Keep looking. Oh, testing. Good afternoon, everyone. I'm Sumant Kulkarni, a senior biotechnology analyst here at Canaccord Genuity, and thanks for joining us in the room and for everyone for tuning in to the webcast as well. We have BioXcel Therapeutics here today. Also a very interesting point of the company's evolution. They have one approved product, IGALMI, and there's BXCL501 that is in at a very interesting stage, and we'll go through all that. But that'll turn it over to CEO, Vimal Mehta. We also have the Head of Product Development, Vince O'Neill. So with that, Vimal, please go ahead and make a few, you know, setting the stage kind of remarks, and then we'll go through a Q&A.
Thank you, Sumant. Thank you for inviting us, and good afternoon, everyone. BioXcel Therapeutics, as Sumant mentioned, that we are a biopharmaceutical company focusing on neuroscience product. Our lead product is BXCL501, and we are now gearing up or getting ready to initiate phase II trials, two pivotal phase II trials. As Sumant mentioned, we already have an approved product, which is called as IGALMI. It's for acute treatment of agitation related to schizophrenia and bipolar. Our first pivotal trial will be to expand the label into the home setting.
So, we're going to discuss more about what we are planning to do about the SERENITY At-Home trial initiation, and then second is our new indication for Alzheimer's-related agitation, related agitation, and, that is our new indication, where we already have a one positive phase II trial, and now we are planning to initiate TRANQUILITY In-Care. That will be a second phase II trial, for that indication. Company also has a, like, you know, oncology product, BXCL701, where we have done proof of concept in some aggressive forms of the cancer, and it's an activator of innate immunity.
Overall, I believe the company is in a good place, that we have two pivotal trials that can help substantially expand the market potential for our product and in agitation, we believe that in acute treatment of agitation, we continue to build a leadership position as we have a most advanced product in the marketplace and as well as we have late-stage clinical trials. So we are very excited, and thank you for joining us today.
Thanks. I'll start with SERENITY At-Home, which is I guess even in general, it's a very important concept, but on your trial, what do you think the key sources of risk are in aligning with the FDA and actually allowing this product to be used at home?
Vince, you want to take that?
Yeah. So let me start on the, the R&D or the development side. So we believe, really over the last six months, we've had multiple interactions with the FDA. We're very aligned with the agency on the design of SERENITY. Fundamentally, by virtue of using 120 micrograms, which is an approved dose of IGALMI, this is a safety study, which makes it a simpler, more direct study to execute on.
Let me put it like that. So that's not directly answering your question. That's lack of risk, I think. I think we've worked hard to reduce the risk and the possibility of things going wrong with that study to as low as possible. Obviously, there's no such thing as risk-free drug development, but we're in a good place there. And let me answer your question this way. In terms of what a win would look like or a positive study, it is a safety study, safety primary. I think if we had a safety profile at home that looks substantially like that described in the label, that would be a good place.
So, I know this is a safety study, but collection of efficacy measures, if they were to be done at home, how would they be done best?
Yeah, so that's a fair point. So we will collect efficacy as an exploratory endpoint, but bear in mind that there are no validated instruments to be used in a home setting. Predominantly, we'll use CGI or versions of that. Again, there is no validated instrument, and I think the important point to bear in mind is that that's an efficacy. Sorry, that's an exploratory outcome in terms of efficacy. So there's no powering, there's no bar beyond which we need to reach for a positive study.
So on this Clinical Global Impressions (CGI), who exactly is taking that measurement, and how are they, I guess, eased into that process?
So that would be either the patient, him or herself, or, we call them dyads, essentially patient informants or someone who's living with the, the patient.
That sounds very, Matrix-like, dyads.
Right. Informant, indeed.
Okay, cool. So I'll move now to Alzheimer's agitation. It's a potentially extremely large market to a high unmet need, and you have TRANQUILITY In-Care.
Correct.
What exactly do you need to align with the FDA on that trial, and what would be the key points of discussion as you approach the FDA?
Yeah. So again, just bear in mind, we've had multiple points of interaction with the agency over the last six, seven, eight months. We have substantial alignment on the design of that study. So the primary endpoint, for example, which is a big-ticket item, we've agreed on, that's change in PEC at two hours for the first treated agitation episode. I think we know from experience and interactions with the agency that they are interested in repeat those efficacy or continued efficacy. That might be a better way to describe it. Actually, not terribly different from TRANQUILITY II. We did those types of analyses in TRANQUILITY II.
But I think it would be important to make sure, that the way we're analyzing those data, which is a little bit different from a primary endpoint, of course, a little bit more complex, are meeting the agency's expectations. So I think that's probably the one thing we want to tidy away. But again, just to stress the big-ticket items, so powering of the study, primary endpoint, sample size, substantially agreed with the agency already.
When is your next interaction going to be with the FDA on that program?
So fundamentally, when we submit the protocol, we will get feedback from the agency. It won't necessarily be live. It's almost certainly gonna be written, written feedback. But just to be clear, that would not stop us from starting the study. We don't have to wait for feedback from the agency before we initiate the study. And again, if I'm correct, and if it's really fundamentally gonna be about how we analyze continued efficacy, that can be finalized in the SAP, the analysis plan, which doesn't have to be finalized until really the database is locked. So we have lots of time.
Got it. So technically, these are going to be supplemental new drug applications or sNDAs, right? In that sense, how does that make things either easier or more logistically, maybe more complicated if you have to go from the approved product right now to an at-home use setting?
I mean, supplemental submissions are always better for sponsors than new NDAs, because the agency has no sense of how the drug, you know, behaves either in terms of efficacy or safety. So arguably, that gives us more confidence in where we're going, because these are supplementals. Is there anything I'm missing in your question? You may have a question behind your question.
No, I think that was it. It's just more about-- I guess we could-- That's a good kind of leading point into the next question, which is, Alzheimer's is an older patient population than what the product is currently approved in- which is schizophrenia, bipolar, on average, that is-
Yeah.
-age-wise.
Agree.
What's the burden of safety in that older patient population? How does that differ in a care setting versus at home, where there's maybe less round-the-clock care?
Yeah, so I think the, the one thing to acknowledge here, we'd be remiss not to acknowledge, is, with any sponsor doing a study in elderly patients and in that home setting, the concern is falls, right? Now, that said, based on TRANQUILITY II data, we did not see evidence of falls that were related to administration of 501 or any falls within 24 hours with administration of 501.
In addition, we have, across the program, at least 200 patients who have been 65 years or older, so therefore elderly. So we have a feel for what safety looks like in that population. Doesn't seem to be substantially different from the broader population And then the third point is, we obviously have drugs on the market. As IGALMI, we have quite a large pharmacovigilance post-marketing safety experience. That, again, doesn't really give us any flags to think that things would be substantially different to what we've seen before.
Got it. And I've asked you this question before, but I'm gonna ask for your latest thought process around it, which is: What is truly considered acute versus subchronic versus chronic in the AD agitation context? And that, I mean, as defined by the FDA.
Yeah. So I think the first thing to say is, we have had that discussion that has come up with the agency. To some extent, any definition is arbitrary, but one definition that the agency is comfortable with, I think drawing from the migraine experience, is less than 15 episodes of agitation per month would be considered acute, and beyond that would be chronic. Again, that's a somewhat arbitrary cut point, but it is one that's accepted.
Yeah. This is another question, which could evolve over time, your answer, I mean. Now that we have, you know, chronic agitation products approved for Alzheimer's, is there a certain patient percentage population that you're targeting within your trial program that might be on brexpiprazole, for example, where you could use 501 as a rescue therapy?
So again, we go back to the TRANQUILITY II experience, and if my recollection is correct, something like 50% of patients were on a background chronic therapy. So we would expect in the in-care study, a substantial minority or maybe even a majority of patients to be on background therapy. And that's fine. I mean, again, to stress, based on the feedback we've had with the FDA, they want a real-world, real-life experience in these studies, and that's exactly, I think, what we'll get.
So this is clearly an indication with lots of unmet need. So in your interactions with the agency, how would you characterize the level of supportiveness, I guess, or collaboration with the agency that you've had so far? And what have been the most, I guess, points of contention that the FDA might have pushed back on?
So I think the FDA has been exceptionally collaborative in this process. I think they certainly appreciate that there is an unmet need here. They also see that this potential approval or use for the drug has societal impact. All right? So they're taking it very seriously. I think that probably partly explains why they're so interested in demonstrating continued efficacy, as we've mentioned. So I think that's the one thing that they've said consistently: "We want to see this." I think beyond that, they've been incredibly collaborative with us.
Sumant, I will add that we have a Breakthrough Therapy Designation for it from the FDA, and there aren't, to our knowledge, any advanced program for acute treatment of agitation in Alzheimer's agitation. So I think we are in a very unique position. That also means that we have to collaborate a lot with the agency, because the agency has never approved a drug in this indication for acute. They have obviously approved the chronic agitation drug, Rexulti, but never an acute. So it requires very, as you, as you mentioned, and as Vince has said, collaborative experience in moving the program forward, and we are very thankful to the agency that they give us the amount of time needed to have those discussions.
Right. 'Cause there was agreement on the PEC score used in this, which is not the usual score, scale in chronic, because, you know, no one's ever done an acute agitation thing before, right? AD.
I mean, so the agency, it certainly accepts that the use of PEC is appropriate in these studies. They accept it for TRANQUILITY II , and that's the expectation for the In-Care trial.
Got it. As your understanding of agitation and Alzheimer's has evolved, because you didn't start TRANQUILITY III, and you figured out in that setting, the patients were more chronic. Was that a function of those patients, or is it that setting where there's the agitation is more chronic than acute?
Yeah, I think it's likely to be-- it could be both, but I think it's likely to be driven by the setting. So patients that are in, you know, heavy nursing care facilities are clearly there because they were not able to be managed at home. It's as simple as that. And we know that Alzheimer's is a progressive disease. As the disease gets worse, the frequency of these incidents increases.
I just want to clarify that in nursing, when we saw some patient will have episodic agitation, but their frequency can exceed than the cutoff of a three or something, what Vince mentioned, like total 15.
Right.
And if you are dosing more than three times a week, and our Breakthrough Therapy Designation is for acute treatment of agitation, that's part of the reason we decided to move in the direction of TRANQUILITY In-Care, where we are making sure these patients that we enroll, in the previous week, they don't have more than three episodes a week or something.
Got it. So this is also kind of an understanding of the evolution of AD agitation question, which, I don't wanna make this a commercial discussion, but how would you characterize unmet need, market size, number of episodes of agitation per year, those kinds of things, and how often do you have to refine those assumptions?
So our initial research that we have done, it has been like, you know, holding up, that it's more than 100 million episodes that happen in this patient population. Some of them are purely acute agitation episode. It can progress, where they can have more subchronic kind of a situation, where they're getting episodes not once a week, maybe three times a week. And then certain patient, as their Alzheimer's disease progresses, it can become more chronic during sundowning and other. So it's a broad spectrum, as Vince mentioned in our trial, we are trying to accommodate the real-world situation. We are accommodating ALF patients, we have memory care patient, and we have nursing home patients, so it will cover the whole spectrum.
And also, we are not limiting the agitation spectrum for, like, you know, what kind of Alzheimer's patient should be enrolled, what is their status? So we are using the whole spectrum of mild, moderate, and Alzheimer's patient, and mild, moderate, and severe agitation. So this trial was very thoughtfully designed after having the experience of the TRANQUILITY II, TRANQUILITY III, and understanding the market, how the market is evolving from a chronic agitation perspective. What kind of a trial will make most sense to continue to get the label that this drug will need so that it can have broader application?
Right. So what is your latest understanding on how agitation might affect cognition in Alzheimer's patients? And does dexmedetomidine have any place in treatment of on the cognitive side of things?
So to paraphrase your question, could we be having a disease-modifying effect? Is that point where you're going?
So any kind of impact on cognition, positive, negative, or none?
I think that's the type of question we'll ask when we have a bigger database and having completed TRANQUILITY In-Care study. That's a very good question, right? We're clearly thinking about this internally, but I think we need more data to see.
Got it. So, in terms of Alzheimer's agitation again, what do you see the key risk is with your ability to move this program forward? Is it not agreeing, agreeing on an FDA construct of what things should be like, or is it conduct of the trial, or what would you say it is? Because we know the product works, it's approved, right? We just have to see that it works in older patients in the setting you'd like to see it work.
Yeah. So I think in terms of the program design, the study, as we've said, I don't see there's much there to that needs finessing, or I think we're fine with the trial design. Yeah, I mean, again, there's no such thing as risk-free drug development. I think we wanna get the study going, we want to recruit the right patients. What helps with that is choosing our sites carefully and our investigators. But beyond that, I, I'm not certain that I see any huge risk aside from that.
Then going back a little bit in time, sites and investigators, you'd have TRANQUILITY II, where the trial was good. You had one unfortunate event at a site.
Correct.
How is all that gonna play out in the larger scheme of things when the FDA looks at this, totality of data kind of package?
So obviously, wouldn't speak on behalf of the agency. It's up to the agency to assess the data after submission, but I think that's the key. They will look at the data in detail after submission. Just as a reminder, we did conduct a third-party, entirely independent audit, and the findings there, subsequent to the event that you allude to, suggested that there was no evidence of impact on data integrity. So we feel comfortable with that.
Yeah. In terms of the potential pace of a trial here, how quickly could a trial like this be completed? Because this is an acute agitation trial, it's not, it's sort of, you know, it's more than what you had acute-wise, schizophrenia and bipolar disorder indications. But how quickly could you conduct this relative to, like, a chronic agitation trial?
So again, I will go back to the experience with TRANQUILITY II. We haven't given firm timeline guidance as of yet. This is going to be a little bit longer than, for example, the SERENITY study, but probably not much longer, maybe by a quarter. These are not terribly long studies to bring in.
Right. So now you have a clear-cut path forward on execution, pending what the FDA says on your design. But let's say all of that falls into place.
Sure.
How would you balance the focus that you need to have on execution versus the focus that you need to have on the financial risk associated with the company?
So, that's a great question, Sumant. Our key focus, as we mentioned, is on two pivotal phase III trial, and we continue to bring operational efficiencies, in terms of our, capital that we have and what we will need. And in terms of the financing, we look at all the possible options. One is equity, and there are a number of non-dilutive options we're always evaluating. And I mentioned last week in our earnings call that we are looking at royalty monetization because 501 is a-- has a, large potential, besides IGALMI into the home setting in schizophrenia and bipolar, as well as in Alzheimer's agitation. So we are evaluating that. And then other things we are looking is, OnkosXcel and monetization and strategic partnership.
So good news is that we have a good clarity on the two phase III pivotal programs. One is very close to initiation, second one, we are preparing to initiate, and in the meantime, we are organizing the capital, the means I have mentioned, to get to the data readouts. And that's where company is totally focused on. IGALMI, the commercialization is very focused. We have five salespeople who are just maintaining the brand and doing the contracting strategy. There's not much resources. All the resources are focused on the clinical trials execution.
Right. This is a bit of a commercial question, but now you have IGALMI out in the market, in an institutional setting with the skeletal sales force. When you do get that product in an at-home use setting, given the convenience and given the unmet need and indications, how could you right-size the pricing on the product?
That's a great question, Suman, and that question is under review by our commercial team. They're looking at the, what should be the right kind of a strategy and value we are bringing for the patient who are in the home setting. So, we will be thinking about any neuropsych drug, what the pricing is for those drugs per month, over a year. And latest, we have seen the Rexulti data, and that tells us the pricing that payers are willing to pay is about $1,400-$1,600 per month. So it gives us, we have some guideposts, but we will need to do the deep dive work to see what the right strategy and plan will be as we get close to the launch.
Sure. So you have two large investors. How would you characterize your latest discussions with them in terms of their collaborativeness, things like that?
So, our large investors are supportive. Like, particularly I can speak about, our strategic financing partner, Oaktree and QIA. They've been very collaborative, they've been very supportive. We have obviously entered into multiple amendments based on the needs of the business. So we are very thankful and, glad that we have such kind of partners. We believe 501 is a very important medication, and, we are doing everything and getting the support of all the stakeholders who are around us to be able to help get to the point where we can announce the data readout, and that's our extreme focus right now.
Yeah. Clearly, agitation is a worldwide problem, right? So what are your thought processes around ex-U.S. initiatives?
So I did mention that strategic partnership is part of one of the pillars for bringing non-dilutive capital. Considering the management bandwidth, we are very cognizant how many things we can do in parallel. So currently, we are focused on financing the company and in parallel, looking at strategic partnership, which can be more global in nature, only U.S.-focused, or it could be ex-U.S. So in a deal-making, it's just natural tendency, they evolve depending on the partner, whom you are dealing with, what kind of a, structure of the relationship will make sense. So we are flexible, and we continue to evaluate that.
Moving to 701 in the last couple of minutes here. You've said publicly in the past that that is also a potential source to unlock value. What is the inflection point there, which will potentially lead to that event?
I think the, the stage we're at now, and we've mentioned before, we're working with a, a firm who professionally does M&A and introductions and so on. At this point, we're doing outreach, or they're doing outreach on our behalf. And I think that potentially is the, the inflection point.
Got it. And then last minute or so, what's the latest you can say on 502, 503, and other initiatives at the company, and how do you balance that with needing to have a laser focus on getting 501 and IGALMI, right?
Considering where we are, I want to reiterate our focus is on BXCL501 and the pivotal trial and getting to the data readout, which is a value driver for all stakeholders. BXCL502 and BXCL503, we have identified using our AI platform, and BXCL502 is in the formulation stage, as we have mentioned. And, currently, those programs are not getting the attention it needs due to the capital needs that are needed to progress BXCL501, but in future, they could become potentially, opportunities to partner and bring in a partner and their resources to move them forward.
All right. Thanks for the moments, and thank you everyone for coming in, for tuning in.
Thank you.
Thank you. Okay.