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Edited Transcript of ITCI earnings conference call or presentation 5-Nov-19 1:30pm GMT

Q3 2019 Intra-Cellular Therapies Inc Earnings Call

NEW YORK Nov 21, 2019 (Thomson StreetEvents) -- Edited Transcript of Intra-Cellular Therapies Inc earnings conference call or presentation Tuesday, November 5, 2019 at 1:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Andrew Satlin

Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer

* Juan Fernando Sanchez

Intra-Cellular Therapies, Inc. - VP of Corporate Communications & IR

* Lawrence J. Hineline

Intra-Cellular Therapies, Inc. - Senior VP of Finance, CFO, Treasurer and Assistant Secretary

* Mark Neumann

Intra-Cellular Therapies, Inc. - EVP & Chief Commercial Officer

* Sharon Mates

Intra-Cellular Therapies, Inc. - Co-Founder, Chairman, CEO & President

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Conference Call Participants

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* Charles Cliff Duncan

Cantor Fitzgerald & Co., Research Division - Senior Analyst

* Jessica Macomber Fye

JP Morgan Chase & Co, Research Division - Analyst

* Lin Tsai

Jefferies LLC, Research Division - Equity Analyst

* Marc Harold Goodman

SVB Leerink LLC, Research Division - MD of Neuroscience & Senior Research Analyst

* Owen J. Drinkwater

RBC Capital Markets, Research Division - Associate

* Raymond Wu

Ladenburg Thalmann Financial Services Inc. - Biotechnology Equity Research Associate

* Robert Cummins Hazlett

BTIG, LLC, Research Division - MD & Biotechnology Equity Research Analyst

* Sumant Satchidanand Kulkarni

Canaccord Genuity Corp., Research Division - Analyst

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Presentation

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Operator [1]

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Good morning, ladies and gentlemen, and welcome to the Intra-Cellular Therapies Third Quarter ended September 30, 2019, Financial Results Conference Call. (Operator Instructions)

As a reminder, today's conference call is being recorded. I'd now like to turn the conference call over to your host, Dr. Juan Sanchez, Vice President, Corporate Communications and Investor Relations. Please go ahead, sir.

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Juan Fernando Sanchez, Intra-Cellular Therapies, Inc. - VP of Corporate Communications & IR [2]

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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 third quarter ended September 30, 2019, 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. Andrew Satlin, Executive Vice President and Chief Medical Officer; Mark Neumann, Executive Vice President and Chief Commercial Officer; Dr. Kimberly Vanover, Senior Vice President of Early-Stage Clinical Development and Translational Medicine; Larry Hineline, Senior Vice President and Chief Financial Officer; and Michael Halstead, Executive Vice President and 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 nonclinical plans, our plans to present or report additional data, the anticipated conduct and results of ongoing and future clinical trials, plans regarding regulatory filings, our ongoing NDA review process with the FDA for lumateperone, future research and development, our plans regarding the commercialization of lumateperone 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'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.

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Sharon Mates, Intra-Cellular Therapies, Inc. - Co-Founder, Chairman, CEO & President [3]

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Thanks, Juan. Good morning, everyone. We are now within 2 months of the potential approval of lumateperone for the treatment of schizophrenia with a PDUFA action date of December 27 of this year. These are very exciting and transformative times for our company. As such, on today's call, we will be updating you on progress made across the company, with particular emphasis on our lumateperone programs and our preparations towards commercialization.

Mark Neumann, our Chief Commercial Officer, will elaborate on our commercial activities; and Andy Satlin, our Chief Medical Officer, will provide an overview of our clinical development programs. Lastly, Larry Hineline, our Chief Financial Officer, will review our financial results, and we will open up the line for Q&A.

Our NDA is supported by 2 adequate and well-controlled clinical trials and the safety database with over 1,900 individuals exposed to the drug, including individuals with long-term exposure. We believe that our lumateperone schizophrenia program provides evidence in support of the efficacy and safety for the treatment of schizophrenia and, if approved, may represent an important new treatment option for health care providers and their patients.

We continue to make substantial progress to support the launch of lumateperone in the first quarter of 2020. We have been building our commercial infrastructure and expanding our commercial organization, including the sales, marketing and market access teams.

In addition, manufacturing and supply chain operations are in place, and we are on track to support commercial supply. Mark will elaborate during his remarks.

We have continued to make significant progress in our other lumateperone clinical programs, including bipolar depression. Bipolar disorder is a highly prevalent disease affecting approximately 6 million adult Americans. This serious psychiatric condition is characterized by episodes of mania in Bipolar I patients or hypomania in Bipolar II patients. Both Bipolar I and Bipolar II patients experienced episodes of depression, which tend to last longer and recur more often than the manic or hypomanic episodes.

While there are several options for the treatment of mania, there are few options for the treatment of depressive episodes. Recently approved drugs for the treatment of bipolar depression are only indicated for Bipolar I patients, a patient population that represents only about half of patients with bipolar disorder.

We are enthusiastic about the potential for lumateperone to advance the treatment of patients with bipolar depression due to its favorable safety and tolerability profile and the potential to treat patients suffering from Bipolar I or Bipolar II disorder.

Our bipolar depression program consists of 3 studies: 2 monotherapy studies and 1 adjunctive study. In the third quarter, we presented robust positive top line results from Study '404, our global clinical trial evaluating lumateperone as monotherapy for the treatment of major depressive episodes in patients with Bipolar I and II disorder.

Results from this study demonstrates the potential of lumateperone as a new treatment option for the treatment of depressive episodes in patients suffering from Bipolar I or Bipolar II disorder. The robust results observed, as measured by improvements over placebo in the Montgomery-Åsberg Depression Rating Scale, or MADRS, total score, the primary endpoint are supported by results in important measurements such as remission and response rate and the Clinical Global Impression Scale, or CGI.

These results are accompanied by the confirmation of the safety profile of lumateperone seen in previous studies. We will be presenting data on this program at scientific conference late this year.

I'm also pleased to announce that Study '402, our global adjunctive study, for the treatment of bipolar depression in both Bipolar I and II patients is progressing well, and we anticipate reporting top line results mid next year.

Beyond the progress made in our lumateperone, schizophrenia and bipolar depression programs, we continue to advance our pipeline, including the development of lumateperone and our ITI-007 platform in other indications, including depressive disorders and our long-acting injectable program for the treatment of schizophrenia, our PDE1 program and our preclinical programs. Andy will provide details on these programs.

We ended the quarter with $255.4 million in cash, cash equivalents and investment securities, which places us in a strong position to fund our commercial activities and continue to advance our development programs.

I'll now turn the call over to Mark.

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Mark Neumann, Intra-Cellular Therapies, Inc. - EVP & Chief Commercial Officer [4]

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Thanks, Sharon, and good morning, everyone. As Sharon mentioned, we are now within 2 months of the potential approval of lumateperone. So I'm pleased to have this opportunity to give you an update on the substantial progress we've been making in our commercial launch, execution preparations.

Pending FDA approval of lumateperone by our PDUFA date of December 27, we are planning for a commercial launch in the first quarter of 2020, and we remain on track in all areas to meet this time line.

Let me begin with an update on our progress in building out the field-based customer-facing teams, including the sales force and market access teams.

We have identified the top 15,000 to 20,000 high prescribers of antipsychotics, who treat schizophrenia, representing the majority of the market potential, and we are confident that we've sized the sales force to have a highly competitive promotional effort.

Our recruiting and hiring process is well advanced, and we have been pleased with both the level of interest in joining our company as well as the quality of the talent that we are attracting.

At this point, all of our area sales directors are on board, and hiring is ongoing for the regional business managers.

Of the sales leaders we have hired thus far, greater than 90% have previous psychiatry experience. This sales leadership team is actively recruiting and interviewing the sales representatives, who we plan to onboard in Q1 in time for the launch, pending approval of lumateperone.

And in addition to our hiring activities, our operational infrastructure in support of the sales force is nearly complete. We also now have our entire market access organization in place, including the leadership team and the national and regional account executives.

As with our sales leadership team, all of these individuals join us with deep biopharmaceutical experience, strong existing payer relationships and specific competencies in ensuring appropriate patient access to neuroscience medicine. We have prioritized the top-tier payers, who represent the vast majority of antipsychotic volume and claims processing for initial engagement in accordance with FDA guidance regarding preapproval communications.

Our account executives are introducing Intra-Cellular Therapies to medical and pharmacy directors as well as engaging in schizophrenia disease awareness and business-to-business planning discussions. These important activities will continue throughout the fourth quarter.

We continue to make strong progress in the area of manufacturing and supply chain, where we are in an excellent position to support launch in the first quarter and to ensure that product supply is available for the Q1 launch timeframe.

And finally, you may recall that we had successfully launched a disease awareness campaign to the medical community in May in conjunction with the American Psychiatric Association meeting to highlight the significant unmet medical needs that remain in the treatment of schizophrenia. This print and digital campaign remains ongoing, and all of our metrics are tracking at or above our expectations. Our print effort has reached 95% of the psychiatry audience. Combined print and digital has delivered over 800,000 touch points, and our website, szjourney.com, has also been well received by the medical community.

We plan to continue this unbranded campaign up to the time of potential approval, when we will then begin to focus on branded promotion of lumateperone. Thank you. And I would now like to hand the call over to Andy to discuss our clinical development program updates. Andy?

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Andrew Satlin, Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer [5]

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Thanks, Mark. We continue to advance our clinical programs for lumateperone and other investigational new drugs in our pipeline. Our team has presented data on our lumateperone programs at medical conferences, and we've been very pleased by the positive reception lumateperone has received during these meetings and the interactions we have had with important stakeholders in psychiatry.

Recently, we made presentations at the European College of Neuropsychopharmacology annual meeting and at the 32nd Annual Psych Congress, highlighting lumateperone's clinical results, including its favorable safety and tolerability profile established in the schizophrenia program.

We are very excited about the robust results observed in Study '404, our global Phase 3 monotherapy study in bipolar depression.

In this study, lumateperone 42 milligrams met the primary endpoint, with statistically significant greater improvement over placebo on MADRS at week 6. The mean improvement from baseline for lumateperone 42 milligrams with 16.7 points versus 12.1 points for placebo for a 4.6-point difference between the 2 groups, a robust effect size of 0.56 and a statistically significant p-value of less than 0.0001. Benefit was seen in both Bipolar I patients and Bipolar II patients, with subgroup analyses for each diagnosis, demonstrating statistically significant improvements versus placebo on the MADRS total score.

This trial was conducted in 6 countries, including the United States and Europe. There was a statistically significant separation versus placebo on the primary endpoint in both the U.S. population subgroup, representing approximately 30% of enrolled patients, and in the ex-U. S. population subgroup.

Lumateperone also met the key secondary endpoint of statistically significant improvement on the Clinical Global Impression Scale for Bipolar for Severity of Illness Total Score with an effect size of 0.46 and on the Clinical Global Impression Scale component that specifically assesses depression with an effect size of 0.5.

We are very encouraged by these robust results, which, in our opinion, uniquely positions lumateperone as a potential advance in the treatment of patients suffering from both Bipolar I and Bipolar II disorder.

In a separate study, Study '401 conducted entirely in the U.S., lumateperone did not separate from placebo. A high placebo response was observed in the trial. Large placebo effects are increasingly common in clinical trials in depression and other psychiatric disorders, especially in the United States, making success in these trials more challenging.

In both trials, lumateperone demonstrated a favorable safety profile and was generally well tolerated, as seen in previous studies in schizophrenia. The rates of akathisia, restlessness and extrapyramidal symptoms combined were less than 1% and similar to placebo in both studies.

Our bipolar depression program continues to advance, and as Sharon mentioned, we anticipate reporting top line results from Study '402 in mid-2020. Study '402 is our study evaluating lumateperone as adjunctive therapy for the treatment of depressive episodes in patients with Bipolar I or Bipolar II disorder. This study is being conducted globally and will include approximately 550 patients, randomized 1:1:1 to receive lumateperone 42 milligrams, 28 milligrams or placebo once daily for 6 weeks. As in our other bipolar depression studies, the prespecified primary endpoint for the trial is changed from baseline at week 6 on the MADRS total score versus placebo.

Our rationale to pursue the development of lumateperone for the treatment of depressive disorders, including MDD, continues to strengthen, and is based on Lumateperone's unique pharmacology and on improvements in depressive symptoms seen in patients with comorbid depression in our schizophrenia program as well as the positive results from Study '404 in bipolar depression.

We believe lumateperone has the potential to exhibit potent and rapid antidepressant effects, and we have an ongoing program in major depressive disorder. In order to explore the effect of different modes of drug administration and the potential for rapid-onset antidepressant activity, our program includes the assessment of novel formulations of lumateperone. We are continuing to explore the pharmacokinetics of these formulations and anticipate initiating a Phase 2 clinical study in major depressive disorder in 2020.

We're also pleased with the progress being made in our PDE1 program as we continue to explore the potential of this novel mechanism of action in CNS, cardiovascular and other conditions. We intend to pursue the development of our PDE1 inhibitors for the treatment of several CNS and non-CNS indications with a focus on diseases where excessive PDE1 activity has been demonstrated and increased inflammation is an important contributor to disease pathogenesis.

We have completed a translational clinical study of ITI-214 in healthy volunteers using functional MRI neuroimaging. This study was designed to provide data supporting proof of mechanism for PDE1 inhibition to indirectly modulate dopaminergic systems in the brain during complex behavioral tasks. The results will inform the development of ITI-214 in a variety of central nervous system disorders. We anticipate top line results from this study later this year.

Our ITI-214 program in heart failure continues to progress. ITI-214 has the potential to increase cardiac contractility and output without increasing vascular resistance. ITI-214 increases heart contractility through a pathway involving adenosine A2B receptor signaling, introducing a new mechanism of action for the treatment of heart failure that is different from beta-adrenergic agonism and PDE3 inhibition. Unlike beta-adrenergic agonists and PDE3 inhibitors, ITI-214 does not increase the inflow of calcium in cardiomyocytes, and therefore, provides the potential for a safer alternative to existing therapies.

Our ongoing Phase 1/2 single ascending dose study aims to replicate the positive inotropic effects of ITI-214 seen in animals. Clinical conduct for the third and final cohort, 90 milligrams, is ongoing, following successful completion of the 10-milligram and 30-milligram dose cohorts, where no safety concerns were identified.

We anticipate reporting top line results from this study in the first half of 2020.

Finally, we expect to initiate our clinical program for ITI-333 in the first half of 2020. ITI-333 is our novel oral modulator of serotonin, dopamine and mu opioid receptors for the treatment of opioid and other substance use disorders, pain and mood disorders.

I will now turn the call over to Larry, who will review the financial results. Larry?

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Lawrence J. Hineline, Intra-Cellular Therapies, Inc. - Senior VP of Finance, CFO, Treasurer and Assistant Secretary [6]

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Thank you, Andy. I will be reviewing our financial results for the quarter ending September 30, 2019, and provide an overview of our expectations for the use of our cash and investments. The net loss for the third quarter of 2019 was $34.9 million compared with a net loss of $41.5 million for the third quarter of 2018. Basic and diluted net loss was $0.63 per share for the third quarter of 2019 compared to a basic and diluted net loss of $0.76 per share for the same period in 2018. Research and development expenses for the third quarter ended September 30, 2019, were $21.3 million compared to $35.4 million for the third quarter of 2018. This decrease of $14.1 million is due primarily to a decrease of approximately $10.7 million of costs associated with the completion of certain lumateperone clinical trials, a decrease of approximately $1.4 million of costs for lumateperone nonclinical efforts and a decrease of approximately $1.8 million of manufacturing costs.

General and administrative expenses for the third quarter of 2019 were $15 million compared to $8 million for the third quarter of 2018. The increase of $7 million is primarily the result of an increase in precommercialization cost of approximately $3.8 million, approximately $1.9 million of higher labor costs and an increase in stock compensation and rent expense.

Cash, cash equivalents and investment securities totaled $255.4 million at September 30, 2019, compared to $347.5 million at December 31, 2018. We expect these existing funds will be used primarily for precommercialization activities; initial commercialization activities, including developing a national sales force and related infrastructure expansion in connection with the commercialization of lumateperone, if approved; for the treatment of schizophrenia; the development of lumateperone in our late-stage clinical programs; the development of our other product candidates, including ITI-214; the continuation of manufacturing activities and general operations.

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

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from the line of Charles Duncan with Cantor Fitzgerald.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [2]

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Congrats on the progress in the quarter. Sharon and team, going to be an exciting time, hopefully, coming up here soon. I'm sure that you won't be able to give us a lot of granularity or information, but I'm wondering if you've had recent discussions with the agency, perhaps even venturing into labeling. Or more importantly, I'm kind of wondering if you've shared observations or actual data with the FDA and discussed for the bipolar program and discussed the challenges with U.S. patients here in the states, not only in bipolar, but schizophrenia?

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Sharon Mates, Intra-Cellular Therapies, Inc. - Co-Founder, Chairman, CEO & President [3]

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Wow, that's a lot of questions, which I was not writing down, so I hope others on our team were, and we'll try and answer all of them. Thank you for your comments, Charles. And we do think it's a very exciting time for us.

I will ask Andy to address the question on -- the first question dealt with our FDA interactions, and there was a part B to that as well, which maybe you remember? Thank you.

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Andrew Satlin, Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer [4]

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Yes. So thanks, Charles. With regard to discussions with the FDA. So this is an active review. We continue to have some back and forth with the FDA regarding information that we've provided. We have had ongoing questions. We've responded to the questions in a timely fashion and within FDA deadline. We believe all the information that we continue to provide to them substantiates the data that we have provided previously. So we're confident that we're moving in the right direction with all of that.

With regard to bipolar, no, we have not yet had a chance to discuss those data with FDA. That's something that's planned. But during the busy time with the FDA review for schizophrenia, that has not happened yet.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [5]

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Okay. That makes sense. But really, really my question is along the lines of, do you think -- is it your sense that the agency gets it with regard to the challenges of placebo effect going up in schizophrenia as well you've shown in bipolar?

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Andrew Satlin, Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer [6]

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Yes. I think they're well aware of this and in a variety of indications they've actually published in this area. So the issue with placebo response rates across psychiatric indications, particularly in depression, perhaps, particularly in the United States are, I think, things that are they're well aware of and we as well.

And yes, you had asked also about whether that any of these discussions concern labeling? Yes. And there have been discussions around labeling issues as well.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [7]

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Okay. One quick question then for Mark, and then I'll hop back in the queue, and that is regarding -- well, it's a veiled question on pricing, but it really is meant to help us think about the pharmacoeconomic value that you see in lumateperone and the feedback that you've gotten in early discussions with reimbursement authorities. I guess, what I'm wondering is, do you feel that the reimbursement authorities understand the potential differentiation of lumateperone and its ability to -- or a patient's ability to take it over time and, therefore, see efficacy? What do you -- how do you think about pharmacoeconomic value?

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Mark Neumann, Intra-Cellular Therapies, Inc. - EVP & Chief Commercial Officer [8]

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Yes. Thanks, Charles, for the question. And we've had, I would say, extensive discussions over the past year or so, in a market research setting and in advisory boards, both with pharmacy directors and medical directors from payers. And a couple of themes have emerged from those discussions that are actually very consistent with how the physicians that we've spoken to in market research have come to us. And 2 themes in particular that are encouraging to us. Number one, the recognition that in spite of there being several antipsychotics on the market, both generic and branded, there's a recognition that because of the dynamic in the marketplace of patients cycling through multiple antipsychotics, there continues to be a very significant unmet need for an effective antipsychotic with a favorable safety and tolerability profile. And so that's well recognized by the payers in addition to the physicians.

And then when we would share the clinical data from our program that Andy has talked about with medical and pharmacy directors, they see the same differentiation of lumateperone that the physicians do and the psychiatrists do, and that is an effective antipsychotic and one that has a favorable safety and tolerability profile in addition to a unique mechanism of action.

And so in our discussions with payers, they recognize that there is a very strong value proposition that lumateperone, if approved, will bring to the marketplace, and it will be our job to make sure that we bring forward the right pharmacoeconomic data to help turn some of the theoretical benefits of adherence due to a favorable safety and tolerability profile into tangible benefits that pharmacy and medical directors will be able to see. So that's a big part of what our medical affairs team is doing as we speak. And certainly, once we get approval, if approved, then real-world data with lumateperone will also play a critical role in helping to establish those benefits as well. So I hope that answered your question, but I wanted to provide at least a little more full of an answer about the kind of feedback that we've been getting from payers in addition to the physicians.

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Operator [9]

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Our next question comes from the line of Jessica Fye with JPMorgan.

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Jessica Macomber Fye, JP Morgan Chase & Co, Research Division - Analyst [10]

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Great. I guess, first, just following up on that question on payer feedback. Should we expect the typical step edits that some physicians have indicated they face with Latuda, for example?

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Mark Neumann, Intra-Cellular Therapies, Inc. - EVP & Chief Commercial Officer [11]

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Yes. Thanks, Jessica, for the question. This is Mark, again. What I would say is that the antipsychotic category has been around for several years. It's a category that payers are familiar with. It's a category that they want to ensure access to the appropriate medications to treat serious diseases, like schizophrenia. And so I think you'll have a mix. There are payers who will provide unrestricted access. We would expect to lumateperone as they do for other agents, and there will be other payers who will employ techniques like step edits, where they'll require 1 or 2 generic products to be used prior to the branded product.

But what I would say about that, in particular, is if you look at the patients who are out there today suffering from schizophrenia, the majority of them, the vast majority of them, have already been on multiple antipsychotics, so they've already met the requirements of many of the step edits that the payers will be putting in place. And so when a physician goes to write a product like lumateperone and can demonstrate that the patient has already been on 1 or 2 other antipsychotics, then typically, that prescription would get approved and get filled. So it's something that we're aware of and something that we think is a manageable piece of the payer dynamic.

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Jessica Macomber Fye, JP Morgan Chase & Co, Research Division - Analyst [12]

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Got it. Okay. Makes sense. You also mentioned that you sized the sales force. Can you tell us what that projected size will be?

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Mark Neumann, Intra-Cellular Therapies, Inc. - EVP & Chief Commercial Officer [13]

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Yes. Thanks, Jessica. Up until this point, we've not communicated the exact number of -- or the size of the sales force for competitive reasons. And we're continuing to keep that a little close to the vest. What I would say, what I said on the call, is we have a very good understanding of the audience of physicians who write the majority of antipsychotic prescriptions for schizophrenic patients. We know which physicians are the high prescribers, and we have sized the sales force to enable us to be highly competitive in those offices with our lumateperone promotion. So at this point, I think that's all I'm going to say on that. But if that at least gives you a sense of the 15,000 to 20,000 physicians who write the majority of prescriptions for schizophrenia of antipsychotics, those are the physician offices where we'll be concentrating in and in those offices, we'll have a highly competitive effort for our sales force.

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Operator [14]

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Our next question comes from the line of Andrew Tsai, Jefferies.

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Lin Tsai, Jefferies LLC, Research Division - Equity Analyst [15]

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So apologies if this has been asked before in prior conference calls, but I believe the FDA canceled your ADCOM about 1 week prior to the actual date, and it's my understanding that companies themselves tend to receive preliminary briefing docs, maybe 2 weeks before and at least as timeline was confirmed by another company this morning. So just wondering if you have received a draft. And if so, what topics did they entail?

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Sharon Mates, Intra-Cellular Therapies, Inc. - Co-Founder, Chairman, CEO & President [16]

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Yes. Thanks. This is Sharon. And you're right. This has been addressed many times before. And really, the FDA had decided to cancel our ADCOM, and really, we don't have much more to say about that other than we're moving forward. I kind of missed some of your timeline in there, and I'm not sure it was actually quite right, but it doesn't matter because we're here today. We, to this date, do not have another ADCOM scheduled, and so we are moving on, looking towards our approval.

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Lin Tsai, Jefferies LLC, Research Division - Equity Analyst [17]

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Sounds good. And also, since early September, has there been any anecdotal evidence out there that you found internally that would support the notion of an approval, perhaps looking at the recent history of PDUFA extensions and your outcomes as an example.

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Sharon Mates, Intra-Cellular Therapies, Inc. - Co-Founder, Chairman, CEO & President [18]

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I'm sorry, I'm not sure I understand the question. Do you understand it?

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Andrew Satlin, Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer [19]

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I'm not sure, except that I would say that we're focused on our own submission and wanting to -- FDA request for our -- around our NDA, and that's our concern at this point, and we think that's progressing in a satisfactory manner.

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Lin Tsai, Jefferies LLC, Research Division - Equity Analyst [20]

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Okay. And my last question is just that for the bipolar program, it sounds like you still need to talk to the FDA to establish a path forward. So when could we expect a meeting? And should investors expect the base case scenario to be a filing after the final Phase 3 study reads out in mid-2020?

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Andrew Satlin, Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer [21]

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So yes, those are the types of questions we would be addressing with FDA, and we don't have a time line yet for it, but it is something that we intend to do in the near future.

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Operator [22]

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

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Marc Harold Goodman, SVB Leerink LLC, Research Division - MD of Neuroscience & Senior Research Analyst [23]

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First, on this bipolar depression adjunctive study, can you just give us a sense of where enrollment is right now? And second question has to do with spending. Just total spending this year seems to be coming in much less than what you thought it was going to be, I guess, 6 months ago. Can you just give us a sense of how you're thinking about spending now for the rest of the year? And then as we think about next year, obviously, the number of reps will kick in, in the first quarter, so that's incremental for next year, and I understand you're not going to disclose that number, but that's incremental spend. And then there's going to be obviously some supporting spending around advertising promotion. Can you just give us a sense of that type of number, and how you're thinking about R&D? What the incremental changes are going to be going into next year, bigger and smaller than this year?

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Sharon Mates, Intra-Cellular Therapies, Inc. - Co-Founder, Chairman, CEO & President [24]

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Sure. So again that's a lot of questions. I'll ask Andy to answer the bipolar and then Larry and I will take the financial.

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Lawrence J. Hineline, Intra-Cellular Therapies, Inc. - Senior VP of Finance, CFO, Treasurer and Assistant Secretary [25]

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Sure.

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Andrew Satlin, Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer [26]

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Yes. So with regard to the bipolar adjunctive study, Study '402, enrollment is going very well and has picked up as we've enlarged the number of countries that are involved in this trial. And as a result, as we said today, we've been -- we're able to state that we anticipate having results from that trial by the middle of 2020. So I think it's going along very nicely with that.

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Lawrence J. Hineline, Intra-Cellular Therapies, Inc. - Senior VP of Finance, CFO, Treasurer and Assistant Secretary [27]

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Marc, this is Larry. Our spend for the fourth quarter, we're estimating it could go as high as $45 million. We've been under that quarterly for the first 3 quarters. And you are right, going forward, we'll see an incremental spend as we do the things that you had mentioned. And you can be guided based on that.

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Sharon Mates, Intra-Cellular Therapies, Inc. - Co-Founder, Chairman, CEO & President [28]

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Yes. We'll give you -- we haven't given you any guidance to spend in 2020 yet other than we've gone through Q4 at the moment.

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Lawrence J. Hineline, Intra-Cellular Therapies, Inc. - Senior VP of Finance, CFO, Treasurer and Assistant Secretary [29]

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Right. And it will be going up incrementally...

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Sharon Mates, Intra-Cellular Therapies, Inc. - Co-Founder, Chairman, CEO & President [30]

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Yes. And certainly and you're absolutely right that we have spent less than we originally projected, and this was done purposely. We've been able to tighten things up, really go back and look at each area of ours. And so we think we've been very prudent on our cash spend.

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Operator [31]

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Our next question comes from the line of Brian Abrahams with RBC Capital Markets.

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Owen J. Drinkwater, RBC Capital Markets, Research Division - Associate [32]

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This is Owen on for Brian. Just a couple of quick ones from me. First one, any more color you could give us on manufacturing and supply chain activities, sort of what are the gating factors there? And have you already built up some commercial supply at this stage or is that still ongoing?

And then on the sales side, you noticed -- you noted you're hiring some regional business managers now, and can you talk a little bit about what still needs to be done on that front in the end of this year and into first quarter?

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Mark Neumann, Intra-Cellular Therapies, Inc. - EVP & Chief Commercial Officer [33]

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Yes. Sure. Thanks. This is Mark. Yes, from a manufacturing and supply chain perspective, we feel very good about where we are. We do have commercial supply ready to go. And as I said in my prepared remarks and Sharon did as well, we feel very confident in the ability to provide commercial supply in line with our planned Q1 launch. So we feel very good there. The supply chain pieces are all coming together in terms of negotiations with wholesalers, et cetera. So we feel we'll be ready to go once we get approved and we get out into the marketplace. So that's manufacturing and supply chain.

From a sales force perspective, yes, I guess, just a little bit more background on that. As I've said in the past, we -- I've had my Head of Sales onboard since the very beginning of the year. The first order of business was getting the area sales directors on board. They are all hired and onboard at this stage, and they've been busy doing the recruiting and hiring of the regional business managers, which are the first-line managers who will be managing the sales representatives. So as I mentioned, our hiring of the regional business managers is ongoing. We have many onboard already and that effort continues. And at the same time, in parallel, with those that are on board, the recruiting, the identification and the interviewing of the sales representatives has already begun as well and that will continue throughout the fourth quarter and into the first quarter next year.

We've said before that we won't onboard the sales representatives until after approval in the first quarter, but our plan is to have them in place in time for the first quarter launch. So hopefully, that provides a little bit more detail in terms of what you were looking for there.

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Operator [34]

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

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Sumant Satchidanand Kulkarni, Canaccord Genuity Corp., Research Division - Analyst [35]

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I have a few here. So first, on the more recent discussions you've had with the FDA on the pending lumateperone NDA, could you help characterize those in the context of whether the agency's relative emphasis has been on preclinical or clinical data or something else entirely like labeling?

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Andrew Satlin, Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer [36]

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Yes. So I think -- thanks, Sumant, for your questions. The discussions have covered all of those areas, and they continue to -- we've had discussions throughout the process with regard to those different areas. I think with regard to the talks, as we mentioned, we had submitted some new data a while back. There's been a bit of discussion around that, some follow-up. But really, as -- labeling discussions as well. So we're moving along, I think, in a way that we've expected.

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Sumant Satchidanand Kulkarni, Canaccord Genuity Corp., Research Division - Analyst [37]

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My second one is on the bipolar depression data, it's a follow-up to, I guess, to a follow-up. Specifically, at what point do you expect to meet with the FDA to discuss the Phase 3 results you have so far? And will that meeting be gated by the availability of data from the global adjunctive trial? And how would that answer change, if at all, if lumateperone is approved for schizophrenia because that would mean a potential sNDA, which may require a single successful trial?

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Andrew Satlin, Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer [38]

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Yes. So all good comments and good questions. No, as I mentioned before, we don't have a definite timeline for our meeting with FDA at this point, although we're moving toward that. And all data that we have available will be discussed. And -- but you're right that it will depend on outcomes in other areas going forward as well.

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Operator [39]

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Our next question comes from the line of Bert Hazlett with BTIG.

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Robert Cummins Hazlett, BTIG, LLC, Research Division - MD & Biotechnology Equity Research Analyst [40]

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I have two. Just pivoting back to market research for the lumateperone. Are there aspects, as you've done your market research, with regard to its profile that materially resonate with physicians, either on the AE side or on the efficacy side, a relative lack of weight gain or movement disorder? And if you could shed any light on what might be particularly resonating, that would be great?

And then a second one just on 214, as you consider the breadth of the indications there, assuming you are successful and you see positive signals with 214, is it your attention to pursue both the CNS and the non-CNS routes internally?

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Mark Neumann, Intra-Cellular Therapies, Inc. - EVP & Chief Commercial Officer [41]

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Yes. So Bert, this is Mark. I'll take the first part of that and then turn it over to Andy or Sharon for the second part. And yes, you're right. We -- as I said before, we've done an extensive amount of market research on the profile of lumateperone and certainly, the themes that have come through from that research is that lumateperone and the clinical data that supports it represents an effective antipsychotic that has a favorable safety and tolerability profile. And as I think you're aware, the dynamics of the marketplace and the existing antipsychotics each of them are effective and have been approved for schizophrenia, but each of them also has some liability or multiple liabilities when it comes to safety and tolerability. And that tends to be in 2 or 3 major areas, either in the metabolic profile, increase in lipids, increase in glucose, weight gain, prolactin abnormalities, et cetera, or on the movement disorder side of things where you have akathisia, other dyskinesias, et cetera.

And many of these side effects are truly intolerable to patients, and that's why you get this dynamic of the frequent cycling through multiple antipsychotics for schizophrenia patients.

Now when they -- when physicians in market research, see the clinical data supporting lumateperone and they see the favorable metabolic and weight results and they see the lack of movement disorders, these are aspects of the profile that they find to be very differentiating from other existing antipsychotics. So I think that's what I'll say about that, and I'll turn it over to Andy for the second part of the question.

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Andrew Satlin, Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer [42]

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Yes. Sure, Bert. So thanks for asking about ITI-214, which we're also very excited about. And as you're right -- as you say, you're absolutely correct. We're looking at a number of different indications, both in the CNS and non-CNS area, and we're considering other indications that could build on what we know about the pharmacology of this compound and PDE1 inhibition, in general.

Right now, everything that we're doing is in the different indications is at the stage of proof of principle, proof of mechanism, proof of concept, and obviously, as data come in, we'll need to do exactly what you suggest, which is to look overall at the portfolio of indications, to make some strategic decisions, to think about whether and how to pursue those and also to potentially have discussions with outside companies or others to help us in moving forward with those. So it's a little preliminary at this stage, but we are looking forward very much to getting a chance to fully explore what this compound can do.

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Operator [43]

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Our next question comes from the line of Matt Kaplan with Ladenburg Thalmann.

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Raymond Wu, Ladenburg Thalmann Financial Services Inc. - Biotechnology Equity Research Associate [44]

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This is Raymond in for Matt. Most of the analysts have asked my question, but I'll just have one question on the pipeline. Can you perhaps give some color on where you are in completing the formulations for the MDD indication perhaps?

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Sharon Mates, Intra-Cellular Therapies, Inc. - Co-Founder, Chairman, CEO & President [45]

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So -- go ahead.

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Andrew Satlin, Intra-Cellular Therapies, Inc. - Executive VP & Chief Medical Officer [46]

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Yes. Work is ongoing there, as we mentioned, with a variety of PK studies. And so that's ongoing work that we're pursuing.

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Operator [47]

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This concludes today's question-and-answer session. I'd like to turn the call back over to Sharon Mates for closing remarks.

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Sharon Mates, Intra-Cellular Therapies, Inc. - Co-Founder, Chairman, CEO & President [48]

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Thank you, operator, and thank you, everyone, for joining our call, and thank you to those who asked questions, they were very in-depth and very useful questions. So we appreciate that. And thanks, everybody, and we look forward to updating you soon. Thank you.

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Operator [49]

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