Intra-Cellular Therapies Inc (ITCI) 2017 Q3 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Intra-Cellular Therapies' Third Quarter 2017 Financial Results Conference Call. As a reminder, today's conference is being recorded. (Operator Instructions) I would now like to turn the conference over to your host, Dr. Juan Sanchez, Vice President, Corporate Communications and Investor Relations. Please go ahead.

Thank you, operator. Good morning, and thank you all for joining us for today's conference call. Our earnings press release provided a corporate update and details for the company's financial results for the quarter ended September 30, 2017, 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. Kimberly Vanover, Senior Vice President of Clinical Development; Larry Hineline, Vice President and Chief Financial Officer; and Michael Halstead, Senior 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 candidate; our clinical and nonclinical plans; our plans to present or report additional data; the anticipated conduct and results of future clinical trials; plans regarding regulatory filings, future research and development, and possible uses of existing cash and investment resources.

These forward-looking statements are based on current information, assumptions and expectations, and are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You 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 thank you for joining us for today's conference call. Today, we will provide an update on our lead drug candidate, lumateperone, which is in late stage clinical development for the treatment of schizophrenia, bipolar depression and agitation associated with dementia including Alzheimer's disease. We will then discuss, for the first time in detail, our Parkinson's disease program with ITI-214, our PDE1 inhibitor, which has recently entered clinical development in this target-patient population. Lastly, we will discuss our novel preclinical program for ITI-333 or triple three, being developed for substance-use disorder, including opioid addiction and pain. Larry will review our financial results, including the recently completed public offering, which provides us with substantial resources to continue the advancement of our program. We will then open the line for Q&A.

Our

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efficacy program includes 2 positive randomized double-blind, placebo-controlled trials and supportive data from a third large double-blind, placebo-controlled trial conducted in the United States. Importantly, in 2 studies with risperidone included as an active control, lumateperone demonstrated a differentiated safety and tolerability profile versus risperidone, most frequently prescribed antipsychotic for the treatment of schizophrenia. In these studies, lumateperone was statistically significantly superior to risperidone on several key safety and tolerability parameters such as triglycerides, cholesterol, glucose, proactin and weight gain.

In addition, we recently completed a 6-week open-label safety switching study, and the second part of the study, our long-term safety study in stable schizophrenia patients treated with lumateperone for up to 1 year, is ongoing. With over 2,000 people exposed to-date, lumateperone has been well tolerated with a safety profile similar to placebo. We are encouraged by the favorable safety and efficacy data generated in our lumateperone schizophrenia studies, and, as previously announced, following FDA guidance received earlier this year regarding our planned new drug application, we intend to submit the NDA for lumateperone for the treatment of schizophrenia by mid-2018.

We are excited about the results from our most recent study, our 6-week open-label safety switching study in stable patients with schizophrenia conducted in an outpatient real-world setting. In this study, patients with stable schizophrenia were switched from their standard-of-care antipsychotic to lumateperone for 6 weeks of treatment without the need for dose titration for lumateperone. Lumateperone was generally well tolerated with a safety profile that was favorable. Statistically significant improvements from standard-of-care were observed in body weight, cardiometabolic and endocrine parameters in patients with stable symptoms of schizophrenia, when switched to lumateperone, and worsened again when switched back to standard-of-care medication. These data are consistent with previous study results, which reflected a safety profile similar to placebo in patients with acutely exacerbated schizophrenia, and extend this favorable safety profile to this stable patient population. It is also notable that in this study, symptoms of schizophrenia did not worsen upon switch to lumateperone from standard-of-care, rather, statistically significant improvement from baseline was observed in the Positive and Negative Syndrome Scale (PANSS) mean total score.

Notably, greater improvements were observed in subgroups of patients with elevated symptomatology, such as those with comorbid symptoms of depression and those with prominent negative symptoms. I refer you to our September 7 press release, where we provide further details. We will provide further analysis later this year at ACNP, the American College of Neuropsychopharmacology meeting.

We continued to advance the development of our ITI-007 long-acting injectable program. The differentiated safety and tolerability data to-date with oral lumateperone suggests that a long-acting injectable formulation may lend itself to being an important option for some patients. This program is in preclinical development and we will continue to update you as we move forward.

In recent months, we made numerous presentations regarding lumateperone and our other programs at scientific and medical conferences. We presented data supporting lumateperone's potential as a potent and rapid antidepressant in a range of

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at the Annual Conference of the International Society for Bipolar Disorders and at the International College of Neuropsychopharmacology Thematic Meeting on treatment-resistent depression. At these meetings, we shared data demonstrating that lumateperone as a standalone agent, indirectly enhances glutamatergic neurotransmission through both AMPA and NMDA channels in the prefrontal cortex, bio lumateperone's dopamine D1 receptor activation. Additionally, we presented data demonstrated in lumateperone activates key proteins in the (inaudible) pathway, similar to ketamine, which has shown rapid antidepressant effects, yet lumateperone has not been associated with ketamine-like safety concerns. These findings, in addition to the potent serotonin transporter inhibition previously described with lumateperone, suggest the potential for lumateperone to exhibit potent and rapid antidepressant effects in patients suffering from the range of mood disorders, including comorbid depression and schizophrenia, bipolar depression, major depressive disorders and treatment-resistant depression. Our lumateperone bipolar depression program consists of 3 Phase III clinical trials: a monotherapy study conducted in the United States, an adjunctive study conducted in the United States and a global monotherapy study.

We anticipate completing patient enrollment in these studies in 2018. Bipolar disorder affects approximately 2.6% or 5.7 million adults in the United States. There are few approved therapies for the treatment of bipolar depression, and they have clinically relevant limitations in terms of safety and tolerability. We believe, the safety profile of lumateperone seen to-date, will translate favorably to people living with bipolar depression.

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we are planning to broaden our program to evaluate lumateperone for the treatment of depressive disorders, including major depressive disorder and treatment-resistant depression. We will provide further update as this exciting expansion of the lumateperone program progresses, and as we enter the clinic for those indications in the next year.

Moving to our dementia program, our lumateperone Phase III development program for the treatment of agitation in patients with dementia, including Alzheimer's disease is ongoing. Agitation is highly prevalent and observed in over half of patients with Alzheimer's disease, and represents a leading cause for institutionalization. There are no approved treatments for agitation and aggression in this patient population. Currently, certain medications are prescribed off-label to manage these behavioral symptoms. These medications are frequently ineffective and associated with deleterious side effects, including those leading to falls and fractures and increased mortality. We believe that low dose lumateperone, which provides complete saturation of the 5HT2A receptor, and also provides modest but necessary D2 receptor blockade for the control of aggressive behaviors, is uniquely positioned to address its unmet need with a favorable safety and tolerability profile and provide relief of a broad array of behavioral symptoms associated with dementia. Our goal is to reduce the significant and costly burden on patients, caregivers and families, by delaying or preventing nursing home placement.

I'd now like to turn to our PDE1 platform. ITI-214 is a potent and selective phosphodiesterase 1, or PDE1 inhibitor, and our clinical lead in our PDE program. The mechanism of action of PDE1 inhibitors suggests therapeutic potential across a variety of

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CNS diseases. In preclinical studies, we have recently demonstrated the importance of ITI-214, an inhibition of PDE1, in reducing neuroinflammation and in regulating microglial function, the primary immune cells under CNS. We will be presenting additional data on the mechanism of ITI-214 and neuroinflammation at the Society for Neuroscience meeting next week. These data suggest that ITI-214, an inhibition of PDE1, may have utility in treating these symptoms and modifying the disease progression in neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and other diseases having a strong neuroinflammatory component.

Preclinical models of Parkinson's disease suggest that our PDE1 inhibitors allow for motor symptom control at lower doses of dopamine replacement therapies while inhibiting adverse dyskinesias induced by these treatments. Additional models have shown the potential for our PDE1 inhibitors to address nonmotor symptoms prevalent in Parkinson's disease, such as reduction in excessive daytime sleepiness, improvement in cognitive function, as well as attenuation of other nonmotor symptoms.

Based on these preclinical results and our Phase I clinical data demonstrating safety in over 150 normal healthy volunteers and patients with schizophrenia, we have recently initiated a Phase I/II randomized double-blind placebo-controlled, multiple rising dose clinical trial to evaluate 214 in patients with Parkinson's disease. In this trial, patients with mild to moderate Parkinson's disease who are maintained on stable Parkinson's disease therapy, receive ITI-214 oral doses once daily for 7 days. The primary objective of this study is to evaluate the safety and tolerability

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Secondary objectives are to evaluate the pharmacokinetic profile of ITI-214 and to explore its potential utility to control motor symptoms and nonmotor symptoms associated with Parkinson's disease. Plasma levels of inflammatory mediators will be assessed as potential biomarkers of neuroinflammation. We expect to complete enrollment in this trial by mid-2018. Future efficacy studies may examine nonmotor symptoms, including depression, psychosis, sleep disturbances, dysautonomia and cognition.

Parkinson's disease affects nearly 1 million people in the U.S., and 1.2 million people in Europe. It is a progressive neurodegenerative disorder largely affecting dopamine neurons in the brain and impairing motor and nonmotor functions. Current dopamine replacement therapies primarily focus on addressing motor symptoms. However, over time, the doses of these therapies need to be increased to maintain motor control and, following long-term treatment, patients commonly develop dyskinesia. Additionally, nonmotor symptoms are highly prevalent in Parkinson's disease. For example, excessive daytime sleepiness affects up to 50% of patients and dysautonomia affects up to 80% of patients. These nonmotor symptoms represent an important cause of patient disability and caregiver distress. These symptoms are often underrecognized and undertreated, partially due to the limited therapeutic options available. We are encouraged about the possibility of ITI-214 to address both motor and nonmotor symptoms of this disease. Importantly, currently available treatments for Parkinson's disease do not modify disease progression. It is critical therefore, to develop therapeutic approaches focused on neuroprotective interventions. Together with evaluating the effects of PDE1 inhibition on clinical symptoms in Parkinson's disease, we are evaluating the potential disease modifying clinical benefit through a reduction of neuroinflammation.

Shifting to other programs. We continue the preclinical development of our novel development candidate ITI-333, or triple three. Triple three is designed as a potential treatment for substance-use disorders, pain and psychiatric comorbidities, including depression and anxiety. As we are now very aware, the United States is faced with an unparalleled substance abuse crisis, which resulted in more than 560,000 deaths between 1999 and 2015 in the U.S., and over 60,000 deaths in 2016 in the U.S. There is a pressing need to develop new drugs to treat opioid addiction and safe effective nonaddictive treatments to manage pain. We believe the potential exists for ITI-333 to address these challenges. In preclinical studies, ITI-333 functions as a partial agonist at new opiate receptors, attenuating the behavioral effects of morphine, while displaying all analgesic efficacy that is reversible by the new opiate antagonist naloxone. ITI-333 also acts as a 5HT2A antagonist with interactions at D1 receptors. Preclinical safety studies are currently ongoing. If successfully translated to humans, this unique pharmacologic profile may yield clinical utility for the treatment of substance-use disorder and pain.

Finally, we ended the quarter with $328.1 million in cash and investments, which, coupled with $162 million

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from our recent financing, places us in a very strong position for corporate activities.

I will now turn the call over to Larry, who will review the financial results for the third quarter.

Thanks, Sharon. I will be reviewing our financial results for the third quarter ending September 30, 2017, including the recent offering of our common stock that raised $172 million with net proceeds of $162 million, and provide an overview of our expectations for the use of our cash and investments.

The net loss for the third quarter of 2017 was $22.9 million, compared with the net loss of $30.3 million for the third quarter of 2016. Basic and diluted net loss was $0.53 per share for the third quarter of 2017, compared to a basic and diluted net loss of $0.70 per share for the same period in 2016.

Research and development expenses for the third quarter of 2017 were $18.5 million, compared to $23.9 million for the third quarter of 2016. The decrease for the third quarter of 2017 is primarily due to lower costs associated with outside clinical and nonclinical activities. In the third quarter of 2016, outside costs were incurred primarily for the second Phase III clinical trial of lumateperone in patients with schizophrenia, which was completed in 2016. In the third quarter of 2017, outside costs were incurred primarily for the Phase III clinical trials of lumateperone in patients with bipolar depression and dementia and other lumateperone-related trials.

General and administrative expenses for the third quarter of 2017 were $5.3 million, compared to $6.3 million for the prior year period. The decrease is primarily the result of decreased stock option expense and legal

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incurred in the third quarter of 2016 for costs relating to the license of certain intellectual property by us to our wholly-owned subsidiary, ITI Limited.

Cash, cash equivalents and investment securities totaled $328.1 million at September 30, 2017, compared to $384.1 million at December 31, 2016. In October 2017, we raised gross proceeds of approximately $172.5 million with net proceeds of $162 million in a public offering of our common stock.

We expect that our cash, cash equivalents and investment securities will be used primarily to advance to lumateperone development programs, to fund precommercial activities for lumateperone for the treatment of schizophrenia and bipolar disorder, and, if lumateperone receives regulatory approval, initial commercialization efforts to fund precommercial activities for lumateperone for the treatment of behavioral disturbances and patients with dementia, including Alzheimer's disease; to fund preclinical and clinical development of the company's ITI-007 long-acting injectable program; and to fund lumateperone related manufacturing activities. Funds will also be used for other clinical and preclinical programs, including the company's phosphodiesterase PDE development activities.

With that, operator, could you please open the line for questions?

(Operator Instructions) And our first question is from the line of Bill Tanner with Cantor Fitzgerald.

(inaudible) 214 interesting comments that you made about the impact on microglial cells and inflammation in PD. So I guess, is the contemplation that if you give the drug and it works quickly, that is anti-inflammatory, that's an anti-microglial effect? Or is there something from a signal transduction perspective that is also involved?

So Bill, and thanks for the question. Yes, we're very excited about 214 and the potential for disease modifying effect. And through the pathway we described in neuroinflammation. And I'm going to turn it over to Kim to talk about your question in a little bit more detail. Kim?

Sure. Bill, so with Parkinson's disease, we are very excited about the 214. We believe with short-term administration, we'll be able to have a good motor control and improve the nonmotor symptoms associated with Parkinson's disease. And then through a decrease in the information pathways that it has a potential disease modifying effect to really have a potential for improvement of the disease to slow the degeneration over time and with longer-term administration. And so these data are really exciting. Our scientists have been doing a tremendous job and looking at some of the effects in the preclinical models to show decreases in the pro-inflammatory markers and we'll be including exploratory biomarkers in our clinical study as well to follow these.

And just thinking about the biology of PDE1. Obviously, isoforms in the PDE family, some of them, you probably don't mind hitting, and some of them, you want to. So I guess, even if 214 is the selected PDE1 inhibitor, are there things that inhibiting PDE1 and various other -- or various parts of the body might be undesirable? I'm just trying to understand what's the therapeutic window here?

Thank you so much for asking that, Bill. Kim, do you want to?

Yes, that's a really good question. And the exciting thing, 214 is very selective for PDE1. And we know that PDE1 is expressed primarily in the brain, in the heart and in the microglia. So it's really exciting. We've done a lot of cardiovascular safety work with ITI-214 and we believe that there's cardiovascular benefit as well, which also ties into the Parkinson's disease for the cardiovascular benefit to see if we can improve some of the nonmotor symptoms in the cardiovascular systems such as the dysautonomia. So we believe that we really are taking this 3-pronged approach with the selective PDE1 inhibitors that are a unique feature for PDE1 over other phosphodiesterases.

And it's very selective. The molecule is very selective for PDE1 over any other PDE.

And Kim, then you mentioned the cardiac. I think, isn't the PDE 3 that's an isoform that you might not really want to hit as it relates to cardiac function? So sounds like in your hands that -- or the company's hands that PDE1 inhibition and the heart may actually have a beneficial effect?

Okay. All right, thanks very much.

And our next question comes from the line of Paul Matteis with Leerink Partners.

Just first on the NDA submission. Sharon, I was wondering if you could just go through the various components and the current status of where you are regarding generating long-term safety data that's needed for the submission. CMC, things like that and just clarify which are most rate limiting at this point?

Thanks, Paul. So I'll just start and then I'll ask Kim to continue. And we are, as we said, we are on track for submission mid-'18. So I think that our long-term safety is ongoing. And I'll ask Kim, again, to comment, but I think that the important take home here is that we're on track for that we will have what we need to have for our submission, which we are anticipating being mid-2018. Kim?

Sure. And I would just like to add that we've been very pleased that we've been able to enroll rapidly for the long-term safety study. And as Sharon says, we'll have what we need and we have a strong CMC package. And so really it's a matter of putting together all the documentation for the NDA, which we're doing now.

Okay, great. And then one clinical question on the broader concept of antipsychotics and the use in for agitation and behavioral disturbances. Sharon, I was wondering if you could just speak generally to how you're thinking about on the dementia behavioral disturbances program has evolved. In the context if it has evolved. In the context of new data we got this year from brexiprazole and then, too, a recent presentation from Acadia, where they showed their ADP data. They showed actually a higher rate of agitation on their drug versus placebo and they also discontinued their agitation study. How does all these decision-making and new data in the field influence the way you're thinking about the mechanistic rationale for ITI-007 in that program?

Well, so this time, we'll reverse the order. I'll ask Kim to comment first, and then I'll chime in.

That's a good question. And we really believe that lumateperone has an important feature in that we have full 5HT2A receptor occupancy in the cortex, and with a little bit of the D2 modulation. And the unique feature with lumateperone is that it acts as a presynaptic partial agonist and a prosynaptic antagonist D2 receptors. And we believe that a little bit of D2 modulation is going to be key for decreasing the agitation and the aggression. Go ahead, Sharon.

And the D1 receptor occupancy as well. But again, I think your comment on the agitation as we do believe that, that little bit of D2 is very necessary for the agitation component. So that's, that comment. I don't think -- we're not well-versed enough on other people's products to really make comments on them at the moment. I think we need to see a little bit more data.

Okay, fair enough. And then just one more question on the bipolar program. Are you still expecting sequential enrollment of those studies, 1 in the first half time frame. And then the other 2 towards the second half? Is that the right way to think about it?

Yes, that's correct.

And our next question comes from the line of Charles Duncan with Piper Jaffray.

I had a couple of questions. Some of them related to the ones that were just asked, but just looking for a little additional color on the long-term safety study with schizophrenia. Would you talk about that in a separate press release when it is completed? Or would you anticipate that the next announcement be submission of the NDA?

Talk about forward-looking statements. I think -- I'm not sure exactly how to answer that for you. I think that we are preparing the NDA as you know. I think that -- see, it's a little early for me to answer that question. So as we go forward, unless Kim, do want to say anything more?

No, that's fine.

Yes, okay.

Okay. I guess what I'm really asking is the completion of the long-term safety study dating to the NDA? Or could you submit that information after you file the NDA?

So maybe, I'll take that, Charles. So I think what -- I think Sharon doesn't want to speak to what press releases we may put out in the future. But from the clinical point of view, certainly, we believe that we have enrolled a sufficient number of patients to meet our long-term safety. We do continue to allow patients to enroll in the study so to say that we've completed the study. So to say that we've completed the study and when that will be announced is, we can't anticipate that right now. But certainly, we're on track to have everything that we need for the submission by mid-2018, and we believe, we'll have everything we'll need to support the approval of lumateperone for the treatment of schizophrenia. And we will be providing additional data of that long-term safety program as it moves forward.

Okay, that's helpful. And then just hopping over to the question. Previous question on the, I guess, it's a behavioral disturbances associated with dementia, or AD. It seems like you folks are very much more focused on agitation aggression versus psychosis symptoms. And I'm wondering if you're using those words interchangeably or specifically in that you want to focus on evaluating agitation and aggression versus psychosis. And if it's that, why aren't you considering a broader psychosis?

So that's a good question, Charles. But I think agitation, which includes aggression in the clinical definition, is more prevalent. It occurs earlier than frank psychosis in dementia, and sometimes, the psychosis symptoms can be more transient and perhaps more difficult. As you lose more insight, those become difficult symptoms to evaluate from a clinical perspective. So with agitation and aggression, there's a clear scale that we can use that the experts have developed to really tap into these aggression and agitation behaviors. And we believe that based on the pharmacology with lumateperone, it really is -- will be helpful for reducing the agitation and aggression. We -- I mean, of course, we believe that it would also reduce the psychosis, but you really have to focus in on a primary endpoint for these studies.

That make sense to me. So it's really -- it's not the activity, it's really about clinical trial and execution. That makes sense.

That's right.

Last question on -- well, I actually had one other earlier stage. On long-acting lumateperone, when would you anticipate that to be in the clinic that looks like an interesting molecule as a follow on?

So we're looking at late '18, early '19, for entering the clinic there.

Sorry to interrupt. And for 214, I'm really intrigued with that and its mechanism. Are you considering also potentially the utility of that mechanism and other degenerative diseases such as MS?

Yes. So we -- other than we mentioned today that we are looking at Alzheimer's disease, we are presently evaluating several other diseases, for which, there are neuroinflammatory components. So stay tuned.

And our next question comes from the line of Bert Hazlett, EIG (sic) [BTIG].

I think I'll will continue along the pharmacology discussion today. The -- I'd just like to -- as you contemplate the 6-week switching study and the breadth of that data. In terms of the improvement in PANSS that you saw in that. I know we talked about it previously, but to what are you attributing the improvement in PANSS with lumateperone? Is it a compliance issue? Is it -- because the pharmacology has lower AEs, at least the lower AEs, and that's leading to better compliance? Or is it the pharmacology of the molecule in terms of efficacy measures where something differentiated is going on? And then, could you comment also on the (inaudible) AEs that you saw in that study, or was there any difference there as well?

So I think all -- this is all really addressed to Kim.

Thanks, Sharon. So thanks for the question. In our 6-week switching study, we did see improvement in the total PANSS switched from a standard-of-care antipsychotics in these stable patients. And there was a larger improvement in those patients who had greater symptomatology which we would anticipate. And we believe this is really driven by the unique pharmacology of lumateperone. Remember that lumateperone is acting synergistically through serotonin, dopamine and glutamate. And we believe that these other components beyond the D2 modulation may help improve symptoms such as the social function. We also have seen a very favorable safety profile. And in respect to your question on the motor AEs that these are very low and similar to the baseline levels and similar to the placebo levels that we've seen in our placebo-controlled trials.

Okay. And then as you've mentioned the movement towards major depressive disorder and depression indications and we'll get more color along those -- with the studies down the road. But as you think about dosing with lumateperone and (inaudible) engagement -- and this indication, should there be a material difference in dosing with the molecule in MDD? Or the depression indications beyond the bipolar depression?

So we believe -- just as a reminder that in bipolar disorder, we are looking at doses of 40 milligrams and 60 milligrams. And this is the range where we saw improvements in the schizophrenia program. The 60 milligrams of ITI-007 was positive in 2 studies, and in one of those schizophrenia studies, the 40 milligram dose did not hit on the primary endpoint, but did improve the positive symptoms of hallucinations and delusions and did improve on the CGI. And these are the 2 doses, the 40 milligrams and 60 milligrams that we've taken forward into our bipolar depression program and they're the same doses that we believe would be useful for the treatment of a major depressive disorder. Sharon, did you want to add?

No, I'd just like to go back to your question on the 6-week open-label safety study and just remind you that the purpose of that study was the primary outcome was the safety and tolerability. And we were very pleased to see that you could, in a real-world setting, take patients, switch them off the drugs that they were on, put them on lumateperone and see the improvements in the cardiometabolic parameters. And then when we switch them back, they again, on certain of these parameters in just a short period of time, worsened. We monitored for the efficacy really to know whether or not we were making patients worse. And we were not making patients worse. They remain stable, and in fact, as Kim said, did improve. So I think I just wanted to put all of that into context.

Right. And then translating that back to the depression question is that then we did see symptoms of depression improved in patients with schizophrenia at these dose ranges as well. And so these are the dose ranges that we would consider taking forward for major depressive disorders.

And just in terms of timing, you mentioned we'll hear something on this potentially later this year. But could that be a 2018 start for the MDD program?

That's right.

And our next question comes from the line of Ritu Baral with Cowen.

This is (inaudible) on for Ritu. I have one question on the NDA and then one on Parkinson's. On the NDA, have you communicated with FDA following the release of the first part of the safety study? And if not, can you update us on your plans to communicate with FDA here? How much long-term safety data that they're going to require at the time of submission?

So we are always in discussions with the FDA on all of our programs. So we are following the ICH and FDA guidelines for our long-term safety database.

Okay. And then on Parkinson's, you mentioned that you're looking at some relevant nonmotor symptoms. Can you give us a sense of what the endpoint would be for depression and psychosis in that trial?

Sure. So we actually are using the MDS UPDRS, which includes a nonmotor symptom subscale that measures all kinds of nonmotor symptoms with depression and anxiety, cognition and other symptoms. And -- so we'll be looking at this actually in a variety of ways as the exploratory measures, keeping in mind that this study is designed as a safety study, and not powered for statistical significance on efficacy measures, but looking for signals for efficacy using these exploratory endpoints.

Right, got it. And just to be clear there won't be an inclusion of something like a MADRS or a HAM-D for depression?

No.

And our last question is from the line of Edward Nash with SunTrust.

I just wanted to ask one question as kind of following up on Charles' question so just so that I am clear on the semantics here. So with regard to long-term safety, so maybe I'll ask it this way. Will you have what the FDA would require by number of patients and time on drug exposure by the time you file? Or do you just need it by the time it's actually approved? That base number, maybe.

Our understanding is that we will have everything we need and what we need is for approval.

Got it. Perfect, okay. That's why I was under the assumption it was approval, not actual submissions, that's great. The other question I had is just (inaudible) I just might have missed, what is the current status with the Phase III with the agitation associated with dementia and Alzheimer's? That's still enrolling at this point.

Yes, that's right. It's still enrolling.

Okay. Will that one be fully enrolled in '18 as well as the other 3 for bipolar depression?

Yes.

And ladies and gentlemen, this concludes the Q&A session for today. I would like to turn the call back to Sharon Mates for her final remarks.

Great. Thank you, operator, and thank you all for joining the call. At ITCI, we are committed to developing novel treatments for patients suffering from neuropsychiatric and neurodegenerative diseases. And as you heard on today's call, we continue to advance lumateperone and our diverse drug development pipeline and we look forward to updating you on our next call. With that, operator, you can disconnect. Thank you.

Thank you, ladies and gentlemen. This concludes the program and you may all disconnect. Have a wonderful day.