BioXcel Therapeutics, Inc. (BTAI) Earnings Call Transcript & Summary

Well, good afternoon, and thank you, everyone for joining the virtual UBS Global Healthcare Conference. I'm Colin Bristow. I'm one of the biotech analysts here at UBS. And it's my pleasure to have with us today, BioXcel. Speaking on behalf of the company, we have Will Kane, the Chief Commercial Officer, and later for Q&A, we'll have Vince O'Neill, the Chief Medical Officer. So Will and Vince, thank you for joining us today. Before we start, if anyone has a question, there is a question function available within this video app or feel free you e-mail me directly at [email protected] and I can try and fill the question for you. And with that, Will, I'll hand it over to you now. Thanks.

Sure. Thank you so much, Colin, and thank you for the opportunity this afternoon to talk about BioXcel Therapeutics. It's a great opportunity for me to share the evolving story and the key catalysts that are coming up. Next slide, please. So the next slide should be forward-looking statements, and I just want to obviously premise by saying that I'll be making statements about financial outlook, product development and commercial planning, and those should all be taken in the context of our forward-looking statement which is appearing on the screen. Next slide speaks to our mission. So at BioXcel Therapeutics, our mission is to engage our artificial intelligence approach in order to identify, develop and deliver what we hope to be transformative medicines to the medical community. We have 2 platforms on which we are advancing this strategy. One is the neuroscience platform and the other is our immuno-oncology platform. Within neuroscience, we have an ambitious program across multiple disease states, neuropsychiatric disease states, including schizophrenia, bipolar disorders, dementia, delirium and opioid withdrawal symptoms. And in each case, we're looking to understand the potential benefits that 501 might have in treating the agitation associated with these conditions. On the immuno-oncology side, we have BXCL701, which is our orally active innate immune activator, which is being studied in our own sponsored trial in prostate cancer, advanced prostate cancer as well as in an investigator-initiated trial at MD Anderson looking at -- a basket trial across multiple tumor types. Next slide underscores how we believe our platform is differentiating and distinguishing in the pharmaceutical industry. We believe our platform will enable greater predictability and efficiency in the identification and the development of new product opportunities. Case in point, the experience we've had to date with BXCL501, which is under study and under FDA review right now in our first indication in schizophrenia bipolar disorder. For the beginning, when it was identified, and to the point we are today, where the NDA has been accepted, it's been just over 2 years. So within a span of 27 months, we have not only identified and translated the information into a bona fide clinical development program, but advanced that program to an NDA submission and now an NDA acceptance. The next slide really underscores the breadth and the depth of our pipeline approach, both in neuroscience and in immuno-oncology. In the neuroscience space with BXCL501, we have our 4 core potential indications that we are advancing, specifically, the 2 front runners being an acute agitation associated with schizophrenia bipolar disorder and also dementia. In addition, we understand the need for potentially multiple formulations in order to address the broader spectrum of patients who may experience agitation. So while our current formulation is an early dissolving thin film, we are also advancing formulation development on a calm pen type device or an injectable that can be used in patients who are on the severe end of the agitation spectrum in order to facilitate rapid calming in those patients. In addition, because of the technology of our film, it lends itself nicely to application of not just one but potentially 2 or more drug products and therefore, allows us to consider potential applications in a chronic treatment setting. And last but not least, we continue to explore and advance the work we're doing with wearable devices, in order to early on identify signals that indicate that agitation is building and escalating to the point where it may be in need of treatment. And we can do that in a way that can facilitate more early on treatment that would obviously benefit the patients and the health care system overall. An then next, on the immuno-oncology front, as I indicated, 701 is making solid progress, both in our own sponsored trial in castrate-resistant prostate can as well as in the basket trial at MD Anderson. Now I'd like to take a few minutes and do a deeper dive into BXCL501. I'd like to cover the condition of agitation, the marketplace in which we hope to compete, the potential mechanism of action that we understand 501 to work by, also the film technology and last, the clinical data to date with a focus on the work we've done in schizophrenia and bipolar disorder as well as in dementia. So agitation is a very debilitating and problematic symptom across multiple neuropsychiatric conditions. It's common and it's difficult to manage. We have done a fair amount of market research and market sizing to understand the impact that agitation can have. Now these diseases, schizophrenia, bipolar disorder, dementia, delirium and opioid use disorder are highly prevalent and database from the WHO indicates that over 150 million people globally actually suffer from these conditions. When we drill down more specifically into the U.S. market, our estimates are that there are about 13 million individuals who across these disease states experience agitation and they can experience agitation on a relatively frequent basis. That leads to hundreds of billion -- hundreds of millions of agitation episodes per year in the U.S. and as you can appreciate, these episodes can have a significant financial impact on the health care delivery system. Case in point, dementia patients who increasingly become agitated as a part of their advancing disease, oftentimes the admission to nursing home or other institutional settings, which can be costly for a long period of time. The current treatment options in the marketplace are somewhat limited. Based on market research and review of product labels, these products, many times because of their injectable formulations, require physical restraining of patients to administer. They can be over sedating, particularly when used in combination with other products to treat the agitation, and they also carry black box warnings. And so while the treatment options today are considered suboptimal based on clinician feedback, we see an opportunity potentially for 501 to fill a gap and to bring another treatment alternative to patients and clinicians in need. We believe the novel mechanism that we understand 501 to offer can be highly differentiating and potentially offer an additional treatment option. Specifically, next slide, to the commercial potential in our 2 front-running indication areas, schizophrenia and bipolar disorder as well as dementia. You can see highlighted here just the high level of prevalence that exists across these conditions and the high rate of agitation that does exist as well. In schizophrenia bipolar disorder, our estimates are that there are 9 million individuals in the U.S., adult individuals, who actually suffer from these conditions. And we estimate about 1/3 of those patients actually experience agitation as a component of their disease. And based on market research data and databases, we've looked at, the frequency on average across treatment settings in these patients can range from 12 to 14 a year, which gives us an estimate of about 40 million agitation episodes per year in the United States. On the dementia side of things, the Alzheimer's Association estimates there are nearly 6 million individuals in the U.S. with Alzheimer's disease today. And their estimates are that, that will double over the next 20 years to reach about 12 million patients. Agitation is a highly frequent symptom associated with Alzheimer's disease. Literature reflects up to 70% of patients with the disease can experience agitation. Now as patients with Alzheimer progress from the mild to the moderate to the severe form of the disease, their agitation can increase in frequency and intensity. And many times, as I mentioned before, this can lead to the need for institutionalization of these patients as then become such a burden to their caregivers that it's no longer feasible for them to live at home. When we consider the doubling of the population and therefore, the doubling of the episodes of agitation that may occur, our estimate is that there could be more than 100 million episodes of agitation per year in the Alzheimer's population today, which would increase significantly in the future. So 501, based on our understanding of its potential mechanism, could be an important new addition to the treatment armamentarium that currently exists. The mechanism of action, we believe, is mediated by the selective alpha-2 adrenergic receptor agonism. This reduces the transmission of norepinephrine across the synapse and by reducing the transmission of norepinephrine, we believe it reduces the incidence of agitation and the severity of agitation. It basically helps to control the fight or flight response. Now to date, we've demonstrated in SERENITY I, SERENITY II and the TRANQUILITY trial positive results that underscore, in our opinion, the role this mechanism may offer in the treatment of these diseases. We also believe that our technology is highly differentiated and offers a valuable -- potential valuable new treatment option in the marketplace. Clearly, as an orally dissolving film, it's noninvasive and nontraumatic. And in all -- in 100% of the patients in our clinical trials, 100% of them self-administered the film. We have a core and a growing patent state, if you will, a portfolio that's emerging. Obviously, last year in the fourth quarter, we announced the receipt of our U.S. patents, which covers the composition of the film, methods of use, dosages and dosage forms, et cetera, out to 2039. And recently, we announced receipt of 2 Japanese patents, one on methods of use, which goes out to 2037 and the other on the design of the film, which expires in '20 -- no earlier than 2045. And we have a multiple patent application portfolio that's pending. Just a word on the film itself, so folks can understand why we think it is differentiating in the marketplace. So it's a thin film, if you consider, for those of you who are familiar with the Listerine pocket back, it is slightly smaller and slightly narrower than that. It is proprietary developed by the company. It's orally dissolving, and it can be used sublingually, which means under the tongue or based on some PK data we've done, it can be put behind the lower lip, between the lower lip and the gum. It has a mucoadhesive property. So when you put it in the mouth, it sticks. We've all tried the placebo formulation here in the company, and it sticks right away. It dissolves in about 1 to 2 minutes and then the drug gets absorbed through the oral mucosa and obviously is allowed to travel to the brain to do its work. The technology is adaptable, as I said before, which allows us to have multiple doses -- dose range, if you will, across the film, and it could be flexible for combination products in the future. And as it relates to our scale-up process for potential commercialization that is on track with our partner, and we will continue to advance that work in order to potentially be ready upon approval -- to be ready, I should say, upon potential approval of our NDA in January of 2022. Turning now to the clinical data that's been accumulated to date. We have conducted since the fourth quarter of 2018, 7 trials across a range of disorders involving more than 800 subjects. It spans the range of our Phase Ib/II trials as well as the pivotal trials that were instrumental to the NDA filing. Specifically now to the work we've done in the schizophrenia and bipolar disorders for SERENITY 1 and SERENITY II, first, we received Fast Track designation for this program back in 2018, in the end of 2018 and has continued to advance, as I mentioned earlier, on a fairly efficient clip. From the data we have in the clinical trials, we noted a clinically meaningful rapid and durable reduction in the agitation symptoms that were measured at the primary endpoint. The onset of action, as measured by the PACT, or the pans excited component total score, was observed as early as 20 minutes in both the schizophrenia and bipolar disorder patients. Now the PEC, or the PANSS excited component total score was observed as early as 20 minutes, statistical significant separation from placebo in both the schizophrenia and the bipolar disorder patients. Now the PEC, just for reference, is a scale that has been used, it has regulatory precedence for approval in this particular indication. It is composed of 5 components that measure poor impulse control, tension, hostility, uncooperativeness and excitement. So it does provide a good perspective on how the product can be used to address the agitation that is present in patients when they present. The other thing we noted in the clinical trials was a durable response that lasted at least out to 4 hours after initial dosing. And as you'll see, we noted also a very high response rate, close to 90% in the 180 microgram arms of both patient populations. And on a tolerability perspective, our observation was that it was well tolerated, and we did not note any severe or serious adverse events associated with use of the product in the clinical trials. And as we announced recently, just last week, based on the submission of our NDA in March, we received an FDA acceptance of that filing, and they have issued a PDUFA date for us of January 5, 2022. Taking a look now at the core efficacy data if you will, from SERENITY I and SERENITY II. As depicted on this slide, you see a couple of important takeaways: one, the onset of action. So in both the SERENITY I trial, which was conducted in patients who have schizophrenia and agitation associated with that disease, and in SERENITY II, which was done in bipolar disorder patients, both bipolar I and bipolar II disorder, you see a common rapid onset of action in 20 minutes in both patient populations at the 180-microgram dose in the schizophrenia population and both the 120 and 180-microgram doses in the SERENITY II trial. You also note duration out to 2 hours in this particular chart. But as I said, that continues out to at least 4 hours and is statistically significant from placebo. And last but certainly not least, at the bottom of the slide, you should note the response rate that we noted in the trial, with nearly 90% of patients in the schizophrenia population reporting a response which is a mean reduction in the PEC score greater than equal to 40% as measured in the trial in schizophrenia patients and also an equivalent number or percentage in the bipolar disorder patients at about 90% as well. And so that is important information and one that we hear positive feedback on from the clinical community with whom we've spoken to as it underscores that the drug could potentially deliver on the rapid onset that they desire, the duration they desire and the high response rate that they need in patients who are agitated. So with that foundation, we continue to advance and plan for potential commercialization of 501 in 2022. On that front, we continue to advance on multiple areas: first, beginning with medical affairs where Reina Benabou, our Chief Development Officer, and her team have deployed the medical science liaison teams in the first quarter of this year, back in March. The MSLs, the clinical MSLs have begun engagement with health care providers and are gaining valuable insight, which they're bringing back to inform our launch planning. And the medical managed care individuals, the AMSLs, if you will, they're also engaging, particularly pharmacy directors and payers in order to understand the receptivity to the product and how we should consider positioning it and pricing it going forward. Recently at both the APA, the American Psychiatric Association meeting as well as the International Society of Bipolar Disorder Meeting, we presented several posters, highlighting key data analyses from the SERENITY I and SERENITY II programs, and we have a full slate of upcoming meetings in the second half of the year to profile and educate on the data that we have from the SERENITY program. On the commercial front, we continue to complete and advance our market research. This research is confirming what we understand to be the high unmet need among the patient population or the clinicians that treat them. And we're also hearing positive reactions to the BXCL501 profile. Recently in sync with the APA as well as Mental Health Awareness Month, we launched an unbranded educational campaign, which we entitled Boiling Point. The campaign is intended to raise awareness and to educate on agitation as it manifests itself in schizophrenia and bipolar disorder, and the campaign has had, I think, a strong start, getting many, many views from health care providers, at which it is targeted, to better understand what is the nature of agitation, how they can intervene earlier with verbal deescalation and advance their overall understanding potential collaborative efforts among the health care team to address these patient needs. From a leadership perspective, I recently hired a market access VP, who joined the company at the end of the first quarter. And she has taken the reins, and she's quickly and rapidly advancing our planning relative to payer engagement and P&T processes. And we hope to begin engagement from a commercial perspective relative to account interactions, both payer and hospital base, towards the end of the second quarter, beginning of the third quarter this year. And from another commercial perspective, we have continued to evaluate and size the sales force that we believe will be necessary to potentially commercialize 501 in the United States. As I mentioned, on the Q1 earnings call, our estimates are that we'll need about 75 representatives to cover about 1,500 or so high priority hospitals, which will be our first point of introduction of 501 into the U.S. marketplace. The operations work to underscore and to support the sales force is advancing at a good pace, and will certainly be ready in advance of our potential launch. And lastly, but certainly not least, regarding our planning outside the United States. We have announced that our intent is to partner 501 in markets such as Europe and Japan. And that is a continuing initiative on our part. And in sync with our Q1 earnings release, we announced that we will be filing our MAA application to the European regularity authority in the second half of this year based on the clinical data from the SERENITY I and II programs that are the basis of our NDA submission here in the United States. So overall, we're making solid and steady progress towards a potential commercialization of 501 in the U.S. market. Turning now to the work we've done to date in our dementia program. So TRANQUILITY is the name of the Phase Ib/II trial that we conducted in this population. And in this trial, we noted significant improvement in agitation associated with dementia. The data were submitted to the FDA regarding Breakthrough Designation and the FDA granted Breakthrough Designation to -- Breakthrough Therapy Designation to us in March. So that's a key sign and a key motivator of what advance -- what will be a continued advance in our dementia program. The summary from the TRANQUILITY trial indicates that we saw significant reductions in agitation at 2 hours post dose using a number of scales, including the PEC, which is the same scale that we used in our schizophrenia and bipolar disorder trials, the PAS or the Pittsburgh Agitation Scale, which is a validated scale in dementia and also a modified Cohen-Mansfield Agitation Inventory, again, another standard scale used in Alzheimer's disease trials measuring agitation. We saw a numerical separation as early as 30 minutes and statistical significance at 60 minutes in both the PEC and the PAS, and our duration of response was out to 8 hours with the 60-microgram dose. And all exploratory endpoints demonstrated significant improvement in agitation at the 60-microgram dose. Again, our observation is that the drug was well tolerated, and we did not note any serious or severe adverse events. And notable, as we've talked about in the past, the exposure levels we observed in the elderly population were higher, which should enable lower doses to be used relative to the schizophrenia and bipolar populations. So this is not unknown because in the Precedex label, in the dexmedetomidine label for the marketed product, there are recommendations to use lower doses in the elderly population. So in the context of the TRANQUILITY trial, we did start low doses and worked our way up. And we saw a nice dose range between 30 micrograms and 60 micrograms of that trial to inform our ongoing planning. The next slide just gives you a recap of key data from the TRANQUILITY program. On the left, you see the PEC score, again the same scale used in schizophrenia and bipolar disorders, and on the right, you see data from the Pittsburgh Agitation Scale. Again, just to reiterate, significance was achieved at 1 hour in terms of separation from placebo at the 60-microgram dose and the duration was measured out to 8 hours in this particular analysis. And on the response side, we saw a high level of response at 70% of the 60-microgram dose and a dose response, as you can see from 30 to 60. That will be informative for us as we continue to advance our understanding of the doses that could be studied in the Phase III program, clearly 30 and 60 micrograms. But as you know, we have an ongoing dose arm in 40 micrograms that will provide us more information relative to a dose response and potentially the right doses, eventually that can be commercialized. Now as we've noted, we have an end of Phase II meeting, next slide, with the FDA this quarter, that will inform the planning of the Phase III program for dementia. We list here some of the potential elements of a registration program. These are based on the experience and the insights we gleaned, not only from the SERENITY program, but also from the TRANQUILITY program as well. Obviously, ongoing dialogue with the FDA will inform and finalize the plan going forward, whether it's 1 study or 2 studies, the doses to be evaluated, although I think given the data we've shown today, 30 and 60 micrograms, clearly, could be included in the Phase III program with 40 as a potential optional arm. And we have multiple endpoints that we used in TRANQUILITY that could be used in a registrational program. So that obviously will be informed by ongoing conversations with the FDA as well as treatment settings for this program. Our aim is to continue to advance the dialogue and to get alignment in order to potentially initiate registration studies in the second half of this year. And lastly, on the dementia program, as we've noted previously, we take a long-range view and a broad vision of the opportunity in dementia. I've talked specifically about the TRANQUILITY study, which was a measure of the acute treatment of agitation in dementia patients, but we also see opportunity for intermittent chronic use in patients that have more repeated episodes of agitation associated with their disease as well as in the potential treatment of chronic -- or the potential chronic treatment of agitation in dementia patients, where the frequency and the intensity becomes such that potential medication to prevent or to lessen the severity could be helpful. And as we've also talked about in the past, we do see broad-based application for this program across multiple treatment settings, whether it be institutional settings, whether that be hospitals or nursing homes and long-term care facilities or eventually in the community for adult use. So with that, I'll just turn and make a few comments on BXCL701. And obviously, Vince and his team I'll leave this effort, and Vince will be available for questions. But regarding the BXCL701, as you know, we believe it's the most advanced orally administered activator of innate immunity, potentially to treat cancers, particularly prostate cancer and potentially others. We believe there's a dual mechanism of action at play here through the DPP8 and 9 system as well as the FAP system that in combination, can increase immune activation while reducing immune evasion. We have 701 in development, as I mentioned earlier, in our own sponsored trial in advanced prostate cancer as well as in the investigator-sponsored trial at MD Anderson, with a goal of basically expanding and documenting activity of the immune agents into cold tumors and reversing resistance in checkpoint-naive and checkpoint-treated hot tumors. Lastly, based on the data that we have to date, we see encouraging signs of activity in these difficult to treat tumors in both trials. We will continue to advance the work on this clinical program. Initial data was presented at SITC from both programs. And later this year, Vincent and his team expect to make additional data presentations midyear and beyond to update the database that is growing behind 701 and its potential use in these conditions. Last, just to summarize what's ahead for us. Obviously, we believe there is some key clinical and commercial catalysts in this year. We announced at the end of Q1, we have $194 million in cash to manage around the company. As we stated, that should certainly support us through 2021 and well into 2022 to execute on both the clinical development and the commercialization fronts as we advance the plan. Key catalysts coming up, clearly for the BXCL501 program is acceptance of the NDA and a PDUFA date in January of 2022 as well as the submission of the MAA to the EMA in the second half of this year. Again, another catalyst would be the end of Phase II meeting with the FDA and inform the design of the Phase III program for that potential indication. The continuing build-out of our commercial infrastructure and our commercial preparedness in order to potentially bring 501 to market in the United States. And last one, not least, is the ongoing trials and data readout from those trials in our immuno-oncology program in the second half of this year. And with that, Colin, I thank you. And we can open it up to questions.

That's great. Thanks, Will. So we have a question in the system, actually. When does BioXcel plan on initiating a new delirium Phase II trial?

So our current delirium trial is on operational hold as we work through a couple of issues relative to patient enrollments. So when the clinical team has completed its evaluation of the situation, then we can announce what plan is -- next step is in the delirium program. As I think folks may know that was a program that we initiated in ICUs in hospitals and so that can be a challenging place right now to conduct clinical studies. And so as the team kind of works with the sites that will provide more information as to what the next steps are there.

That's great. It's helpful. And then one by my e-mail is what is the stage of launch preparation you're at for 501, obviously, in the agitation in schizophrenia and bipolar settings?

Stage at -- where are we at with our launch prep?

Yes.

So I think we're in really good position for launch preparation. As I mentioned, from a medical affairs perspective, the MSLs are in field and gaining valuable insights for us and also building relationships. These relationships will be particularly important since the way hospital formulary consideration works, we'll need local advocates who see great value in 501, we are willing to not propose that a hospital review it for formulary coverage. So we'll begin that process now from a medical to medical perspective and a much better field force. We'll begin to do that from an obviously sales perspective. We continue to build out the leadership team, as I mentioned, we'll be bringing on our account management team very shortly, and we will be building the sales force in the fourth quarter. Now that we have to do but I think we will gauge everything towards that in order to train them and have them ready to go upon approval, we can finalize the training with package insert and get them ready to launch some time in the beginning of the year.

Okay. Great. And what are you -- what can you tell us about how you're thinking about pricing for 501 and what interactions have you had to date with payers?

Sure. So what we've done to date, we've done a couple of different research projects to inform our thinking to both payers and also, we talk to hospital P&T committee members. And the feedback on the unmet need is consistent with what we've heard from clinicians, both payers and hospital pharmacists have recognized the unmet need. They certainly understand current treatment options and some of the limitations with them, both the benefits but also the limitations. And so they do give positive feedback on the 501 profile, which we obviously find very encouraging. We haven't obviously given guidance on pricing. We're still working on that. We obviously did a long-range view on pricing because we have potentially multiple indications to come, and we want to always keep that in the forefront of our mind. What we've said to date is relative to benchmarking, there really are very few benchmarks. But attitude is one. It was obviously a branded product launched 8 years ago for the acute treatment of agitation in schizophrenia and bipolar disorder. At the time they launched, they listed at a WACC price or a list price of $150 per dose. And so we just use that as a gauge in our dialogue. And as we continue throughout the balance of this year, as we learn more about the profile and the label, then we'll be able to inform that with the payer discussions and hone in on the right pricing by treatment setting.

Okay. And how should we think about launch trajectory? Is there -- can you give us an ounce that we should be thinking about as examples of launches or anything you can say there, that would be helpful to us.

Sure. Well, as I think you can appreciate, there aren't a lot of analogs, particularly in the hospital space that we think are actually appropriate. So we continue to do a lot of work here. But what I would say is relative to how hospitals work, it's basically a 3-step process. First, as I mentioned, building local advocates who see value in 501, who approval -- can make the request that hospitals actually consider the product for formulary addition. Formulary addition, obviously, is quite key because once that goes on the hospital formulary, then it can be used broadly throughout the hospital. The second step is working again with those advocates to request stocking in the hospital. So getting the product, particularly in the emergency department and getting some use there, while the P&T process may be unfolding, we think is particularly valuable. So we'll be working with the individual target hospitals, just how we can engage them in that process. And then the third leg of the stool is actual P&T committee review. And that will inform the adoption of the 501. Hospitals have their own processes and time lines. On average, it can take 6 to 12 months for a hospital from beginning to end in order to consider a new product candidate, not specific to 501, that's just their process, but we will be working to understand each of the processes in the target hospitals. And we'll be gauging our efforts against those hospitals that may have more efficient P&T review processes, who can be prepared to support them.

Okay, great. And then on 501 in dementia, for the Phase III program, I think you're expecting to initiate in the second half. Anything you can tell us about the anticipated trial design endpoints?

So as I mentioned earlier, we'll have the end of Phase II meeting with the FDA this quarter, and that will clearly inform kind of the next steps in the program. We have the benefit of the experience we've had in both the SERENITY and the TRANQUILITY programs to inform us. We see dementia as a sequence of steps, obviously, acute treatment and that becomes the chronic treatment, et cetera. We have good data from TRANQUILITY, on which to have conversations with the FDA at 2 dose levels, which we believe will be important. We have a number of endpoints that were studied that can certainly be considered for inclusion in the Phase III program. And we think that obviously, is an area that the FDA can work with us on, et cetera. So these things are to be determined based on that dialogue, but I think we have a good foundation on which to have that discussion.

And when do we expect to see the data from the 40-microgram cohort? And can you just talk us to the importance of that?

Sure. So we haven't given guidance on when that data will report out top line. That dose cohort has been initiated at this enrolling. So we'll track that in the future, we can provide update on where that stands. And I think the value of 40 micrograms is it gives us more information about the dose response, a midpoint and the development and the potential commercialization of a treatment in the dementia population. Obviously, lower doses that provide efficacy with the appropriate tolerability and [indiscernible], particularly important in the elderly population. So by having 30, potentially 40 and 60, we will have a range that we can consider that we believe will help to engage and potentially address needs across treatment settings, whether it be the institutional or at health. So it gives us some versatility, gives us some optionality, if you will, to think about how to advance the program in multiple settings.

Okay. That's helpful. And then on -- in terms of the opioid withdrawal setting, what are the critical time lines of the next steps for that program?

Sure. So as you know, Colin, we reported the top line from the OWS study at the end of March. There was a confounding factor in that trial, which was the high rate of fentanyl that we saw in the patient population at enrollment, nearly 90% of patients had fentanyl in their systems. And that did persist over the course of the stabilization phase and also the treatment phase. So we did confound the results of that trial. A couple of key takeaways that were that we were able to dose 501 twice a day over 7 days. So it's the first time we had an extended dosing on the BID basis. So that was informative. We saw a numerically higher rate of retention of patients in the trial at certain days post-treatment phase. So that was encouraging. What we need to do now, though, is to work with our advisers, to better understand the data set that we have and also the marketplace and how fentanyl needs to be considered in the conduct of these trials, since it's become so pervasive. And clearly, in confounded trials. So that's to come. We haven't issued any guidance on the time line according -- that we're pursuing there because we want to have those discussions and be as informed as possible about potential next steps with that program.

Okay. And no early thoughts on how you're going to manage or fentanyl issue?

Well, that's a conversation we want to have with the advisers since it -- while fentanyl has been available for a while, it seems to be increasingly used, which was one of the learnings actually we had from the trial, right, that fentanyl was so pervasive. So that will require more dialogue to understand how best to conduct a clinical trial to control for that, if you will. In this particular trial, we did have a 5-day stabilization phase with morphine that apparently added much value. So -- maybe there are other options that don't require a stabilization phase that might actually give us more optionality there. But again, that is all going to depend on conversations we have with our advisers about potential next steps.

Okay. Great. Well, maybe give you a breather and we'll switch to Vince on 701. I think we're expecting to get another cut of the interim data from the Phase Ib/II trial in prostate cancer on midyear, but this is being pushed to the second half. What was the reason -- Vince, do we have you?

Yes. Hopefully, you can hear me and also see me. Can you hear me?

Definitely. Yes.

Okay. I can see a gray box. So perhaps you can't see me. So just to go back a bit and remind people. So we did present -- this was a very early efficacy cut at ASCO GU this year that was in February. We reported data on 10 evaluable patients. We saw one formal PSA response, but multiple PSA dropped, haven't quite met the PSA 50 criteria, but follow-up time was short. We did though a couple of weeks ago, announce on our Q1 earnings call that we have now met the 3 composite endpoints required to move from stage I, which was first 15 patients, to stage II of this study. So the intent in that is actually relevant to give another interim data cut, essentially allow the study to run to completion, which will be approximately 30 patients, technically 28, but it's quite likely, we will over accrue by 100 patients, that's kind of typical. And that allows us to potentially present -- release or present data towards the end of the year. And just to remind you, there are some big conferences coming up without necessarily stating, we're going to present that one or even many of those, we have ESMO in September. We have PCF in October, Prostate Cancer Foundation, and then we have SITC in November. So we certainly have a number of opportunities to present data at a good scientific forum. Hopefully, that all makes sense.

Okay. That's great. And then the basket study in solid tumors, can you talk about what we'll see at ASCO -- what you are hoping to see and what the steps are?

Sure. So just to put that in context and remind people, this is a 2-arm study. It is an ISD. So technically, it is run and controlled by MD Anderson. They hold the IND for the study. It's not a company-sponsored trial. But of course, we're aware of what's going on. The abstract data, which I think a number of outlets are really excited, includes 16 patients, I'm sorry. So 5 patients from the checkpoint naïve or arm A and 11 from the checkpoint refractory. Just remember that the data cut point supporting the abstract submission would have been back in January. So the expectation would be you would see a little bit more data by the time we get to the ASCO presentation. Again, quite how much additional data, we'll have to wait and see, as it's an MD Anderson study, but we feel this will be incremental on the data that [indiscernible] and his associates presented at SITC at the end of last year. I think, honestly, one of the bigger takeaways from that study, obviously, we're encouraged to see activity responses in both arms of the study. We did experience cytokine release syndrome early on. We've instituted a number of safety mitigation measures and again, that would be a good take-home message from even the abstract, you'll see more data based on the poster that we have indeed really got that under control, and we can move forward. In other words, we've optimized the dosing schedule in combination with KEYTRUDA.

Okay. Great. And then maybe just we're approaching the end of the time, but yes, we'll -- Vince, maybe you could just comment on beyond 501, 701, what should we be looking out for there?

Certainly, I can speak to the well or events. I mean, I can take this, obviously, from the oncology angle, we are interested, of course, to share news with the broader audience on 702 and 703. We're not quite ready to do that yet. But without question, we have pipeline activity ongoing. We have an R&D team, and that will become a fuller story going forward. On the neuro, side, I would pass it to Will.

On Neuroscience, I would echo Vince's comments. We have pipeline work ongoing. The R&D team is continuing to advance. We haven't obviously, given any guidance on timing other than in 2021, but we obviously will be closer.

Fantastic. Well, I think that really does bring us to the end of time. Will, Vince, thank you so much for your time today. It's been great. Thank you, everyone, for joining us. If you have any follow-ups, feel free to e-mail me at [email protected] And with that, have a great day.