Intra-Cellular Therapies Inc

NASDAQ:ITCI

Earnings Call Transcript 2020-Q3

[Operator]

Good morning, ladies and gentlemen, and welcome to the Intra-Cellular Therapies' Third Quarter Ended September 30, 2020 Financial Results Conference Call. At this time, all participant lines are in a listen-only mode. After the speakers' 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 your host Dr. Juan Sanchez, Vice President, Corporate Communications and Investor Relations. Please go ahead.

[Juan Sanchez]

Thank you, operator. Good morning and thank you all for joining us for today's conference call. Our earnings press release providing a corporate update and details of the company's financial results for the second quarter ended September 30, 2020 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; Dr. Suresh Durgam, Chief Medical Officer; Mark Neumann, Chief Commercial Officer; Larry Hineline, Chief Financial Officer; and Michael Halstead, General Counsel.

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 utilization 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, 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 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 obligation to update such statements.

I will now turn the call over to Sharon.

[Sharon Mates, Chairman and Chief Executive Officer]

Thanks, Juan. Good morning, everyone. We hope you remain safe and healthy during this time of COVID. Since we last spoke to you in August, we've made substantial progress in executing our commercial objectives, and our clinical and preclinical development programs. I am pleased to update you on this progress today. Following my remarks, Mark Newman, our Chief Commercial Officer will provide an overview of our commercial activities. Suresh Durgam, our Chief Medical Officer will discuss our clinical development programs and Larry Hineline, our CFO will provide details of our third quarter financials.

We continue to operate in an environment impacted by COVID. I am particularly proud of our team's resilience, focus and innovative spirit in supporting our growing number of CAPLYTA prescribers and patients during these unprecedented times. We are proud of our almost four-fold increase in total prescriptions in Q3 versus Q2. We also continue to receive positive feedback from healthcare practitioners on their patients' experience. We are confident and expect continued prescription growth and are actively preparing for lumateperone label expansion with a second indication in bipolar depression.

We have also continued to advance our clinical development programs and increased our strong financial position. During the third quarter, we reported positive top line results from Study 402 evaluating lumateperone as an adjunctive treatment to mood stabilizers in patients with bipolar depression. With these positive results and the positive results of our monotherapy study Study 404, we are preparing the submission to the FDA of our supplemental new drug application for the treatment of bipolar depression in patients with Bipolar I or Bipolar II disorder treated as monotherapy or as adjunctive therapy to lithium or valproate.

We expect to complete this submission in the near term and would anticipate an FDA target action date in the second half of 2021. We believe lumateperone has the potential to become a major product in bipolar depression. There are over 11 million adult Americans living with bipolar disorder with only a few approved therapies for bipolar depression. There is an important need for safe and well tolerated alternatives. Lumateperone has the potential to be the only approved treatment for a broad population, which includes patients with either Bipolar I or Bipolar II disorder as the monotherapy or as adjunctive treatment to mood stabilizers.

The benefit of lumateperone as a broad treatment for bipolar depression is further enhanced by its efficacy and favorable safety and tolerability profile. Rates of akathisia, restlessness, extrapyramidal symptoms, and changes in weight and metabolic parameters in our bipolar studies were similar to placebo, consistent with the safety profile demonstrated in all other lumateperone studies. We've designed a broad clinical development program as we believe lumateperone will become a major player in the treatment of depressive disorders, including bipolar depression, Major Depressive Disorder, or MDD, and other depressive disorders.

Lumateperone has shown its antidepressant effects throughout our development programs. Lumateperone has generated positive outcomes in two large Phase III bipolar depression studies. In addition, antidepressant effects were seen in a subgroup of patients with co-morbid depression in short term schizophrenia studies, as well as in our long-term study. In our long-term open label study in patients with schizophrenia, a strong antidepressant effect was observed in patients with co-morbid depression, regardless of whether they were receiving any depressants or not. This provides further support for our Major Depressive Disorder development programs.

Today Dr. Suresh Durgam, our Chief Medical Officer will outline our plans to advance in the tech rounds in MDD, including the changes we've made to Study 403, and our plans for our Phase III studies for lumateperone as an adjunctive therapy in patients with MDD. Following our positive results, and the recently completed Study 402, we have amended Study 403 to expand the opportunity for lumateperone. In a post-hoc analysis of Study 404 in a subgroup of patients with bipolar depression with mixed features, lumateperone 42 milligrams had a statistically significant improvement from baseline on the MADRS total score versus placebo.

Study 403 now evaluates patients with mixed features who have MDD, or bipolar depression. About a third of patients with MDD or bipolar depression exhibit mixed features. These patients respond poorly to antidepressants, have greater symptom severity, have a higher risk of suicide attempts and experienced severe illness with more co-morbidities. Suresh will further explain the unmet need in this patient population. This has been a very busy quarter and we have several other clinical updates. We are excited to announce that following a recent successful Type C meeting with the FDA, we will commence early clinical development of our long-acting injectable, the subcutaneous formulation of lumateperone later this year. Given the safety and efficacy profile of lumateperone, we believe this formulation can be an important option for patients.

Lastly, the clinical development of ITI-333 our novel molecule for the treatment of substance use disorders is advancing. Following a recent successful pre-IND meeting with the FDA, we expect to initiate a Phase I single ascending dose safety and tolerability study evaluating ITI-333 in late 2020 or early '21. We received a grant from the National Institute on Drug Abuse as part of the NIH helping to end addiction long-term, initiative or HEAL to support the early clinical development of ITI-333 for the treatment of opioid use disorder. Further details will be provided as this program progresses.

Our company is in a strong position. CAPLYTA is approved for the treatment of schizophrenia in adults and we have an experienced commercial organization supporting CAPLYTA. We expect to soon submit an sNDA for lumateperone for a second major indication bipolar depression expanding the market opportunity for lumateperone and we have a broad development plan for lumateperone in Major Depressive Disorder and other major neuropsychiatric conditions. We're well capitalized and we ended the quarter with over $723 million in cash and investments.

I'll now turn the call over to Mark. Mark?

[Mark Neumann, Chief Commercial Officer]

Thank you, Sharon and good morning everyone. I appreciate the opportunity to expand on Sharon's remarks regarding our commercialization progress. We continue to be very pleased with the strong commercial execution of our launch and the performance of CAPLYTA in the marketplace despite continued COVID related disruptions to the healthcare system. As COVID conditions remain fluid throughout the US, we continue to innovate, adapt and execute our commercialization strategy, deploying a hybrid model of in person and virtual sales force and medical education capabilities to support CAPLYTAs ongoing launch efforts.

We have also enhanced our digital marketing initiatives, effectively expanding our target audience reach and optimizing our engagements with physicians and consumers. CAPLYTAs level of awareness, trial and usage has grown significantly over the first six months of launch, and this is reflected in our recent prescription performance. During the third quarter CAPLYTAs new and total prescriptions grew by 229% and 279% respectively, relative to Q2 during a time period, when the overall anti-psychotic market was essentially flat due to COVID constraints. This robust growth has continued into the fourth quarter.

We're also very encouraged by physician feedback that patient experience has been highly positive. In our post launch market research surveys, prescribers have CAPLYTA rate overall drug performance higher than other branded anti-psychotics. They highlight the efficacy and favorable metabolic weight and movement disorder profile, the ease of reaching a therapeutic dose with no need for titration as well as the drugs novel mechanism of action. This adds to our confidence that CAPLYTA is performing in the real world as we expected based on the clinical trial results.

CAPLYTAs market access position continues to be strong, payer access for CAPLYTA remains highly favorable and on track with our previously stated expectations. We believe that this strong access position in the largest payer channels Medicare Part D and state Medicaid, having greater than 95% access in both channels is a contributing factor driving physician confidence when choosing to prescribe CAPLYTA for their patients. In addition to updating you on the launch of CAPLYTA in schizophrenia, I'd like to provide you with an early commercial perspective on the exciting potential opportunity for lumateperone in bipolar depression.

We believe lumateperone has the characteristics to become a market leader in this multibillion dollar indication, and we are laser focused on preparing to achieve this objective. According to the National Institute of Mental Health, there are about 11 million people living with bipolar disorder. On an annual basis bipolar disorder affects about 6 million patients per year. There remains a significant unmet medical need in bipolar depression with few approved treatment options for this underserved patient population. The commercial success of recent branded entrance highlights this medical need, and we expect the potential introduction of lumateperone to continue to expand this market.

We also believe that lumateperone has demonstrated a highly favorable profile as the only treatment for bipolar depression in patients with either Bipolar I or Bipolar II disorder and as an adjunctive treatment to mood stabilizers or as monotherapy. We look forward to the potential for an expanded indication in bipolar depression that will complement our promotional efforts today in the schizophrenia market. And we will continue to share our planning progress for the bipolar launch throughout the coming year.

In closing, we are encouraged by our launch performance progress to date. Amidst the market condition challenges presented by COVID, we believe our launch fundamentals are well established giving us increased confidence and optimism in CAPLYTAs bright future. We are pleased with our week-over-week prescription growth, the accumulation of new brand prescribers, our increased reach supported by our comprehensive medical education programs, our real progress direct-to-consumer advertising campaign and CAPLYTAs strong market access coverage. We believe CAPLYTA will continue on the path to become the leading choice for healthcare providers treating adults living with schizophrenia and are excited about the potential of lumateperone in Bipolar I and Bipolar II depression.

I'd now like to hand the call over to Suresh. Suresh?

[Suresh Durgam, Chief Medical Officer]

Thanks Mark. I will provide an overview of our regulatory and research and development plans. Our team has been working diligently preparing the submission for our supplemental NDA for the treatment of bipolar depression in patients with Bipolar I or Bipolar II disorder as monotherapy and adjunctive therapy. I'm happy to share our plans to develop lumateperone for the treatment of other mood disorders. We are expanding our program to address millions of patients suffering from mood disorders, for which there still is a need for safe and effective treatments.

Let me start with our Phase III program in Major Depressive Disorder. We have commenced our Phase III clinical program, evaluating lumateperone 42 milligrams as an adjunctive treatment to antidepressants for Major Depressive Disorder. Clinical conduct in two Phase III studies will begin in 2021. Major Depressive Disorder affects 10% to 15% of US population every year. The response rates to the first pharmacological intervention is 47%, meaning over 50% of patients are candidates for either adjunctive or switching treatment strategies.

Let me continue with our plans to study lumateperone in patients with Major Depressive Disorder and bipolar depression, with mixed features in Study 403. Patients with a unipolar, also known as Major Depressive Disorder or bipolar disorder can exhibit manic symptoms that are below the clinical threshold for mania or hypomania during their depressive episodes. These patients respond poorly to antidepressants, have great symptom severity, have higher risk for suicide attempts and experience severe illness with more co-morbidities. The Diagnostic and Statistical Manual of Mental Disorders or DSM-5 acknowledges this reality and incorporates a mixed features specifier to better characterize these patients.

The number of patients with either unipolar or bipolar depression, presenting clinically with mixed features is significant. There are approximately 17 million patients experiencing a major depressive episode each year in the US, with about a third of these episodes, being accompanied by mixed features. Importantly, mixed features associated with MDD represent an important risk factor for the development of Bipolar I and Bipolar II disorder highlighting the importance of identifying the presence of the specifier to monitor patient's treatment. Bipolar disorder is also highly prevalent psychiatric condition, affecting approximately 11 million Americans. About a third of patients with bipolar depression are estimated to have mixed features. There are no drugs approved for either MDD with mixed features, or bipolar depression with mixed features.

Lumateperone has shown its antidepressant effect in two Phase III bipolar depression studies as well as in patients with co-morbid depression in our schizophrenia program. Importantly, in Study 404, our global safety study in bipolar depression, a post-hoc analysis showed lumateperone was effective in a subset of patients with mixed features with a p value of 0.003. We will be presenting these data at future medical meetings. We have amended Study 403 to study lumateperone in patients with bipolar depression, and MDD with mixed features. This global study evaluates all lumateperone 42 milligrams as monotherapy versus placebo and the primary endpoint is changed from baseline on MADRS total score at week six. Sharon has discussed our progress regarding our early stage programs. We look forward to continue to update you on our future developments.

I will now turn the call over to Larry. Larry?

[Larry Hineline, Chief Financial Officer]

Thanks Suresh. I will be reviewing our financial results for the quarter ending September 30, 2020. We recorded net product sales of CAPLYTA for the third quarter of 2020 of approximately $7.4 million. No net product sales were reported in the same period of 2019.

Research and Development expenses for the third quarter of 2020 were $10.3 million compared to $21.3 million for the third quarter of 2019. The $11 million decrease is due primarily to a decrease of approximately $6.2 million of lumateperone clinical and non-clinical cost, a decrease of approximately 2.9 million in research manufacturing cost and overhead, a decrease of $2.6 million for other projects, and is offset by an increase of $0.7 million for stock based compensation.

Selling, general and administrative expenses were $52.5 million for the third quarter of 2020, compared to $15 million for the same period in 2019. Selling expenses were $38.3 million for the three-month period ended September 30, 2020, as compared to pre-commercialization expenses of $6.4 million in the same period in 2019. This increase in selling related expenses is primarily due to an increase in sales related labor expenses of $15.4 million, and commercialization and marketing expenses of $15.2 million.

General and administrative expenses were $14 million in the three-month period ended September 30, 2020, as compared to $8.6 million for the same period in 2019. This increase is primarily due to increased Information Technology cost of $2.4 million, professional fees of $1.4 million, and stock compensation expense of $1.4 million.

Cash, cash equivalents restricted cash and Investment Securities totaled $723.3 million at September 30, 2020, compared to $224 million at December 31, 2019. In September 2020, we completed a public offering, resulting in net proceeds to the company of approximately $358 million from the sale of 12.7 million shares of our common stock.

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

[Operator]

Thank you. [Operator Instructions] Our first question comes from a line of Jessica Fye with JP Morgan. Your line is now open.

[Jessica Fye, JP Morgan]

Hey there. Good morning. Thanks so much for taking my questions. Maybe first, were there any changes to the amount of inventory in the channel at the end of the third quarter relative to the end of the second quarter?

[Sharon Mates, Chairman and Chief Executive Officer]

Hi, Jess. This is Sharon. I'm going to ask Larry to take that.

[Larry Hineline, Chief Financial Officer]

When you mean changes in inventory, you mean quantities?

[Jessica Fye, JP Morgan]

In the channel, yeah, the amount of inventory held by wholesalers any different at the end of 3Q relative to 2Q.

[Sharon Mates, Chairman and Chief Executive Officer]

Yeah, let me just remind you that this is a business that it's unlike many years ago, where there was a lot of stocking, there isn't stocking going on in this class. We have movement of product that happens very rapidly, within 24 hours, usually. So it's not an inventory laden product. At this point in time, the wholesalers actually are able to move product extremely efficiently. And

[Larry Hineline, Chief Financial Officer]

And I'll add to what Sharon saying. As we're increasing sales, we're increasing inventory. And that goes along with the sort of just in time inventory system that we're seeing. So as sales increase the inventory in the channel obviously will increase.

[Jessica Fye, JP Morgan]

Okay, makes sense. So it looks like gross amounts were fairly modest in the third quarter. And I'm wondering, is this average net selling price, you're seeing a good run rate to think about going forward? Or are there other swing factors that could cause it to differ in subsequent quarters? In particular, I'm just trying to think ahead to 2021. And if we should anticipate any variability in quarterly growth to net looking ahead,

[Larry Hineline, Chief Financial Officer]

As you know, we've never really commented on gross to net and gross to net is, as you know, dependent upon several factors, some of which is product mix, and the like. So and you're seeing it from compare - I'm assuming comparing scripts to our revenue. And so as we're maturing into in our sales, and our product mix, you'll see changes but we're not an outlier with regards to other companies that are in our same position but in our evolution. So I really can't comment too much on the changes of gross to net as you see them, but I can say that there weren't - they're not an outlier and they're reasonable.

[Jessica Fye, JP Morgan]

Okay, just thinking about how some companies feel a little bit more of an impact in Part D in the first part of the calendar year relative to later in the year. So we'll just keep an eye out on that.

[Larry Hineline, Chief Financial Officer]

Yeah.

[Jessica Fye, JP Morgan]

Maybe switching to Study 403, just want to make sure I understand the changes this here. So these patients can have either MDD or bipolar depression. They all need to have mixed features now, is that correct?

[Sharon Mates, Chairman and Chief Executive Officer]

I'll ask Suresh to answer that.

[Suresh Durgam, Chief Medical Officer]

Yes. Hi. Good morning. The 403 has been amended to include patients both with Major Depressive Disorder and bipolar depression. And the patient's will exclusively have mixed features in this new amendment.

[Jessica Fye, JP Morgan]

Okay, and when you say that third of patients have mixed features between MDD and bipolar depression, is that proportion the same in each respective group? It's a third in MDD and the third in bipolar depression?

[Suresh Durgam, Chief Medical Officer]

Yes, in terms of the literature, there is varying ranges. And a third would - a reasonable estimate and equity conservative estimate both for Major Depressive Disorder and for bipolar depression, you will see a mixed feature about a third in both populations.

[Operator]

Thank you. Our next question comes from the line of Charles Duncan with Cantor Fitzgerald. Your line is now open. Hi, this

[Pete Stavropoulos]

Hi, this is Pete Stavropoulos on for Charles, congratulations on the quarter.

[Sharon Mates, Chairman and Chief Executive Officer]

Thank you.

[Pete Stavropoulos]

Yeah, I was just wondering, from your perspective, are there any specific analogues that can sort of help us think through the ramp rate and ultimately, the time it takes to develop the traction you're anticipating for lumateperone or CAPLYTA?

[Sharon Mates, Chairman and Chief Executive Officer]

I don't know. Mark, do you want to take that? Or would you like me to?

[Mark Neumann, Chief Commercial Officer]

Yeah. No, I can make a couple comments, Sharon and you can add to it if you'd like. Analogues are challenging, both in this category and because of the COVID related conditions that we've been operating under since the beginning of the launch. I would say when we look at the various recent brand - and I say recent over the past five to seven years, branded antipsychotics, part of the challenge in an analogue is many of the products launched with multiple indications, whereas we're launching with just a schizophrenia indication. So we look - we try to triangulate and look at a variety of the different branded antipsychotic uptakes, and then do some adjustments based on some of the COVID related disruptions that we've mentioned.

And overall, I would say that when we look at that, we are very pleased with both the commercial execution that we've been able to deliver during this time, as well as the uptake trajectory and the consistency of the growth that we've seen week-over-week in prescriptions and as we mentioned in the quarter-over-quarter growth. So we're pleased with where we are. And we'll have to see as time goes on with COVID, we believe we can operate very effectively in this environment and adapt as we need to. And then as the COVID period passes and we get back to a new normal, we would look for continued acceleration and prescription. So Sharon, I don't know if you want to add anything to that.

[Sharon Mates, Chairman and Chief Executive Officer]

I have nothing to add.

[Mark Neumann, Chief Commercial Officer]

Okay.

[Pete Stavropoulos]

Thank you, very helpful. One more question, with the sNDA filing in the near future for BPD, what should we think about how the current commercial organization could be leveraged? And what needs to be put in place as you address the new indication if anything?

[Sharon Mates, Chairman and Chief Executive Officer]

So Mark, do you want to take that one too?

[Mark Neumann, Chief Commercial Officer]

Yeah. Sure. I think the biggest area would be in the area of our sales force. As we think about the opportunity in bipolar depression. The good news for us is that our current target audience of 23,000 physicians that represents 80% of the branded antipsychotic opportunity in schizophrenia, virtually all of those 23,000 also treat patients with bipolar depression. So we will be able to leverage our existing footprint, our existing sales force. However, as you've heard some of the prevalence numbers, the prevalence of bipolar depression is significantly higher than schizophrenia. So the patient numbers are very high, much higher than schizophrenia, and therefore, the physicians target audience will be larger as well. So there is another subset of physicians who treat bipolar depression patients in significant numbers, who don't currently treat schizophrenia patients.

And so that would be the physician subset that we would look to expand our sales force. We're in the middle of doing that work right now. We don't have specific numbers for you. But we would expect to expand our sales force in order to ensure that we have sufficient coverage to get to the opportunity that we see in bipolar depression. I would say that's probably the biggest area of expansion for the organization. Now, as we do that we also have to bear in mind some of the changes to that COVID has brought on and some of the permanent changes that we think will take place in terms of virtual engagement of physicians and their preference for virtual engagement. And we're factoring all of that into our final decisions about the magnitude of the expansion of the sales force that we would have.

[Operator]

Thank you. Our next question comes from the line of Sumant Kulkarni with Canaccord. Your line is open.

[Sumant Kulkarni, Canaccord]

Good morning, thanks for taking my question. We know you've spoken about newer formulations of lumateperone potentially for MDD. But do any of the planned trials involve a new formulation? And does the monotherapy trial specifically evaluate the potential for lumateperone as a rapid acting product for MBD?

[Sharon Mates, Chairman and Chief Executive Officer]

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

[Suresh Durgam, Chief Medical Officer]

Yes, I can. The MDD programs are being studied with lumateperone - adjunctive treatment program is going to be studied with lumateperone. And we will update you on the formulations at a later part.

[Sumant Kulkarni, Canaccord]

Yeah, and then on the commercial side a question from Mark, I'm sorry if I missed this, but do - now that you're into the launch for a few months. Do you have any better sense of how many patients were on how many drugs before cycling through to lumateperone for schizophrenia or CAPLYTA?

[Mark Neumann, Chief Commercial Officer]

Yeah, thanks Sumant. As you know the category and a therapeutic area that it has as its hallmark, significant cycling through various antipsychotics by patients because of some of the limitations of the existing anti psychotics whether it's on the efficacy side or on the safety and tolerability side. And what we're seeing in terms of the patients that we are sourcing for CAPLYTA is really across the board, we are seeing initial starts, new patient starts for CAPLYTA, as well as those patients that have been on multiple antipsychotic. So I would say the vast majority of patients living with schizophrenia have been on multiple antipsychotics, two, three, four antipsychotic. And this is really where the most significant opportunity for a switch to CAPLYTA exists. So I'm not sure if that answers your question, Sumant. Specifically, but I guess what I would say is we're seeing patients being sourced across the board, whether they've been on one antipsychotic, two antipsychotics, three antipsychotic, as well as some patients if their insurance allows for initial therapy following diagnosis as well.

[Sumant Kulkarni, Canaccord]

Got it, thank you.

[Operator]

Thank you. Our next question comes from the line of Umer Raffat with Evercore. Your line is now open.

[Bo Chen, Evercore]

Hi, this is Bo. Thanks for taking our questions. We'll have to if we may. And first on the pattern status, how should we think about the CAPLYTA exclusivity, given the Orange Book patents on the salt patent - on the salt crystal form that has 2029 expiry? And how important should we think about the method of used patents and like the injectable formulation and lifecycle management? The second question if we may is on the Study 403 with the amendment. We're curious given the primary endpoint still MADRS change at week six. It's a depression rating scale. How should we think about the efficacy measure for the manic symptoms? Thanks a lot.

[Sharon Mates, Chairman and Chief Executive Officer]

Great. Hi, Bo. This is Sharon and I'll take the first part about patents. And I'll ask Suresh to address the second part about the MADRS and how you're going to measure and what you're going to use for the mania portion. So first, let me just start with an overall statement about, we believe we have a very strong patent portfolio that we expect will protect lumateperone into the mid-2013. We have multiple Orange Book listed patents with expirations ranging from 2028 through out to 2039. In addition, as you know, we have the option to select one of the earlier expiring patents for extension to the mid-2030s. We also expect to list additional patents in the Orange Book following approval of lumateperone for bipolar that will run well into the 2030s.

So I would not focus on the one patent that you did focus on. I don't think that's the right place to be. Our patents include coverage of any pharmaceutical composition containing the active ingredient lumateperone, cover use of lumateperone to treat schizophrenia and bipolar following its approval, lumateperone in various dosage forms, including the 42 milligram dose lumateperone crystals. And so we believe that our position is extremely strong and that generics cannot avoid using of the approved drug substance, the approved indication or the approved dose. So we believe these patents are not readily circumventable. So I think that that's really the answer to your question. And then Suresh, would you like to comment on, if you remember now, the question. Okay.

[Suresh Durgam, Chief Medical Officer]

Yeah, regarding the 403, we have amended to study both populations Major Depressive Disorder and bipolar disorder and mixed features. And the primary efficacy endpoint will be MADRS total score, because the primary diagnosis is depression with mixed features. And for the mixed features for the hypomanic symptoms and the manic symptoms that we see, we are also measuring YMRS, Young Mania Rating Scale in the study. So that will give us the information regarding the manic symptoms.

[Operator]

Thank you. Our next question comes from the line of Marc Goodman with SVB Leerink. Your line is now open.

[Roanna Ruiz, SVB Leerink]

Hi, this is Roanna on the line for Marc. Thanks for taking the question. I have two, first on the 403 study. Could you remind us about your expected top line readout timing given the amendment? And second question is flipping to schizophrenia. I was curious if you could give us any color possible on any persistence rates or discontinuation rates you're observing from 2Q to 3Q? Thanks.

[Sharon Mates, Chairman and Chief Executive Officer]

So I'll take the first part. And I will start with saying that I'd like to remind you that this study is not part of sNDA. Of course, safety data is always reported where you are, but it is - it will not be on - our sNDA is not dependent upon Study 403. That's first. Then you asked about the readout time. Because of these times of COVID we're giving ourselves a lot of time here. And what we're going to say is in 2022. I guess for your next question is about persistence. And I think it's a little early to talk about that. But Mark, do you want to add anything about that?

[Mark Neumann, Chief Commercial Officer]

Yeah. No, that's right Sharon. It is too early to get sort of the longitudinal persistence and compliance. Great that you're asking about, but what I would say is what we are tracking very closely is the refill rate of prescriptions. And we've been very pleased to see a high refill rate consistent with our expectations, given the profile of CAPLYTA over the favorable safety and tolerability profile and the efficacy profile that it has. And as we track those and look at historical benchmarks, we are tracking ahead of historical benchmarks in this area. So we're actually very pleased with the refill rates that we're seeing.

[Operator]

Thank you. [Operator Instructions] Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open.

[Leo Timashev, RBC Capital Markets]

Hi, it's Leo on for Brian. Thanks for taking my question. I guess I had a kind of a multi-part question on MDD. So just to clarify is Study 403 going to be in monotherapy for MDD. And is this going to be able to support an sNDA for MTD? And then looking ahead to the other two MDD trials that you're going to be running, can you give any initial thoughts on what you think are going to be primary and secondary endpoints, patient enrollment numbers? And then I guess just lastly, on that same point, I mean, MDD and bipolar, often there's the misdiagnosis there. So I'm just wondering if you've had an opportunity to look back across the bipolar trials and perhaps see any initial sense of efficacy in MDD. Thanks.

[Suresh Durgam, Chief Medical Officer]

Yes, in terms of -

[Sharon Mates, Chairman and Chief Executive Officer]

Go ahead Suresh. I was going to just shorten it for the sake of time, but go ahead and then I'll also add.

[Suresh Durgam, Chief Medical Officer]

Sure, in terms of the first question for the 403, it is in monotherapy. We're studying patients with Major Depressive Disorder and bipolar depression, with mixed features, so that is a monotherapy trial. In terms of the adjunctive treatment, as we said that clinical conduct will begin in 2021. And we will update shortly, once the trials are started on ClinicalTrials.gov the details of the primary endpoint and other details in terms of the sample size, all that will be posted at ClinicalTrials.gov.

[Operator]

Thank you. Our next question comes from the line of Jason Butler for JMP Securities. Your line is now open.

[Roy Buchanan, JMP Securities]

Hi, Roy in for Jason. Thanks for taking the question. Just a quick one, can you give us an update on the plans and timing for ITI-214? Thanks.

[Sharon Mates, Chairman and Chief Executive Officer]

Yeah. Hi, this is Sharon. Thanks for the question. So we had a lot going on this quarter. And we really had wanted to make sure that we spent all the time on lumateperone and those products. We did talk about the long acting injectable. And we also did talk about 333, the PDE1 programs, of which there are a few both preclinical and that will go into clinical study - more clinical studies, for instance, in Parkinson's disease, we will update you on that on our next call.

[Operator]

Thank you. Our next question comes from the line of Andrew Tsai with Jefferies. Your line is now open.

[Andrew Tsai, Jefferies]

Thanks. Good morning. I guess my question is as investors do more work in the bipolar depression market. Can you maybe just kind of explain how physicians are currently treating Bipolar I and II depression? Are all, I guess patients in the US treated by antipsychotic, lithium or valproate or is there going to be some white space out there for CAPLYTA? And I guess a secondary question to that is just within bipolar depression are patients cycling through available therapy similar to the dynamic we see in the schizophrenia market? Thanks.

[Sharon Mates, Chairman and Chief Executive Officer]

Okay, I'll start and I'll ask if Suresh wants to fill anything in. And I'll sort of go backwards. There's definitely white space, as you call it, because there are many patients with bipolar disorder who are not being treated right now. As Mark mentioned, there are 11 million Americans with bipolar disorder. Patients do cycle through these drugs. As well as what we see with schizophrenia. Of course, there are fewer of these drugs so they do. So they have fewer options to cycle through. I missed some of your other questions. I know you had a couple more. Andrew, are you there? Me?

[Andrew Tsai, Jefferies]

Hello.

[Sharon Mates, Chairman and Chief Executive Officer]

Yeah, I'm sorry, we couldn't hear you.

[Andrew Tsai, Jefferies]

Okay, I personally just want to understand if within the Bipolar II space if Seroquel is being used for all Bipolar II patients and patients have exhausted that antipsychotic and there are no treatment options left.

[Sharon Mates, Chairman and Chief Executive Officer]

Seroquel is being used. Other drugs are being used as well. And the extent to which they're used is a little bit - the numbers are not exact. Mark, do you want to fill in? Do you want to add to that?

[Mark Neumann, Chief Commercial Officer]

Yeah, I'm sorry. Andrew, could you just restate your question on that?

[Andrew Tsai, Jefferies]

Yeah, I mean, there seems to be a lot of - in theory Bipolar II depression patients in the US and so given that Seroquel is only drug approved technically in the label for Bipolar II, I mean, have all patients essentially gone on Seroquel, Bipolar II patients? Thanks.

[Mark Neumann, Chief Commercial Officer]

Yeah. No, I wouldn't think that all patients have gone on to Seroquel. What I would say for us from a commercial perspective, having the indication for which we would expect upon approval gives us the opportunity as a commercial organization to actively promote in that patient population. And I also think that it gives physicians added confidence that the FDA has approved for efficacy and safety specifically in that patient population and we believe that will be a very strong, compelling message for CAPLYTA, again, if and when we are approved in bipolar depression.

[Andrew Tsai, Jefferies]

Makes sense, okay. Thank you.

[Operator]

Thank you. This concludes today's question-and-answer session. I would now like to turn the call over to Dr. Sharon Mates for closing remarks.

[Sharon Mates, Chairman and Chief Executive Officer]

Great. Thank you, operator and thank you all for participating on today's call. We're very excited as we move forward with our next indication filing for the treatment of bipolar depression, and with our long acting injectable as well as our programs like 333 and 214 program. So we look forward to updating you in the near future. And I think operator you can now disconnect. Thank you.

[Operator]

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.