star 11 on your telephone. You would then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to your speaker today, Dr. Juan Sanchez, Vice President, Corporate Communication and Investor Relations. Please go ahead.
spk53: Good morning and thank you all for joining us on our first quarter 2024 earnings call.
spk54: Joining me today on the call are Dr. Sharon Nates, Chairman and Chief Executive Officer, Mark Newman, Chief Commercial Officer, Dr. Suresh Dorgam, Chief Medical Officer, and Larry Heinlein, Chief Financial Officer. The slides to help guide today's call are available on the Investor Events section of our corporate website. I'm on slide number two. 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. You are cautioned not to place on due reliance on these forward-looking statements. These statements are made only as the date of this conference call, and the company claims any obligation to update such statements. I will now turn the call over to Sharon. Sharon will begin on slide four. Sharon?
spk16: Thanks, Juan. Good morning, everyone, and welcome to today's call. We are pleased to share our results for the first quarter of 2024 and to provide updates on our clinical studies. Our team continued to deliver strong growth for Keplida in our current indications of bipolar depression and schizophrenia. With the overwhelmingly positive top line results from study 501, we achieved a major milestone as we worked to expand Keplida's label into major depressive disorder and establish Keplida as a drug of choice for broad patient populations with mood disorders. I'll talk more about this in a moment, but first, let's start with our commercial performance. Our strong growth continued. First quarter total revenues increased to $144.9 million. As we pre-announced, Cap Lida net sales increased to $144.8 million, representing a 53% growth versus the same period in 2023. We are pleased with our performance, and we are confident in the continued growth of Keplida. Consequently, we are reiterating our guidance for full-year Keplida net sales between $645 and $675 million. Mark and Larry will provide a more detailed picture of our performance later in the call. Let me highlight our most recent clinical development news. Last month, we announced robust positive top-line results from Study 501, evaluating Lumetepirone as an adjunctive treatment to any depressants in patients with MDD. These results are shown in slides 7 through 10. In this adjunctive study, Lumetepirone met the primary endpoint of change from baseline at week 6 on the Madras total score versus placebo with an impressive 4.9 point reduction. The p-value was less than 0.00 01, with a robust Cone's V effect size of 0.61. As you can see, statistically significant reductions in depressive symptoms as measured by the madras were seen at the earliest time point tested, week one, and these improvements continued throughout the course of the trial. Lumotepirone also met the key secondary endpoint of change from baseline on the clinician-rated CGIS with a p-value of less than 0.0001 and a robust effect size of 0.67. The CGIS also statistically significantly improved at the earliest time point tested, week one. In this study, we also included a measure of the patient's voice to complement the clinician-rated scales. On a patient-reported measure, the quick inventory of depressive symptomatology self-report scale, or QIDS, patients reported robust reduction in their depressive symptoms. There was a robust reduction in symptoms with a p-value of less than 0.0001. We are very pleased that the patient-reported improvements in depressive symptoms support the clinician-rated endpoints in this study. We continue to see a favorable safety and tolerability profile. Adverse events were similar to those seen in prior studies of Lumetepirone as a treatment for bipolar depression and schizophrenia. Today, we are pleased to report the results of additional safety information, demonstrating that mean changes in key metabolic parameters, including glucose, insulin, triglycerides, and total LDL and HDL cholesterol were similar between Lumetepirone and placebo. Importantly, mean changes in weight were also similar to placebo. These strong results from study 501 underscore the potential for Lumetepirone to treat a broad spectrum of mood disorders. We have now shown Lumetepirone's strong antidepressant activity in patients with MDD as an adjunctive therapy, in patients with bipolar I and bipolar II both as a monotherapy and as adjunctive therapy, in patients with MDD and bipolar depression exhibiting mixed features, and in patients with comorbid depression in our schizophrenia program. The results of study 501, coupled with Lumetepirone's distinct pharmacology, reinforce our label expansion strategy and the long-term prospects for Lumetepirone across mood disorders. Our second phase three trial in MDD, study 502, has recently completed clinical conduct. We expect to report top line results from study 502 later this quarter. Subject to the results, we anticipate filing a supplemental new drug application with the FDA in the second half of 2024. MDD is a highly prevalent disorder with approximately 21 million adults affected every year thus presenting a large opportunity to expand on our already approved indications of schizophrenia and bipolar disorder. MDD accounts for 30% of the approximately 68 million annual antipsychotic market prescriptions. Therefore, as seen on slide 12, the total addressable market for Capilita increases to approximately 80% of the annual antipsychotic market prescriptions with the addition of an MDD indication from nearly 50% with bipolar and schizophrenia indications. We are very excited about the possibility of providing a new treatment option for these patients. Let me now provide an update on our pipeline, starting with other Lumateparone programs. Our Lumateparone 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. Patient enrollment is ongoing in the open-label safety study, as well as in the double-blind placebo-controlled bipolar depression study. We anticipate beginning patient enrollment in the autism spectrum disorder studies in the third quarter of this year. Additionally, we continue to advance our long-acting injectable Lumetepirone with the initiation of Phase I studies with additional formulations later this year. We continue to advance our other pipeline programs, including 1284. ITI-1284 is a deuterated Lumetepirone and is an important drug candidate as we continue to build our neuropsychiatry franchise. This quarter, we expect to initiate patient enrollment in our Phase 2 clinical trial, evaluating ITI-1284 as adjunctive therapy to anti-anxiety medications in patients with generalized anxiety disorder, or GAD. There are approximately 10 million diagnosed adults in the U.S. with GAD. It is important to note that about half of patients who receive treatment do not respond adequately to initial therapy. We believe ITI1284 is well-suited for this patient population and could offer an effective, safe, and well-tolerated treatment. Also later this quarter, we plan to initiate patient enrollment in Phase II clinical study in psychosis associated with Alzheimer's disease, as well as a Phase II study in agitation associated with Alzheimer's disease. Our phosphodiesterase-1 inhibitor program includes lenrispotin and ITI-1020. Our Phase II study with lenrispotin in Parkinson's disease is ongoing, and top-line results are expected in 2025. Besides motor symptom improvement, we are exploring the effects of lenrispotin in cognition, a key non-motor manifestation of the disease, and measuring biomarkers of neuroinflammation to help inform next steps. Our second PDE1 product candidate, ITI1020, is being developed for oncology indications. We are currently conducting a phase one single ascending dose study with ITI1020 and healthy volunteers. I'd also like to give a quick update on our earlier stage programs. We're exploring ITI333 to treat opioid use disorder and pain. Our multiple ascending dose study and a positron emission tomography study are both ongoing. Finally, last year we introduced a portfolio of non-hallucinogenic psychedelics for the treatment of mood, anxiety, and other neuropsychiatric disorders. ITI 1549, the lead candidate, is advancing preclinical development, and we expect to begin clinical testing in 2025. A scientific poster describing the preclinical advancement of ITI 1549 will be presented next week at the Society of Biological Psychiatry annual meeting. In this poster, we further describe the novel mechanism of action of ITI 1549. We also demonstrate improvement in preclinical models of anhedonia and a reduction in symptoms of anxiety. We look forward to sharing this information following our poster presentation. We are in a strong financial position to maximize the opportunities ahead of us with CapLida, and we continue to build our robust pipeline. We ended the first quarter with approximately $477.4 million in cash, cash equivalents, and investment securities. In April of 2024, we received approximately $575 million in gross proceeds from our public offering of common stock. Additionally, we have no debt. I'll now turn the call over to Mark to further discuss this quarter's Kaplida performance. Mark?
spk47: Thanks, Sharon, and good morning, everyone. Kaplida's strong performance continued in Q1 of 2024 with robust year-over-year growth in total prescriptions of 39%, despite typical first quarter seasonal dynamics, as well as the industry disruption caused by the Change Health cyber attack that occurred during the quarter. Capillitis growth continues to be driven by a strong uptake in bipolar depression, where it has solidified its position as the first and only treatment option indicated for patients with bipolar I and bipolar II depression as monotherapy and as adjunctive therapy with lithium or valproate. We also continue to see steady growth in schizophrenia. We continue to expand our prescriber base, which now stands at more than 39,000 healthcare providers since launch. Physicians appreciate Capilet's proven efficacy, favorable safety and tolerability profile, and convenient once-daily dosing with no titration required. Beyond a compelling product profile, the team's commercial execution continues to be very strong. Our sales team is currently educating our prescriber base, which includes psychiatrists, nurse practitioners, and primary care physicians. Our sales efforts are complemented by a comprehensive marketing program, including extensive peer-to-peer medical education programming, digital promotion, and a broad national consumer advertising campaign delivered through television and social media. We're very pleased to have just launched a new consumer TV advertisement, which depicts the experience of people living with bipolar depression and the benefits Capuleta may provide them. We also continue to enjoy a strong market access position with broad access with over 99% of lives covered in Medicare and Medicaid and about 90% of lives covered in commercial. In early Q4 2023, Capilita gained unrestricted status on two of the largest Medicare Part D plans. We are pleased with the initial results of these changes and expect to see the full impact of these changes throughout 2024. As Sharon mentioned, the commercial opportunity for Capilita within its current indications is large and represents nearly half of the approximately 68 million annual antipsychotic prescriptions in the U.S. We will continue to invest behind the brand, build on our strong momentum, and fully optimize the current opportunity as we further penetrate the bipolar depression and schizophrenia markets. In closing, we are pleased with Capilita's strong performance. Keplita has a very compelling product profile, and we are well positioned for continued growth, both in the short term and the long term, as we work to establish Keplita as a first-choice treatment across mood disorders. We look forward to continuing to update you on the success of Keplita. I'll now turn the call over to Larry to further discuss our financial performance. Larry?
spk24: Thank you, Mark. I will provide highlights of our financial results for the first quarter ending March 31, 2024. In the first quarter, net product sales of Capilito were $144.8 million, compared to $94.7 million for the same period in 2023, representing a year-over-year increase of 53%. Our net sales growth in the first quarter was primarily driven by increased prescription demand and, to a lesser extent, higher inventory levels. Our gross net percentage in the first quarter increased to the mid-30s, consistent with our guidance. We expect our gross net percentage to remain in the mid-30s for the remainder of the year. We believe underlying demand for Capilata will remain strong, and we are reiterating our full-year 2024 Capilata net sales guidance of $645 to $675 million. Selling general and administrative expenses were $113.1 million for the first quarter of 2024, compared to $98.9 million for the same period in 2023. Research and development expenses for the first quarter of 2024 were $42.8 million, compared to $38 million for the same period in 2023. Our financial position remains strong. Cash-to-cash equivalents and investment securities totaled $477.4 million at March 31, 2024, compared to $499.7 million at December 31, 2023. In April 2024, we completed a public offering of our common stock, in which we sold approximately 7.9 million shares for aggregate gross proceeds of $575 million and net proceeds of approximately $543 million. This concludes our prepared remarks. Operator, please open the line for questions.
spk45: Thank you. As a reminder to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. to withdraw your question please press star 1 1 again please limit to one question each please stand by while we compile the q a roster the first question comes from jessica phi with jp morgan your line is open hey guys good morning thanks for taking my question so i was wondering with the
spk07: Demonstrated commercial track record and a robust balance sheet. I'm curious how you think about the possibility of adding another product to the bag and how you think about the right time to do that, i.e., if it's something you wouldn't want to do simultaneous with the MDD launch, for example, or if you think there is the organizational capacity to do both at the same time. Thank you.
spk16: Hi, Jessica. This is Sharon. Thanks for the question. So, yes, we're always looking for new opportunities. And as you said, with our robust balance sheet, that certainly allows us to contemplate opportunities that are marketed products. As to, I'll let Mark speak, but I know what he's going to tell you about. You probably don't want to launch simultaneously two new products. However, we do certainly have the bandwidth that we could stagger these and have two products in their launch phases simultaneously. Mark, did you want to add anything to that? And we're very excited to do that, and we keep looking for new products to add.
spk47: Yeah, no, Sharon. Yep, I think you've got it right. Certainly, we have the capacity and the capability of doing it. I think when you have a product as strong as Capilita, you want to make sure that the focus stays there and we continue to execute well. So as we look at these opportunities, we look for strategic fits. We look for products that have compelling product profiles and would be a good fit with the call points that our Salesforce currently has in their call universe. So we look at all those things and up until this point, we haven't found the right fit, but as Sharon said, we would certainly welcome another product into the portfolio and certainly have the capacity and the capability to do that.
spk45: One moment for the next question. The next question comes from Brian Abrahams with RBC Capital Markets. Your line is open.
spk36: Hi there. Good morning. Thanks for taking my question. I'm curious if you could talk about any initial KOL feedback that you received on the MDD data and where CapLida could potentially fit in. And I guess along those lines, I'm also curious, you know, how the top line MDD data may have impacted or may be impacting uptake in bipolar depression if you're seeing it. any pull-throughs or sort of early shifts in use patterns there. Thanks.
spk16: Great. Hi, Brian. Thanks for the questions. And maybe Suresh, would you like to start? I'll just give you an overall on the KOLs. It's been very gratifying to hear their responses and their enthusiasm at Blida. Suresh is at APA. I think he's sitting in some room off to the side right now. So maybe, Suresh, do you want to say whether you've had any further feedback and what your conversations with KOLs are like?
spk19: Yes. In terms of the conversations with KOLs, I have met several KOLs here at the APA, and the feedback on our data on 501 study is very, very positive, and also with the robustness of the data showing in all endpoints, both the primary and key secondary endpoints, and also the self-rated, patient-rated scale. So they were very happy to see the results and are looking forward for the second study.
spk16: And as to the uptake on if there's any pull-through, I think I'm not sure. Mark, are you comfortable speaking to that?
spk47: Yeah, sure, Brian. I think it's far too early to see an impact of the most recent results on prescribing, as you say, within bipolar depression. Typically, any kind of lift that you might get on your current indications usually comes after data is presented in the scientific literature. And I know Suresh and his team are working hard on that for future presentations of the data. But at this point, I don't think we've seen any kind of material lift in our existing indications from presentation of the data.
spk35: Got it. That's all really helpful. Thanks so much.
spk16: And just to say that we hope to be presenting the 501 data at medical meetings later this year.
spk45: One moment for the next question. The next question comes from Andrew Tsai with Jefferies. Your line is open.
spk38: Hey, good morning. Thanks for taking my question. Maybe on MDD, since we're one to two months away from second half 2024, is a Q3 filing a possibility after the second data set reads out or should the street be thinking Q4? at this juncture, and then in the scenario in which the second data set did look different, would you still look to file in second half, or is there a scenario in which you waited for the third data set later in 2025 before filing the SNDA? Thank you.
spk16: Thanks. I didn't write down your question, so I hope I remember all of them. So first, I think on our potential filing, later this year in the second half, what that would be. So we've said that our readout of 502 was going to be late in the second quarter. So you can anticipate that that most likely means June. So then you have to drop everything into shells that are being created and put all the data together. So when we say a filing in the second half, I would tell you Q3, is aggressive, not doable, but aggressive. So that's the answer to that question. And then you asked, oh, about what is our filing strategy. And I think, first of all, we need to see the data, which we will do soon. We do believe in the very robustness of our package as it exists now. So I think we are working very hard on timeline of we will be submitting our application in the second half of this year.
spk38: Great. Thank you.
spk33: Thank you.
spk45: One moment for the next question. The next question comes from Charles Duncan with Cantor. Your line is open.
spk06: Morning, Sharon and team. Congrats on a strong commercial performance in the quarter as well as recent data. I had a two-part question. One is if CapLida is approved as adjunctive therapy in MDD, can you provide us a little color on what you would anticipate Salesforce sizing to be and if eventual demand for the product in that market could drive the franchise to profitability. And then with regard to 502, could you remind us of the sample in terms of it being comprised of number of patients from clinical sites other than from 501? Thanks.
spk16: Mark, do you want to take the first part and then Suresh the second part?
spk47: Yeah, sure. Hi, Charles. Yes, what we said in the past about Salesforce size with an eventual approval in MVD is that we certainly would expect to significantly increase the size of our Salesforce. As you know, currently, our Salesforce has a target audience of about 43,000 physicians, the vast majority of them being psychiatrists and the nurse practitioners that support them. So We have very good coverage of the psychiatry community. We do have a segment of primary care that we currently call on. Those are primary care physicians who are comfortable treating bipolar depression and are high-volume prescribers of antipsychotics for that condition. But as we contemplate an approval in MDD, the expansion would come by a much larger target audience within the primary care community. There aren't many more psychiatrists that we don't already call on for our current indications, but it would be for an expansion into primary care. As we get closer to the timing of a potential approval, we'll come back to you with more details about the specific size and timing that we would be executing against. And Suresh, I think there's a second part.
spk19: Yes. In terms of the sample size, it's a very similar sample size for 502 compared to 501. And in terms of the clinical sites, there is no overlap of sites. But, however, we tend to include about 30% of patients coming from U.S. and about the remaining coming from ex-U.S. sites.
spk15: So there's some contextual overlap, but site overlap.
spk02: Yes.
spk16: Because you don't want to be competing with yourself when you're enrolling patients.
spk05: Got it. Makes sense. Thank you.
spk45: One moment for the next question. The next question comes from Mark Goodman with Learing Partners. Your line is open.
spk41: Yes, on ITI 214, can you remind us of the differentiation in this product and how you look to kind of break into the Parkinson's market, which is a tough market over the past decade for new products? And, Larry, could you also just tell us what the inventory change was in the quarter? Thanks.
spk16: Okay. Suresh, do you want to start with talking about 214?
spk19: Yes, 214, that is the hindus spodum. We have an ongoing study in Parkinson's disease, and that is a proof-of-concept study. In that study, we are evaluating several things. One, evaluating the motor symptom improvement. We are also evaluating cognition measures, as well as biomarkers for inflammation. So based on the data from that, will decide on the next steps uh looking at uh the data we read from that that that study is a four-week study it's the uh the primary endpoint is the hauser diary we're looking for increase in on time without troublesome dyskinesia and the key secondary is the mds updrs part two which measures motor aspects of experiences of daily living and we also as i indicated One of the things we're looking at is looking for biomarkers for inflammation in that study.
spk16: And to the second part on inventory, Larry, do you want to take that?
spk24: Yes, sure. During this quarter, we experienced strong prescription growth that's continued over the last several quarters. And in this quarter, this prescription demand was the primary driver for revenue. There was, to a lesser extent, an inventory increase for this quarter, but the primary driver was Scripps.
spk42: Can you quantify the inventory change?
spk24: No, we've not given that sort of granular detail before, and it's difficult to do. Okay.
spk55: One moment for the next question.
spk45: The next question comes from Umar Rafat with Evercore. Your line is open.
spk27: Hi, guys. This is Mike DeFiori in for Umar. Thanks so much for taking my question and congrats on all the success. Just two quick ones from me. Any updated thoughts on pursuing a monotherapy indication for MDD given Capilates' improved safety profile compared to second-generation atypical antipsychotics? I'm asking because Seroquel pursued this in the past and although it was efficacious, The FDA didn't approve the monotherapy indication for MDD due to CH concerns. And my follow-up is on the, I guess, separate follow-up is on the PDE1 program. Just a quick observation. Last quarter, they said the top line was expected in one-half-25. Now, this quarter, it's just 20-25. I was wondering if there's any sort of recruiting or trial delays on that front. Thank you.
spk16: Okay. Suresh, do you want to take that?
spk19: In terms of the... Yeah, you can start, Sharon, and I can... Go ahead. Okay. In terms of the study itself, the recruitment is slower, and we are... Wait a minute.
spk16: Wait, wait, wait. The 214, the first part of the question... was an update on monotherapy for MDD and that Seroquel did try for monotherapy and as you correctly pointed out, Mike, that the FDA was concerned about their metabolic consequences, etc. I think that we're evaluating all of this and Obviously, as you know, there isn't the safety concerns that one sees with Seroquel with Lumetepirone. So we're looking at that. There are a lot of things to look at. It's also different times than when Seroquel was first approved. On the PDE program, recruitment has gone slower than we originally expected. thought that could be because of studies that are ongoing. It could also be because we try to ensure that we get in appropriate patients, et cetera. But we still are in 2025 in our timeline. So we've just left out saying first half, second half, or anything, which I don't think we had said before either. Maybe we did. I can't remember. So I think it is 2025. And also you're correct that or actually I think the speaker before you was correct in talking about that Parkinson's is a crowded market. But we think that we're getting or we should be getting some very good data on the use of these PDE1 inhibitors in neuro inflammation. And that should help inform us both on taking forward 214 and Parkinson's disease and in taking forward other molecules within the PDE1 space into several different arenas. With that Suresh, did you want to add anything else? I'm sorry, I didn't mean to cut you off.
spk19: No, in terms of the 501 study, yeah, the MDD program, that's true. That, again, we'll be looking at the data, and then we'll figure it out what to do next steps for the monotherapy.
spk28: Very helpful. Thanks so much.
spk45: Please stand by for the next question. The next question comes from Jason Gerbery with Bank of America. Your line is open.
spk50: Hey, guys. Good morning, and thank you for taking my question. On ITI1284, I'm not seeing this on ct.gov yet, but maybe I'm missing something, but just generally trying to get a sense, you know, how big are these trials, how many dose arms, are these going to be like 12-week treatment periods to get to proof of concept and figure out dose, and just trying to get a rough sense of timeline here ultimately. And then just as my follow-up, if I can squeeze it in, I didn't hear an update on mixed features. I think you guys were waiting for the minutes which tend to come like I think 30 days after the meeting. So just curious if there's a mixed features update. Thanks.
spk16: I'll start with the second part and then I'll ask Suresh to chime in on the first part. So we did update you on the mixed features and said that we would come back to you after our readout of 502. and as we continue to put together our strategy for mixed features in MDD. So stay tuned. Hopefully in the near future we'll have some updates for you on the mixed features. And I'll give you the short answer on 1284 is we will be posting these studies, we said, before the end of this quarter. And I'll leave it to Suresh to talk to you about the design and powering of these studies.
spk19: Yes. Regarding the 1284 studies, we have three programs right now. That is the GAD program, the psychosis in Alzheimer's disease, and agitation in Alzheimer's disease. The first study we will be starting is the GAD program. That is a fully powered study as a registration study. It's as an adjunct to treatment and it is sample size would be somewhere in the range of about 600 patients. It's going to be three arms placebo versus two doses. Again, the details once we start the trial soon in the next few we will be posting that online for the clintiles.gov. Similarly for the agitation and psychosis and Alzheimer's, those are Phase II studies but are powered as registrational studies. Those details also will be posted as soon as we start the studies. And they are intended to start in the second quarter. Thank you.
spk45: Please stand by for the next question. The next question comes from Sumant Kulkarni with Canaccord. Your line is open.
spk18: Thanks for taking my question. Sorry about the two-parter. So on the last MDD data-focused call, I know you'd requested me to hold off on this question until this update, so I'll ask it now. 1284, are you planning to specifically develop that product in the various subindications of depression? And on Lumetapirone for autism spectrum disorder, I'm asking because unmet need is high, how is the company thinking about dosing for pediatric patients? Is there a weight-based dosing paradigm or will it be as simple as the product that's out there on the market right now in terms of logistics around dosing?
spk16: Thanks. Suresh, you want to take the second part and then I'll need you to repeat the first part. Yes.
spk19: Regarding the second part about the autism for Lumotepirone, we are going to be starting those studies for irritability in autism. And regarding the dosing, we are looking at we have to first finish the PK studies for the lower age group between 5 to 10 years old based on the PK exposure levels that comes from that study, we will be deciding on the dosing for those patients. For patients in the upper age group, it will be similar to what it is in adults, for example. From 13 to 17, it will be similar to 42 milligrams. So the lower age groups we have to figure out by the PK studies.
spk18: And the first part was on 1284. We know you're developing it for Alzheimer's disease, psychosis, and agitation, and generalized anxiety disorder, but are there any specific plans to develop that within the depression context?
spk16: Yeah, well, we are contemplating other indications within 1284, but let us get these studies started first, and then we'll come back to you with the other studies that we'll be doing. Thank you.
spk48: one moment for the next question the next question comes from jeffrey hung with morgan stanley your line is open hi this is michael rian on for jeff hung thank you for taking our question um thinking more generally about the results from study 501 versus 403 um how important is it to get dsm-5 classifiers
spk16: into the label versus a more broad label like adjunct mdd i guess i'm just trying to ask what happens more regularly in standard clinical practice and to what extent do classifiers influence treatment decisions thanks so much so i think our broad label um is obviously what we always aim for and what we're doing is exploring um value of having anything you know, specific in any label that we have. And again, as we get the 502 readout, we'll come back to you with further updates on exactly what it is that our strategy is now and will be. Mark, did you want to add anything to that?
spk43: No, I think that's good.
spk16: Okay.
spk45: One moment for the next question. The next question comes from Greg Suvanavage with Mizuho. Your line is open.
spk37: Good morning, everyone. This is Charles Wayne off with Greg. Thanks for taking our question. Given study 501 indicated a very strong placebo-adjusted effect size of 4.9, does the company expect to see similar efficacy in study 502?
spk16: Yeah, that was a point change. That wasn't the effect size. But the effect size was very strong as well. And I think what you're looking for, the studies are powered to show, actually this study was powered to show a two-point change. Because in adjunctive studies, typically you are at the lower end of the two to four point change in the madras that you're seeing. So I think we're very close to the data. We hope very much that we have as strong a readout as we saw in 501. But no two studies are alike. And as you know, if you look at precedent at other studies, no two studies are exactly the same, even within a program. So we look forward to seeing the data. And we'll update you as soon as we get it. Suresh, did you want to?
spk19: No, that's correct. Yeah, I would agree with that.
spk45: One moment for the next question. The next question comes from Troy Langford with TV Cohen. Your line is open.
spk39: Hi, congrats on all the progress this quarter, and thanks for taking our questions. Just on the capitalized commercial performance, Do you think we've already seen the majority of the impact of the expanded Salesforce, or do you think we could see this impact play out gradually over the course of the rest of this year? And how long do you think it will take for us to see the impact of the new TV app on capitalized sales trajectory? Yeah, sure.
spk47: I could take that. Yeah, I think we are. We've been very pleased with the impact that the additional 50 representatives that we brought on a little over a year ago. Typically, it takes up to six months for representatives to see an optimized performance in their territory, so I think they're hitting on all cylinders now, and I think you can expect a continued impact from them as you can with all of our representatives in all of our territories. And in terms of the DTC impact, we've been continuously running our DTC with the Let in the Light campaign. As I mentioned in the prepared remarks, we're very pleased to have just very recently launched a new campaign that builds on the Lead in the Light campaign. And we would expect to see the impact of that over the course of the year as well. We've been pleased with the response that we've seen in all of the metrics that we track for our DTC programs. And we're very pleased to be able to refresh the creative campaign So keep an eye out for that in the coming weeks and months. Great.
spk33: Thanks for the call.
spk45: One moment for the next question. The next question comes from Ash Verma with UBS. Your line is open.
spk34: Hi. Good morning. Thanks for taking our question. Just quickly on the pipeline, IDI 1500D psychedelic, Just wanted to understand, like, what's the base molecule you're pursuing here? What is the target that it is hitting? Just mechanistically, if you can talk about, like, what is the value proposition? That would be great. Thanks.
spk16: Yeah, thanks. The first part of your question got a little muffled, so I may need to ask you to repeat it. But I think you were asking about the mechanism of the 1500 series and where it comes from. It is the entire program has been developed in-house, has been discovered, the scaffolds have been discovered and worked on internally going based off of our many years of knowledge in serotonin biology and in particular in 5HT2 biology. So that's what these molecules have been molded around. And we are very excited because they are agonists, but they do not have the hallucinogenic activity in animals. And also they do not have the cardiovascular side effects that you see. with 5-HTPA agonists in general. So we're very pleased with that.
spk45: As a reminder, please limit to one question. Please stand by for the next question. The next question comes from Ami Fadia with Needham. Your line is now open.
spk04: Hi, good morning. Thanks for my question. I had a quick follow-up on ITI 214. You mentioned you're going to collect some biomarker data on inflammation. Could you elaborate a little bit more about how that could translate into differentiation versus existing treatment options within Parkinson's? And also in the past, you've talked about potentially looking at impact on movement and cognition. Could you sort of remind us if there are ways in which you're going to be measuring that in the four-week study? Thanks. Juresh?
spk19: Yes. In terms of the 214 Parkinson study, that is a proof-of-concept study, As indicated, we are looking at the moment scales, cognition, and inflammatory biomarkers. Your question specifically regarding the cognition, we are measuring what is called symbol digit modalities test. This measures the processing speed with a simple substitution task that is sensitive to detect cognitive dysfunction. this scale is similar to the DSST version, but for Parkinson's patients, this is a better version of that for Parkinson's patients. In terms of the biomarkers, we are testing biomarkers for inflammation. IL-6, IL-18, CCL are being tested and other biomarkers are tested to see if the effect on these biomarkers. And in terms of the utility of that, that will help for us in our other indications we are pursuing in inflammation. That will help us figure out what other things we can do with that.
spk55: One moment for the next question.
spk45: Our next question comes from Corinne Johnson with Goldman Sachs. Your line is open.
spk09: Good morning, everyone. I wanted to circle back to your answer to Jessica's question earlier around potential interest in asset acquisition. And I guess as you think about and evaluate the assets that are out there, what sort of parameters do you have in mind as you evaluate these opportunities? And how do you think about that? development or business development in the context of not just the commercial priorities, but also your other pipeline products.
spk16: Right. I'll start and I'll ask Mark if he wants to add anything. So hi, Corinne, and thanks for the question. So obviously, the best case scenario would be the addition of a marketed product that our present sales force can add to their bag, so to speak. so that as they're out there, they can be speaking about both CapLida and another product. Going down the wrong one step, if we are not successful there, which we do look, and to date we haven't brought in anything there, we go to adjacencies.
spk03: So
spk16: marketed products that may require adding another sales force, but it really depends on the product and the size of the sales force that you would need. And then we also look at late-stage development assets, and we've been moving earlier and earlier. And you're absolutely right in implying or suggesting or asking a question of, How do you then prioritize bringing in an early stage product to our own pipeline? And I have to tell you, every time we evaluate something that's early stage, that's exactly what happens. We need to weigh it against what we already have. And you can't just keep adding early stage programs. So it would probably displace one of our own early stage programs. So you're always weighing these things. You know, we do look across the spectrum now from the marketed products that I gave you the order that we look at these all the way down to early stage programs. Thanks. That's super helpful. Appreciate that.
spk45: One moment for the next question. The next question comes from David Amselem with Piper Sandler. Your line is open.
spk31: Hey, thanks. So I wanted to drill down a little more deeply on the deuterated lumetepirone program. I'm particularly interested in your thoughts on the path forward in Alzheimer's agitation with one product already approved for the setting and axon's ability in late stage development. But I'm just wondering out loud, You've got a couple of randomized withdrawal studies that Axome's running on or has run on Avelity, but then you also have more regular way randomized studies. And I'm just trying to get a sense from you of how you're thinking about what you're going to need to do to move AD agitation through, just given that it's not exactly a well-worn regulatory pathway. Thank you.
spk16: Sure. Thanks for the question. I'll start and then I'll ask Suresh if he wants to add anything. You're correct. It's not a well-worn regulatory pathway, but the pathway is becoming clearer and clearer. With the approval of Rick Salty in Alzheimer's agitation, we know what are allowed. We also, you know, the FDA has been refining their requirements, et cetera. So, I think that the study that we're doing that Suresh told you about, it is a phase two study powered as a phase three study. So, we look forward to that data. And by the way, the study has been, we've gone back and forth with the FDA. They are completely apprised. have had input into how you do these studies and what you do and what scales you use in these studies, how you use them. So I think that, and the randomized withdrawal is something that is oftentimes used. And again, that would be with discussion with the FDA as we go forward, should we choose to want to use that paradigm. Suresh, did you want to add anything?
spk19: Just, again, to reiterate that the path, as you said, you know, while it is not fully there, but at least with the breakfast proposal, there is a path forward from that angle. We have to see if other designs would be okay with FDA at this point.
spk29: Okay. Helpful. Thank you.
spk45: And our last question will come from Joel. Your line is now open.
spk32: Thanks for taking the question. For capillitis sales, how much growth is coming from new first-time prescribers versus greater depth from existing prescribers?
spk13: Mark, do you want to take that?
spk47: Yeah, Sharon, I can take that. So, we're seeing a nice balanced contribution both of increasing new prescribers as well as depth of prescribing. Over time, as I mentioned in my prepared remarks, we now have over 39,000 unique prescribers of Cap Lida. That continues to grow at a strong rate each quarter. We're adding 3,000 to 4,000 new first-time prescribers every quarter, and we really haven't seen that slow down. over the quarters. So, we look at our depth and our breadth metrics for the launch, and we're very encouraged by what we're seeing there. So, we continue to put effort toward both getting new prescribers of Capilita as well as increasing the depth of prescribing for each of those prescribers.
spk12: Thank you.
spk45: At this time, I would now like to turn the call back over to Sharon for closing remarks.
spk16: Well, thanks everyone for participating on today's call and thanks for all of your questions as well. We look forward to updating you on our MDD studies as well as on our other studies. We think it's a very exciting time. for itci and we look forward to continuing to help patients and to develop new medicines to treat patients with that i can ask the operator to please disconnect thanks very much bye-bye this concludes today's conference call thank you for your participation you may now disconnect
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