Good morning, and welcome to the BioXcel Therapeutics BXCL501 phase I-B data results conference call. Before we start, I would like to inform you that this conference is being recorded and all participants are in a listen-only mode. At the request of the company, we will open the conference up for questions and answers after the presentation. Should you have any problems during the call, please press star for the conference call operator. I'll now turn the call over to Carol Ruth of The Ruth Group. Please go ahead.
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 and/or the future financial performance of the company. Actual results could differ materially from those anticipated in these forward-looking statements. The risk factors that may affect results are detailed in the company's most recent public filings with the U.S. Securities and Exchange Commission, including its quarterly report on Form 10-Q for the quarter year ended March 31, 2019, which can be found on its website, www.bioxceltherapeutics.com, or on www.sec.gov. I would now like to turn the call over to Dr. Vimal Mehta, Chief Executive Officer of BioXcel Therapeutics.
Thanks, Carol.
Vimal?
Thanks, Carol. Good morning, thank you all for joining us today for the BioXcel Therapeutics BXCL501 phase I-B trial results conference call and webcast. I would like to add our welcome to everyone joining us via phone and the webcast. I would also like to note that the slides for today's conference call are available on our website under the Investors section. Joining me today are Dr. Rob Risinger, Vice President of Clinical Development, Neuroscience, Dr. Vince O'Neill, Chief Medical Officer, Dr. Frank Yocca, Chief Scientific Officer, Dr. Chetan Lathia, Senior VP of Translational Medicine and Regulatory Affairs, and Richard Steinhart, our Chief Financial Officer. This morning, we released encouraging data from the phase I-B study of BXCL501. We are very excited about these strong data results, highlighting the potential of BXCL501 as an acute treatment option for agitation.
Let me provide a summary of the outstanding results we received from the trial, which we believe provides strong validation for the future of BXCL501 as a therapeutic option. Recall, BXCL501 is a potential first-in-class proprietary sublingual thin film of dexmedetomidine. Dex, a selective alpha-2A receptor agonist. In our trial, we observed clinically meaningful, rapid, and durable reductions in PEC score in the acute treatment of agitation in schizophrenia patients. There was a statistically significant mean reduction in PEC score at two hours compared to placebo, following a single dose of 180 microgram. P-values are less than 0.0001, with rapid and durable effects maintained for up to six hours. Just to remind, the PEC score is a validated regulatory registration endpoint for measuring acute agitation in schizophrenia and bipolar patients.
A broad benefit was observed with approximately 90% of patients having met criteria with a reduction in PEC score greater than 40% with 180 microgram. The drug was well-tolerated, with no serious or severe adverse events across the dose range. We believe that our data supports progressing BXCL501 program to potential pivotal trials subject to further discussions with the FDA. We're going to move to slide number 6. Agitation is a common and costly market behavioral phenomena associated with multiple neuropsychiatric conditions, including schizophrenia and bipolar disorder. Our research indicates that agitation is a sizable market with approximately 19 million people at risk and 8.3 million people in the U.S. suffering from agitation each year. We are targeting the patients with mild to moderate agitation, which account for a total of 3 million-5 million patients, including schizophrenia, bipolar, dementia, and delirium.
These numbers are much higher for the global population. Agitation results in an approximately $40 billion per year healthcare burden in the U.S. and is a major cost to today's healthcare system. Consensus guidelines have highlighted the need for non-coercive management strategies to protect the therapeutic alliance between patients and their healthcare providers. There is an urgent necessity to develop therapies that provide rapid symptom relief with a non-invasive approach to deescalate agitation and to avoid the costly and traumatic use of coercive techniques of physical restraint and seclusion. Therefore there is a strong unmet need for a new innovative approach. At BioXcel Therapeutics, we are focused on developing an innovative therapeutic option that addresses current treatment challenges and meets the needs of patients. Now we're going to shift to slide number seven.
Our development plans for the acute treatment of agitation, besides schizophrenia and bipolar disorder, also include dementia, opioid withdrawal symptoms, and hyperactive delirium. These plans are outlined on slide number seven. We believe the results of this trial, along with our earlier efforts, demonstrate that BXCL501 directly targets a causal mechanism which will allow us to treat agitation in a variety of neuropsychiatric disorders, creating what we believe will be a very large market potential for BXCL501 following regulatory approval. We expect to be able to share results of this work over the next several months. I will now turn the call over to Dr. Rob Risinger to discuss the phase I-B trial design and results. Rob?
Thanks, Vimal. Hello everyone, thank you for joining us today. We developed BXCL501 because we believe that current therapies for the treatment of agitation are suboptimal. On slide nine, you see in dementia, antipsychotic drugs carry black box warnings for use in the elderly. Many current drugs are often invasive with severe side effects, and the consensus opinion on ideal treatment for agitation includes drugs that are non-invasive, create calmness without sedation, easy to administer, exhibit rapid onset, are non-traumatic and non-coercive, have a good safety profile, and exhibit favorable tolerability, and of course, are patient-friendly. We believe that BXCL501 meets these criteria. BXCL501 has a novel mechanism of action. The drug is non-invasive. It is easy to administer in a sublingual thin film that exhibits a rapid onset of action. On slide 10, let me quickly review our trial. This is a phase I-B BXCL501 trial.
It was double-blinded, placebo-controlled, multi-center U.S. trial. The dose-ranging study evaluated multiple doses of BXCL501 for acute treatment of agitation in schizophrenia patients. The trial enrolled a total of 135 adult patients with a confirmed diagnosis of schizophrenia. There was a six-hour treatment period. Dose groups were randomized 2 to 1. A single dose of BXCL501 was administered. Doses administered were 20, 60, 80, 120, and 180 micrograms, along with placebo. Please note that the 20-microgram dose was repeated one hour later, but all other doses were single doses. On slide 11, the primary endpoint of the study was the change from baseline as measured by the total PEC score. Remember that the PEC score is the PANSS Excited Component, as Vimal noted earlier, and is the study's primary regulatory endpoint.
Slide 12, the demographics for our study were as follows: The mean age in years was 48.4 for the placebo group and 47.2 for the BXCL501 group. There were 89 males and 46 females. The mean PEC score at baseline was 18.1, ranging from 14-25 for the placebo, and 17.8, ranging from 14-26 for the BXCL501 group. Subjects were on a range of typically prescribed antipsychotics, and our chart on slide 13 now clearly indicates the separation of 180 microgram dose versus placebo. The study was initiated in May of 2019 and completed its first stage earlier this month in July of 2019. Our acute agitation studies are generally of short duration and have easily measurable clinical endpoints.
We're pleased to report that BXCL501 met the primary endpoint, with a reduction in the PEC score for agitation and a clinical display of rapid calming without excessive sedation at the regulatory endpoint and at earlier time points. Notably, three of the doses tested showed high statistical significance in patients treated with BXCL501 compared to with placebo, with a P value of less than or equal to 0.0001, with clinically meaningful, rapid, and durable reductions in PEC score. The 80, 120, and 180 microgram dose of BXCL501 showed reductions of PEC score of -7.1, -9.2, and -10.8 respectively, compared to -4.1 for placebo at the clinical regulatory endpoint measured at two hours. This effect continued with statistical separation maintained for at least six hours for the 80, 120, and 180 microgram doses. On slide 14, the secondary evaluations included the assessment using the Agitation-Calmness Evaluation Scale, or ACES.
Let me explain what ACES is. It consists of a single item that rates overall agitation and sedation at the time of evaluation. Where 1 indicates marked agitation, 2 moderate, 3 mild agitation, 4 is normal behavior, 5 mild calmness, 6 moderate, 7 marked calmness, and 8 deep sleep, with 9 being unarousable. Our chart on slide 14 displays the changes in ACES from baseline. Consistent with the PEC score reductions, when compared with placebo, the 80, 120, and 180 microgram doses demonstrated increasingly statistically significant calming at the two-hour endpoint by the ACES scale, which confirms the findings using the PEC scale measurement at two hours. Slide 15. The trial results also demonstrated that BXCL501 was well-tolerated. It showed no severe adverse events across the entire dose range that was evaluated, and there were no discontinuations due to adverse events.
The most common adverse events observed in the 501 treatment group was mild somnolence and dry mouth. The maximum tolerated dose was not reached, and all subjects enrolled in the study were able to self-administer the film and completed the study. Slide 16. In summary, we've observed a statistically significant improvement in PEC score and the secondary efficacy endpoints in the 80, 120, and 180 microgram groups of BXCL501 in patients with schizophrenia. The results were clinically meaningful and sustained in their separation from placebo through at least six hours. The drug was safe and well-tolerated across all doses tested. A maximum tolerated dose was not observed. We believe that our data supports progressing the BXCL501 program directly to phase III pivotal trials, subject to discussions with the FDA.
On slide 17, in terms of the next steps, we plan to meet with the FDA to obtain additional feedback in order to optimize the path forward regarding further late-stage clinical development of our BXCL501 program. As previously announced, we plan to enroll approximately 700 patients, 350 each in schizophrenia and bipolar disorder in these pivotal phase III trials, which we do expect to start in the second half of 2019. On slide 18, we have outlined multiple upcoming value creation milestones for the BXCL501 program. Now that we've completed the phase I-B portion of our BXCL501 program, we're truly excited about our plans for the next 12 months. The pivotal phase III trial is anticipated to commence in the fourth quarter of this year, with a data readout expected in the first half of 2020.
We're confident that our timelines will support our objective of submitting our first NDA for BXCL501 in the second half of 2020. We're working diligently to achieve these goals based on the timeline suggested above. Let me hand this back to our CEO, Dr. Vimal Mehta.
Once again, I would like to thank you again for joining us today via phone and webcast, and also for your continued support of BioXcel Therapeutics as we develop our innovative program for acute agitation. We look forward to sharing further updates on BXCL501, our lead neuroscience candidate, as we move forward with its late-stage clinical development. We would now like to open it for questions.
Thank you. If you'd like to ask a question, please signal by pressing *1 on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, press *1 to ask a question. We'll just pause for a moment to allow everyone an opportunity to signal for questions. Once again, if you'd like to ask a question, please press *1. We'll now take our first question from Do Kim from BMO. Please go ahead. Your line is open.
Hi. This is Jameson Kao calling on behalf of Do Kim with BMO Capital Markets. Could you talk about the quality control measures when assessing PEC scores ? To elaborate, how do you control for the subjectiveness across investigators and were there independent central reviewers?
Sure. We did conduct centralized rater training such that each rater was evaluating the same item and using the exact same anchors. Recall that the PEC consists of five items from the PANSS. Each of those items is rated 1 through 7. They were using, for example, the same anchor. If a rater at one site rated an item as 3, the rater on the other side of the country would use the exact same anchor to rate that item on a 3. We did not use centralized raters, for example, video monitoring. We did do comprehensive training for these raters. Of course, we used sites that are familiar and well-trained in conducting clinical trials. Each of our raters had many years of experience in rating both the PEC and the PANSS.
Thank you.
We'll now take our next question Carter Gould from UBS, please go ahead. Your line is open.
Yeah. Good morning, and congratulations to Vimal and team on the data. I guess just two from me. I guess first off, you guys didn't specify what doses you're taking forward. Can you maybe just elaborate a bit on how you're thinking about dose selection, and if there are any other additional data analyses or I guess FDA feedback you're waiting for? Then I guess following up on that, when you think about the discussion points for that conversation with the FDA, what do you think are the key variables or toggles to be locked down? It seems like the phase III design is pretty well already settled upon. Thank you.
In terms of doses, we have not selected the doses. However, we're conducting extensive PK/PD modeling. With that modeling, we will decide which doses that we'd like to take to phase III. That is currently underway. It's an extensive effort. Of course, we're looking at the overall benefit and risk ratio, which is ultimately what the FDA determines your approval on. As you said, the phase III designs are pretty much locked down, and it's the niggling details that we want to review with the regulators and get their sign-off on. We expect to be able to achieve both dose selection, our PK/PD modeling, and a review by the FDA well before we begin the phase III studies by the end of this year.
Thank you.
We'll now take our next question from Sumant Kulkarni from Canaccord. Please go ahead. Your line is open.
Good morning. Thanks for taking my questions. I have several. Sorry if I missed this, how soon after administration was statistical significance hit for the doses that worked?
Statistical significance was achieved as early as 45 minutes for the 180 microgram dose. I believe that's in the plot. You can see that on the slide.
Got it. Yep. Other than the 20 microgram dose, there were no repeat doses. Would there be any rescue doses needed in the six hours? If it was possible in the real-world setting, how would that change the response rate?
No rescue doses were required in the six hours. 90% of the patients responded, 80.89% or 89% actually to be specific. 89% responded with a greater than or equal to 40% reduction in PEC score for the 180 microgram dose. At least for the 180 microgram dose, there was no reason, and there is no reason why you would want to repeat the dose. Lower doses continued to maintain their separation from placebo. Again, in the trial, 0 patients required either a repeat dose or rescue medication. Our goal, of course, in fact, the goal of any treatment that you wish to get approved is not to require another dose and for the single dose to be adequate to maintain the indication. In our case, to maintain control of the agitation.
Sure. Now that you're well on your way to de-risking the program and agitation, what are your latest thoughts on pricing and average number of treatments needed per month or a year in the schizophrenia and bipolar disorder setting?
I would say at least 12 per year on average. It's a rather large patient population. We know these patients frequently have episodes. Our best estimate at this point would be about 12 per year.
Thank you.
As a reminder, if you'd like to ask a question, please press star one. We'll now take our next question from Ram Selvaraju from H.C. Wainwright. Please go ahead.
Hi. Thanks so much for taking my questions. Just a couple of detail ones. On slide 12, you discussed the mean PEC score at baseline for this study, and I was wondering if you could just provide a little bit of additional color regarding what that range and what that mean score represents in terms of where on the spectrum these patients are with regard to the extent of their sedation. Secondly, referring to the plot on slide 13, I wanted to know with what sort of kinetics you see the effect of the mild sedation caused by 501 actually wearing off. At what point after these patients have gone through this timeframe here, where you see the maximum effect do they start to sort of return to normal? To what extent was that captured in the study?
Lastly, with respect to the design of the phase III, I wanted to better understand whether there's likely to be any requirement for more detailed or lengthier follow-up versus the paradigm that was used in this study. Thank you.
Let me answer those in reverse. With regard to phase III and the timeline for follow-up, we may in fact expand the assessment of efficacy over a longer timeframe. We honestly didn't expect to see an effect out to 6 hours. We chose a 6-hour endpoint because we thought we might start to see the effect wear off, and clearly it is not. The effect is lasting at least 6 hours. With respect to the duration of follow-up in the study, I'll remind you that these patients were followed over a week. We don't believe that we'll require more than a week of follow-up, but we did not measure the efficacy well beyond the 6-hour endpoint. We may measure the efficacy in terms of PEC score past a 6-hour endpoint.
In terms of sedation, these patients were not demonstrating sedation out anywhere near that six-hour time point. Any adverse events that were reported related sedation, drowsiness, for example. There's a lot of descriptors for sedation, but that mild somnolence that was typically reported was truly mild and tended to be transient. It did not last on the duration of six hours. It's a very different kind of effect in terms of mild somnolence. We did track that in this trial. It was not clinically meaningful. We'll be perhaps trying to better characterize what that is in the registration trial. With respect to the PEC score changes over time, I think I covered that. In terms of our registration trials, we'll likely measure out, for example, to maybe eight or 12 hours after dosing.
There may be a confound, because if someone's dosed during the day and you're assessing their agitation at midnight or 1:00 A.M. in the morning, there may be a confound in terms of sleep. We'll be addressing all of that in the design of the phase III trial and of course, in discussions with the regulators.
Just with respect to the PEC score at baseline, just wanted to know sort of how agitated those patients were just in general.
Correct. I apologize. They were agitated. We ensured that the minimum was 14. That's why 14 was the lower range. They had to have at least a level of agitation of 14 and greater. We achieved, in fact, enrolling patients with total PEC scores of 25 or 26. 25 or 26 is truly significantly agitated. This is moderate, and many patients or many clinicians would consider this severe agitation. We included, if you will, almost all brackets. These patients, of course, had to agree. They had to undergo consent. They were not necessarily patients who would be extremely agitated, but they were definitely mild to severe.
Do you expect to keep the same kind of baseline range in the phase III, or would you narrow the range at all? It looks like you have pretty uniform efficacy across this range. At least from an efficacy standpoint, it looks like you can keep this range without any issue. I was just wondering from a registration perspective if you need to?
We are keeping this range. That's right.
Okay. Thank you.
At this time, there appears to be no further questions. I'd like to turn the conference back to you for any additional or closing remarks.
Thank you everyone for joining us today. We appreciate your continued support, and we will be happy to answer any questions that anybody may have over the period of next several days and weeks. Thank you all for joining us.
This concludes today's call. Thank you for your participation. You may now disconnect.