Good morning, and welcome to the BioXcel Therapeutics Phase I Pharmacokinetic Bioavailability and Safety Study results of BXCL501 conference call and webcast. Before we start, I would like to inform you that this conference is being recorded and that all the participants are in a listen-only mode. The executives of the company will open the conference up for questions and answers after the presentation. If you have any problems during the call, please press star zero for the conference call operator. I will now turn the conference over to Carol Ruth. Please go ahead, ma'am.
Okay. Thank you, operator. Just to remind everyone, certain matters discussed in today's conference call or answers that may be given to questions asked are forward-looking statements that are subject to risks and uncertainties relating to future events, including, but not limited to, the advancement and development of BXCL501. Actual results could differ materially than those anticipated in these forward-looking statements. Risk factors and other uncertainties that may affect results are detailed in our most recent public filings with the SEC, including our quarterly report on Form 10-Q for the quarter period ending March 31, 2019, which can be found on our website, www.bioxceltherapeutics.com, or on www.sec.com. Before turning the call over to Dr. Vimal Mehta, founder and chief executive officer of BioXcel Therapeutics, I'd like to point out that we have slides accompanying the presentation that you can access off the investor relations site of the company's website.
Vimal.
Thanks, Carol. Good morning, and thank you all for joining us today to discuss the results of our Phase I pharmacokinetic and safety study of BXCL501. Our proprietary sublingual thin film formulation of dexmedetomidine, we will refer as DEX, for acute treatment of agitation across neuropsychiatric diseases. Joining me on the call today are Dr. Robert Risinger, VP of Clinical Development, Dr. Chetan Lathia , Senior VP and Head of Translational Medicine, Clinical Pharmacology, and Regulatory Affairs, Dr. Vincent O'Neill, Chief Medical Officer, Dr. Frank Yocca, Chief Scientific Officer, Richard Steinhart, Chief Financial Officer. Earlier today, we announced positive results from a Phase I pharmacokinetic PK and safety study for BXCL501 for the acute treatment of agitation. The study met its primary endpoint for PK and safety and achieved the targeted exposure level.
The results of this study have laid the foundation for a Phase II efficacy trial, which is anticipated to commence imminently. The results from the Phase II study are expected to support statistical powering of a planned Phase III pivotal trial in second half of 2019. We expect to be in a position to file an NDA in 2020. Earlier this year, we have previously announced encouraging human proof of concept data from the IV DEX study in patients suffering from acute agitation associated with schizophrenia, Alzheimer's disease, and opiate withdrawal symptoms, as well as healthy volunteers. On today's call, we will provide an overview of BXCL501 program, review the results of Phase I PK and safety study, and provide an update on the global development plan for our lead neuroscience program. Following our prepared remarks, we'll be happy to answer any questions you may have.
With that, I would like to turn the call over to our VP of Clinical Development, Robert Risinger, to provide an overview of BXCL501 program and results from our current study. Bob.
Thank you, Vimal. On slide four, describe agitation as a global and growing multibillion-dollar healthcare issue. For many patients, a safer and non-invasive treatment for agitation is desperately needed. Approved antipsychotics are invasive, and other agents have major sedative effects. In dementia, for example, treatment choices are extremely limited. Benzodiazepines sedate, which causes worsening already impaired memory, and the use of antipsychotic drugs carry a black box warning of increased risk of death in the elderly. Experts agree that there is a need for a non-invasive treatment that is easy to administer and provides calmness without sedation, along with a good safety profile and tolerability. In BXCL501, we have taken an innovative approach to treating agitation using a first-in-class agent that targets a core causal agitation mechanism and created a non-invasive, easy-to-administer sublingual film designed for rapid onset of action.
The FDA has acknowledged that this is a significant unmet medical need in granting us a Fast Track regulatory path for our development plans in agitation. On the next slide, here is a spectrum of agitation encountered by providers that starts with mild severity, where relatively cooperative patients are able to take pills. The goal of treatment is to deescalate the emerging agitation and keep patients from becoming more agitated. At the opposite end of the spectrum are patients with severe agitation that are uncooperative, often to the point of requiring seclusion, even physical restraint, and are unable to take a pill. These subjects require urgent treatment to keep them from hurting themselves or others. In this condition, as you might imagine, a nurse approaching them with a needle risks even further escalation.
For escalating patients, the effect of pills may be too gradual and slow, while giving an injection is too invasive and risks further escalation. We believe the greater unmet need is providing a treatment option that rapidly intervenes before the patient is fully uncooperative and out of control, which nicely fits into existing treatment guidelines designed to identify and de-escalate before patients are out of control. On the next slide, today, we are announcing the top-line results of our first-in-human study of this sublingual film. To describe the study, I'd like to introduce Dr. Chetan Lathia, the Senior Vice President of pharmacokinetics and Head of Regulatory Affairs, who will elaborate the study design, objectives, and our pharmacokinetic findings.
Thank you, Rob. I'm now going to slide number seven, which describes the study design. We conducted a first-in-human study to evaluate the PK and safety of the sublingual film formulation. This was designed as a standard single ascending dose study. The key purpose of this study was to evaluate doses that would yield target exposures. This was a double-blind, placebo-controlled, single ascending dose PK study. It enrolled healthy adult volunteers ages 18 through 65, with 20 females and 22 males. This was a single-center study, and three doses were evaluated in this study, 10 micrograms, 20 micrograms, and 40 micrograms. The primary objective of this study was to determine the PK, safety, and tolerability of the doses that were administered in this study. Now I'll go to slide number eight, which describes the PK results.
On the left side of the slide is a plot of the mean concentration time data. Observed mean concentrations from the 10, 20, and 40 microgram doses are shown in this plot. Data from the IV Dex study in schizophrenia patients show that the lowest efficacious exposure is 22 nanograms per mL. This is shown as the dotted line on the plot. Data from the film formulation shows that the film rapidly delivers targeted exposures. These targeted exposures are consistent with the therapeutic responses seen in the schizophrenia study. Half of the subjects in the schizophrenia study who demonstrated a clinically significant reduction in PEC score achieved exposures that were consistent with those observed with the 40 microgram film. These data show that BXCL501 offers predictable and dose-proportional pharmacokinetics, which in turn enables dosing the film to achieve targeted exposures.
Pharmacodynamic data evaluated in the study show that the effects last four to six hours. These data are consistent with the duration of action data from approved therapeutic agents in this setting. With this, I'll turn it back over to Rob.
Thank you, Chetan. On slide nine, let's review our top-line findings by describing the safety and tolerability from this first-in-human study. We found that dosing with BXCL501 was safe and well-tolerated across a range of tested doses. There were no serious adverse events reported. The severity of adverse events was mild to moderate, meaning grade 2 or below. All adverse events were transient and required no intervention and completely resolved. The most common adverse event reported was drowsiness, and the rates of drowsiness in the treatment group were similar to that reported by the placebo group. Cardiovascular changes were not clinically meaningful. Further, we saw no clear sedative effects in comparison with the placebo. A maximum tolerated dose was not reached. On these results and the PK observations, we are confidently advancing clinical development to dose agitated patients with BXCL501.
Before I describe our development plans, however, let me share the context as to why we are so excited to have achieved these results with the film. On slide 10, in order to develop rapid proof of concept in agitation, we generated IV Dex data across four diseases and healthy volunteers. In schizophrenia, on the top left, we saw a 90% response rate with a reduction in agitation using the PANSS Excited Component or PEC scale without excessive sedation as measured by the RASS. Do we have the operator? Yes. Where? That's a wrap. I thought it might be. Are we on? Yes, you're on. Please go ahead. Thank you. I believe we were disconnected in the middle of my description of the agitation scale. Let me start again at slide number 10. In our proof-of-concept studies in agitation, we generated IV Dex data for four diseases and healthy volunteers.
In schizophrenia, we saw a 90% response rate with a reduction in agitation using the PANSS-EC component or PEC scale without excessive sedation as measured by the RASS scale. In dementia, we saw 70% response. In opioid withdrawal, we saw 100% response. In a separate public study of agitated delirium, there was a 100% response. Pharmacokinetics and safety profile from these three studies are remarkably consistent across the disease population. Let me detail the proof-of-concept study completed in agitated patients with schizophrenia in slide 11. In our IV Dex proof-of-concept study, agitated subjects with schizophrenia demonstrated a clinically significant reduction in PEC scores, had exposures that were consistent with those observed in our film formulation. Recall that PEC is an FDA agreed upon regulatory endpoint for registration trials to obtain the indication of treatment of acute agitation associated with schizophrenia and bipolar disorder.
In this proof-of-concept trial, PEC scores were reduced before sedation was evident, providing us with plasma levels that calm patients without inducing sedative effects. This degree of calming was robust. Not just a few points on a scale, but the degree of calming that clinicians like to see as a result of treatment. When developing the film formulation, we targeted exposures that produce this robust reduction in PEC scores. The film achieved exposures that equate with the clinical PEC reduction in agitated schizophrenia patients, and that is why we are confident the films can provide exposures which are potentially therapeutic in the patient population. Reassuringly, the PK and safety profile has been consistent across schizophrenia, dementia, and opioid withdrawal. Moving to slide 12. With the wealth of data, let me describe at a high level our plan to progress to our first NDA. Slide 13.
We have a Phase II study in a total of 200 agitated patients with schizophrenia, which we'll initiate soon. This is a two-part study. The first half of the study will dial in the dose group, and the second half will then allow us to characterize efficacy. Following this, we will initiate two Phase III registration trials later this year for a total of about 700 agitated patients, one in schizophrenia and one in bipolar disorder. These trials use the same endpoints and design as previously discussed for registration studies. We expect to complete the registration trials in the first half of 2020, enabling NDA submission in the second half of 2020. The design and endpoint are comparable to other agents which have achieved regulatory success.
We have considered multiple options, we believe this plan robustly increases the potential probability of success in separating clinical POC in Phase III while gaining regulatory approval. We believe the Phase II trial potentially de-risks development in the most capital-efficient manner without any impact on timelines. Let me outline development timeline on slide 14. This is the development for acute agitation associated with schizophrenia and bipolar disorder in terms of catalysts. We will initiate our Phase II trial in the first half of 2019. These are short trials to execute and rapidly enroll, principally because agitation is a commonly encountered condition. We expect to have data readout in the third quarter of 2019, that enables us to initiate our Phase III trial in the fourth quarter.
Data from global Phase III trials will read out in the first half of 2020, that enables filing our first NDA in the second half of 2020. Finally, let me point out that in parallel, we have staggered development plans for agitated dementia, opioid withdrawal, and delirium, which we'll be rolled out throughout 2019. With that, let me hand it over to Dr. Mehta.
Thanks, Rob. This slide shows that agitation is a real unmet medical need for the U.S. population. There are 19 million total beds for agitation in the country. We take from three million presently suffering from agitation. A major cost to today's healthcare system. At BioXcel Therapeutics, we have total patients with moderate agitation, which account for a total of three million patients, including schizophrenia, bipolar disorder, dementia, opioid use disorder, and delirium. Each of our products address a real unmet medical need and could bring relief to millions of patients and has broad market potential. Let me remind you to join us for our BXCL501 Investor Event for an in-depth covering of the Phase I safety study results on this Wednesday, May 22nd at the Four Seasons Hotel in New York City. You can find the agenda for the event in the press release issued on May 15th.
If you'd like to attend the event, please contact Grant Desnoyers at the Booth Group at 643-536-7026. To summarize, we believe the data results we have reported today are highly promising and positive. We remain on track to launch a Phase II trial for BXCL501 independently, which is expected to support the statistic powering of a planned Phase III pivotal study. As previously mentioned, this timeline would optimally position us for submission by the FDA in 2020. We are optimistic that BioXcel's BXCL501 central agitation property, which appears to be independent of underlying disease pathologies, offers the product broad market potential. This concludes our prepared remarks. We would like to open the line for questions. Operator.
Thank you, sir. Ladies and gentlemen, if you'd like to ask a question, please signal by pressing star one on your telephone keypad. If you're using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Once again, please press star one to ask a question. We will pause for just a moment to allow everyone an opportunity to signal for questions. We will now take our first question from Geoff Whitehand from Baillie Gifford.
Hey, guys. Congrats on the data. I have a couple questions. One of them is, I think you guys have talked about two hours being the effect, and this is a little longer, four to six. Am I remembering incorrectly? Maybe just help us put these results in context maybe of what you view as a meaningful sedation with respect to time. I have one follow-up.
Yeah. This is Chetan Lathia. To answer your question, we have mentioned in the past that the half-life of this product is two hours, and that's what we have seen. The onset of effect is very rapid. It's observed in the plot on slide eight. What I mentioned in slide eight is that our pharmacodynamic effects last between four to six hours. We have a duration of action of four to six hours. Hopefully that clarifies the point that you are trying to make.
Okay. Makes sense. Then I just saw something in the press release that said cardiovascular changes were not clinically. I wasn't sure what this meant. Was there something that you guys saw in this study on the cardio side that was numerically different? Maybe just help put that into context. Thank you.
Sure. Not clinically meaningful. There were three total events in the study. Two were on drug, one was on placebo. We don't believe this really was any different from placebo.
Okay. Thanks.
Thank you. Ladies and gentlemen, if you'd like to ask a question, please press star zero on your telephone keypad. We will now take our next question from Keith Anker from BMO Capital Markets.
Morning, guys. This is Keith Anker. Thanks for taking my questions, and congrats on the progress. I had two quick questions. The first, I think you touched upon this a little earlier. Did you see any variation among patients presenting with different neuropathology or demographics in terms of age, gender, weight, et cetera? Was the variation related to dose, pharmacokinetics, or none? Then I have one more to follow up.
Yeah. This is Chetan Lathia again. In the PK study, we evaluated the effect of age, gender, ethnicity, et cetera, on pharmacokinetics. We did not see any effect of those variables on pharmacokinetics.
Okay. That's all. Thank you. Yeah. Just one more is, can you talk a little bit about how the sublingual film is unique to, for example, monolithic film? I understand that it attaches to the oral mucosa. Is there any concern if the film lands somewhere else, like the pharynx, with respect to a numbing effect? That's all.
Let me take that question. This is Frank Yocca, CSO. The film is different than a monolithic film in that the drug substance is micro-deposited onto the film. As soon as the film touches the mucosa, it's delivering the drug rapidly. We look at that as a distinct advantage. Not only that, the drug had to be given in such small quantities that we needed to come up with a different way of delivering it. This really fits it quite well. In terms of your second point, which is whether or not the film is swallowed. The film has a mutual adhesive property that's associated with it. As soon as it touches the tongue or what have you, it sticks. We've all tried Placebo. We can tell you that it works quite well.
Okay, that's great. If I could ask one more. Just any reason you're looking into schizophrenia for the Phase II rather than bipolar?
There's far more data in patients with schizophrenia, and therefore it makes sense from a development standpoint to initiate with patients with schizophrenia. There's precedent, multiple trials, and so we feel it's the lowest risk for us to proceed in schizophrenia.
Okay, that's great. Congrats again, Dan.
Thank you.
Thank you. Ladies and gentlemen, if you would like to ask a question, please press star one on your telephone keypad. It appears there are no further questions, sir, at this time. I would like to turn the conference back to you, sir, for any additional closing remarks. Sorry, there's one question lined up now. Can we take that?
Oh, yes, please. Go ahead.
Thank you. We'll now take the next question from Sumant Kulkarni from Canaccord Genuity.
Hi, good morning. Thanks for taking my question. Now that you have more info on your PK and PD profile of the film, how should we think about timelines on the other agitation indications that you might be going after?
We're developing plans for the other indications because each indication will be different. The plans are slightly different, and we're going to outline those plans in greater detail at the upcoming Investor Day on Wednesday.
Sure. Thank you.
There are no further questions, sir.
We would like to thank you again for participating in this call and for your continuous support of BioXcel Therapeutics and our innovative program. We look forward to sharing further updates on BXCL501, our lead neuroscience candidate, as well as other clinical assets as we move forward with development. Thank you.
Thank you. Ladies and gentlemen, this will conclude this conference call. Thank you for your participation. You may now disconnect.