Intra-Cellular Therapies Inc (ITCI) 2021 Q3 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to our Intra-Cellular Therapies third quarter financial results conference call. 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. Please go ahead.

Good morning and thank you all for joining us today. Our earnings press release provides a corporate update and details of the company's financial results for the third quarter, which ended September 30, 2021. This press release crossed the wire a short time ago 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 Durgam, Senior 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 or 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 the COVID-19 pandemic in our -- on our business; and possible uses of existing cash and investment resources.

These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve a number of risks and uncertainties that might cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements, and the company disclaims any obligations to update such statements.

I will now turn the call over to Sharon.

Thanks, Juan. Good morning, everyone, and welcome to today's call. We're excited to share our third quarter progress, update you on our programs and describe our upcoming plans.

In the third quarter, we continued to successfully execute our commercial plan for CAPLYTA, our FDA-approved medicine for the treatment of schizophrenia in adults. CAPLYTA's prescription growth trajectory continued quarter-over-quarter. We have an upcoming milestone rapidly approaching with our FDA PDUFA date of December 17 for CAPLYTA's label expansion into bipolar depression in adults. We also continued to advance several other promising development programs.

Before I provide further details on our programs, let me first provide an overview of our financial and commercial performance. Total revenues for the third quarter grew to $22.2 million. CAPLYTA net product revenues were $21.6 million compared to $19 million in Q2 2021 and $7.4 million in the same quarter last year. Total prescriptions increased 15% quarter-over-quarter and approximately 200% versus Q3 of 2020. We achieved this sequential growth in spite of disruptions due to the latest surge of COVID-19 during Q3.

CAPLYTA has a compelling clinical profile having demonstrated efficacy coupled with favorable safety and tolerability with no dose titration required. In our clinical trials in schizophrenia, CAPLYTA results were similar to placebo for changes in weight, fasting glucose, total cholesterol, triglycerides and extrapyramidal symptoms, including akathisia. Market research and feedback from the field continues to indicate that patients and physician real-life experiences with CAPLYTA are consistent with what was demonstrated in clinical trials.

We're very excited about CAPLYTA's potential as an important treatment option for patients with bipolar depression. This label expansion would significantly extend the patient opportunity for CAPLYTA to more than 11 million Americans living with bipolar disorder. There are only a few approved treatment options for bipolar depression, the most common and debilitating manifestation of this disorder.

If approved, CAPLYTA could help fill an existing need for effective treatment with a favorable safety and tolerability profile. The FDA is currently reviewing our sNDAs for the treatment of bipolar depression in adults. Our applications are supported by robust positive results from 2 Phase III studies that evaluated the effects of lumateperone in patients with either bipolar I or bipolar II disorder. In both studies, treatment with lumateperone substantially reduced depressive symptoms on both primary and key secondary end points. Importantly, the favorable safety and tolerability profile in our bipolar depression program is consistent with that of our schizophrenia program.

During the quarter, results from Study 404, our monotherapy study, were published in The American Journal of Psychiatry, a highly respected psychiatric journal. Upon approval, we expect to launch this important new option for patients with bipolar depression. Our sales force expansion is substantially complete, and Mark will provide further details in a few moments.

Our longer-term vision is to establish lumateperone as the treatment of choice across a broad range of depressive disorders. Bipolar depression is the first indication in this strategy. This is followed by our Phase III studies in MDD, which are double-blind, placebo-controlled, 6-week studies evaluating lumateperone 42 milligrams as adjunctive treatment to antidepressants for patients who have an inadequate response to antidepressive therapy.

In addition, we have an ongoing program evaluating lumateperone in patients who exhibit mixed features. Study 403 is a double-blind, placebo-controlled, 6-week study evaluating lumateperone 42 milligrams as monotherapy for patients with MDD or bipolar depression exhibiting mixed features. Patients with mixed features, who make up roughly 1/3 of those with bipolar depression and MDD, have greater symptom severity, a higher risk of suicide attempts and higher comorbidities. They also respond poorly to antidepressants. We expect to complete our ongoing 403 study in the second half of 2022.

We recently held our first Research and Development Day where we had the opportunity to hear from a group of prominent experts in psychiatry who shared their perspectives on therapeutic needs in major psychiatric conditions, including schizophrenia and mood disorders with an emphasis on bipolar depression. They provided insights into lumateperone's potential to address these needs, which was consistent with feedback we have received. We are confident that lumateperone addresses an unmet medical need. And if approved, lumateperone will have broad utility across a range of depressive disorders with bipolar depression being the first approval within this category.

During the event, we provided an overview of molecules in our robust pipeline, including the lumateperone long-acting injectable formulations and ITI-1284 ODT-SL programs. We have initiated our program for the development of ITI-1284 for the treatment of agitation in patients with probable Alzheimer's. Clinical conduct in this program is expected to begin early next year. Studies in dementia-related psychosis and certain depressive disorders in the elderly are planned for the first half of next year.

We also presented important aspects of the mechanistic underpinning our existing data and our clinical development plans for our PDE1 inhibitors and ITI-333 platforms. We discussed the features that make PDE1 enzyme unique among the large family of phosphodiesterases. We also discussed the PDE1's unique tissue distribution and the selective pathway regulation that allows for a broad therapeutic opportunity for our portfolio of PDE1 inhibitors.

We presented preclinical and early-stage clinical results in Parkinson's disease, supporting the recent advancement of lenrispodun into Phase II clinical development. Our external expert explained the therapeutic needs for treating motor symptoms and nonmotor symptoms, including cognition, in this patient population. Our goal for this program is to study lenrispodun's potential to improve motor and nonmotor symptoms, including cognition, by enhancing or restoring neuronal function in affected brain regions.

We also highlighted ITI-333, a promising drug candidate to address important unmet therapeutic needs in opioid use disorder and pain. ITI-333 is a novel compound that acts as a partial agonist at mu-opioid receptors and as an antagonist at the serotonin 5-HT2A receptors. At mu-opioid receptors, it acts as a partial agonist signaling through G-protein-coupled pathways, but acts as an antagonist at the beta-arrestin pathway. Our external experts explained the current opioid use crisis in the U.S. and outlined the unmet therapeutic needs. Results from an ongoing Phase I single ascending dose study are anticipated in the fourth quarter of 2021.

We ended the third quarter in a strong financial position with $478.7 million in cash, cash equivalents and restricted cash. We're very proud of our performance and our team's efforts over the last quarter. As we continue to grow and expand, we remain committed to fulfilling our mission to develop innovative treatments to improve the lives of individuals with neuropsychiatric and neurologic disorders.

Mark will now share details of our ongoing commercial activities, including our plans for bipolar depression. Following his remarks, Larry will provide additional details on our financial performance. Mark?

Thank you, Sharon. It's a pleasure to be here with all of you today to provide an update on the commercial performance of CAPLYTA in schizophrenia and to share our launch readiness progress for the exciting potential opportunity in bipolar depression.

As Sharon noted, CAPLYTA performed well in the third quarter, increasing total prescriptions by 15% sequentially over the second quarter. This growth was achieved in spite of the latest Delta surge in the pandemic, which impacted the care of patients with schizophrenia and suppressed the overall antipsychotic market during the quarter. While restrictions continue to exist, COVID case numbers are decreasing across the country and vaccination rates are gradually improving. As a result, more psychiatry offices are reopening for patient appointments and our sales team is gaining greater in-person access to health care providers in some practices. These encouraging market developments coincide with the expected approval timing of CAPLYTA in bipolar depression, putting us in a stronger position for the upcoming months.

I'm pleased to report that our bipolar launch preparations are all on track, and we expect the launch will be successful for several reasons. There remains a very significant unmet medical need in bipolar depression and additional treatment options are required for this debilitating disorder. CAPLYTA has demonstrated strong efficacy and favorable safety and tolerability results in our clinical trials and has the potential to be approved in the broadest range of adult patients with bipolar depression, including those with bipolar I and II, and as monotherapy or as adjunctive therapy to lithium or valproate.

We have a multifaceted commercial plan in place and are ready to hit the ground running to maximize this exciting opportunity. We believe this plan will significantly accelerate the use of CAPLYTA. We have conducted extensive market research that shows physicians, payers and patients all have a favorable impression of the clinical profile of CAPLYTA in bipolar depression. They cited efficacy in both bipolar I and bipolar II and as both monotherapy and adjunctive therapy across a broad patient population as well as its favorable safety and tolerability profile. They are especially impressed by its low risk of weight gain, metabolic changes and movement disorders.

To ensure broad awareness of CAPLYTA's potential bipolar indication and clinical profile, we are increasing our target audience to the 43,000 prescribers who account for approximately 85% of all oral branded antipsychotic prescriptions written for schizophrenia and bipolar disorder. This will include psychiatrists, nurse practitioners and primary care physicians who treat significant numbers of patients with bipolar depression. We have expanded our sales force from 240 representatives to a total of 320. This will ensure a highly competitive share of voice with the expanded prescriber target base.

We are pleased with the talent that has been attracted to our company and have hired experienced sales representatives with proven track records prior to and during the pandemic. We are confident in their ability to drive strong results. Our sales efforts will be complemented by a comprehensive multichannel promotional campaign to optimize adoption of CAPLYTA, including peer-to-peer medical education, digital media promotions and DTC advertising to increase awareness of CAPLYTA among health care providers and patients.

On the market access front, CAPLYTA continues to maintain broad coverage in the Medicare Part D and Medicaid channels with greater than 95% of lives covered. These are the 2 primary channels through which the majority of schizophrenia prescriptions flow. In our preparations for the bipolar depression label expansion, our team operating under the FDA pre-PDUFA guidance has completed comprehensive bipolar disease awareness and clinical trial data presentations with the formulary decision makers at strategic payer accounts, including the largest commercial insurers and PBMs.

With the potential approval of CAPLYTA for bipolar depression, we would, over time, expect to see an increasingly larger percent of our prescriptions coming through the commercial channel due to the nature of the bipolar patient population. Recently, we have improved our coverage in this channel to approximately 70% of lives and expect that to continue to increase in the coming months. Additionally, we see competitive reimbursement approval rates for CAPLYTA consistent with other branded antipsychotics and our LYTAlink patient support program has been very effective in supporting the prescription process and in minimizing out-of-pocket expenses for our commercially insured patients.

In summary, we are extremely excited about the potential label expansion of CAPLYTA for bipolar depression and we are confident that we have a highly effective and competitive commercial plan in place to achieve a strong uptake in prescriptions.

I'll now turn the call over to Larry to share our financial results. Larry?

Thank you, Mark.

I will now provide a summary of our financial results for the third quarter ended September 30, 2021. Total revenues in Q3 grew to $22.2 million compared to $7.4 million of total revenues in the third quarter of 2020. CAPLYTA's third quarter net product revenues reached $21.6 million compared to $19 million in the second quarter of 2021 and $7.4 million in the same period last year.

Cost of product sales were $2 million in the third quarter of 2021 compared to $0.6 million in the third quarter of 2020. Research and development expenses for the third quarter of 2021 were $27 million compared to $10.3 million for the third quarter of 2020. This increase is due to higher lumateperone clinical trials cost and an increase in other development programs.

Selling, general and administrative expenses were $70.5 million for the third quarter of 2021 compared to $52.5 million for the same period in 2020. This increase is primarily due to increased marketing and commercialization costs.

Net loss for the third quarter of 2021 was $76.9 million compared to a net loss of $55.2 million for the third quarter of 2020.

Cash, cash equivalents, restricted cash and investment securities totaled $478.7 million at the close of the third quarter of 2021 compared to $658.8 million at December 31, 2020.

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

(Operator Instructions) Our first question will come from the line of Brian Abrahams from RBC Capital Markets.

Congrats on the continued progress. My first question is on the overall, I guess, commercial landscape. And I'm sort of curious, with COVID having spiked and now waning, the sort of dynamics that you're seeing on the ground in terms of physician-patient engagement, how that may be shifting as we get towards the end of the year, any changes in telemedicine? And how you expect those trends might shape both fourth quarter sales in schizophrenia as well as the bipolar launch as we think about that into the early part of next year?

Brian, thanks for the question. And I'll ask Mark, would you like to just address that? First, I would go into the landscape for schizophrenia patients in particular. And then I'd go on from there, please.

Yes. Sure. Thanks for the question, Brian. And yes, we were pleased with the performance of CAPLYTA during the third quarter where COVID and the Delta variant was present during the quarter. Now as we came out of the third quarter and into the fourth quarter, as you know, the cases overall have been decreasing and vaccination rates have been increasing. And so what we're seeing as a result of that are more psychiatry offices are reopening for in-person patient visits. Our sales force is gaining, in some practices, greater access for in-person detailing. And we would expect to see that continue into the fourth quarter and into next year.

So we expect to continue to see the quarter-over-quarter growth of CAPLYTA. And in particular, I think, as Sharon mentioned, the patients with schizophrenia, when the COVID cases are high, they're probably more impacted than some other patient populations. But even in the schizophrenia area, we're beginning to see more patient flow coming back into the offices and a greater access for our sales force.

So we're encouraged by those market developments both for our fourth quarter with schizophrenia and also as we prepare to launch for the potential approval of the bipolar depression indication, the timing is coinciding with that launch as well. So we think that puts us in a stronger position going forward as we close out the year and as we head into 2022.

Got it. And then maybe one more, if I could. As we look towards the PDUFA in December, can you maybe just characterize, I guess -- if you could give us any sense as to whether those remain on track and your level of confidence? And should we be thinking about these as sort of 2 different decision points that may come out at different times and maybe different for the different indications? Or should we assume that this will be, I guess, grouped together as one?

So I'll take that. This is Sharon. And we do expect everything to come out together and we are on track.

Great.

So I think that's short and sweet. Okay.

Our next question will come from the line of Andrew Tsai from Jefferies.

I did want to build off of Brian's question just a little bit just to see if you can provide a little bit more color because we are essentially 1 month into your PDUFA essentially. So when I look at the guidelines, it sounds like companies generally enter final labeling discussions with the FDA. So I don't know, to the extent that you can share, I mean any additional color might be helpful. And is it also fair to assume within this sNDA package, we're not -- the FDA is not even looking at CMC or anything of that sort because this sNDA builds on the fundamental initial NDA filing, right? Just wanted to ask those questions.

Andrew, thanks for your question. And yes, you're right, this does -- an sNDA builds on your NDA, but they do look at everything in your package. They look at everything as they should as it pertains to the indication that you're filing for. So as you mentioned, our PDUFA date is coming up. It's December 17, and we're working towards that diligently. And as I said to Brian, everything is on track and we're looking forward to our PDUFA date.

Fantastic. And one more follow-up is in terms of the launch, obviously, we'll be tracking sales in 2022 and beyond. So maybe as we think about the launch dynamics, and I appreciate all the color that you provided why this could be a strong launch, can you talk about maybe other launches happening in parallel, why that should not impede with your own launch expansion? And then maybe, I don't know, I mean as we head into 2023 when a branded drug is expected to go generic, fundamentally, can you kind of discuss why that should not impact CAPLYTA's launch?

So Mark, would you like to take that? And I can add at the end, if required. Yes.

Sure. Let me start with the second part of your question, Andrew, first. What we've seen historically in the antipsychotic class is when a branded product goes generic, obviously, there's an impact on that brand. But generally, there's not a significant impact on the remaining other branded products. You're well aware, Andrew, of the dynamic that exists in this category where you have the frequent cycling through multiple different antipsychotics. And it's a condition that physicians are used to, payers are used to. And we really don't see that there will be a significant impact of another branded product going generic on the rest of the branded market.

In terms of the other launches, we're focused on our launch. We're extremely excited about the opportunity. Our sales force expansion is essentially complete. All of the representatives will be trained and ready to go for launch. We'll be launching immediately upon approval. We feel like we've got the right size of the sales force to cover the vast majority of the opportunity both in bipolar as well as in schizophrenia and feel like we have a comprehensive commercial plan in place from a medical education perspective, from a digital media perspective, an advertising perspective.

So we feel like we have all of the elements in place and we're just ready and waiting on the approval to press go, and we're excited to get out there and begin to educate the physician base on the terrific profile we think we have of CAPLYTA in bipolar depression.

Next question is coming from the line of Umer Raffat from Evercore.

Maybe let me focus on the depression study today, if I may, and perhaps three questions in particular. One, what do you expect the baseline MADRS to look like in that trial? And I know the inclusion criteria is MADRS above 24. Should we be thinking around 28 or perhaps higher?

Second, I noticed in both the Phase IIIs in this adjunct MDD, the trial sites are in U.S. only. And I'd be curious what the thought process was on sort of not doing ex U.S.

And then finally, I was particularly interested in noting that there's an exclusion criteria whereby if a patient has a 25% MADRS decrease between screening and baseline, they're excluded from the trial. And I was trying to understand how long is that interval between screening and baseline which allows you to sort of manage this placebo response, if I may, and have other depression studies done that.

Thanks, Umer, and thanks for your questions. I think Suresh, would you like to answer? And I can chime in as well.

Sure. Thanks for the question. For the first question in terms of the MADRS baseline scores, we have to see usually with entry criteria of 24 and above, you expect a higher baseline scores. And these are also adjunctive treatment trials. So you typically see in that range anywhere, but we are wait and see what that will be. 28 to 30 is reasonable to expect or maybe even slightly higher.

In terms of your question regarding U.S. sites, as you know that once we enroll patients, we have started off with U.S. sites. The ex U.S. typically, generally takes a few more months to add because they have to get approvals from the individual countries. So we will see later on the global sites also coming on board soon for both the studies.

And the third question?

Basically, the interval between screening and baseline because you know how you can exclude patients if they have a MADRS drop by 25%. And I'm trying to understand, this is effectively a sort of a lead-in that you guys have, and I know a couple of trials have done it. So I was trying to understand how long is that interval between screening and baseline that allows you to exclude perhaps hyperresponders on placebo.

So the screening between screening and baseline, so there's a screening period of up to 14 days. It's a 2-week screening period. So again, you're right that several studies have included several -- different studies have included different strategies to control for placebo, which is one of the strategies.

Right. And to answer, this is not uncommon. And most, if not all, studies imply either this or other ways of trying to reduce the placebo response of patients coming in. Also, on the global trial sites, this too is a standard practice that your U.S. site start up and running first. And then your -- substantially, the rest of your sites will come on board pretty quickly, pretty soon afterwards. So nothing here is unusual.

Got it. And Sharon, would you describe the study as a partial responder or a nonresponder study?

Suresh?

Yes. These are partial responder studies.

Our next question will come from the line of Marc Goodman from SVB Leerink.

Two questions. First of all, as market -- are we having any off-label usage at all for this product, bipolar depression specifically?

Second of all, curious what the team has thought of the Vraylar MDD data and if there are any learnings there that will help you.

And then third, just what was the gross to net in the third quarter? How should we think about those changing into next year?

Yes. Marc, this is Sharon. Thanks for your questions. So as you know, we don't speak to off-label use. Suffice it to say, though, that physicians are allowed to prescribe once your product is approved. And I think if you look at IQVIA and Symphony, you can see whether or not there's been any off-label use.

As to the gross to net, I'll ask Larry to respond.

Yes. This is Larry. Our gross to nets have been pretty consistent over the last several quarters, and we don't expect much change in that. We did disclose that we were in the mid-20s to the low 30s range, and we expect to stay in that range even after bipolar approval if it comes or when it comes.

Okay.

Does that help, Marc?

I'm not sure he heard you, Larry.

I'm sorry, what's that?

Did you hear me? Did you hear me on my response?

Yes. Yes. Yes.

Okay. That's fine.

All right. And on your...

Yes. And then the last one is about the learnings from the Vraylar data.

Right. So I think the -- just so everybody is on the same page, Vraylar has had ongoing studies in adjunctive treatment with major depressive disorder. They have done many studies, 5 studies, and they just reported out on 2 studies, one being negative and one having one dose being positive. Now they didn't tell us a whole lot about the studies. They told us p-values. They didn't tell us anything else.

So we really don't know much. They say they are filing on this. Again, we don't comment on other studies. I think the take-home message is that CNS studies are very complex that the FDA is very accustomed to seeing some studies work. Some studies have complicating factors that makes them not work.

Again, we don't know what happened in these studies. I'm sure that AbbVie will present all of their data at some point, and then we'll know more and then we can say more. Suffice it to say, these are very large markets. These are underserved markets still. And the more opportunities patients have for new treatments, the better for the patients. So I think that we're encouraged and we move forward.

And our next question will come from the line of Jessica Fye from JPMorgan.

Once you're launched in bipolar depression, will you or will we have any way of discerning which scripts are being written for schizophrenia and which are being written for bipolar depression? I'm curious how you're going to gauge your performance and execution in each of those indications.

Mark, do you want to take that?

Yes. Sure. Jessica, there are data sources that allow us to understand for which indications prescriptions are being written. They're not perfect data sources and you have to take them directionally, but it is something that we'll be watching. And certainly, we'll be following and tracking typical metrics that you would in any launch in terms of new patient starts and new prescribers, looking at total prescriptions, looking at our market access coverage, rejection rates, reversal rates, et cetera. But yes, there are data sources that allow you to take a look at that, and we'll be following those.

Okay. And then again, on the bipolar depression launch, can you help us think about the time frame within which you expect to have coverage in that indication?

Yes. So Jessica, the payers don't manage the different indications differently. They manage it at the brand level. So we expect for bipolar depression to be added to the formularies at the coverage just as the schizophrenia patient population is. So we will continue to have very broad coverage in Medicare and Medicaid with over 95% of the covered lives. And as we mentioned, our coverage in commercial is growing steadily. We're up to about 70% coverage, and we expect that to continue to improve and increase over the coming weeks and months.

Okay. And just the last one. How are you thinking about the growth in the schizophrenia indication going forward?

Yes. So we've been -- despite the COVID pandemic with the challenges that, that presents for the schizophrenia patient population, we've been pleased with the continuous quarter-over-quarter growth in schizophrenia that we've seen with CAPLYTA, and we expect that to continue in addition to launching the bipolar depression indication where we expect to see a further acceleration in the overall prescribing of CAPLYTA given the opportunity that we have in the marketplace.

It's a large market opportunity. There's 11 million patients compared to 2.4 million with schizophrenia. There are fewer treatment options available to treat these patients. And we feel very confident in the profile of CAPLYTA that emerged from the bipolar depression trials with the robust efficacy, the favorable safety and tolerability that we essentially replicated, the safety and tolerability profile that we saw in schizophrenia in the bipolar depression population as well. And as I mentioned, we feel we have a very strong commercial plan, comprehensive in place, ready to go, and we expect to see an acceleration in prescriptions due to that.

Yes. And given the favorable safety and tolerability profile, we would expect that in a non-COVID environment, you will see even more of an uptake in the schizophrenic population.

(Operator Instructions) Our next question will come from the line of Ashwani Verma from Bank of America.

I wanted to ask, Mark, how do you think your commercial investments compared to your peers in the antipsychotic space? I see that you have a decent sized sales force that rivals the peers. So you'll be at 320 in [terms of] sales at LATUDA, they started with 340 reps, now they are down to 260, you're kind of in the same ballpark. I'm just curious, I wanted to see like if you could compare your DTC investment or strategy or any kind of metric on number of spots that you're running versus the competitors.

Yes, Ash, thanks for the question. Our goal is to have a highly competitive share of voice in the bipolar depression space. And so we sized our sales force to reach the prescribers that generate 85% of the oral branded antipsychotic prescriptions that are written for the combination of bipolar and schizophrenia. So we feel like we're covering the vast majority of the opportunity there. And in addition to that, with our peer-to-peer medical education, our digital media promotions and our DTC advertising, our goal is to ensure that the benefits of CAPLYTA and the messaging that we have around CAPLYTA are heard in the marketplace. And we feel like the plan that we have in place will do exactly that.

And just to remind you, in a pre-COVID environment, one operated a little bit differently. And as we told you, pre-COVID, we were expecting that with a bipolar indication, we would just about double our sales force. Now with COVID, I think we've all learned how to do things a little bit differently.

So while we do still need to increase our presence because of the increase in the number of docs and offices, et cetera, as you see, it's not a doubling of the sales force. And we think we've sized it appropriately from what we've learned of these hybrid both virtual and in-person meetings.

Our next question will come from the line of Chang Liu from Needham.

This is Chang for Ami. So we just wanted to ask you, can you talk about your expectations for the pace of the launch in bipolar depression post approval? What may be the positive challenges heading into the launch?

And if we may have a second question, can you tell us whether the preapproval site inspection has been completed for bipolar depression and if there were any 483 observations at the site.

Mark, I'll ask you to take the first part, and I'll address the second part. So do you want to take the first part, please?

Yes. Sure. And let me take a shot at it if I understand the question correctly. If this misses the mark, please let me know, and I'm happy to provide further color. But we do plan to launch in bipolar depression immediately upon approval. Our sales force expansion is essentially complete. All of our representatives, including the new representatives, will be trained and ready to go. Right after the launch, all of our marketing materials, the patient support services that we have in place, the infrastructure commercially that we built for the schizophrenia launch and we leveraged for the bipolar launch will be ready to go.

As you know, our PDUFA date is December 17. The last 2 weeks of the year are holiday weeks. But we'll be out there. We'll be out there with our sales force. We'll be out there with our nonpersonal promotion. Many of the offices during that time are closed or they're not seeing representatives. So we wouldn't expect a huge spike in prescriptions those first couple of weeks after the launch. But we will be out there and ready to go from day 1. So I hope that provides some color for the question that you were asking.

Now I'll turn it back to Sharon for the second part of the question.

Yes. And as we said earlier, we're not going through the nitty gritty of our sNDA application. Suffice it to say, though, this should answer your question that we are completely on track and all has been going well, and we're looking forward to our PDUFA date.

Our next question comes from the line of Sumant Kulkarni from Canaccord.

This is a conceptual one. So your adjunctive MDD trial has begun enrollment. It's one of the first waves of trials in this indication that might be able to benefit from our learnings during this pandemic. So just as we've learned on the sales force side that you may not need as many as you had in the past, are there any specific differences or variables you may have needed to adjust, to optimize your Phase III design solely based on the pandemic?

Suresh, do you want to take that or would you like for me to?

Yes. I didn't understand the question you're asking.

I was asking if there was anything that you've learned from the COVID-19 pandemic that might help you to optimize Phase III trial design in the adjunctive for MDD, any variables that you might have otherwise done differently if this pandemic were not around?

Why don't I start and then -- while Suresh is thinking? I think that, as you know, during the pandemic, FDA put out a guidance document on what -- how one should conduct their clinical studies if necessary. And so we have put in -- this is for monitoring and their visits during COVID. And we did put that into place for our bipolar studies that were still ongoing. And we have put that in place here for the MDD studies.

Just as for the bipolar study that was ongoing during COVID, we really did not need to employ those methods. We -- if COVID doesn't spike again, we probably won't need to employ those methods again. But they are in place. They are ready to go. They can be used if necessary. So that was a learn as you go during COVID. So -- and I think right now, the trial is being conducted as you've seen on ClinicalTrials.gov.

And our last question will come from the line of Charles Duncan from Cantor Fitzgerald.

Sharon and team, thanks for fitting us in. We're juggling calls this morning. So I apologize if our question's been asked. So regarding the in-market experience in schizophrenia with regard to CAPLYTA, can you glean any anecdotal evidence of persistence and reduced health care resource utilization in schizophrenics that you may be able to apply to your efforts in bipolar? And then I had a follow-up, if I could, on the pipeline.

So Charles, and yes, we understand it's an extremely busy morning today. Maybe, Mark, do you want to address the question, and I'm not sure that we'll actually have the time to get into the pipeline. But let's see how long the answer to this first question takes. So Mark, do you want to go ahead?

Yes. Sure. Yes, Charles, all signs point to CAPLYTA having a very strong persistency profile in schizophrenia. The caveat is it's too early to do the classical persistency curves where you follow cohorts of patients over time. We probably need another 6 to 9 more months until we have that. But what we do look at very closely each month are refill rates and the TRx to NRx ratio. And when we do that with CAPLYTA and we compare that to historical benchmarks, we find that CAPLYTA is outperforming the other antipsychotics at the same time during their launches.

So we do believe we're seeing a strong persistency profile for CAPLYTA in schizophrenia. And we know from historical data that persistency tends to be a bit better in bipolar patients than it is in schizophrenia. So we think that's a very encouraging sign for the persistency profile for CAPLYTA in bipolar depression once we get approved there.

In addition, I think that our refill rate really not only speak to the tolerability of CAPLYTA, but also to the efficacy. Patients are not having breakthrough cases of schizophrenia of acute exacerbations. And so we think that our refill rates do speak to both the safety and tolerability as well as the efficacy of CAPLYTA.

It's a great segue in terms of that differentiated profile both efficacy and tolerability, how do you think about ex U.S. opportunities, if at all?

So I think that what we have said is we right now are very focused on the bipolar indication, and that we will be turning to looking at ex U.S. opportunities following the bipolar indication. So we'll come back to you on that hopefully very soon.

And I'm not showing any further questions in the queue. I'd like to turn the call over to the speakers for any closing remarks.

Yes. Thank you. So thank you all for joining today. As I said, I know this morning became, as the morning went on, an extremely busy morning. So thank you for participating. And it's really a very exciting time for us at Intra-Cellular Therapies, and we look forward to updating you, to providing innovative medicines to patients going forward, and we look forward to speaking with you soon.

So with that, operator, you can disconnect. Thanks.

Thank you. And this will conclude today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.