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 would now like to turn the conference over to Dr. Juan Sanchez, Vice President and Corporate Communications and Investor Relations. Please go ahead..

Good morning and thank you all for joining us for 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 non-clinical 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, the potential impact of the 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 that 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're 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 continue 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 continue 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 extra parameters 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, most common and debilitating manifestation of this disorder, if approved CAPLYTA could help fill an existing need for effective treatments with a favorable safety and tolerability profile. The FDA is currently reviewing our sNDA for the treatment of bipolar depression in adults.

Our applications are supported by robust positive results from two Phase 3 studies that evaluated the effects of lumateperone in patients with either bipolar I or bipolar II disorder. In both studies, treatment lumateperone substantially reduced depressive symptoms on both primary and key secondary endpoints.

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 salesforce 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 the strategy. This is followed by our Phase 3 studies in MDD, which are double blind placebo controlled six week studies, evaluating lumateperone 42 milligrams as adjunctive treatment any depressants for patients who have an inadequate response to any depressant therapy.

In addition, we have an ongoing program evaluating lumateperone in patients who exhibit next features. Study 403 is a double blind placebo controlled six 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, 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 the 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, an ITI-1284-ODT-SL program. We have initiated our program for the development of ITI-1284-ODT-SL 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 underpinnings our existing data and our clinical development plans for our PDE1 inhibitors and ITI-333 platforms. We discuss the features that make PDE1 isozymes unique among the large family of phosphodiesterase.

We also discussed PDE1's unique tissue distribution and the selective pathway regulation that allows for 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 2 clinical development.

Our external expert explained the therapeutic needs for treating motor symptoms and non motor symptoms, including cognition in this patient population. Our goal for this program is to study lenrispodun potential to improve motor and non motor symptoms, including cognition by enhancing or restoring neuronal function in effective brain regions.

We also have divided ITI-333, a promising drug candidate to address important unmet therapeutic needs and 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 5HT2A 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 explain the current opioid use crisis in the US and outline the unmet therapeutic needs.

Results from an ongoing Phase 1 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 suppress the overall anti psychotic 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 cite its 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 a 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 anti psychotic 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 salesforce 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 healthcare 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 two 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 anti-psychotics and are lighter link 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 $90 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 $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 increases due to higher lumateperone clinical trials costs 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 increase 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?.

Our first question comes from line of Brian Abrahams from RBC Capital Markets..

Hi, good morning. And thank you for taking my questions. 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 for schizophrenia, as well as the bipolar launches you think about that into the early part next year..

Hi, Brian. Thank 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 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 were 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 incursion patient visits, our salesforce 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 that the patients with schizophrenia, when the COVID cases are high, they're probably more impacted than some other patient population.

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 salesforce. 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. Thank you, Mark. And then maybe one more, if I could.

As we look towards the PDUFA in December, can you maybe just characterize I guess, 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 two different decision points that may come out at different times and maybe different for the different indications, or should we assume that these will be I guess, grouped together as one.

Thanks..

So I'll take that, this is Sharon, and we do expect everything to come out together. And we are on track. So I think that's short and sweet, okay..

Next question with line of Andrew Tsai from Jefferies..

Okay, great. Thanks. Good morning. Thanks for taking my questions. 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 one month into PDUFA essentially.

So when I look at the guidelines, it sounds like companies generally enter finally label just labeling discussions with 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 this question. Thanks..

Hi, Andrew. Thanks for your question. And yes, you're right, this does -- and 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 is coming off. It's December 17. And we're working toward that diligently.

And as I said to Brian, everything's 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 or 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 as launch? Thank you..

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

Sure, Sharon. Let me start with the second part of your question, Andrew. First, what we've seen historically in the anti psychotic club 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 anti psychotic. And it's a condition that physicians are used to payers are used to.

And we really don't see that there'll 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 salesforce expansion is essentially complete, all the representatives will be trained and ready to go for launch will be launching immediately upon approval.

We feel like we've got the right size of the salesforce 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 and 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 based on the terrific profile we think we have of CAPLYTA and bipolar depression..

Our next question comes from the line of Umer Raffat from Evercore..

Hi, guys. Thanks for taking my question.

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 matter s to look like in that trial? And I know the inclusion criteria does matter as above 24? Should we be thinking around 28 or perhaps higher? Second, I noticed in both the Phase 3 and this adjunct MDD, the trial sites are in US only.

And I'd be curious what the thought process was on sort of not doing x-US. 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 on that. Thank you so much..

Thanks. Hi, Umer 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 an entry criteria of 24 and above, you expect the higher baseline scores. And these are also adjunctive treatment trials.

So you typically see in that range anywhere, but we have to wait and see what that will be, 28 to 30 is reasonable to expect maybe even slightly higher. In terms of your question regarding US sites. As you know that once we enroll patients, they have started off with US sites.

The x-US typically generally takes few more months to add, because they have to get approvals from the individual countries. So we -- you will see later the global sites also coming on board soon for both the studies.

And the third question?.

Basically the interval between screening and baseline because how you can exclude patients of MADRS dropped by 25% And I'm trying to understand this is effectively a sort of a lead in that you guys haven't 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 hyper responders on placebo?.

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

Right and to answer, this is not uncommon. And most, if not all, studies imply for higher risk or other ways of trying to reduce the placebo response of patients coming in.

Also, on the global trial sites this too is standard practice, that your US 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 non responder Study?.

Suresh?.

Yes, these partial responder studies..

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

Two questions. First US market, are we having any off label usage at all for this product? I call it depression specifically.

And second I am curious with the team thought of the Vraylar MDD data? And if there any learnings there that will help you? And then third, just what was their gross net in the third quarter? How should we think about those changing into next year? Thank you..

Yes. Hi, 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 net, I'll ask Larry to respond..

Yes, hi, it's Larry. Our gross to net have been pretty consistent over the last several quarters. And we don't expect much change in that week; we did disclose that we're in the mid-20s to the low 30s range. And we expect to stay in that range even after bipolar approval if comes or when it comes..

I'm not sure he heard you, Larry..

Did you hear me on my response?.

Yes..

Okay, that's fine. .

And then last question learning from the Vraylar data..

Right. So I think the -- just so everybody's on the same page Vraylar, has had ongoing studies and adjunctive treatment with major depressive disorder. They have done many studies, five studies, and they just reported out on two 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. 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 is that our studies are very complex, that the FDA is very accustomed to seeing some studies work some studies have no complicating factors that makes them not work.

Again, we don't know what happened in these studies, I'm sure that 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 under 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..

Our next question comes from the line of Jessica Fye from J.P. Morgan..

Hey, guys. Good morning. Thanks for taking my questions. 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, 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, and 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 timeframe 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 formulary, that 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 and 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 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 tolerability profile that we saw on 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 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..

Our next question comes from the line of Ashwani Verma from Bank of America..

Hi, thanks for taking our question. I want to ask Mark, how do you think your commercial investments compared to your peers in the anti psychotic space? I see that you have a decent sized salesforce that rivals the peers so you will be at 320. says that Latuda they started with 340 reps now they're down to 260.

So kind of in the same ballpark and just curious wanted to see like if you could compare your DDC 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 salesforce to reach the prescribers that generate 85% of the oral branded and a psychotic prescription, better written for the combination of bipolar and schizophrenia.

So we feel like recovering 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 salesforce. 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 salesforce and we think we've sized it appropriately, from what we've learned of this hybrid, both virtual and in person meetings..

Our next question comes from the line of Chang Liu from Needham..

Hey, this is Chang for Amy.

So we just wanted to ask, can you talk about your expectations for the pace of the launch in bipolar depression, post approval? What may be the positives and challenges heading to the launch? And if we may have a second question can you tell us whether the pre approval 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 you want to take the first part, please?.

Yes, sure. And let me take a shot at 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 salesforce 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 the leverage for the bipolar launch, will be ready to go.

As you know, our PDUFA date is December 17, the last two weeks of the year are holiday weeks, but we'll be out there with our salesforce, we'll be out there with our non personal promotion. Many of the offices during that time are closed or they're not seeing representative.

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 one. So I hope that provides some color for the question that you're asking. Now 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 day. .

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

Good morning. Thanks for taking my question. 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 learning during the pandemic.

So just as we've learned on the salesforce site 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 3 design solely based on pandemic..

Suresh, do you want to take that? Or would you like 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 3 trial designs 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 study, that we are 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 learning as you go during COVID. So and I think right now, the trial is being conducted, as you seen on clinical trials.gov..

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

Hi, Sharon and team, thanks for fitting as same we're juggling calls this morning. So I apologize if our questions been asked.

So regarding that in market experience in schizophrenia with regard to CAPLYTA, can you glean any anecdotal evidence of persistence and reduce healthcare 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 hi, 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 question -- the 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 too early to do the classical persistency curves, where you follow cohorts of patients over time; we probably need another six to nine more months until we have that.

But what we do look at very closely each month, our refill rates and the TRx to NRx ratio. And when we do that with CAPLYTA and we compare that to historical benchmarks, we find the CAPLYTA is outperforming the others anti-psychotics 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 rates 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 x-US opportunities, if at all? Thanks..

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 x-US opportunities following 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 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..