Good morning, ladies and gentlemen, and welcome to Intra-Cellular Therapies Fourth Quarter and Year-End Financial Results Conference Call. At this time all participants are in a listen-only mode. [Operator Instructions] As a reminder, today’s conference call is being recorded. I’d now like to turn the conference over to Dr.

Juan Sanchez, Vice President, Corporate Communications and Investor Relations. Please go ahead..

Good morning and thank you all for joining us today. Our earnings press release provides our corporate update and details of the company’s financial results for the fourth quarter and year ended December 31, 2021. This press release crossed the wire a short time ago and is available on our website. Joining me on the call today are Dr.

Sharon Mates, Chairman and Chief Executive Officer; Mark Neumann, Executive Vice President and Chief Commercial 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 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 are excited to be here today to discuss our fourth quarter and full year results. 2021 was an extremely productive year for our company, highlighted by the FDA approval and commercial launch in late December of CAPLYTA for bipolar depression.

We are very excited about this label expansion and the opportunity to help patients with bipolar disorder in addition to patients with schizophrenia. CAPLYTA is the first and only treatment indicated for depressive episodes associated with bipolar I or bipolar II disorder in adults as monotherapy or as adjunctive therapy with lithium or valproate.

We believe this establishes strong differentiation in the market and provides an important advance for patients with bipolar I and bipolar II disorder, underserved conditions that have had limited approved treatment options for bipolar depression until now.

Throughout 2021, we achieved consistent quarter-over-quarter prescription growth with CAPLYTA’s schizophrenia indication, even in the face of a challenging pandemic environment. This growth has accelerated in 2022 with the robust initial prescription uptake following the expansion of our label for bipolar disorder.

We have seen a significant inflection in both new and total prescriptions in the early weeks of the launch and we are encouraged by the highly positive feedback we’ve been receiving from prescribers and patients. Our commercial team is executing a comprehensive launch plan, and we are confident in CAPLYTA’s continued growth.

We believe CAPLYTA is well positioned to become a leading product for patients with bipolar depression. Bipolar depression is the most common and debilitating clinical presentation of bipolar disorder. These depressive episodes last longer are more difficult to treat recur more often and have a worse prognosis than manic and hypomanic episodes.

There are only a few treatments approved for bipolar depression. Bipolar I depression tends to receive more attention because prior to CAPLYTA, there was only one medicine approved for bipolar II depression, and only as monotherapy.

Bipolar II is a complex clinical condition with depressive episodes that last longer and are more severe than bipolar I depressive episodes with patients having a higher risk of suicide. The patient populations for bipolar I and bipolar II disorder are of similar size. Safety and tolerability trade-off can limit use of agents.

Side effects such as weight gain, cardiometabolic disturbances and movement disorders are common reasons for patients to switch or discontinue treatment. A favorable safety profile is important and there is demand for effective, safe, and well tolerated treatment options.

In clinical trials, CAPLYTA has consistently shown a favorable profile on weight cardiometabolic parameters and extrapyramidal symptoms or EPS. Specifically, EPS, including akathisia and changes in weight were similar to placebo in our registration trials.

In our long-term open-label studies, patients with bipolar depression were stable with respect to weight, with no weight gain from baseline at six months, while patients with schizophrenia lost in average of about seven pounds at one year. Now turning to the progress we have made in our other clinical development programs.

Our goal is to establish CAPLYTA as the treatment of choice across a broad range of mood disorders, that has already started with our approval for the treatment of bipolar depression.

Bipolar disorder affects approximately 11 million adults in the United States and our plan is to expand our label to include major depressive disorder or MDD, which affects another approximately 21 million adults. Only half of patients with MDD respond to initial therapy and only one-third achieve remission.

Patient enrollment is ongoing in our MDD registration studies. These are double-blind placebo controlled six-week studies evaluating lumateperone 42 milligrams as adjunctive treatment to antidepressants.

In addition to our adjunctive MDD program in study 403, we are evaluating lumateperone as monotherapy in patients with MDD or bipolar depression, exhibiting mixed features. Roughly one-third of patients with MDD and bipolar disorder who experienced depressive episodes have mixed features.

Additionally, we are developing long-acting injectable formulations of lumateperone. We have completed initial clinical conduct in our Phase 1 single ascending dose study to evaluate the pharmacokinetics safety and tolerability of our long-acting injectable formulation in patients with schizophrenia.

We are encouraged by the safety and tolerability results we have seen in this study to date. We are now exploring alternate sites of injection with this formulation, as well as progressing other formulations. This will assist us in evaluating dosing strategies and formulation for our efficacy study.

The goal of our program is to develop formulations that are effective, safe, and well tolerated with treatment durations of one month and longer. In addition to lumateperone, we have continued to advance other programs in our pipe line.

In our it ITI-1284-ODT-SL program, we have completed single and multiple ascending dose studies in healthy, young and elderly subject demonstrating rapid absorption and excellent drug exposure, allowing doses to be selected for our next studies. In these studies, 1284 was shown to be safe and generally well tolerated at all doses tested.

Additional Phase 1 studies are either ongoing or planned, including food effect and brain imaging studies. We expect to commence clinical conduct in our ITI-1284 Alzheimer’s disease agitation program in 2022. We also have additional studies planned in 2022 in dementia-related psychosis and certain depressive disorders in the elderly.

Additionally, we are making progress in our phosphodiesterase type I inhibitor or PDE1 program. We are evaluating our lead PDE1 compound lenrispodun in a Phase 2 clinical program for Parkinson’s disease. We expect to begin patient enrollment in the first half of this year. We continue to explore additional potential applications of our PDE1 inhibitors.

Last year, we presented preclinical data describing the antitumor effects of PDE1 inhibitors when administered in conjunction with checkpoint inhibitor immunotherapy. We continued to be excited by the prospect of treating cancers with limited treatment options by combining our PDE1 inhibitors with other immunotherapies.

We look forward to presenting additional preclinical data later this year. Finally, we continue to make progress on our ITI-333 drug candidate for the treatment of opioid use disorder and pain. We recently completed of Phase 1 single ascending dose study, evaluating the safety, tolerability and pharmacokinetics of ITI-333.

In this study, ITI-333 was generally safe and well tolerated and achieved plasma exposures at or above those required for efficacy as determined in preclinical models. We look forward to providing further details as this program progresses, I’ll end my remarks with a brief summary of our Q4 2021 and full year financial performance.

Last year, we continued to deliver consistent quarter-over-quarter, CAPLYTA prescription growth in a market environment, still constrained by the coronavirus pandemic. This growth is a Testament to the commitment, agility, and resilience of our commercial organization.

Total revenues were $25.7 million for the fourth quarter 2021, representing 106% increase over the same period in 2020 and $83.8 million for the full year of 2021, representing a 267% year-over-year increase. Larry will provide additional details on our financial performance in his remarks.

We’re in a strong financial position, we ended Q4 2021 with approximately $412.3 million in cash, cash equivalents and investment securities. In January, 2022, we received approximately $433 million in net proceeds from our public offering of common stocks, additionally, we have no debt.

In summary, I’m very proud of our team, our accomplishments, and our commitment to patients. I look forward to continued productivity and growth and sharing updates on our progress with you in the year ahead. I’ll now turn the call over to Mark, who will provide further granularity on our bipolar launch and our commercial performance.

Mark?.

Thanks, Sharon, and good morning, everyone. I’m very pleased to have the opportunity to highlight our commercial accomplishments during 2021 and provide an update on the strong start to the launch of our new bipolar depression indication.

We are very encouraged by the robust initial uptake and accelerated prescription trends for CAPLYTA following FDA approval of our label expansion. We are also encouraged by the positive physician receptivity to CAPLYTA’s bipolar approval in a broad patient population and in its favorable weight metabolic and EPS profile.

More on the bipolar launch in just a moment. Throughout 2021, we drove consistent quarter-over-quarter, CAPLYTA prescription growth demonstrating strong execution in the COVID environment. Total prescriptions for the fourth quarter increased 15% sequentially over the third quarter and increased 98% year-over-year versus the fourth quarter of 2020.

This growth performance significantly outpaced the branded and overall antipsychotic markets for both periods.

CAPLYTA maintain broad market access coverage throughout 2021 in the Medicare Part D and Medicaid channels with greater than 98% of lives covered, and we expanded coverage in the commercial channel from approximately 55% to over 80% by year end.

In Q4, we increased our sales force to 320 neuroscience sales specialists to cover an expanded customer base of approximately 43,000 prescribers, including psychiatrists, nurse practitioners, and primary care physicians who treat bipolar depression.

Our sales force continues to effectively execute a hybrid commercialization model, combining primarily in person presentations with supplemental virtual engagements. Now let me provide some additional detail on our bipolar launch.

We initiated the commercial launch of CAPLYTA for bipolar depression immediately following FDA approval in late December, and have subsequently seen a significant inflection in both new and total prescriptions.

Comparing the first seven weeks of this quarter, following the launch to the same period in the prior quarter, CAPLYTA has grown new prescriptions by 48% and total prescriptions by 35%. We have also seen a significant increase in CAPLYTA sample requests, a leading indicator signaling future prescription growth.

Physicians typically dispense product samples to patients to evaluate effectiveness and tolerability of a new medication. It’s important to note that these samples not captured as prescriptions in the data services.

Early physician feedback on CAPLYTA’s clinical profile in bipolar depression and their patient’s initial experience with the product has been highly positive. Physicians cite the approved indications in both bipolar I and bipolar II in adults as monotherapy and adjunctive therapy with lithium or valproate as unique and addressing and unmet need.

They point to the proven efficacy in both bipolar I and bipolar II, as well as the favorable safety and tolerability profile with weight metabolic changes, EPS, and akathisia all similar to placebo as powerful reasons to prescribe.

And they appreciate the convenience of CAPLYTA’s titration free, once daily dosing that can be taken with, or without food. Looking forward, we see a major opportunity for brand growth by increasing market penetration for CAPLYTA and by expanding the market.

CAPLYTA’s new indications, including both bipolar I and bipolar II combined with proven safety and tolerability and convenient dosing provide an important treatment option for newly diagnosed patients or those seeking a treatment change due to either suboptimal, efficacy or tolerability issues or existing antipsychotic.

This will drive market penetration for CAPLYTA. Additionally, we expect the bipolar market to continue to expand. Many patients with bipolar disorder are initially misdiagnosed with unipolar depression resulting in a delay in inappropriate treatment.

Over time with education, we see the number of patients being properly diagnosed and receiving effective therapies increasing. This is especially true for bipolar II patients where CAPLYTA is one of only two drugs approved.

In summary, we are very encouraged with the initial stages of CAPLYTA’s launched in bipolar depression and our current launch trajectory. We are privileged to be able to help patients with bipolar depression, and we are confident that CAPLYTA’s prescription growth will continue to accelerate. I’ll now turn the call over to Larry..

Thank you, Mark. I will now provide a summary of our financial results for the fourth quarter and for the year ending December 31, 2021.

Total revenues in the fourth quarter grew to $25.7 million compared to $12.5 million in the fourth quarter of 2020, we’ve recorded net product revenue of CAPLYTA of $25.5 million in the fourth quarter of 2021, compared to $21.6 million in the third quarter of 2021 and $12.4 million for the same period in 2020, representing an 18% growth versus Q3 2021 and a year-over-year quarterly increase of 106%.

Research and development expenses for the fourth quarter of 2021 were $29.5 million compared to $14.3 million for the fourth quarter of 2020. Selling, general and administrative expenses were $79.7 million for the fourth quarter of 2021, compared to $58.3 million for the same period in 2020.

For the full year 2021, total revenues were $83.8 million compared to $22.8 million in total revenues for 2020. Net product revenues of CAPLYTA were $81.7 million for the full year 2021, compared to $22.5 million for 2020. Cost of product sales was approximately $8 million for the year ended December 31, 2021 compared to $1.9 million for 2020.

Research and development expenses for the year ended December 31, 2021 were $88.8 million compared to $65.8 million for 2020. This increase is due to higher lumateperone clinical and non-clinical trial cost and an increase in share based compensation cost.

Selling, general and administrative expenses were $272.6 million for the year ended December 31, 2021 compared to $186.4 million for 2020. This increase is primarily due to an increase in marketing, labor and share-based compensation cost.

Net loss for the year ended December 31, 2021 was $284.1 million or $3.50 per share compared to a net loss of $227 million or $3.23 per share for 2020. Cash, cash equivalents and investment securities, totaled $412.3 million at December 31, 2021 compared to $657.4 million at December 31, 2020.

In January, 2022, we completed a public offering of our common stock in which we sold approximately 10.95 million shares of common stock for aggregate gross proceeds of $460 million and net proceeds of approximately $433.7 million. This concludes our prepared remarks. Operator, please open the line for questions..

[Operator Instructions] Our first question comes from the line of Jessica Fye from JPMorgan. Your line is now open..

Hey there. Good morning. Thanks for taking my questions. Couple on CAPLYTA. Can you talk about your DTC strategy here? I guess, what is the strategy? How do you measure its success? And how do you kind of measure the return on those efforts? And then another commercial question.

How leverageable is your current sales infrastructure when we think about future expansion into adjunctive MDD? Would this require a sales force expansion to target even more prescribers? And if so, what’s a good framework to use to think about that?.

Great. Good morning, Jessica. And thanks for the questions. I’ll ask Mark to take these questions, please..

Yes. Sure, Sharon, and thanks, Jessica.

Yes, we believed from the start that the patient and consumer is an important part of our strategy overall for CAPLYTA, starting with schizophrenia, and we certainly believe continuing on into bipolar that reaching out, driving awareness with potential patients, having them ask their physician if CAPLYTA is an appropriate treatment for them, is an important part of the marketing mix, and we expect to continue to do that.

Certainly, as we execute on that plan, we track prescriptions, we track awareness levels, we track receptivity to message. All of those things will tell us just how successful our consumer efforts are being.

Regarding the sales force infrastructure, I think it’s still a little early to talk about the sales force – any potential sales force expansion into MDD. Certainly, there is overlap with the psychiatry community, with nurse practitioners and with primary care.

But I think at this stage, it’s probably a little too early to be commenting on any kind of specific numbers or magnitude of a potential expansion..

Okay, thank you..

Thank you. Our next question comes from the line of Brian Abrahams from RBC Capital Markets. Your line is open..

Hey guys good morning. Congrats on the launch progress and thanks for taking my question. I guess on – it sounds like you’ve made a lot of headway on – in terms of patient access for commercial payers.

I’m curious, when you think we can get to a point where it’s comparable access to public payer, whether you’re still anticipating comparable gross to nets there? And then any differences we should be thinking about with respect to the time or effort required to convert scripts for commercial patients versus public pay patients and how that might evolve? And then just real quick, I was wondering if you could comment on the degree to which timing and conduct of the ongoing mixed feature and MDD studies might be impacted by having Ukraine and Russia sites.

Thanks..

Good morning, Brian. This is Sharon. And thanks for your questions. I tried to write them as quickly as you were speaking, but we may need for you to repeat some of them. I’ll ask Mark to start with payer access, then Larry to talk about our gross to net. And then I will talk about impact of ongoing conflict on our clinical studies.

So Mark, would you like to start, please?.

Yes, sure. Thanks for the questions, Brian. And yes, just to take a step back on the payer access, as you’re aware, when we had the schizophrenia indication only, it was very important for us to have very broad access in Medicare Part D and Medicaid.

We achieved that early on in the launch, and we’ve maintained that broad access in those two channels over the course of the launch in over 98% of patients.

As we began to prepare for the bipolar depression opportunity, we recognized that there would be a shift in patient mix more towards the commercial channel as with schizophrenia, only about 15% to 20% of patients come through the commercial channel, but with bipolar, it is closer to 50-50 commercial and public markets.

So we increased our commercial coverage from about 55% in the middle of the year, up to over 80% by year-end, and we do expect that to continue to grow and expand in the coming weeks and the coming months. So maybe I can turn it over to Larry to comment on gross to nets..

Yes, sure. And as you would expect, with the bipolar launch off to a very good start and our commercial channel increasing, that would have a potential impact on the amount of co-pay assistance provided to patients.

As a result, I think you would look for our gross to net to be at the higher end of the range that we had previously disclosed to you, which is the mid-20s to the low-30s..

Well, so now we’re looking at the higher range of a gross to net in the low-30s. Okay. I think then I’ll take the last of your questions, I think, and that is an impact of the ongoing conflict on our clinical studies.

So again, let’s just take another step back and look at our clinical program, and again, in particular, those that may have exposure from the ongoing conflict. Let’s start with our mixed features or Study 403. As you know, this is a global study and includes sites that have been enrolling in the Ukraine and Russia.

We have implemented mitigation strategies in response to recent events. And given these strategies, we continue to expect that we will complete clinical conduct later this year. As we have said previously, depending on when the clinical conduct is completed, we anticipate reporting top-line data, either late this year or early next year.

Now let’s look at our MDD program, which has also been designed as a global program with sites in the U.S. and numerous countries in Europe. As you know, regulatory approvals take longer at international sites than in the U.S.

We have recently received approvals to begin clinical conduct in several European countries and also in the Ukraine, and we expect approval shortly in Russia. We have, however, not commenced patient enrollment in the Ukraine or Russia. And in these studies, we have also implemented mitigation strategies as well.

And so we continue to expect our filing for FDA approval, those timelines to remain intact and with our filings in 2024. I would like to make an additional comment and it’s in response to some comments made by some of the analysts and some of their questions about these clinical studies and clinical sites.

Clinical – and sometimes people have tended to just take your number of clinical sites and divide them up by the number of patients you’re enrolling and saying, okay, therefore, we’re getting X number of patients from a particular country. That isn’t the way one should be thinking about this. Each site does not enroll the same number of patients.

So I wouldn’t put equal weight on each site.

So I’d ask you to keep that in mind as well, okay?.

That’s really helpful, Sharon. Thanks so much.

Maybe just to quickly clarify the mid-20s to low-30s gross to net, was that for first quarter or for this full year 2022 expectation?.

No, Sharon said that we – and we propose that the low-30s is where we’ll be headed in 2022..

That’s really helpful. Thanks again..

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

Okay. Thanks. Good morning everyone. So first question is more about the outlook for 2022.

And as we’re wrapping up Q1, can you maybe talk about how you feel going into Q2 as well as second half? And in addition to sampling, are there other kind of leading indicators that you’re paying attention to and if they are indeed pointing to continued acceleration? And then secondly is – you’re increasing your target prescriber base to include PCP.

It seems like a very interesting dynamic to me. So how much do you think that setting can drive growth for CAPLYTA? And I also wonder if the other branded antipsychotics or once-branded drugs are being promoted in that setting. So yes, just curious whether the PCP marketplace could be a big opportunity for CAPLYTA’s uptake. Thank you..

Mark, do you want to take that? Mark, you are on mute..

I knew, I was going to do that at least once today. So Andrew, thanks and let me go back to the first part of your question about leading indicators that signal continued accelerating growth with CAPLYTA. Certainly, sampling is one of those things that we believe signals that.

When we look at – in addition to looking at total prescriptions and new prescriptions, we also look at new-to-brand prescriptions, which is a strong indicator of true new patient acquisition.

And when we look at the NBRx levels for CAPLYTA in the first seven or eight weeks of the launch, there’s been a very significant inflection in those and the levels that we’re at now are about triple what they were right before the approval in bipolar depression.

So that’s a signal to us that we’re gaining new patient acquisition and that’s a very strong signal for continued future growth. In addition, we look at things like general awareness levels, awareness of the indication, and all of those key performance indicators are signaling to us that the growth is going to continue and it is going to accelerate.

Regarding the PCPs, yes, when we expanded our sales force and we expanded our target prescriber base, in addition to psychiatrists and nurse practitioners, we added a group of primary care physicians who are high prescribers of branded antipsychotics and treat bipolar depression.

And we do believe that this will contribute to the ongoing growth and acceleration in growth for CAPLYTA over the course of 2022. So I hope that’s helpful..

Yes, very helpful. Thank you guys..

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

Hey guys. This is Mike DiFiore in for Umer. Thank so much for taking my questions and congrats on the quarter. Just two for me. With Omicron subsiding, I guess the key question remains as to whether CAPLYTA sales will continue to beat Street expectations this year.

That said, any updated thoughts on you guys giving potential guidance for this year or either for on a quarterly basis? And my second question is, if there’s any updates to the additional bipolar depression patents that you guys are seeking? I think last time we spoke, you were about one and half years into the application process.

So I want to see if there’s any updates on that front. Thank you..

Hi, thanks Mike. I think maybe we’ll take this in reverse order so that I can remember the questions.

When you said update to bipolar patents, I think you meant updates to the – both the Orange Book listed patents as well as to extensions, right? Is that correct?.

That’s correct, yes..

Okay. All right. So on the extensions, typically, it’s about a three-year process, and we’re – so we’re getting there. But the simple answer is, we haven’t had any updates on that yet. And you’ll be sure to know when we do because we will obviously list that. So then – so that’s a quick one.

Then the next one is maybe, Mark, would you like to talk a little bit about what you’ve seen with Omicron and what you’re seeing now? And then I can talk about guidance very simply and saying we’re not providing guidance this year.

So Mark, why don’t you go ahead?.

Yes, sure. I guess I would just simply say that we are seeing continued improvements in the environment out there as Omicron begins to subside and things begin to return back to normal. For us, what that means is greater access for our sales representatives to physicians.

I think the declining cases, the lifting of restrictions and, quite honestly, the excitement about the new indication in bipolar depression is opening a lot more doors for our sales representatives than perhaps in the past. And so we see that as an encouraging sign, and we certainly hope that this progress will continue as we go throughout the year..

Great. Thank you..

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

Yes. Good morning, Sharon and team, congrats on the recent approval and launch as well as pipeline progress. Thanks for taking the questions. I had a question about CAPLYTA with regard to the initial launch. Mark provided some color, but I’m wondering if he might expand on the initial feedback from prescribers relative to the patient experience.

Is it mostly about efficacy or is it about tolerability that he’s hearing good feedback? And is it across the board in both BPD I and II? And then back to your statement on guidance, you mentioned you wouldn’t be giving that this year, but could you imagine giving that next year, what are the pushes and pulls on that?.

I’ll ask Mark, you start, and then I’ll come up with the rear on the last part on guidance..

Yes. So Charles, the short answer is, we’re hearing very positive feedback on all – I’d say all three of the areas.

You mentioned efficacy and tolerability, I would also add to that the convenience of CAPLYTA’s single 42-milligram dose where the physician can start the patient at the effective dose without having to titrate and the medicine can be taken with or without food.

So, we do get a lot of really good feedback from physicians on the clinical profile when they see and learn and are educated on our clinical trials, the efficacy that they see in both bipolar I and bipolar II.

And in particular in bipolar II, they recognize that this is an underserved condition, it’s an area where there’s only one other product indicated and proven in that area, that’s a big deal to them.

So when they see the proven efficacy in both bipolar I and bipolar II, this is something they see as unique for the product and certainly addresses an unmet need that they have.

For those physicians that were familiar with CAPLYTA through their experience with the schizophrenia indication, when they see in our clinical data that the safety and tolerability, particularly around weight and akathisia, which are the two tolerability issues that concern bipolar patients the most, and when they see that our profile in each of those is similar to placebo, and they recognize that, that’s essentially replicated with what we saw in schizophrenia, that gives them a great deal of confidence as well and another reason to prescribe CAPLYTA.

So, I think all of these things together, we’re hearing very positive physician feedback and they also relay a lot of terrific patient stories to us of successes that their patients are having. So, we find all of that highly encouraging. So Sharon, I’ll turn it back to you for the rest of the question..

Great, thanks. Charles, I think we’re taking it one year at a time. We said this year, we’re not providing guidance. At some point in the future, we will. But I think for right now, we’re taking it one year at a time..

Okay. Makes sense. Back to – I know just one question, but I wanted to ask relative to the tolerability, Mark, are you seeing persistence in schizophrenia that perhaps is consistent with or beyond what you would’ve expected given in the improved tolerability profile? Thanks..

Yes. Thanks, Charles. We are. We had a hypothesis even prior to the launch when we saw the safety and tolerability profile from our clinical trials in schizophrenia.

And while it’s still a little too early to do the classical persistency curves, we need a bit more data to do that, we have been tracking proxies for that ever since the launch, mostly looking at refill rates and TRx to NRx ratio.

And when you do that for CAPLYTA and you compare that to other branded antipsychotics at the same time in their launch, we find that CAPLYTA is outpacing those other branded antipsychotics, which is not a surprise to us. But to us, it’s a strong signal that patients are persisting longer on CAPLYTA.

And when you also look back, it’s very early with CAPLYTA, obviously, in bipolar depression, but when you look back historically at other products and you look at the persistency in bipolar disorder, it tends to be longer than in schizophrenia. So, we would expect to see the same with CAPLYTA as well..

Thank you. [Operator Instructions] Our next question comes on the line of Marc Goodman from SVB Leerink. Your line is now open..

This is Rudy on the line for Marc.

Regarding CAPLYTA’s accelerated growth trajectory in the first quarter, can you provide more color on the impact of your sales force expansion that was completed in 4Q? And I have another question, how should we think about antipsychotic market dynamics, especially with the upcoming generic entry of Latuda and the potential label expansion of [indiscernible] in MDD? Thanks..

So thanks questions, Rudy. I think it was a little bit difficult to understand what you were saying.

You were coming through a little bit muffle, but Mark, were you able to get the questions?.

Yes, I think so. And, Rudy, if I don’t hit on it exactly, just follow-up with a follow-up question. But in terms of our sales force productivity and the level of detailing out in the marketplace, you’re right. We expanded our sales force just before the approval of bipolar last year from approximately 240 representatives up to 320 representatives.

And what we’re seeing in the early weeks of the bipolar launch is a significantly higher level of detailing due in part to having additional sales representatives as part of our overall sales force structure. But also, as I mentioned before, we are seeing improvements in the environment from a COVID perspective.

And in addition, the excitement of a new indication in bipolar depression is something that physicians are very interested in hearing about. So all of those things are leading to a high level of detailing in the marketplace and at a level that we believe is – gives us a very strong share of voice to communicate the CAPLYTA message.

In terms of potential impact of a Latuda patent expiry, we don’t believe that, that will have a significant impact on CAPLYTA or the other branded products in the marketplace. Typically, when you look back historically in this category, certainly, the – that brand is impacted by a generic entry. So Latuda will obviously be very impacted by that.

But the other brands tend not to be impacted. And that’s because this is a category that there’s an awful lot of churn, there’s an awful lot of discontinuation and switching of medicines. And quite honestly, many of these patients have already been on Latuda by the time it goes generic.

So, we don’t foresee a significant impact on CAPLYTA of that event in the marketplace..

Thank you. Our next question comes from the line of Jason Gerberry from Bank of America. Your line is now open..

Hey guys. Thanks for taking my questions. Just following up on the last question, I just wanted to confirm. So my understanding is in some of the more generic antipsychotic markets, there’s typically a two step edit rule, but in BPD, there’s only one generic step edit.

So is it your kind of assumption that Latuda going generic would not shift the balance to a two generic step edit type of dynamic? And then just on the BPD launch, curious, early days, but do you have a sense what line of therapy, what prior treatments is the typical profile of a patient getting CAPLYTA for BPD? Or is it just too early to say? Thanks..

Mark?.

Yes, thanks, Jason. Yes, when you look at the utilization criteria that exists across the various payers, across various channels for antipsychotics, it really varies depending on the payer. You have unrestricted access available through certain payers, you have those payers who employ step edits.

Typically, it’s either one or two generic steps, usually not more than that. And then you have those that manage the category to – through a prior authorization and possibly a step edit associated with that. So it really varies across the board. What I would say, certainly, unrestricted status is the best electronic step edit.

Whether it’s a single step or two steps, we don’t see as a significant barrier in the marketplace. This is not something that the physician or the physician staff has to do anything for. They write the prescription, the patient shows up at the pharmacy, and this is all done behind the scenes electronically.

So it really isn’t a barrier to usage in the marketplace. In terms of the second question, you said, lines of therapy, again, still early on in the launch, but what we are seeing, similar to what we saw in schizophrenia, in this regard is utilization across all lines of therapy.

We’re seeing newly diagnosed patients being placed on CAPLYTA as well as second line, third line, et cetera. And we’re also – when we look at the products, the antipsychotics that they’re being switched from, they’re being switched from a wide variety of antipsychotics as well.

So it’s not like there’s just one or two specific products that physicians are looking to switch from to CAPLYTA it really is coming across the board, which, to us, again, is a very encouraging sign..

Thank you. Our next question comes from the line of Ami Fadia from Needham. Your line is now open..

Thanks. Good morning. I have one question and one follow-up.

Just with regards to the sampling, can you give us some color with regards to the volume of samples that you may have distributed so far? And if you can give us some sense of how that might be a leading indicator for new prescriptions or total prescriptions? And then secondly, just with regard to a prior question around guidance, in the past, you’ve given us some color with regards to your comfort level with consensus numbers for the year.

I’m seeing consensus stands at roughly $214 million for the year. Could you give us a comment on how comfortable you are with regards to being able to achieve that? Thank you..

Okay. Mark, I’ll ask you to start with defining the sampling parameters as you see them, and then I’ll come back on the consensus..

Yes, sure. I think as most of you are aware, physicians utilize samples in order to try a new medicine for the patients. So typically, they will give them a week or two of samples to test early on the effectiveness in that patient to see if there’s any tolerability issues.

And if all goes well, then those samples then typically are followed by a prescription. Sometimes the physician will give them the samples and a prescription at the same time. They take the samples and then they fill it when they’re done.

Sometimes the physician will want to hear back from the patient and then write a prescription, but we believe it’s a future indicator of prescription growth because it signals a willingness and a commitment to try the medicine in a new patient, which ultimately results in a prescription.

In terms of the magnitude, what I would say is, we have seen a significant increase, both in physician requests for samples, unsolicited requests for samples as well as the sampling that our sales force provides to physicians as they make their sales calls. So Sharon, I’ll turn it back to you for the second part of the question..

Yes. So, no, we said we’re not giving you guidance this year, so we’re not giving you any guidance on numbers, consensus, et cetera, for this year..

Operator, I think if there is not another question, we can wrap this up or if there is one more question, we can have that one asked..

At this time, showing no further questions, I would like to turn the call back over to Dr. Sharon Mates for closing remarks..

Great. Thank you so much. We thank everyone for participating this morning. We’re very excited about our launch and the continuing expansion of CAPLYTA. And we’re very, very excited about the possibility and probability of helping patients. So with that, operator, you can disconnect..

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