BioXcel Therapeutics Inc (BTAI) 2022 Q4 法說會逐字稿

Good morning, and welcome to the BioXcel Therapeutics Fourth Quarter and Full Year 2022 Financial Results Conference Call. (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 that are subject to risks and uncertainties related to future events and/or the future financial or business performance of the company.

Actual results could differ materially from those anticipated in these forward-looking statements. Risk factors that may affect future results are detailed in the company's quarterly earnings report on Form 10-Q for the quarter ended September 30, 2022, which can be found at www.bioxceltherapeutics.com or on www.sec.gov and which will be updated in its Annual Report on Form 10-K for the year-end December 31, 2022.

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; Matt Wiley, Chief Commercial Officer; Dr. Vincent O'Neill, Chief R&D Officer of OnkosXcel Therapeutics; Dr. Rob Risinger, Chief Medical Officer of Neuroscience; and Dr. Frank Yocca, Chief Scientific Officer.

It is now my pleasure to turn the call over to Dr. Mehta, the CEO and Founder of BioXcel Therapeutics. Please go ahead.

Thank you, operator. Welcome, everyone, and thank you for joining our call today to discuss BioXcel Therapeutics fourth quarter and full year 2022 financial performance and business highlights. It was exactly five years ago that BioXcel Therapeutics became a public company and we embarked on our journey with a clear mission to build a uniquely disruptive biopharmaceutical company model using artificial intelligence approaches to bring transformative medicines in neuroscience and immuno-oncology to patients. We are proud of what we have accomplished. At the same time, we are even more excited about what lies ahead.

And so it is with great pride and enthusiasm that I share with you why I believe the company has never been better positioned to potentially bring new treatment options to millions of patients in areas of high unmet need and deliver significant value to our shareholders. We are making great strides in building on our accomplishments in 2022, which was truly a transformative period for BioXcel Therapeutics as we transitioned to a commercial stage company. Last year, we received FDA approval for our first drug, IGALMI for the acute treatment of mild, moderate and severe forms of agitation for schizophrenia and bipolar disorder in adults.

This broad label has brought in new treatment option for patients in a nascent market where there had been no innovation in nearly a decade. Most notably, using our AI platform, we advanced from IND to commercial launch in less than four years. We believe that we have introduced the first AI discovered drug for an acute neuropsychiatric condition. Today, we are building on these accomplishments and remain laser-focused on accelerating our growth in 2023 and beyond. There are many reasons why we are so excited about our near-term opportunities. First, our commercial execution of IGALMI is fully underway.

We believe that IGALMI's unique mechanism of action and ability to treat agitation creates a commercial path in an institutional setting with no obvious (inaudible). To-date, we have made impressive progress with our initial field force of 26 sales reps now with our commercial operation fully deployed with 70 sales reps in all major markets across the U.S., we look forward to accelerating this momentum. We are pleased with the market reception of IGALMI, which is supported by highly favorable market dynamics, initial response from healthcare providers has been extremely positive especially rewarding to hear about the difference IGALMI is already making for patients, families and healthcare providers.

Matt will share more details about our commercial progress and launch metrics that we are excited about in his remarks that follow. Second, turning to our robust clinical pipeline; we believe the upcoming quarter may represent a watershed moment for the company. In the second quarter, we expect to announce pivotal clinical data that potentially supports significant market expansion opportunities for our lead neuropsychiatric program, BXCL501. We believe this agitation market remains under-diagnosed and underserved. It is comprised of an estimated 139 million agitation episodes per year across bipolar disorder, schizophrenia and Alzheimer's; our three priority indications across various medical settings.

Specifically, we expect to announce data from two Phase III pivotal studies for 501 in the second quarter. These studies include TRANQUILITY II trial and SERENITY III trials. Our TRANQUILITY program is designed to evaluate 501 for the acute treatment of Alzheimer's-related agitation; up to 100 million agitation episodes are estimated to occur annually in this patient population in the U.S. where currently, there are no approved FDA therapies. The TRANQUILITY II trial is fully enrolled and then -- and the data cleaning and verification process has begun.

In TRANQUILITY III, we are accelerating enrollment of patients with moderate to severe dementia in nursing homes with first patient dosing having occurred last December. Turning to SERENITY III, we built this program upon 501's demonstrated benefit for agitation associated with schizophrenia or bipolar I or II disorders in adults. The two part pivotal trial is evaluating the safety and efficacy of a 16 microgram dose in acutely agitated bipolar I and II disorder and schizophrenia patients who support use of 501 in the at-home setting. We estimated 23 million agitation episodes occur in the U.S. each year in this setting.

With SERENITY III part 1, more than 90% of patients have already enrolled with complete enrollment imminent. We plan to enter the data cleaning and validation phase shortly. Part 2 of the trial is expected to begin in the second quarter. In addition, we anticipate reporting topline results from our Phase Ib multiple-ascending dose style for Major Depressive Disorders in the second quarter. There are over 300 million antidepressant prescriptions filled annually in the U.S. and treatment options are suboptimal due to slow onset of action and incomplete response.

For the first time, we are conducting chronic dosing of 501 in healthy volunteers and evaluating its safety and tolerability on a daily or twice daily dosing basis over a 7-day period, including in combination with an antidepressant. The trial outcome is expected to inform dose selection in combination with selective serotonin or serotonin-norepinephrine reuptake inhibitors in MDD patients. Beyond these three important near-term data readouts, we are advancing our research and development pipeline. We are developing BXCL502 in novel strategic serotonergic receptor antagonist as a potential therapy for chronic treatment of agitation in patients with dementia and other related neuropsychiatric conditions.

I'm pleased to announce that prototype formulation has been developed, and we are initiating IND-enabling studies. Our advancements have continued to validate our unique AI approach in discovering novel pathways and product candidates for neuropsychiatric disorders and for neuro-rare diseases. This is a new area of focus for the company. We have identified more than 10 product concepts that are being evaluated as we look to expand our neuro pipeline beyond 501 and 502. We plan to host an R&D Day in the near future to outline our strategy and progress in more detail.

Lastly, we are thrilled with our progress with BXCL701. It has a compelling value proposition in hard-to-treat tumors and is one of the most clinically advanced oral innate immune activators. It has demonstrated positive efficacy results in two cancer types and CRPC small cell neuroendocrine prostate cancer, SCNC and adenocarcinoma, which is supported by 800 subject clinical safety database, the 701 [MO] is novel and has been published in a peer review journal. As presented at ASCO GU in February, BXCL701 in combination with KEYTRUDA demonstrated a complete response rate of 25% in SCNC.

This is a promising result in heavily pretreated patients with no FDA-approved therapy. We believe the results support moving forward with a potential pivotal study for BXCL701 as a monotherapy and in combination with KEYTRUDA in SCNC in second half of this year, ending FDA discussions. Finally, we are excited about the tremendous potential of OnkosXcel Therapeutics and are actively seeking to unlock its full value for our shareholders. We expect to provide an update on this shortly.

Looking back, I can proudly say that 2022 was a year of significant accomplishment for BioXcel Therapeutics on all fronts. The approval and launch of IGALMI validates our use of AI with positive impacts on the drug discovery and development paradigm and on patients' lives. We are truly a driver of the industry change and have demonstrated that our AI-based approach can improve the probability of success, reduce development timelines and enhance R&D economics. These accomplishments reflect the mission of the company that we set out to fulfill when we became a public company five years ago.

I would now like to turn the call over to Matt Wiley to review our commercial progress and exciting launch (inaudible). Matt?

Thank you, Vimal, and good morning, everyone. Before I provide an update on our commercial activities, I want to reinforce Vimal's message of how proud we are of what we accomplished last year with the approval and launch of IGALMI. Not only did we focus on building a strong commercial organization, we took the necessary steps and investment in building an entirely new market for the treatment of agitation episodes, an area which there have been no new developments in more than a decade. It's important to understand this context as we move from launch to market development to sales acceleration later this year.

Our commercial engine is running efficiently and firing on all cylinders as we move into the heart of the New Year. Looking back to 2022, I can report that the fourth quarter was transformational for the commercial organization. Most importantly, we improved the volume of potential patient exposures to IGALMI and continue to pave the way for broader access to this meaningful treatment. We are working hard to change the lives of patients and each one matters to us. Considering that objective, we successfully expanded the sales force to 70 representatives with full deployment commencing last December.

This allowed us to expand our reach from 700 target hospitals to more than 1,700 and positioned us to fully launch IGALMI as we enter 2023. The new sales team members have the same depth of experience necessary to continue our launch momentum as our original team members from the original sales team last year did with an average of 21 years of industry experience and an average of eight or more product launches. This expanded team has already begun making an impact. They have extended our reach to more than 1,100 of our target hospitals to-date and are reaching over 7,000 unique healthcare providers.

Interest in IGALMI continues to grow, and this increase in share of voice is expected to accelerate P&T reviews and process and formulary adoptions this year. With that in mind, I'll provide some updates on our formulary adoption progress. As you know, we launched IGALMI last year with a small team of 26 representatives. This team has secured formulary access in more than 65 total hospitals to-date with 39 of those as Tier 1 and 27 as Tier 2. We have also -- we also have more than 600 P&T reviews in process that should take place over the next few months. Of these, approximately 280 are Tier 1 hospitals.

We are right now within that window of the typical review time of 6 to 12 months. So the original sales team has made significant progress in lining these meetings up with 46% of its original targets, either approved or scheduled to vote. We expect more of these efforts to matriculate into P&T scheduled votes in the coming months. Our second hiring wave and newly deployed 44 representatives have just begun their efforts, and we expect to see a meaningful uptick in formulary votes in process in the second and third quarters due to their efforts.

Market research prior to launch indicate that we should expect to see a majority of P&T votes would result in formulary wins for IGALMI. This has been our experience to-date, and we continue to be pleased with the perceived value of IGALMI to hospitals, patients and healthcare providers. We are encouraged that several hospitals and systems have already begun ordering the product to develop first-hand experience prior to full approval. We see this as a significant win. As hospitals gain experience with IGALMI, we have received positive anecdotal feedback regarding patient response, throughput and staff safety.

On this topic, we expect to launch a free trial program to qualifying hospitals later this quarter. This program is designed to facilitate early experience with IGALMI and to provide hospital and system-specific metrics they can analyze to determine their own value. We expect this program to accelerate the demand of IGALMI with de novo institutions nationwide. Turning to market access; we have now contracted with three Group Purchasing Organizations, or GPOs, covering half of the targeted hospital beds.

While we are in negotiations and discussions with the remaining two major GPOs, we have focused our attention on system-specific contracting that will help accelerate the pace of Integrated Delivery Network, or IDN reviews and adoption to provide system-wide access to IGALMI. As noted in previous calls, our corporate account director team is targeting 59 IDNs, having a total of approximately 280,000 beds in the United States. So far, we have secured formulary approval for just over 7,000 of those beds or 2%, with more than 70,000 or 25% anticipating a vote over the next two quarters or so.

Selective contracting with these entities may further accelerate the review process with some of the remaining systems that have not yet to engage. At the same time, we are beginning to gain access -- we are ramping up our marketing efforts significantly to support our field teams. We are launching a new HCP targeted advertising campaign focused on IGALMI as a collaborative approach to managing agitation in bipolar and schizophrenia patients. Based on our research, this campaign is motivating to healthcare providers and helps us position IGALMI as a positive solution for both patients and advanced practice providers such as ER staff and nurses.

We are deploying this campaign through print media, digital media and our sales team and expect to generate more than 10.5 million impressions in the second quarter. We have also deployed a geo-targeting media effort to digitally encircle our target institutions in the U.S. This means anyone in those hospitals with a smartphone or computer may see IGALMI advertising on popular websites and applications. In addition, the marketing team deployed a large-scale peer speaker effort to provide a comprehensive presentation on IGALMI to targeted HCPs.

We have also planned promotional attendance at [six] national conferences with more than 150 regional or local conferences this year that will further amplify our message and exposure. I'm proud of the commercial organization's tremendous progress with the launch of IGALMI to bring this important new treatment option to patients. Our early success and interest in the brand is palpable, and our field team energy continues to outpace industry norms. While there is an expected protraction to hospital launches and uptake, market receptivity and excitement continues to grow and the promise of this drug to patients is peerless. We are disrupting and creating a market in agitation and our confidence in this brand could not be higher.

Now, I'll turn the call over to Vince, who will provide an overview of OnkosXcel's recent progress. Vince?

Thanks, Matt, and good morning, everyone. So I'd like to spend a few minutes reviewing the many exciting milestones recently achieved by our subsidiary, OnkosXcel Therapeutics. So let me start with our lead immunotherapy candidate, BXCL701, which is our investigational oral innate immune activator designed to turn cold tumors to hot via DPP9 inhibition. This is a novel mechanism of action identified by our AI platform. In combination with KEYTRUDA, we believe 701 can expand the activity of immunotherapy into large underserved patient populations. This combo potentially addresses a very high unmet medical need by focusing on cold tumors, the major challenge in immunotherapy today.

This is even more relevant given recent setbacks in the immunotherapy development landscape for aggressive forms of prostate cancer. So as Vimal mentioned, our Phase IIa results for 701 in combination with KEYTRUDA demonstrated very promising safety and efficacy data in a rare aggressive form of prostate cancer. Importantly, we believe 701's clinical pathway continues to be derisked as we now have demonstrated clinical POC in both adenocarcinoma and small cell neuroendocrine cancer. In the second half of this year, we intend to initiate a potential registrational Phase IIb study for BXCL701 in small cell neuroendocrine cancer subject to FDA [line].

Building on the positive clinical data for 701 and based on our deep knowledge of DPP biology in cancer, we are pursuing new indications. We plan to initiate a Phase Ib/II trial in small cell lung cancer in the second half of this year. We're particularly excited about 701's potential in this indication because it shares many, many commonalities with small cell neuroendocrine cancer.

In addition, we're partnering with two premier academic cancer institutes to explore 701's potential beyond our company-sponsored trials first with Georgetown Lombardi Cancer Center in a Phase II trial in pancreatic cancer and secondly, with Dana-Farber Cancer Institute in a Phase Ib/II trial in AML. We're also continuing to evaluate DPP9 overexpression as our lead biomarker candidate and are developing a next-generation DPP 8/9 inhibitor. So taken together, we're very pleased with the recent progress for our lead immunotherapy program, 701 and are excited about the future for OnkosXcel.

I'd now like to hand over to our CFO. Rich?

Thank you, Vince. I will now review our fourth quarter and full year 2022 financial results. Net revenue was approximately $238,000 for the quarter and $375,000 for the full year 2022, which resulted from early product trials and reflects limited market access. Due to the company's direct shipping model to hospitals, wholesaler stocking was neither expected nor occurred. Research and development expenses were $32.5 million for the fourth quarter of 2022 compared to $12.5 million for the same period in 2021. R&D expenses were $91.2 million for the full year 2022 compared to $52.7 million for the same period in 2021.

The increased expenses for both the fourth quarter and the full year were primarily attributable to an increase in clinical trial costs related to our multiple pivotal BXCL501 clinical programs. SG&A expenses were $20.7 million for the quarter of 2022 as compared to $13.6 million for the same period in 2021. SG&A expenses were $68.8 million for the full year 2022 as compared to $54.2 million in 2021. The increased costs for both the fourth quarter and the full year were primarily due to personnel and costs related to the launch of IGALMI in the United States.

BioXcel Therapeutics had a $54.8 million -- had a loss -- a net loss of $54.8 million for the fourth quarter of 2022 compared to a net loss of $26.1 million for the same period in 2021. For the full year, the company reported a net loss of $165.8 million compared to a net loss of $106.9 million for the same period in 2021. The loss for the year includes approximately $17.3 million in non-cash stock-based compensation.

Total cash expenditures for 2022 totaled approximately $135.3 million. Cash and cash equivalents totaled $193.7 million at December 31, 2022, compared to $233 million at December 31, 2021. The company believes that full execution of our strategic financing with Oaktree and the Qatar Investment Authority would result in a cash runway into 2025.

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 comes from the line of Colin Bristow with UBS.

Congrats on all the continued progress. So first on the IGALMI ongoing launch, you have 65 formulary wins. Could you just help us what is the denominator here in terms of how many formularies have actually voted? And then maybe just walk us through the typical timeline from a formulary win to the drug being on hand and available for use in the hospital. Secondly, just looking a bit further into the future, just given the progress you are making, what's the potential to provide some sort of revenue guidance in 2024? I know I keep pushing you guys on this. And then lastly, just on TRANQUILITY III, could you just give us an update on how enrollment is progressing?

Well, good morning Colin, this is Matt. On your first question about the denominator, so one of the things I said in the prepared remarks is that we're winning a majority of our wins. And that's around -- I'm sorry, we're winning about two-thirds of our formularies in process. And so what that means is we have 65 out of roughly 100, and that's what we expect. We saw that in market research, and we would expect that to continue. The primary driver for exclusion right now is cost. And what we're finding, Colin, is that no doesn't necessarily mean no.

In many cases, they just want more experience. So they want to trial the drug in their hospital or in a site or two in a system to assess their own value. So we're not getting the hard no come back in a year. We're getting the -- we want a little bit more information to understand how the offset of cost impacts our hospital or system. So the timeline between a formulary win and uptake, I think that's the second question. There was actually a couple of slides in the commercial bay deck that I would point you to. So the formulary process takes about 6 to 12 months on average.

And then thereafter, in market research, we anticipated that roughly a third of healthcare providers would trial the drug in the first six months, and that goes up to somewhere between 67% to 70% between six months and a year. So there is a lag between P&T approval. That's really when we have freedom to operate and generate demand as a sales organization and that's when we begin to pull it through. So there is a -- as I said, there's a protraction in the hospital process. That's why the ramp to peak is somewhere between 8 to 10 years for these types of products.

So let me Colin take the third question. Good morning. Now TRANQUILITY II enrollment has been completed. That was our primary focus, and we wanted to learn as much we can with TRANQUILITY II. As you know, that trial is in ALF and residential setting. Now we are moving for the nursing home setting. So all resources have been directed to TRANQUILITY III. We don't expect trial enrollment to be any different than the TRANQUILITY II but we have not conducted any trial and we're collecting the data. Once we have all the data, we'll provide a guidance when the data readout is expected.

Great. And on the guidance in '24?

I think that's a fair question. I keep asking Matt, once we have a high level of confidence in our launch metrics that he has been providing, and we have multiple quarters under our belt, where we know launch metrics is robust and then launch metrics is resulting in a demand. Once we have the confidence in the demand, we will start projecting the revenues. So 2024, we will provide how the 2023 goes, what guidance we can provide. Matt, you like to add anything?

Yes, just that revenue is a lagging indicator. So a lot of the metrics that we're providing now should give you some idea of how we're progressing. The revenue as it comes behind that, you should be able to be able to add those things up and get a decent idea. But Vimal is right, we'll provide as we get more of a steady ramp up.

Our next question comes from the line of Robyn Karnauskas with Truist Securities.

So not to drill down deeper into the (inaudible) of this launch but it looks like your sales implies over 200 scripts to-date used. And you said that there are some orders coming in. I guess several questions here first. So once you get a hospital or a hospital is now on formulary, how are they stocking the drug?

Like when you look at that number, how much of it is stocking because you said you had 7,000 beds available. So I'm just trying to understand that amount. And then of the 65 total formulary wins to-date, how many have actually had purchases so that gives us a good amount of color how we could apply that 2,000 number. And then lastly, you mentioned cost was sort of a factor for no. For certain situations are you adjusting the cost, have you thought about adjusting the cost to improve market access?

All right. There's quite a bit to unpack there. So let me take a shot at it. So I think that it's a fair assessment that you could draw the number of total units in those hospitals that shipped in Q4. How many of those films went into patients, we wouldn't necessarily know that yet. Typically, we look at reordering patterns, and we're not disclosing those metrics, but that would indicate just how many patient exposures we might have. So there are going to be hospitals that bring in units and it could be several units, it could be just one of each strings to give it a shot to see how it works in their patients or they may be waiting for some type of protocol development in order to help guide them and utilize the drug.

So not every carton that's been ordered necessarily has triggered a reorder yet, but we're still early in the process. So the 7,000 number is actually the number of unique healthcare providers that we saw year or actually launched to-date through both our original and expanded sales organization. So we continue to see an inflection on the number of physicians that we see and the number of contacts we're making in hospitals. Again, we were at over 1,100 hospitals within our target universe that we've seen. We actually are around 2,000 hospitals total that we've seen. So we've seen non-target hospitals as well when necessary.

And those might be in systems where there are downstream institutions that want to hear from us. But that represents about 64% reach, which is really good considering we just expanded our team back in December. So that's where the 7,000 number comes from. Right now, when we look at the P&T reviews and process, there are over 600 or so in process. Roughly half of those -- 280 of those are within our targeted institutions for the original sales team for the original 26, which means it implies that they have almost half of their original targets that are either -- they either have formulary access or they have those hospitals in process to vote.

So of the formulary wins, how many of those have purchased. We haven't given any guidance on that historically. I think it's a little too early to kind of bifurcate the ordering patterns we've had. Those that have approved the drug order, we've had those that have non-formulary access or order. And so we would expect that pattern to continue as we bring more of these hospitals online. What I can tell you is that once the product is on formulary, it makes it easier for them to reorder because they're not just trialing the product at the time.

Adjusting the cost, no, we're not considering adjusting the WAC price of the drug. We wouldn't anticipate doing that at all. We will have contracts in place with the GPOs, and we may do selective contracting with the IDNs. And so the gross net implication of that is quite small. However, it's something that we may do to get access to a broader swath of hospitals, especially those that are not within our target universe. So that has always been part of the plan, and we expect that, that will help accelerate the pace of those system-wide approvals throughout the course of the year.

Great. That's really helpful. And just one on 701. Given that you turn cold tumors hot, you're going to -- have to combine with the checkpoint inhibitor. I know you're doing a lot of these academic studies to reduce the cost. How are you thinking about going forward as you expand, obviously, KEYTRUDA is expensive? Would you consider a partnership to help with supply or even in-licensing in your own checkpoint inhibitor?

Robyn, this is Vince. So most definitely we would be open to discussing some kind of supply agreement or partnership. But as you know, to-date, we have purchased KEYTRUDA on the open market, and that certainly has given us flexibility since we wouldn't then need to deal with or negotiate with a partner. So we're certainly open to that is the short answer.

Our next question comes from Greg Harrison with Bank of America.

Just two for me. First, what responses have you heard from providers who have used IGALMI in the clinic so far and what interest have they expressed in the home setting? And then how will you disclose the SERENITY II and TRANQUILITY III? And what are your expectations there?

So Greg, I'll handle the first one with Rob. So what we're hearing from the field is everything that we would expect. Promise of IGALMI is landing exactly the way that we want it to. They're seeing better throughput. They're using it to potentially avoid staff injuries. The onset of action has been everything they thought it would be. They consider it rapid. And so it does fulfill that cooperative care experience we want them to have. And so we've gotten great feedback in the field. I'll turn it to Rob for a specific example.

Sure. So I get frequent contact e-mail and text messages. And of course, providers are seemingly trying this on the worst of the worst. So I'll give you the anecdote, physicians saw a patient in 4-point restraints, both wrists, both ankles are shackled to the [gurney], and they released one arm to provide the film. And within 15 minutes, the patient was out of 4-point restraints. They were clearly improving, and they were discharged some hours later from the hospital. This was such an impressive result that in fact, they reached out to us and wanted to let us know. So I think the reception of physicians is very positive at this point. And it's clearly having an effect in clinical practice. And we hope that this fits nicely with the new sort of standards of care, certainly a more humane way to treat people.

And I just like to add on top of that, that if you think of our label, it says mild, moderate and severe. And in real life, we are seeing severe patients are being treated. So that market is not excluded. We will have market from mild to severe. Regarding your second question, Greg, this is Vimal. Regarding your second question, how we plan to disclose the data, we'll follow the company process, which we have done in the past. We will have a press release of the topline data, have a call with The Street. That's the pattern we have followed and we plan to follow that for release of those two data sets, and we are all gearing for it. It's happening in the next several weeks.

Our next question comes from the line of Graig Suvannavejh with Mizuho Securities.

That's good. I just had two in particular. One, just wanted to get a better sense of how you think the uptake is going and whether the first quarter and second quarter sales number that you've reported is pretty much in line with how you were thinking. I think you have done a good job resetting expectations that the uptake would be slow and gradual given the process on getting into hospital formularies, it is still lower than I think many of us expected. So just comments around that?

And then secondly, I just wanted to also ask about your efforts to kind of maybe raise the awareness of the product. I think previously, we had an impression that perhaps comments you had made that the product is basically selling itself. But yet, I think what we're hearing on this call is that there's now a free drug program, there's clinician targeting campaigns and just wanted to know if these are newer initiatives in response to the uptake or are these in line with how you've been planning the whole time?

So Graig, as a commercial guy, I'll be the first to say that no drug sells itself. We put a lot of sales and marketing effort behind it. Let me talk first about the uptake. So the uptake curve, I would think about it this way, is it takes, again, 6 to 12 months for the formulary process to really take place. So for our first 26 reps, recall that (inaudible) launch was in July of last year. So we're right in that 6- to 12-month window for the original 26 representatives. Thereafter, once you have P&T formulary approval, that's when your uptake curve begins. And I just shared some of those data from Commercial Day earlier.

And so that will take place over another 6 to 12 months. And so that's the timeline that we should expect. Now keep in mind that our next 44 representatives started this cycle beginning in December. So their 6- to 12-month window for P&T review and formulary approval is going to be in the May-June timeframe, that's when it's going to start. So that's how I would think about the uptake curve. Theoretically, you shouldn't really see a lot of revenue for the first 6 months of the drug launch in the hospital. They simply have to go through their process, and there's a lot of mechanics to do that.

Regarding your question about marketing effort and the free trial program, so one of the things that I have said before is that when physicians try it and they experience IGALMI in patients themselves, they see exactly what we're talking about. So we're not a big hat, no cattle drug launch. This drug delivers as promised. And it certainly is making a huge impact when it's tried. And so doing a free trial program where there is some pushback on cost or some evaluation that needs to be had to see value in their own hospital.

That's exactly why we're doing it. We want them to cross that chasm a little bit quicker. As it relates to the marketing efforts, we want to raise awareness to put additional pressure on the P&Ts and on these formulary decision-makers in a hospital. So we have geo-fenced every target hospital in the United States, and they're going to see IGALMI a lot. And that's all part of the process to drive not just awareness but pressure on the P&T process and then demand.

And what I will add, Graig, is while you are seeing more marketing effort because we have 70 member team deployed. So we learned a lot with our first 26 rep team, and then we were like designing the strategy for 2023. So I would say the commercial full efforts are underway in 2023 with an integrated commercial infrastructure.

And our next question comes from the line of Sumant Kulkarni with Canaccord.

I have three quick ones. The first is very specific. And on behalf of investors that might be very sales-focused given we're now two-thirds of the way into the first quarter what can you specifically say about actual film sales into hospitals relative to the 4Q performance?

Yeah, we're not -- so Sumant, it's a great question, but we're not going to provide guidance on this quarter on this call.

Got it. Are there any quarters in 2023 that might be especially heavy in terms of the 600 pending P&T committee meetings? And my last question is on TRANQUILITY II, what is the typical timeline for data verification and cleaning for a relatively quick trial like this?

So to answer the question about the 600 hospital P&T decisions in process, I would expect that to happen over the next several months. It depends on their schedule. Certainly -- and I think we saw this in Commercial Day that P&T committees may not get through full agenda, may push out their meetings. They may cancel meetings if they don't have quorum. So we're really at the whims of the P&T meetings themselves and operationally getting those done. But we feel pretty good about what we've been able to put on the books so far, and we expect to not just see those matriculate to see a lot more come online and take up to those over the next couple of quarters.

So your next question about the data cleanup and verification. As you can imagine, we have three data readouts and they're all going in parallel. Rob can provide you what normally it takes for a pivotal trial because you have a lot more higher standard than when you're running a Phase II trial, so Rob?

So realize this is not -- although it's a quick trial, it's a three-month duration for any particular patient. And so there's a range of dosing for patients, some doses or some patients may have only had a couple of doses, other have had many, and we have to deal with what's called source data verification. So we literally check the numbers that are entered in our database against what's in the clinical medical records. That's actually a lot of work. So it's anywhere from 8 to 10 weeks of literally daily work by many people to make sure our data is accurate, correct and precise.

Our next question comes from the line of Yatin Suneja swith Guggenheim.

This is Eddie on for Yatin. Just a few from us on the Alzheimer's disease agitation side. Given the older population for ADA, are there other safety data required for that filing that go beyond what you've already showed or spoken about? And then if you are able to get that approval and label expansion, can you just give us a little bit more details on how the prescribing and patient monitoring, re-dosing and reimbursement would work in an outpatient setting versus what you've been showing with the hospital formularies?

So I'll just address it very straightforward. There's no additional safety requirements we're doing and in fact, going above and beyond what's necessary to demonstrate the safety. And so the label we expect will be very similar to the current labeling in terms of adverse events and safety requirements. We know that lower doses have a greater safety margin. And that is, in fact, why we're taking the lower dose in outpatient setting. So we fully expect to demonstrate the safety in the outpatient setting, and that will be one of the label expansions as a result of these trials. I'll leave the reimbursement because it is very different in an outpatient or at-home setting than within the hospital or within a clinic setting.

And Eddie, this is Vimal. Let me add a little bit more to what Rob said. In terms of the safety, obviously, we are doing three-month follow-up monitoring. So if they have more episode, we are trying to show what the safety and efficacy of the drug is after the -- primary endpoint is to (inaudible) and that's the primary endpoint in terms of the efficacy, what we need to show. And also, we have already outlined that a 12-month safety open-label study we will be initiating for the dementia patient. So in terms of the -- what our current understanding or what we know as of today is to our endpoint, primary endpoint in terms of the efficacy win, three-month follow-up to show the drug works over a period of time, both in terms of the efficacy and safety and then there is a 12-month open-label safety study. Did it answer your question?

Yes, that's helpful. And then on the second part about just sort of how would it work if you did get the label on like who would decide if the patient needs to be re-dosed, if they need to be monitored, how would the reimbursement work for those in that setting?

Yeah. So at home, when a patient feels agitation, they're well aware of it. It's a very aversive state. This is, in fact, what brings them to go to the hospital for treatment in the worst cases. So the patient may take the medication. And of course, after a period of time, if there is no improvement, they may be able to take a second dose. In terms of who would be prescribing this, there are outpatient, mental health provider, typically a psychiatrist or a nurse practitioner, etcetera, might be prescribing this for them and reimbursement would be done.

Yeah, I can (inaudible) that. I mean so Eddie, one of the things that we've done, we're working on market entry strategy for this. So we're breaking down the market. When we look at those prescribers who are either initiating therapy or switching therapy for Alzheimer's dementia patients, roughly half of the prescribers are neurologists, some are psyche and then some are what I put in the primary care bucket, although if they're double boarded, I don't know what they are. They could be in memory centers as well. So that being said, the reimbursement is traditional retail reimbursement. It could be through (inaudible) or Medicaid. They're in that bucket. So it's more of a traditional reimbursement model than it is in the hospital.

Our next question comes from the line of Corinne Jenkins with Goldman Sachs.

Maybe just on the free drug program, how do you think about like designing and constraining that sampling program to optimize getting physicians interested in the drug, but maybe not overdoing in terms of providing free product over too long of a period.

So it's a great question. And the long-acting injectables in the hospitals kind of paved the way for this. So there is OIG guidance on it. We have very specific belts and suspenders on quantities. So the hospital is not going to be able to order more than a very, what I'll call, a very limited trial program. So right now, the limits are two cartons per six months. And so that's in our business rules. We want these hospitals to get experience and we want to make sure that they get experience with the right patients, but we certainly don't want to flood the market with free goods.

Okay, helpful. And then maybe on the TRANQUILITY program, just assuming TRANQUILITY meets statistical (inaudible) primary endpoint, how should we think about kind of best case scenarios that could happen over the three-month observation period? And what are you watching? And what's most important to both investigators and regulators for that portion of the study?

So the primarily -- hi Corinne, this is Vimal. The primarily in the three-month period, it's if they have another episode, they get another dose so that we can demonstrate that if they have episodic agitation, which is three episodes a month or they start getting into more three episodes a week, the drug is effective, and that's what we are trying to show in the three-month follow-up. Rob?

Of course, the FDA is interested in not just efficacy but also safety, and that is what the study is designed to do. We met with them extensively to come up with this trial design and statistical powering. We have agreement. This is a pivotal trial for both safety and efficacy.

Our next question comes from the line of Ram Selvaraju with H.C. Wainwright.

Just a few quick ones. Firstly, I was wondering if you could comment on the degree to which formularies that have said no, but not a hard no are looking for trends in demand and what kinds of trends they are looking to see before they reconsider their decision with respect to IGALMI? Secondly, I was wondering if you could comment a little bit about the timing and prioritization of the development of the rest of the neuroscience pipeline beyond 501? And lastly, if you could just clarify whether at this juncture, the potential spinout of OnkosXcel is no longer being considered and you are simply focusing on partnering opportunities for 701.

Right. Thanks Ram. So on the formularies that have given the -- what I'll call the soft no, certainly, they're looking for more evidence, specifically in their own institution or institutions to evaluate the value. So whether the value to them is improved throughput, reduction of staff injuries, they just want to see the patient response or response time. Those are the sorts of things that they might be looking for. Certainly, the more noise in the hospital from their stakeholders that want this drug, that's going to help.

And so we're doing everything. All the marketing efforts are intended to do that is to really push those decisions forward and maybe turn the soft no into a yes over time. And then as we think about the larger systems like the IDNs, they're looking for more of their hospitals to raise their hand and say, I want this in my institution. So we're working on all those fronts to make sure that anywhere where there is a concern, a question mark about the value of IGALMI that we're able to solve it for them and certainly, we want to create the noise in the ground -- the groundswell to push them to a decision, a positive decision.

Ram, I will just add to the cost question. It depends who we are talking to. I've heard from so many salespeople that hospital things, if they can avoid one injury to a staff member, IGALMI will pay for way beyond. So that's a very big favorable market driver. And obviously, like as IGALMI gets used, we are seeing the reordering pattern once people know what value it's bringing and the case study that Rob presented to you. People -- even before we launched always said will it ever be used in the severely agitated patient.

Now we are seeing that drug is being used in the patient who came completely changed like and then drug allowed them to get out of that situation within 25 minutes. So I think market feedback could not have been any better what we have observed. That's part of the reason we decided to make the -- continue to make the investment in our commercial infrastructure. And I'm very pleased that we are at a point where we have a full commercial apparatus in place. And I think IGALMI reception is great from the healthcare provider. Now we're working through the hospitals. Coming back to your timing and prioritization on neuro pipeline, 501, 139 million episodes, 16 million already covered with IGALMI, 23 million at-home setting and 100 million with Alzheimer's agitation. All investments and plans have been put in place so that we can get two additional sNDAs for at-home setting and Alzheimer, and that will expand our market.

All of you know this is a $15 billion target addressable market, it's a huge opportunity, and we have a leadership position in this space. So we are continuing that. But our AI platform is very productive, and it has been generating more assets. And we had already announced 502. So we are pursuing 502. We have created a new formulation. We are initiating the IND-enabling study. And we believe it can go to the clinic in first half of 2024. So that's kind of timeline we are targeting for 502. Partly, there was no bandwidth in the company whether clinical or regulatory to execute on more things when you are conducting four pivotal trials like the TRANQUILITY II, TRANQUILITY III, SERENITY Part I, SERENITY Part II.

So timing is really good for 502 to execute in the clinic. In addition, we have almost now 10 product concepts. And normally, we will have about a dozen product concepts before we select our next agent. They are going through a prioritization process. Once that has happened, that will generate a sustainable R&D pipeline outside 501 and 502. So that's the game plan for next three to five years. Focus is neuropsychiatry, symptoms as well as the neuro-rare. Now we are focusing on both of them.

In terms of the OnkosXcel, I think this is that timing couldn't be any better. Time is now. We have presented the data at ASCO GU. We had just hosted a KOL Day. All the information is there, and we have very actively started pursuing both options, partnering as well as seeking independent investment so that OnkosXcel can execute on their business plan and the upcoming plan that Vince has already outlined a potential Phase II pivotal trial, SCLC human proof of concept and exploring 701 potential outside prostate cancer and pancreatic and AML.

Our next question comes from the line of Samir Devani with Rx Securities.

Really, I'm just, I guess, a little bit more interested in terms of the operating costs for this year. I think in the release, you talked about a $14 million incremental sales and marketing spend. And obviously, now we've got the [four 702] reps on board. So I'm just wondering how we should be thinking about incremental sales and marketing costs this year? And also on R&D, obviously, we saw the ramp reflecting the ongoing pivotal studies. Just wondering on a quarterly basis, how we should be thinking about that? Is it sort of Q1 similar levels to Q4 last year, maybe Q1 and Q2 and then dropping away in Q3 and Q4?

Thanks Samir. Our -- if you look at our quarterly cost was around $32 million or so in the previous three quarters in 2022. The cost in Q4 was a little bit extraordinary because we were conducting multiple pivotal programs. And now some of them have completed and some are still continuing. I would say that you should be thinking of the cost if you are thinking not Q4 should be outlier. And what it was in 2022, somewhere in between, I would say. Richard?

Yeah, I completely agree with that, Samir. So as we go through this year, several of these significant and pivotal trials will start to drop off as you suggest, and we should be not burning quite as much money. In terms of the sales force, that's fully deployed. And so we will spend money at throughout the year.

And just a follow-up, all the sales force fully deployed in Q4 or is there going to be still some incremental in Q1 for that?

No. We have full commercial apparatus in place 70 sales team. We have care team, we are marketing, we have commercial operations. We have full MSL team. I think its execution time now.

And our next question comes from the line of Graig Suvannavejh with Mizuho Securities.

I forgot to ask this before. Just on the comments you made about your discussions with the two other major GPOs. I was curious as to whether the fact that they -- those haven't been secured yet is related more to the timelines with which they run their process or I was wondering if you could give color whether they are providing some sort of pushback, whether it's related to price or any other discussions that are separate from a timeline perspective?

Thanks, Graig. And so one of them is progressing quite nicely. And I can report that we're close to the finish line. And so we'll report out on that when we do. And then there's another one that is notoriously slow. They wait to see a whole host of their hospitals downstream raise their hands. So we're working through those hospitals to build some momentum for them to engage further. We have had discussions with them, but we expect them to be a protracted process on our side. So we feel good about one out of the two, and the other one will come along.

And we have reached the end of the question-and-answer session. And I'll now turn the call back over to CEO, Dr. Vimal Mehta for closing remarks.

Thank you, everyone, for joining us today and for your interest in BioXcel Therapeutics. Have a great day.

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