Good morning and welcome to BioXcel Therapeutics' Fourth Quarter and Full Year 2022 [ph] Financial Results Conference Call. At this time, all participants are in a listen-only mode. [Operator Instructions] After the presentation, there will be a question-and-answer session. [Operator Instructions] Just to remind everyone, certain matters discussed in today's conference call and/or answers that may be given to questions asked are forward-looking statements subject to risks and uncertainties related 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. 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 it's quarterly report on Form 10-Q for the quarterly period ended September 30, 2021, as will be updated by it's annual report on Form 10-K for the year ended December 31, 2021 which can be found at bioxceltherapeutics.com or on sec.gov. As a reminder, today's conference is being recorded. Joining us on today's call are Dr. Vimal Mehta, Chief Executive Officer; Richard Steinhart, Chief Financial Officer; Dr. Vince O'Neill, Chief Medical Officer; Dr. Frank Yocca, Chief Scientific Officer; Dr. Rob Risinger, Senior Vice President of Clinical Development; and Matt Wiley, Chief Commercial Officer. It is now my pleasure to turn the call over to Dr. Mehta, the CEO of BioXcel Therapeutics. Please go ahead.

Thank you, operator. Welcome, everyone and thank you for joining our call today to discuss BioXcel Therapeutics' financial performance and business highlights for the fourth quarter and the full year of 2021. We have a lot to discuss as we embark on a potentially monumental year for the company, so let's get right into it. As you know, BioXcel Therapeutics is a clinical-stage biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology. As we near our April 5 PDUFA date for our lead asset, BXCL501, I would like to reflect on the significance of 2021, a landmark year for the company with numerous achievements across neuroscience and immuno-oncology franchises. Starting with BXCL501 which is currently under FDA review for the acute treatment of agitation associated with schizophrenia and bipolar disorders I and II. We capped an unprecedented journey in 2021, having regulatory submission in just under three years from first-in-human trials. We are not aware of any other AI-driven drug discovery and development company that has achieved this milestone as efficiently as we have. We view this impressive timeline as for the validation of our AI platform and R&D capabilities. We are now less than one month away from potential approval of 501 as our first marketed drug. Since joining as our Chief Commercial Officer, Matt Wiley has led the development of an integrated commercial strategy to support our potential near- and long-term commercial vision, including launch readiness activities and the build-out of our national sales force which is progressing as planned. We are focused on hiring sales representatives with extensive experience and are finalizing our marketing materials and market access and pricing strategies. Our medical science liaison and medical managed care teams are actively educating health care providers and payers on unmet market needs…

Thank you, Vimal. I will now review our fourth quarter and full year 2021 financial results. Research and development expenses were $12.5 million for the fourth quarter of 2021 compared to $11.4 million for the same period in 2020. The increased expenses were primarily attributable to increased headcount and related costs during the three month period of 2021. Research and development expenses were $52.7 million for the full year 2021 as compared to $58 million for the same period in 2020. The decrease for the year ended December 31, 2021, was primarily attributable to decreased clinical trial expenses related to BXCL501 which were partially offset by increased trial expenses related to BXCL701 clinical trials. General and administrative expenses were $13.6 million for the fourth quarter of 2021 as compared to $9.7 million for the same period in 2020. The increase was primarily due to increased headcount and related costs, including higher stock-based compensation, increased marketing and commercial costs related to the potential launch of BXCL501 in the United States as well as increased legal and professional fees and insurance costs. General and administrative expenses were $54.2 million for the full year 2021 as compared to $24.3 million for the same period in 2020. The increase for the year ended December 31, 2021, was primarily attributable to increased headcount and associated costs, including noncash stock-based compensation. We also incurred significant commercial costs in preparation for a potential U.S. launch of BXCL501. BioXcel Therapeutics reported a net loss of $26.1 million for the fourth quarter of 2021 compared to a net loss of $21.1 million for the same period in 2020. For the full year, BioXcel reported a net loss of $106.9 million compared to a net loss of $82.2 million for the same period in 2020. As of December 31, 2021, cash and cash equivalents totaled approximately $233 million. Now, I'd like to turn the call back to Vimal.

Thank you, Richard. We would now like to open the call for questions. Operator?

[Operator Instructions] Our first question today is from Greg Harrison of Bank of America.

So now that the 501 PDUFA is right around the corner, are you in label discussions currently? And how would you characterize them so far?

Greg, our NDA remains under review by the FDA and we continue to expect the response of our NDA by the April 5 PDUFA date.

Got it. And then if I could hit on a different topic. What is the status of any discussions with partners to commercialize 501 in the EU? And what attributes are you looking for in a future partner?

So as we mentioned that we are getting ready to submit a MAA in first half of this year. That will also facilitate our discussions with our partners. And we are just holding on to submitting MAA unless we get - unless we're at a point where we have got the approval from the FDA. And the attributes we are looking in a partner is that who can be a very strategic partner in terms of not only our first two indications which is schizophrenia and bipolar but also for our upcoming sNDAs in Alzheimer's and MDD. So if a partner has a neuropsychiatric franchise and they have those kind of capabilities, those are the key attributes we will be seeking in a partner.

The next question is from Chris Howerton of Jefferies.

I'm super excited to have the PDUFA just about a month away. So for the - I guess the question that I would have with respect to the EU, what indication do you have there from the EMA that the current data package would be acceptable for a submission? I just - my recollection was there was an extensive amount of European patients that were actually evaluated in the pivotal study. So maybe just a little clarity on that. And then, the second question I would have would be - obviously, some early encouraging results on 701. But what is the decision-making moving forward in terms of deploying capital towards those programs versus expanding 501? And then the third question, if you'll allow me to sneak it in, I think it's a quickie, is for 502, you said you're in the process of formulation work. Could you just tell us about the expected timelines for that and what the final dosage form that you're expecting to have?

Thank you, Chris. I have noted on all three questions. I will try to go through them one by one. Regarding your question that what package is required for the MAA, we had extensive discussions with the authorities, European authorities. And we presented the package that we have presented to FDA and they were aligned, that data we have currently and the package we have, that it's sufficient to submit the MAA in Europe. Primarily, all our patients in our SERENITY I and II trials were from U.S., not from Europe, just to clarify on that. But agency is comfortable in using the current package to submit the MAA. Coming to the second - yes, go ahead? Coming to your second question regarding the 701, we have already outlined our five year vision for BioXcel Therapeutics. We want to be a leading neuroscience company, AI-enabled neuroscience company. And we will continue to focus and deploy our resources from AI all the way to the commercialization in the neuroscience space. And that's the commitment we have made. And we have the most advanced product which is a pipeline within a product with first two indications very close to the NDA PDUFA date and then Alzheimer's in a pivotal Phase III program. And then we will be initiating the MDD program shortly. So that commitment has already been made. In terms of the 701, now we have a clinical proof of concept in hard-to-treat tumors. So we'll continue to explore strategic options which could include like potentially a spinout. It could be a partnering. It could be a JV and/or co-development. We truly believe in the mechanism of 701 and we think we have proven following things. We have demonstrated that it is safe and tolerable. It can be combined with KEYTRUDA. We have demonstrated clinical activity. We have published the mechanism in JITC. So we have achieved a lot with 701. And as - just to remind everyone, when we became a public company in March of 2018, we had selected these two assets, BXCL501 and 701. One of them is very close to approval and another one has demonstrated cleaner proof of concept. So we are super excited for both the assets we have in our portfolio. And I will now go for the 502 formulation. Formulation work has recently begun in last several months. So we will - developing timelines and what our timelines are, what test we need to do, it is going to be an oral therapy. And once we have all of that worked out, we'll provide a clarity on our timeline to enter the clinic. But we are getting to that point and we will be in that position to provide in 2022.

The next question is from Robyn Karnauskas of Truist Securities.

Two questions for you. So on TRANQUILITY I and II, are you planning on reading that the same time as you thought through how are you reading out and how you might disclose the data? And then I have a follow-up.

Sure. Great question, Robyn. We - as you know, we initiated this program, got alignment with the FDA, initiated the program in December. And at that point in time, Omicron was almost at the peak. So we started opening our clinical sites because when there is some COVID or Omicron situation, access can sometimes be limiting to the elderly care centers. So we now have a very good clarity going forward that how many sites we need. As you know, we have 150 patients in each trial, so it's not a big ask. So we are just determining how many sites we need and how we're going to stagger these two programs. So TRANQUILITY II will be the first one that we will have the data readout, followed by data readout from the TRANQUILITY III. But as you can imagine, these trials are conducted in elderly care centers and residential facilities and nursing home and some of these places, all - both the facilities are in the same building. So these trials will be staggered and data readout will come out in a staggered fashion for the TRANQUILITY program.

And a follow-up there. And I guess, obviously, people asked about like the label discussions for your initial indication. But when you think about living facility versus nursing homes and for those that are not in the same center, are there any differences in the type of patients that you're dealing with, like one population more mild than the other? So should we be thinking that there's differences in the data sets that we'll be seeing?

Let me pass this question to Rob, so he can describe what the patient populations are and what kind of Alzheimer's patients are in these two centers.

Yes, the patient - the fundamental difference between someone who can live by themselves with minimal supervision and someone who requires monitoring 24/7 a day has to do with their ability to sort of complete activities of daily life, as we call it in medicine. So we do not believe that there is any substantial difference in terms of the efficacy. However, we want to demonstrate efficacy across the entire spectrum of care for patients with dementia who become agitated.

The next question comes from Sumant Kulkarni of Canaccord.

I have three. I'll start with one on the TRANQUILITY trial. We saw ClinicalTrials.gov had an update posted as of yesterday on one of the Phase III trials that has a primary and study completion date of December 2022 and for a maximum of 28 doses over 12 weeks. Could you confirm the maximum number of doses which appears to be more than what we thought it might be? And given the update was just posted yesterday in light of your Omicron comments, does that December '22 completion date reflect your latest expectations now that the Omicron seems to be behind us? That's my first question.

So Sumant, I will take the first question and I will pass it on to Rob about the other portions of the question. We have not provided the guidance that when - like no data readout will be. But as I indicated earlier that there are only 150 patients, so it's not a big trial from a patient enrollment perspective. We just want to be sure that we have sufficient number of sites open. We want to be sure that we can have the enrollment and we can complete the trial. Like there are two key pieces. One is - first is acute agitation. And then, as you said, over a three year period, testing up to 28 doses to see what the repaid [ph] dose effect is. As you know, in Alzheimer's, these patients have multiple episodes. So we are trying to capture not only the acute, we are trying to capture the intermittent chronic when they have multiple episodes so that when we go out, our sNDA has a broader level. So with that background, I will pass it on to Rob. Rob?

Yes. I think the trial completion date will entirely depend upon our ability to enroll the 150 patient subjects. Now no one predicted the pandemic before it began. And it seems people have difficulty predicting the waves of Omicron and who knows what the next Greek letter is. But that has the potential to slow down enrollment and that's precisely why we have not given numbers and dates for our readout yet until we have accrual moving forward and we have a bead and solid data on when the final patient will be dosed in that trial. So we have great confidence. After all, we initiated the trial as Omicron was increasing. And soon, we'll be able to report accrual and enrollment rates and much better information.

Got it. And my second question, you cited a market research survey that you conducted. I want to focus a little bit on the - a little bit of the glass that is not full which is the 17% survey participants that did not seem to have a positive response on 501. What were the key points that those participants saw in being impediments to their use of the product? And on the 40% prescribing, what delivery setting was assumed?

So Sumant, thank you for the question. Matt will take this question.

Yes. So there was not qualitative feedback on the 17%. This is just a quantitative survey or part of the survey where we found the 83% had a positive reaction. So we did not dig in qualitatively on the remaining 17% but that's something we'll find over time.

How about the prescribing setting? And then I'll ask my last question, too which is 701, what are your latest plans to ascertain single-agent activity?

So in relation to the prescribing setting, we would expect our base case in the hospital and institution type setting. That's where we're building out the sales team to focus on at launch.

So Sumant, I would say we are a few weeks away from understanding what our label will look like and we will have a clarity. But as Matt said, our base case has been that like under the supervision of a health care provider. Coming back to the single-agent activity for 701, let me pass this question to Vince. Vince?

Thanks, Vimal. Sumant, yes, that's exactly the logical next step, right? As we've previously said, we would need to develop - or as part of the development plan, test single agent. So at the ASCO GU 2022 presentation, we did announce that we will proceed into a randomization portion for adenocarcinoma. So that is the next step.

The next question comes from Yatin Suneja of Guggenheim Partners.

It's Eddie [ph] on for Yatin. Congrats on all the progress. Just a few from us. Maybe for Matt, assuming approval in April, how should we think about the first year of launch from both a script number and a revenue perspective? And can you talk about what metrics you'll be providing in the first few quarters to help us track the launch? And what do you see as sort of the key gating factor for that trajectory?

So we have identified a number of key performance indicators that we're going to be tracking internally. And so what we will do is, in future communications with investors, provide some of those that are relevant.

Got you. And then can you talk about what the average number of agitation episode is for these patients? And sort of how often do those episodes bring the patients to a care center where 501 would be administered, just in terms of like how often there's a chance for this drug to be used?

So Eddie, as we have indicated, these patients get about a dozen episodes a year and they end up in the emergency rooms. That's kind of been on an average. And every market research we have done, that tends to be the case. 2/3 of the patients basically end up in the emergency rooms out of 25 million episodes and 1/3 get treated at home. And the reason for that dynamic is that there is no current treatment options that the patients can take it at home. So whenever there is episode and it escalates, they end up in the emergency room or they could go - even if they go to their neuropsychiatric physician or they go to any of the critical care centers, they send them to the emergency room because not much is available in terms of the therapeutic option. And our goal with 501 will be how to change these dynamics over a period of time. When they are coming in the emergency room, they get treated with 501. And as we move, I have always said we have a strategic plan and vision to expand the medical setting for this program. As we move this into the community and home care setting, these dynamics of the patient will change how many go to the hospital setting and how many are treated at home. So that's pretty much what we know today that there are a lot of episodes, about 25 million episodes, for about 7 million of it is schizophrenia and bipolar patients.

The next question comes from Corinne Jenkins of Goldman Sachs.

This is Maddie [ph] on for Corrine. The first one is currently most focused on with respect to the launch preparation in 501. And second, do you expect any off-table use in the Alzheimer's setting?

Thank you for your question. As we have indicated, we are waiting for the approval. Once we have a full understanding about our label, what our label is, then we will be able to provide what our launch settings are. But as we have said, that like our trial was conducted in a - under the supervision of a health care provider. So if that's the condition, we are prepared to launch. And we will continue to explore additional settings as we go and expand the potential of 501. Did I answer your question?

Yes. I also wanted to ask one in terms of launch preparation, what are the things that you're most focused on right now?

I think we were ready to launch the product in January for our original PDUFA date. And we are, in fact, better prepared to launch now. So all the provisions that are needed in terms of having a recruitment and build-out of the national sales force, market access, pricing strategies, marketing materials that have been like built for that sales force and ready to go. So we feel very good and confident that we have all the pieces in place to launch this product.

The next question comes from Colin Bristow of UBS.

I wanted to push you guys on something. So it sounds like you do not yet have a label in hand. I was just wondering, has FDA set an expectation specifically of when this label will arrive? And then just secondly, as we think about the post-approval setting, is it reasonable to expect some sort of launch guidance? And if so, what metrics do you anticipate giving us?

Thank you, Colin, for your questions. To answer your first question, I already reiterated that per company policy, we are not commenting on the subject matter of ongoing and potential ongoing conversation at this time with the FDA. We continue to expect a response from the FDA with regards to our NDA by the April 5 PDUFA date. So that's kind of answering your first question about the label, where we are. And regarding the launch metrics, Matt has joined us recently in January. He is building all those launch metrics. And once we have the approval, he will be in a position to share what metrics to track to see the performance of the launch. Matt, would you like to add anything?

Yes, that's right. I mean as we get into market, we'll share the key performance indicators that are relevant.

The next question is from Ram Selvaraju of H.C. Wainwright.

Three relatively straightforward ones, hopefully. Firstly, I wanted to ask if you could comment on your ex U.S. partnering strategy with particular emphasis on the European outlook given your stated timeline for filing of the MAA but also any other regions that you may be exploring at this time with respect to 501.

So that's a great question, Ram. Thank you. Geographical expansion is critical part of our growth for BXCL501 program because there are a lot of patients or equal amount of patients outside than U.S. So in terms of the European strategy, we wanted to file MAA once we have clarity on our approval from the FDA. And as I said, that we will be ready to file in first half of this year. As we file our MAA, that basically gives us about 15 months of time window for approval and then the launch. So we will initiate our business development effort to look for a partner. And also, we get approached obviously by - actively by the partners also. So that process will continue and our focus will be that we have a partner who has right kind of attributes, not only for our first two indications in schizophrenia and bipolar but they have the capability to be able to follow on for our follow-on sNDAs. In terms of other regions, I would say Japan is a very important territory. As you know, that particularly in Alzheimer's, there is a very large patient pool and it's a big, big unmet medical need. So we will be considering those options. So I think after we get approval of our first product, both Europe and Japan will be very viable partnering opportunities for BXCL501 from a commercialization perspective.

Great. Secondly, I wanted to ask about your plans in major depressive disorder and if you could clarify specifically what you envision as the optimum treatment setting. You're talking about adjunctive therapy but adjunctive to what and in what specific subgroup of patients within MDD? Are we talking here about treatment-resistant depression? And how is this being quantified or classified? As well as if you could comment on the nature of the competitive landscape in MDD and how you anticipate being able to obtain optimum positioning within this indication.

Sure, Ram. So this is Rob Risinger again. We do plan to take this into major depression. We anticipate that we would be studying patients with simple major depression as an adjunct to an SS or SNRI. We don't intend to specify that SS or SNRI. So this would be used in the outpatient setting for patients who have major depression as a sort of accelerant, as an adjunctive in order to treat patients more rapidly and sort of get them on their feet. We know that the landscape is changing in terms of treatments for depression. We're not specifically targeting TRD, or treatment refractory depression, at this point.

Okay. And then lastly, with respect to 502, I was wondering if you could talk a little bit more about potential unique areas of patient evaluation efficacy-related outcome measures in the chronic context of Alzheimer's disease and dementia. And in particular, if you have plans to include sleep monitoring as an integral part of the clinical development effort on 502.

We - let me think. Let me take the first part. There are additional potential indications rather than simply - I'll call it simply but that's a pejorative, I suppose, dimension agitation associated with dementia. There are other potential indications which we're exploring.

So let me help you out.

Yes, yes.

This is Frank, Ram. So we're dealing with a molecule now with a different mechanism of action. We're approaching it because we have good preclinical data on chronic agitation and the profile that it gives us. But our approach will be very similar to what we did with 501. We'll look at the molecule, see how it behaves and go into different directions that it really points us to. But the initial approach will be to fit - a fit for chronic agitation.

The next question comes from Anita Dushyanth of Berenberg.

I just have a follow-up on some of them that you already answered. So with respect to the study in Alzheimer's, the two Phase III studies, could you provide some clarity on how we should think about like the number of patients that might actually benefit from the higher dose between the two different settings?

Anita, as you know, in our TRANQUILITY trial, our lower dose as well as higher dose, it's a dose-dependent response. So we don't see that like what the differences will be from each doses. We are testing two doses to see how the patient will benefit and what the response rate looks like, like we exactly did it in our SERENITY I and II trials for schizophrenia and bipolar, 120 and 180. So that's the purpose. And once we have the data, we will know like now, do we take both doses forward or we take single dose forward? So those are the things will come out of our Phase III program. Rob, do you like to add anything else?

No, it's - as is typically done, particularly for registration, we simply characterize those who may benefit from a higher dose versus a lower dose. And if we find factors, we'll put that in the label, helps to guide dosing.

Yes, definitely. And then a question on the MDD program. I was wondering, like is there a specific subset of population from the 27 million cases that might actually benefit from this adjunct treatment?

What I like about clinical development is we discover things along the way. Rats and mice don't necessarily predict everything in humans. And so we intend to characterize the effects in the general population of those with depression. If we find subpopulations, as you're suggesting, that may well be another development pathway or it may steer us in that direction.

So Anita, let me put a little - add more color. In general, these antidepressants don't work in first four to six weeks. And that's what we are targeting, how to accelerate the effect of some of these agents. So that's the unmet need we are targeting.

The next question comes from Samir Devani of Rx Securities.

It's just the one. Congrats on getting the data published in JAMA. Obviously, that's - and it's clearly a very positive article. But I was just caught by one phrase or one comment in the paper where the author discusses no consensus on the change in PEC score that represents the minimally clinically important difference. Can you just comment on that phrase for me?

Samir, so let me pass this question to Rob.

I wish I could delve into the intricacies of defining a "minimally important clinical difference" but there's a lot of discussion over that. I think what the manuscript shows in the publication is that we have far greater than a minimal and arguing over what a minimal clinical difference is a bit pedantic. We showed a robust response that no one argues. The change in PEC score was quite high. The percent who respond by almost any criteria is 70%, 80%, almost 90%. It's simply irrefutable. So I'll be happy to play professor and we can talk for an hour but we showed far greater than a minimal clinical significant difference.

There are no additional questions at this time. I'd like to turn the call back to Dr. Vimal Mehta for closing remarks.

Thank you, everyone, for joining us today. I look forward to connecting with many of you in the coming weeks and updating you on our continued progress. Have a great day.

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.