Intra-Cellular Therapies Inc

NASDAQ:ITCI

Earnings Call Transcript 2022-Q3

[Operator]

Good morning, ladies and gentlemen, and welcome to intracellular Therapies Third Quarter Earnings Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. [Operator Instructions]. As a reminder, today's conference call is being recorded. I'd now like to turn the conference over to Dr. Juan Sanchez, Vice President, Corporate Communications and Investor Relations.

[Juan Sanchez, VP, Corporate Communications & IR]

Good morning, and thank you all for joining us on the call today. Our earnings press release provides a corporate update and details of the company's financial results for the third quarter ended September 30th, 2022. This press release class award this morning and is available on our website at intracellulartherapies.com. Joining me on the call today are Dr. Sharon Mates, Chairman and Chief Executive Officer; Mark Neumann, Executive Vice President and Chief Commercial Officer; Dr. Suresh Dargan, Executive Vice President and Chief Medical Officer; and Larry Hineline, Senior Vice President and Chief Financial Officer. As a reminder, during today's call, we will be making certain forward-looking statements.

These statements may include statements regarding, among other things, the efficacy, safety and intended use of the company's product development candidates, our clinical and nonclinical plans, our plans to present and report additional data, the anticipated conduct and results of ongoing and future clinical trials, plans regarding regulatory filings, future research and development, our plans and expectations regarding the commercialization of CAPLYTA; potential impact of COVID-19 pandemic on our business; and possible uses of existing cash and investment resources. These forward-looking statements are based on current information, assumptions and expectations which are subject to change and involve a number of risks and uncertainties that might cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are discussed in our [indiscernible] filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You're cautioned not to place undue reliance on these forward-looking statements, and the company disclaims any obligation to base such statements. I will now turn the call over to Sharon.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

Thanks, Juan. Good morning, everyone. I'm excited to be here today to share our third quarter results, including our ongoing success with CAPLYTA's launch in bipolar I and bipolar II depression. I will also share our progress on our pipeline. Following my remarks, Mark will elaborate on our commercial progress, and Larry will provide details on our financial performance. We will then open the call for questions. We are pleased with the continued performance of CAPLYTA and this quarter, we are reporting robust net product revenues of $71.9 million. This represents a 233% increase over the same period in 2021 and a sequential increase of 30% over the second quarter 2022.

The fundamental growth indicators for CAPLYTA are strong. We are making appropriate investments in our business to maximize the full potential of this important medicine and are highly confident in our continued growth. The acceleration in CAPLYTA uptake following our label expansion of bipolar disorder to our indication of schizophrenia confirms the continued medical need in these disorders and the value CAPLYTA brings to patients. We are excited to see the acceleration in bipolar prescriptions as these disorders are 4 to 5x more prevalent than schizophrenia.

CAPLYTA's proven efficacy is combined with a favorable safety and tolerability profile and ease of administration with once-a-day dosing and no titration needed. In clinical trials, changes in key safety metrics, including weight change, fasting glucose, total cholesterol and triglycerides were all similar to placebo. In addition, lumateperone uniquely interacts with the dopamine system and in our clinical trials, dopaminergic adverse events, such as movement disturbances, including akathesia, were not common and were similar to placebo. We continue to receive positive feedback from health care providers and patients on CAPLYTA in the real-world setting with clinical experience consistent to those observed in our clinical trials. We continue to invest in clinical programs to develop CAPLYTA for broader patient populations, including mood disorders. Mood disorders are highly prevalent.

There are more than 11 million people in the U.S. living with bipolar disorder. In addition, more than 20 million Americans experienced unipolar depression referred to as major depressive disorder, or MDD. Patients with these disorders are often highly functional and are significantly involved in their treatment decisions. It is important to highlight that the majority of these patients are not adequately treated with initial therapies. There are only a few FDA-approved antipsychotic treatment options for these conditions and patients need options for treatment with proven efficacy and favorable safety profile. Major antipsychotic brands have achieved commercial success primarily as a result of their mood disorder approval, resulting in the uptake of these drugs in populations with large numbers of patients.

This is proving true with CAPLYTA with an increasingly larger portion of prescriptions coming from bipolar depression. CAPLYTA is the first and only antipsychotic approved for the treatment of Bipolar 1 or Bipolar II depression in adults as monotherapy and as adjunctive therapy with lithium or valproate. We expect continued growth in bipolar depression and schizophrenia as we continue to pursue additional label expansion opportunities. We have a pivotal program evaluating lumateperone as an adjunctive therapy to antidepressants for the treatment of MDD in those patients who have had inadequate response to antidepressants. Patient enrollment is ongoing in studies 501 and 502, our global Phase III MDD study evaluating lumateperone 42 milligrams for the adjunctive treatment of depression.

The primary endpoint is changed from baseline on the MADRS total score at week 6. In addition to the efficacy studies, we have an ongoing long-term open-label rollover study to further assess safety in this patient population. Patient enrollment is in line with our expectations. We expect to file a supplemental new drug application with the FDA for approval of lumateperone as an adjunctive therapy to antidepressants for the treatment of MDD in 2024. We have a great deal of confidence in our MDD program. The depressive episodes within MDD and bipolar disorder have the same characteristics, and we measure the depressive episodes with the same scale, the MADRS total score in both MDD and bipolar disorder.

The positive results from our bipolar depression studies and the robust evidence coming from the demonstration of efficacy in these studies, coupled with the positive real-life feedback we received on patients with bipolar depression being treated with CAPLYTA gives us further confidence for our ongoing programs in mood disorders. We are also evaluating lumateperone in patients with MDD or bipolar depression who exhibit mixed features. We are pleased to announce that we recently completed patient enrollment in Study 403 and expect to report top line results in the first quarter of 2023. Study 403 is a well-controlled global clinical trial evaluating lumateperone 42 milligrams as monotherapy in patients with MDD or bipolar disorder who exhibit mixed features during their current depressive episode. Efficacy is assessed at week 6, and there is a follow-up safety visit 2 weeks after the last medication dose.

The primary endpoint of this study is changed from baseline versus placebo on the MADRS total score at week 6, and the secondary endpoint is the change from baseline on the CGI-S. Our confidence in this program is, in part, guided by our previous study. We have conducted a retrospective analysis of Study 404, evaluating the antidepressant effects of lumateperone in a subgroup of bipolar depression patients meeting the criteria for mixed features at baseline. In this analysis, lumateperone had robust antidepressant effect as measured at week 6 by the MADRS total score and the CGIF. Just to remind you, the mix feature specifier in the DSM 5 highlights an important group of patients with MDD and bipolar depression. When patients experience a major depressive episode, their symptoms can be accompanied by subthreshold manic or hypomanic symptoms. 25%to 40% of patients experience these symptoms, which often correlates with a worse disease prognosis.

These patients have more severe illness and higher recurrence rates, comorbidities and rates of suicide and suicidal ideation. MDD patients with mixed features respond poorly to antidepressants and are at higher risk of developing bipolar disorder. There are no approved MDD or bipolar depression medicines that include this important specifier in their label. We believe lumateperone's safety and tolerability make it a strong treatment option for these patients, and we look forward to sharing the top line results from Study 403 with you. Turning to our ongoing lumateperone long-acting injectable program. Our goal with this program is to develop long-acting injectable formulations of lumateperone that are effective, safe and well tolerated and last one month and longer.

We have conducted a Phase I single ascending dose study with our first formulation. This study evaluated the pharmacokinetic safety and tolerability of lumateperone long-acting injectable in patients with stable symptoms of schizophrenia. We have also explored alternate site of injection with this formulation, and we have been progressing additional formulations. We are finishing the analysis of these studies and will enable us to define the next steps in this program. We expect to provide an update on this program on our next call. Let me provide a brief summary of our other clinical trial activity, starting with lumateperone.

We are conducting a relapse prevention study in patients with schizophrenia and expect patient enrollment to complete in late 2023. The timing of data release will depend on the rate of relapse in the trial. We will update you as the trial progresses. We recently completed several lumateperone Phase I study, including a study evaluating the PK, safety and tolerability profile in pediatric patients with schizophrenia. This study demonstrated that lumateperone is generally safe and well tolerated in this patient population and patients achieved comparable drug levels to the adult population with 42 milligrams lumateperone. Other early-stage trials with lumateperone are ongoing or planed.

Turning to 1284 our deuterated form of lumateperone, a new chemical entity formulated as an oral disintegrating tablet for sublingual administration. We recently completed a food intake study. The study demonstrated that food had no significant impact on the PK profile. So we expect ITI-1284 can be given with or without food. We have also completed Phase I safety studies demonstrating ITI-1284 is safe and generally well tolerated in normal healthy volunteers and normal healthy elderly volunteers. Other Phase I studies are ongoing or planned and include drug-drug interaction studies and mass balance studies.

We also continue to progress our toxicology program. We expect to commence clinical conduct in Phase II clinical trials in agitation in patients with probable Alzheimer's disease in dementia-related psychosis and certain other disorders in 2023. In our PDE-1 inhibitor program, we've recently completed or have ongoing Phase I trials with our lead molecule, Lenrispotent, including drug-drug interaction, bioavailability from scale-up batches and food effect studies. Our ITI-333 program for opioid use disorder and pain is also progressing. We have completed a single ascending dose study, and our neuroimaging study is ongoing. The objective of this study is to investigate brain occupancy for target receptors that play a role in these conditions. Following our neuroimaging studies, which will help determine the dose selection for future studies, we plan to initiate a multiple ascending dose study.

The progress being made across our programs underscores our commitment to invest in the building blocks for our long-term growth. We ended the quarter in a strong financial position with $630.5 million in cash, cash equivalents and investment securities, and we have no debt. With CAPLYTA and our pipeline of promising new treatments, we continue to fulfill our mission to develop safe, effective and innovative medicines that improve the lives of patients with neuropsychiatric and neurologic disorders. CAPLYTA had a very strong quarter, and we are confident in the continuation of CAPLYTA's growth momentum throughout next year and years to come. I will now turn the call over to Mark who will provide additional information on CAPLYTA's commercial performance. Mark.

[Mark Neumann, EVP & Chief Commercial Officer]

Thanks, Sharon, and good morning, everyone. CAPLYTA's launch in bipolar depression continues to go very well. Our launch fundamentals are strong across all commercial metrics, and we remain confident that CAPLYTA will experience continued robust growth. During the third quarter, CAPLYTA's total prescriptions grew 26% sequentially versus the second quarter of 2022 and 220% year-over-year versus the third quarter of 2021. CAPLYTA's growth this quarter is particularly impressive, considering the impact of summer seasonality that saw the overall oral antipsychotic market register no growth for the quarter.

We expect the market to return to growth in Q4, and with that, a further acceleration in CAPLYTA prescription growth to close out the year. In fact, CAPLYTA has posted week-over-week increases in total prescriptions in 5 of the last 6 weeks. Looking at the longer-term trends, while our schizophrenia franchise continues to grow nicely, CAPLYTA has experienced substantial growth in the first 9 months following our launch in bipolar depression. Since launch, new prescriptions have tripled and weekly new patient starts are at levels 5x higher than they were prior to our label expansion. We are encouraged with CAPLYTA's uptake across a broad range of patients with bipolar depression, consistent with our approved indication.

As Sharon mentioned, an increasing proportion of prescriptions are coming from bipolar depression. Bipolar depression already accounts for the largest share of both new patient starts and total patients. CAPLYTA's compelling profile is resonating well with prescribers. CAPLYTA is the only antipsychotic with proven efficacy in adults with both bipolar I and bipolar II depression as monotherapy and adjunctive therapy with lithium or valproate. It has a favorable safety and tolerability profile with weight and metabolic changes, EPS and acathesia, all similar to placebo. CAPLYTA is a once-a-day medication that does not need titration and can be taken with or without food. These are powerful reasons to prescribe. CAPLYTA market access coverage remains very strong. Coverage in the Medicare Part D and Medicaid channels remains greater than 98%, and we have approximately 85% coverage in the commercial channel.

In addition, CAPLYTA's wider length patient and prescriber support programs continue to be very effective at addressing coverage and reimbursement processes and overall patient affordability where appropriate. Our broad market access and commercial efforts, including sales activity and well-attended medical education events combined with CAPLYTA's favorable profile are driving the robust uptake in prescriptions. In mid-August, we introduced 2 new dosage strengths of CAPLYTA for use in special populations, specifically those with hepatic impairment and those concomitantly taking CYP3A4 inhibitors. The launch of these doses makes CAPLYTA available to a broader population of patients living with bipolar depression as well as schizophrenia. In summary, we are very pleased with CAPLYTA's strong growth, and we are making the appropriate investments to ensure continued commercial success. We are very confident in our ability to drive long-term value creation, and we continue to work with health care providers to help patients with bipolar depression and schizophrenia. I will now turn the call over to Larry. Larry?

[Lawrence Hineline]

Thank you, Mark. I will provide a summary of our financial results for the third quarter ending September 30, 2022. Total revenues in the third quarter grew to $71.9 million compared to $22.2 million in the third quarter of 2021. In the third quarter, we recorded net product revenue of CAPLYTA of $71.9 million compared to $21.6 million for the same period in 2021 and $55.1 million in the second quarter of 2022. This represents a year-over-year increase of 233% and a 30% increase over the second quarter of 2022. In the third quarter, our gross to net adjustment percentage remained in the low 30s, consistent with our previously communicated guidance.

We expect the gross to net percentage for the fourth quarter to remain in the low 30s. Inventory levels in the trade, measured by days on hand of CAPLYTA at the wholesaler level remained consistent throughout the third quarter, in line with historical and expected levels. Cost of product sales were $5.9 million in the third quarter of 2022 compared to $2 million for the same period in 2021. Selling, general and administrative expenses were $88.4 million for the third quarter of 2022 compared to $70.5 million for the same period in 2021. This increase is primarily due to an increase in marketing and advertising expenses and labor-related costs. Research and development expenses for the third quarter of 2022 were $33.3 million compared to $27 million for the third quarter of 2021.

This increase is due to higher lumateperone clinical trial and nonclinical related costs and an increase in non-lumateperone program cost. Net loss for the third quarter of 2022 was $53.5 million compared to a net loss of $76.9 million for the third quarter of 2021. Cash, cash equivalents, restricted cash and investment securities totaled $630.5 million at September 30, 2022, compared to $413.7 million at December 31st, 2021. In January 2022, we completed a $460 million public offering, resulting in net proceeds to the company of approximately $433.7 million.

This concludes our prepared remarks. Operator, please open the line for questions.

[Operator]

[Operator Instructions]. Our first question comes from Jessica Fye with JPMorgan. You may proceed.

[Unidentified Analyst]

Hi guys, this is Nick on for Jessica, thanks for taking our questions. With data for mixed features study expected in 1Q '23, how should we be thinking about good data for the benchmark? And when that data reads out, what level of read across do you see in the NBB501 and 502 studies, thanks?

[Sharon Mates, Co-Founder, Chairman, CEO & President]

So thanks for the question. And Suresh, I'll ask you to start and maybe you want to start with the second part of the question on what you think about a read-through between MDD and mixed features and bipolar and mixed features and then we'll go from there.

[Suresh Durgam, EVP & Chief Medical Officer]

Okay. Thank you for the question. Regarding the mixed features and objectivity to MDD, these are different patient populations and that they have different studies. The mixed features population study is a MANAT study and the adjective treatment of 100% is an agent to treatment in partial responders. Patients with mixed features tend to be more difficult to treat a more severe types have 5 difference rates and have high-comorbidities and a discovery taken. Having said that, we are optimistic about this program given the data that we have from our retrospective analysis of Study 404 evaluating the anti-depresant effect of lumateperone in the subgroup of bipolar depression patients meeting the criteria for mixed speakers at baseline. In this analysis, lumateperone had robust antidepressant effects. And these patients are difficult to treat and right now, there are no treatments available at this time that have a labeled indications for mixed features. And the path forward for this is not laid out yet.

So we are doing the study, and there have not been so far any studies at this time in terms of getting an approval for this. For the agent treatment of MDD, there is a path already laid out. There are a few drugs that are already approved for coverage in retreatment. However, there is still room for improvement in terms of the safety profile of the compound. Mechanistically, the lumateperone looks strong in terms of the 5-HT2A antagorism, the chiron weatake inhibition and also the indirect effects on D1, which acts through NMDA and Ampower receptors. In addition, in our bipolar depression programs, both as monotherapy as well as hedging to treatment, we have shown that lumateperone has shown significant improvement in deposit symptoms. In addition, in our schizophrenia trial, we have also shown that a subset of patients have depression and are concomitant antidepressants and also those patients who are not on antidepressants both showed significant improvement in depressants symptoms. In essence, I would say that these 2 are different populations, and I would see them as independent studies, not making any judgement for one way or the other.

[Unidentified Analyst]

Okay. Thank you.

[Operator]

Thank you. One moment for questions. Our next question comes from Andrew Tsai with Jefferies. You may proceed.

[Andrew Tsai, Jefferies]

Hi, thanks and good morning. A big congrats on another great quarter, nice job in execution. I guess my question is around CAPLYTA's trajectory over the next 6 to 12 months. As you think about the acceleration what would be the specific drivers in terms of increasing demand and growing market penetration? And what, I guess, specific leading indicators will you be looking at to give you that type of confidence, thanks.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

Great. Hi, Andrew, and thanks for the questions. Maybe, Mark, would you like to take that?

[Mark Neumann, EVP & Chief Commercial Officer]

Yes, sure. Thanks, Andrew. And yes, we do, we continue to see very strong underlying demand in the marketplace for CAPLYTA as well as increasing prescriber adoption both in terms of breadth of prescribing, adding significantly more new prescribers to CAPLYTA as well as existing prescribers increasing their depth of prescribing and both of those indicators are very positive to us. I think what I would say is we're highly confident that CAPLYTA will continue to experience the kind of robust growth that we've seen in the first 3 quarters of the launch. And there are several reasons for that. First and foremost, we continue to have the potential to significantly increase our prescriber base.

We're pleased with our prescriber reach to date and the growth that you've seen over the last several quarters, but we're still early in the launch, and we have a significant additional prescriber pool that we expect to access in the coming months. And as the COVID environment continues to stabilize, that will improve our ability to access providers and increase patient flow, perhaps less telemedicine. So all of these things in the market dynamics create an opportunity to further penetrate our prescriber base. And I think if you look at sort of longer term and historically, branded antipsychotics have these long growth trajectories as their prescriber base grows, that their patient base grows, so too does their business.

So Latuda, Berila, Rexulti have been generating positive growth for years, and we would expect the same for CAPLYTA especially with our favorable product profile. Now more near term, one of the things that was really encouraging to us is the third quarter has summer seasonality in it. So on the backdrop of an overall market for oral antipsychotics that essentially saw no growth during the quarter, CAPLYTA was able to drive 26% quarter-over-quarter growth. And even more encouraging is now that we're past the summer months and we're into the fall, people return to work, students go back to school we're seeing renewed branded market growth and we expect that to continue in the fourth quarter. And with that market growth, we also expect CAPLYTA growth to accelerate as we continue to gain market share in that market. So reflective of that in my comments, prepared remarks, if you look at the last 6 weeks, essentially after the Labor Day holiday, we've seen week-over-week increases in CAPLYTA prescription.

And I think, Andrew, what's driving that we continue to get very favorable feedback on the clinical data and the early patient experience that physicians are having. And we continue to increase our brand awareness. So our sales force continues to penetrate this large prescriber base of branded antipsychotics. We're very pleased with the attendance and the reception to the information presented in our medical education programs. And we're also pleased with our DTC campaign, and we expect to initiate a second campaign in 2023, which will further drive brand awareness and contribute to growth. So a little bit of a long-winded answer, but I'd say we're very confident in our ability to continue to drive robust growth through the end of this year and well into next year and beyond.

[Andrew Tsai, Jefferies]

Very clear. And may I ask a follow-up question about Nick's features?

[Mark Neumann, EVP & Chief Commercial Officer]

Sure.

[Andrew Tsai, Jefferies]

Just because it's right around the corner. So as we think about this top line release, would you consider breaking out the efficacy data by subgroup within for instance, BPD mix feature subgroup and then MDD subgroup? And then secondly, for the overall result, is the kind of bar points versus placebo for success? Thank you.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

So I'll start, and then I'll ask if Suresh wants to add anything. So first of all, we'll tell you more as we get closer to the date of the top line results. So I think right now, we can't give you any of those specifics. So I would say just stay tuned on that. As to what you're looking for, typically, you look for 2 to 4 points. And in this case, you would be looking to the lower end, especially in these areas. So Suresh, do you want to add anything to that?

[Suresh Durgam, EVP & Chief Medical Officer]

Again, just again to emphasize that the primary endpoint is at week 6 total mega store and CGI is in a [indiscernible] secondary. We are stratifying the patients at baseline. And as you said, we are doing several analyses that are being planned, and we will go into the details once we announce the results.

[Andrew Tsai, Jefferies]

Thanks, very clear on and congrats again.

[Operator]

Our next question comes from Brian Abrahams with RBC Capital Markets. You may proceed.

[Brian Abrahams, RBC Capital Markets]

Hi, it's Lena on for Brian. I wanted to also ask on the commercial performance. I guess, can you talk about what you're thinking on how to best continue to add that next incremental patient to a prescriber who's already using CAPLYTA? Is it just really a matter of time? Are there issues you're educating docks on? I guess what I'm thinking is when a doctor is considering using CAPLYTA versus another branded. I guess, what are the top factors they're thinking about and how are you working to get CAPLYTA to be top mind for them?

[Mark Neumann, EVP & Chief Commercial Officer]

Yes, sure, I'll take that. And yes, I think it is a matter of time, [indiscernible] as physicians become more and more aware of CAPLYTA as they gain more and more patient experience with CAPLYTA and that patient experience comes back in a positive way, and that's the feedback that we've been getting. Early on in the launch, it's critical that when physicians try your product and patients try your product that they have a positive experience and all of the early patient experience and feedback that we've been getting on that has been highly positive. And as our sample size, if you will, grows of increasing prescribers and increasing patients, the positive feedback we continue to get just reinforces our belief in the growth prospects for the brand in the future.

And I think it all comes down to the product profile and the performance of that product. And so certainly, efficacy, safety and dosing convenience are top factors when physicians decide what to prescribe. And with CAPLYTA in bipolar depression, we think we have a very favorable profile with proven efficacy in both bipolar I and bipolar II as monotherapy and as adjunctive therapy.

We have a very favorable safety and tolerability profile across both metabolic parameters as well as EPS and movement disorders, essentially all comparable to placebo. And we have a medication that's once a day with no titration required. All of these attributes of the brand are viewed highly favorably by physicians and again, the good news is the feedback that we get is the experience that their patients are having is consistent with the data and the results we saw in the clinical trial and that's always a very positive thing. So we continue to increase our brand awareness across all of our marketing mix, with our sales force efforts, our medical education. And on the consumer side, increasing awareness and educating patients on bipolar depression and looking to have patients ask their physicians if CAPLYTA would be appropriate for them. So all of these things work together to allow us to continue to drive, again, both increased breadth of prescribing, but as you're asking, increased depth of prescribing by prescribers as well.

[Brian Abrahams, RBC Capital Markets]

That's very helpful, thank you.

[Operator]

Our next question comes from Umer Raffat form Evercore. You may proceed.

[Michael DiFiore, Evercore ISI]

Hi guys, this is Mike DiFiore in for Umer. Congrats on the quarter. Two for me. One is regarding mix features. Given that around you said 30% of bipolar and unipolar press patients have mixed features, what proportion of them are already being treated for these conditions, albeit sub-optimally. And if a patient with bipolar depression presents with mixed features, wouldn't they be covered by taking CAPLYTA since it's already indicated for this for bipolar depression. And if this is true, would the incremental opportunity just be patients who've given up or have dropped out of treatment because nothing works. And my follow-up question is just regarding your mix feature subgroup analysis from Study 404. You used YMRS as greater than 4 as a proxy for mixed features. Is this a reasonable proxy and have other antipsychotics used this proxy for mixed features in the past? Thank you.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

Hi Mike. So thanks for the questions, and it's a 2-part question, which has both a commercial aspect to it as well as a clinical aspect. And I'll ask Suresh to start with and I don't know if you want to start Suresh with why we used YMRS in our study and what is conventional to use and then we'll go and then if patients are being treated right now in bipolar depression. And we'll ask Mark to talk a little bit about the commercial benefits of being on label, okay?

[Suresh Durgam, EVP & Chief Medical Officer]

Okay.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

So Suresh, you want to start? Great.

[Suresh Durgam, EVP & Chief Medical Officer]

Yes, I can. So first, coming to the question about using YMRS 4 or about as a proxy for mixed features. This has been used in several retrospective analysis done for a few of the antipsychotics. We have used the same method approximating that anybody who has a score of many are rating scale emanating scale of more than 4 to be considered as having mixed features. And there are several publications with other antipsychotics, which have used the same methodology. And we didn't deviate from this methodology. We want to also keep it similar to what others have done in the field. And also in the field, this is considered a reasonable approach, and that's what we have taken. In terms of the patients that are already being prescribed, there is, to some extent, that is true because for the bipolar depression studies or there is no specifics included in our label. So all patients, all the subspecies could be a small set of patients in each of those indications that have become part of that trial. But since these are difficult to treat patients because this subset is very difficult to treat because they have high core morbidities, there is high recurrence rates, they have high suicide and suicide ideation as well as suicide attempts. And also, they have difficulty getting [indiscernible] difficulty with the higher recurrence rates and difficult to treat, having this specific indication in the label will help us promote and talk to the prescribers about this.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

And maybe I could ask, Mark, do you want to follow on that as to why from a commercial perspective, the benefits of having an expansion of the label.

[Mark Neumann, EVP & Chief Commercial Officer]

Yes, sure. And I'll pick up where Suresh left off, Mike. And specifically, as Suresh said, on the bipolar side it would be covered by the general bipolar and broad bipolar indication that we have. But I wouldn't underestimate the value and impact of being able to have clinical data specifically in a patient population with mixed features in bipolar depression, so that the physician can see in that patient type, the efficacy and safety of a medicine like CAPLYTA, and that provides additional confidence that physician to write a prescription for CAPLYTA in a patient specifically with bipolar depression and mixed features. And certainly, inclusion in the label allows promotion on the commercial side, which is also a powerful lever for us. And then certainly, the MDD component of this with an indication there would also be an expansion of the label there. So I hope that makes sense, but we do see this as a real opportunity to have specific clinical data in this patient subset.

[Operator]

Our next question comes from Charles Duncan with Cantor. You may proceed.

[Charles Duncan, Cantor Fitzgerald]

Super. Good morning, Sharon and team, congratulations on a very strong quarter as well as 403 enrollment update. Thanks for taking our questions. I had one commercial actually multipart commercial and then one pipeline to follow up. Regarding commercial question, I'm just wondering perhaps for Mark, if he could speak to the profile driving persistence levels or would you think that new growth or growth would come more from new patients or longer term on drug? And then for Larry, was there any pricing change in the quarter?

[Mark Neumann, EVP & Chief Commercial Officer]

So I'm happy to start.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

Well, actually, Larry can go first since you addressed it to him. It's a very short answer. Larry?

[Lawrence Hineline]

Sorry to answer, no, we didn't raise or change prices in the quarter.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

Yes. We had no price change. Yes. Okay. So now for the longer answer, if you can remember it, Mark. Please go ahead.

[Mark Neumann, EVP & Chief Commercial Officer]

Yes, I know, Charles question is about future growth and will it be driven by new patient starts or continuing strong persistency. And the answer, Charles, is both. We continue to drive very strong new patient acquisition, particularly with the bipolar depression indication, and we expect that to continue into the future. And as we've talked in the past about the favorable product profile of CAPLYTA, especially with its safety and tolerability attributes, these are aspects of the profile that we believe contributes to very strong compliance and persistency, and we expect that certainly to continue as well. So long answer, but we do expect both to contribute to growth.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

I think we also get comments on the ease of use so it's an effective dose on day 1. And so we think that's beneficial. And we've had other compounds that we don't have any off-target side effects that some of the antipsychotics have. So I think that, again, the overall positive impressions from patients and physicians is very encouraging to us towards continued growth.

[Operator]

Thank you. And as a reminder, please limit yourself to one question. Our next question comes from Marc Goodman with SVB Securities. You may proceed.

[Marc Goodman, SVB Securities]

Yes, good morning Larry, a lot of payer discussions, I'm sure, have already taken place for next year. Can you give us a sense of gross to net into next year, whether we should be thinking there'll be any real change from the way that we've seen it pretty much all year this year. And I guess that includes bipolar depression, pretty much dominating the new prescriptions. And so just curious about that. And it just seems like spending is coming in a late just later than we thought, later than you guys just curious if that's just a seasonal thing. And fourth quarter is going to make up for that and how we should think about spending in the next year given you talked about DTC. Thanks.

[Lawrence Hineline]

Sure. Well, as I previously guided, everyone, our gross to net is in the low 30s. We haven't really projected for next year. We're working on that now. We're looking at the contracting and so forth. So in our next earnings call, we'll be ready to update you on the gross to net changes, if any, there will be. So unfortunately, I can't give you that information now. As far as the spending, I think we're right on target for what we had projected. For the year, we said we'd spend 500 million on operations, exclusive of cost of sales. Through the first 9 months, we spent 370 million and then we expect to spend 130 in the fourth quarter, which is pretty much ratable spending for the quarter and for the year. So I'm not sure where we're late. I think we're right on target but if you have a specific question, I'd be happy to dive a little deeper, if you like.

[Operator]

Our next question comes from David Amsellem with Piper Sandler. You may proceed.

[David Amsellem, Piper Sandler & Co.]

Thanks. So I apologize if you may have addressed this earlier in the Q&A, I jumped on late, but I wanted to get your thoughts longer term regarding the muscarinic agonist in schizophrenia and specifically, the extent to which you think it could be disruptive to CAPLYTA's longer-term trajectory or not. I just wanted to get your thoughts on how that might change competitive dynamics, how that even could impact payer dynamics over the long term. Again, bearing in mind that this is schizophrenia limited, but I wanted to get your thoughts there. Thank you.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

Thanks, I'll start, and then I'll ask Suresh from a clinical perspective, if he wants to add anything. So as I've said before, any drug that can help patients is great for patients, and we're pleased to see more drugs to be available for patients. I would tell you, as you said, this is for schizophrenia only at the moment. And I think that a dose an hour while we are increasing our schizophrenia activity, I think we are moving more towards the trajectory in the mood disorder space, as we've said. I think as you know, these patients cycle through drugs and so we've seen many antipsychotics come to market, come to then turn to be generic, et cetera. And any time there are these entrants, they really haven't affected negatively to the branded products that are on the market. So we would welcome new entrants. We don't believe that it will have a negative impact on CAPLYTA revenues at all. And if we expand the market by having more players in the market, that would be great, too.

[Operator]

Our next question comes from Greg Suvannavejh with Mizuho. You may proceed

[Graig Suvannavejh, Mizuho Securities]

Hi, good morning, thanks so much for taking my question and congrats on a great third quarter. I just wanted to ask perhaps a bigger picture question around profitability and the company's view or philosophy around profitability vis-a-vis its desire to invest in the commercial and R&D aspirations for the company? In other words, how are you trying to balance the 2, thanks?

[Sharon Mates, Co-Founder, Chairman, CEO & President]

I'll ask Larry to take that understanding full well though, that we haven't given you any forward-looking guidance, yes.

[Lawrence Hineline]

Yes. We haven't given forward-looking guidance. I mean we have given expense guidance in 2022. We are critically looking at our spend going forward. We are positioning ourselves towards profitability. But again, that's obviously dependent upon the trajectory of sales, which we believe is going to be very strong. So without giving you specifics, I mean, our goal is to get to profitability. We keep our spending under control. We look at all our projects and development programs critically and our goal is to become profitable as soon as we can.

[Operator]

Our next question comes from Jason Gerberry with Bank of America. You may proceed.

[Unidentified Analyst]

Hi, this is Perry on the line for Jason. Just a quick follow-up on selling and marketing spend. Sort of given guidance, how you're seeing selling and marketing spend to evolve over the next year? I'd imagine with meaningful discretionary EPC spend. The question is whether that's going to be recurrent more of a onetime investment that you might scale back over time? And then I have another question on the MDD indication. So can you speak to the upcoming Vraylar, PDUFA and post-marketing MDD indication? I guess in terms of MDD adjunct, if the FDA requires 2 positive Phase IIs, I mean, Phase IIIs. First, do you think CAPLYTA needs to hit on both MDD Phase III or in the event there's a split of the Phase IIIs would a mix feature or the previous favorable BBB data still provides support for a second pivotal, thank you

[Sharon Mates, Co-Founder, Chairman, CEO & President]

Okay. Thanks for the several questions. I'm not sure I got all of them. But the first one, I think, went to Larry about is this or one is our commercial spend, et cetera, onetime or do we expect to continue? Do you want me to take that or you want to take it later? Larry, why don't you go ahead?

[Lawrence Hineline]

Yes, sure. Obviously, on our commercial side, we have various means that we're promoting our product. We have different mediums and so forth. And we gauge the effectiveness and are gauging the effectiveness of those and going forward, we're going to have those same programs, and we're working on the mix of the spending amongst the program. So I would say our spending in this line is pretty, we've given you guidance for this year and it's been pretty straight on. And we're looking at our spend now in the budgeting process. So if we find opportunities that can increase our trajectory, we'll certainly take those and so that would be spend that would be in the right direction. We're not going to frivolously spend and take chances. But I think we're really going to be focusing on what we're doing right. And I think Mark alluded to the things that we're looking at for next year to drive sales. So I think we're in good shape with our spending patterns, if you will.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

And as we said in our prepared remarks, we continue to invest in the business as we move forward. So I think you can expect to continue to see the spending in our business in order to continue the trajectory that we're on for CAPLYTA. And then to the question of how many studies do you need, et cetera, I think it really depends on how the data looks, okay? If you're too overwhelmingly positive studies, then it's a home run, if you're very close that's another question. I think it's always going to be a discussion with the FDA if one is, it really depends on the outcome of the study. And as to would it be prudent to have another study, I think we constantly evaluate the opportunities and so stay tuned as we continuously evaluate these things.

[Operator]

Our next question comes from Ami Fadia with Needham. You may proceed.

[Ami Fadia, Needham & Company]

Good morning, congrats for the nice quarter. I had a question about your comments around acceleration into the fourth quarter. You talked about the strength in the recent weeks. Can you more broadly discuss your expectations around how you see the growth trajectory the next couple of months? Do you see that accelerating further from here? That would be helpful. And then as we enter 2023, what are your thoughts on providing guidance for CAPLYTA for next year? Thank you.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

So Mark, do you want to take the first part, and I'll take the I can do the last part right now and then you do the first part.

[Mark Neumann, EVP & Chief Commercial Officer]

Okay.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

We're currently evaluating exactly when we'll start giving guidance. I think so by our next earnings call, we will have decided the appropriate time to start giving you guidance. But at the moment, we don't have that answer for you, but we're looking at it very closely. We know that you're extremely interested in such metrics. So I hate to say it again, but stay tuned. And Mark, do you want to take the first part of the question?

[Mark Neumann, EVP & Chief Commercial Officer]

Yes. Sure, Ami, thanks for your question. I would say we were very pleased with the 26% total prescription growth in the third quarter on the backdrop of a market during the summer months that had 0 growth in it, which reflects the fact that we were able to continue to drive market share and continue to penetrate the prescriber base to drive that growth. Now as we come out of the summer months where you have this summer seasonality, we do expect and we've actually seen signs of the branded market growing in the fourth quarter, where it was more flat during the third quarter, which is a positive thing. So we'll have some tailwinds behind this. And in addition to that, additional market share gains in the fourth quarter should accelerate our growth in the fourth quarter versus the third quarter. So again, we feel confident that we will continue to experience robust growth and in an accelerating fashion in the fourth quarter.

[Operator]

Thank you. One moment for our next question.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

Operator, we're going to have to be wrapping this up if there's I mean, it's 9:30. Maybe if there's one more question.

[Operator]

Sounds good. Our last question comes from Ash Verma with UBS. You may proceed.

[Ashwani Verma, UBS]

Hi. So we see that the CAPLYTA NBRx share has been strong consistently. In this antipsychotic category, like how much time does it take for the TRx or NRx share to start to track at the same level as the NBRx share, if you can comment on that.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

Mark, do you want to address that?

[Mark Neumann, EVP & Chief Commercial Officer]

Yes, sure. So Ash yes, we have been pleased with our new patient acquisition, which is what NBRx is reflective of. And as I mentioned in my prepared remarks, the weekly levels of new-to-brand prescriptions for CAPLYTA are now at 5x what they were prior to the label expansion into bipolar depression. And I think NBRx is the driver. So NBRx results in higher new prescriptions, NRx, and those new prescriptions result in higher TRx. And then obviously, as you're adding new patients all the time, weekly, monthly, quarterly, those patients, combined with the compliance and persistency profile for CAPLYTA is what drives that total prescription line. And if you look at the trajectory of our TRx line, we've been very pleased with the continued significant growth that we've seen there, and we expect that to continue into the fourth quarter and into the future years as well.

[Sharon Mates, Co-Founder, Chairman, CEO & President]

Great. Well, in the interest of time, I want to just thank everybody for participating today. And we are very pleased with the growth that we're seeing and the trajectory of growth that we're seeing for CAPLYTA as well as we advance our other programs, both for label expansion for CAPLYTA as well as other programs. We look forward to updating you on our next call and we're very pleased with the growth in our company as well. So with that, I would say, operator, you can now disconnect. Thank you.

[Operator]

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