Good morning, and welcome to the BioXcel Therapeutics conference call to review the positive overall survival results from the company's phase II trial of BXCL701 for patients with small cell neuroendocrine prostate cancer. At this time, all participants are in a listen-only mode. If during the conference you require operator assistance, please press star zero on your telephone keypad. After the presentation, there will be a question and answer session. If you'd like to register a question, you may press star one on your telephone keypad. 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 report on Form 10-Q for the quarterly period ended June 30, 2023, which can be found at www.bioxceltherapeutics.com or on www.sec.gov. As a reminder, today's conference call and webcast are being recorded. Joining us are Dr. Vimal Mehta, Chief Executive Officer of BioXcel Therapeutics, and Dr. Vince O'Neill, Chief R&D Officer of OnkosXcel Therapeutics. It's now my pleasure to turn the floor over to Dr. Mehta, the CEO and founder of BioXcel Therapeutics. Please go ahead, Doctor.
Thank you, Operator. Welcome, everyone, and thank you for joining our call and webcast today. Today, we are excited to share important overall survival results from our phase II trial of BXCL701. BXCL701 represents our lead asset in immuno-oncology that we discovered through our proprietary AI reinnovation platform. We believe our progress with BXCL701 further supports our unique business model of drug reinnovation. The FDA approval of IGALMI was the first validation of our AI-based approach. We are excited to continue advancing our two late-stage clinical programs for BXCL501. Our upcoming FDA meetings for these programs are on track, and we look forward to sharing the outcomes of these meetings. Turning back to BXCL701, this important asset continues to add value to our overall business. We have established human proof of concepts and will utilize this new data to pursue a strategic path forward.
We are evaluating strategic options for OnkosXcel, including potential financing, strategic partnership, or M&A. I will now turn the call over to Vince to discuss our exciting phase II results in more detail. Vince?
Thanks, Vimal. So starting with slide number six, I think many people have, will have seen a version of this slide before. This is essentially a timeline of development for 701, beginning with the opening, or actually more correctly, the reopening of the IND. Bear in mind that Point Therapeutics did develop this molecule at least 20 years ago. A number of data readouts along the way, interim data, culminating in the final primary endpoint readout early this year at ASCO GU. And the next step, as we will discuss later, almost certainly, the FDA meeting to discuss data and next steps. Next slide, please. Okay, and the next one.
So just a brief reminder of what small cell neuroendocrine prostate cancer is, a highly aggressive form of prostate cancer, about 12,000 new patients a year, viewed by most essentially as an escape mechanism or a resistance mechanism to androgen blockade. As we've said many times before, the only standard of care, the only therapy approaching standard of care, would be first-line use of platinum-based therapy. After that, most patients progress quickly and unfortunately die within weeks to months. Next slide. So this is a summary of the top-line results. Most of these were covered in the press release issued this morning. Just to make the point that we will be making cross-trial comparisons, and there are definitely caveats to that, and we'll discuss those as we go through the study, but please bear that in mind.
Looking at the data, again, bearing in mind the historic data, and this would be the Armstrong et al. presentation study, published about three years ago, we have a median overall survival approaching 14 months. That clearly compares very favorably to historic data. A 12-month survival rate, which is actually a good way to look at the Kaplan-Meier results, and we'll discuss that in more detail when we get there, of approaching 60% versus an expected around 30%. We previously presented data on antitumor activity, so we have a composite response rate at 25% and overall response rate RECIST-defined at 20%. Clearly, again, in excess of what was seen with the only published series with checkpoint. Again, that's the Armstrong et al. publication, 6.7%.
That number is actually one responder, and that responder was an MSI high patient. We've also presented data, again, ASCO GU earlier this year, final data demonstrating a high rate of disease control. Again, almost 50% versus the historic data publication of about 30%. Next slide, please. This is, just on slide number 10, just a reminder, really, of the study design. This was an open label, single arm phase II study, Simon two-stage, 15 patients, interim analysis, which we did present, and then a final 13 patients, so N of 28 evaluable. Important point, this was a multicenter study across 13 centers in the U.S. and U.K. Primary objective or primary endpoint, as I'd mentioned, composite response rate, additional objectives, duration response, overall survival, PFS, and some biomarker work. Next slide.
Again, data that we presented at ASCO GU earlier this year. Important baseline characteristics for our patients. The median age is approaching 70, as you would expect. Virtually all patients, two exceptions, were performance status zero and one. Most patients, as you would expect with this disease, had visceral metastases. That's about two-thirds of patients. Three prior lines of therapy with a range of 1-8. Again, underscores the fact that our patients were pretty heavily pretreated. As you would expect, all patients, this was obviously an inclusion criterion, had to have prior systemic therapy, and you see that. Most, over two-thirds, received platinum-based therapy, to the point I made earlier. Again, the vast majority of patients received androgen blockers. Next slide. This is the swimmer plot.
So based on our final data sweep, dated 6th September this year, we have a median duration of follow-up of almost 24 months. I'll just draw attention to, we may come back to this, in discussion. Six of our patients, 21% of the entire group, approximately 25% of our measurable disease patients, were treated beyond progression. That means that they were allowed, using iRECIST criteria, actually, to continue on drug if they had minor progression, but were feeling well and were doing well in the opinion of the investigator. Next slide, please. So again, data that we presented earlier this year. Just a reminder, composite response rate, as I've said, 25%. RECIST-defined response, 20%, with a median duration of response of between 6-7 months. Next slide.
Another reminder, again, a slide taken directly from the podium presentation earlier this year by Dr. Rahul Aggarwal, our PI. This is the classic waterfall plot. Anything below the line represents tumor shrinkage, anything above actually represents tumor growth. Two important points here, as we've said before, all of our responders, actually, all of our patients with tumor shrinkage were microsatellite stable and/or TMB low. And the other point is, we did see tumor shrinkage in both prior platinum-treated and non-prior platinum-treated patients. Next slide. So this is the Kaplan-Meier curve for overall survival. I'm excited and happy to share this with you. Obviously, the black line is the curve, and the gray to either side is the confidence bars, 95% confidence intervals.
So you can see here, and you can clearly read this directly from the curve, the median overall survival is approximately 14 months, with a range of approximately 11 months to not reached, and the 12-month survival rate. Again, that's a useful handle of how these patients did. Approaching 60%, and that is pretty unusual in this patient population. Next slide, please. So this is the PFS curve. Again, approaching it the same way. So the median PFS in excess of 2 months, the range shown there with the 6-month PFS rate. Again, this, the 6 months would be the landmark analysis you would typically do for PFS and allows for comparability between studies is in excess of 25% with the confidence bands shown there. I'll just make the last point, again, we may come back to this in discussion.
This is radiographic PFS, not iPFS, which would be iRECIST PFS. The latter was used by the Armstrong publication. So there's one difference, and we can talk about this later, between the two datasets. So this is radiographic. We will do an iRECIST PFS analysis. We just haven't done it yet. The data are very fresh. Slide number 17. Again, just a reminder of the safety experience. This slide was presented again by Dr. Aggarwal on the podium. Treatment emergent adverse events on the right, treatment-related on the left, and treatment-related on the right. We did see one fatal adverse event, and we've discussed that previously. That was a grade 5 tumor lysis syndrome. And on the right, in terms of treatment-related events, in general, low grade, in general, transient, and in general, highly manageable.
Next slide, please. This is one of a couple of slides covering the comparison with the historic data. There's one more slide in appendix and backup, if you want to look at it, that covers the design of the study. There are some subtle differences there as well. Just to start with the sample size, we had 28 patients. The Armstrong publication, a bit smaller, N of 15. Importantly, all of our patients had histological confirmation of NEPC or small cell. That's difficult to do, I'll say as an aside, but I, we thought it was important to do that. Contrast that with the Armstrong experience, where only about a third of patients were confirmed. And small cell, that doesn't mean the remainder were bog standard classic Adeno.
All patients had to have features, either clinical or circulating marker, that fit with a diagnosis of NEPC. Median age, fairly similar. Prior lines of therapy, our patients were a bit more heavily pretreated. You can see that on the median, but probably more on the, on the range. For the Armstrong publication, a max of three prior lines, for other max of eight. Another important difference is that the majority of our patients, as you would expect to date, receive prior platinum for the Armstrong publication, just over a quarter or just under a third, maybe better said. And treatment with prior platinum and progression after prior platinum is a poor prognostic factor. And then lastly, taxane use. So essentially all patients receive some form of chemotherapy. Most of our patients were previously treated with platinum.
This is really a side-to-side comparison of the data. Again, I'm gonna state the obvious and just make the point that cross-trial comparisons do come with caveats. I've tried to stress that throughout the presentation, but I think it's still useful to put our data in some kind of context. Again, the Avelumab study did not use composite response rates, so focusing on RECIST response, 20%, as we've said. All of our responders, in fact, all of our patients tested, were either microsatellite stable or TMB low. That was essentially our patient population, versus the Armstrong publication, which did include MSI High, and in fact, that was the only responder seen, so one of 15. Duration response is meaningless, really, with a single responder, so we'll skip that.
The disease control rate, as we've discussed, approximately 50% versus approximately 30%, so we're in excess of historic data. Same for PSA response, and as we've discussed, PFS, numerically better, median OS, numerically better, substantially so, and 12-month survival rate, again, substantially different from historic data. So just to sum up and conclude, we believe these data are clearly positive. These are strong data. They're clearly in excess of the historic data set. We can discuss that obviously further. OS really represents the, the best and arguably the gold standard, people describe it as such, for measuring effectiveness in oncology. And importantly, our patient population was microsatellite stable. That's different from, from the Armstrong publication. We have shown, we believe, that the combination of BXCL701 and Pembro demonstrates manageable safety.
Certainly, the split and step dosing has mitigated the on-target toxicity, namely the cytokine-related phenomena. We're glad to see that. And importantly, there's no clear evidence it is N of 28, but there's no clear evidence that we potentiate immune-related adverse events, i.e., those that would typically be associated with checkpoint therapy. Like, for example, hepatitis, colitis, et cetera, et cetera. Last two points really talk about where we go from here. So obviously, the next steps will be to discuss with the FDA the data, of course, and also a pivotal study design. And then lastly, I think this does have clear implications and knock-on effects for other potential development of BXCL701, specifically in high-grade neuroendocrine tumors, and more specifically, still small cell lung cancer, and we've discussed that previously.
So with that, I'd like to stop and open it up to questions.
Thank you. We'll now be conducting a question- and- answer session. If you'd like to be placed in the question queue, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing star one. One moment, please, while we pull for questions. Our first question today is coming from Robyn Karnauskas from Truist Securities. Your line is now live.
Great. Thanks for taking my question, and congratulations on the data and great presentation. So I have two questions. The first one is: What is the next clinical trial, like, steps for clinical trial and regulatory steps that you guys plan to do for BXCL701? So what's your best guess on what the FDA is gonna see and say regarding this data, and, and any cons of some similar data and gotten approval? And then I have a follow-up.
Sure. So the crux of the FDA discussion is gonna be around obviously the endpoint. We previously said, we'll get to this in a minute. I mean, there are strong precedents for using response rate as the primary, with potentially some supporting survival data. Best example of that is Lurbinectedin, which is the Jazz Pharmaceuticals compound in second-line small cell. Very close parallels, very similar diseases, and very recent. So that regulatory precedent was only about maybe 3 years ago, 2.5, 3 years ago. So I think that's probably the closest parallel. So it'll basically be about the primary endpoint and why we think a surrogate endpoint is best in this situation. All right?
I mean, the obvious question will be, the FDA may look at the survival data and say, "That's encouraging. Now go do a survival study." That study is simply not feasible. It's too large. There essentially are not enough trials to see these patients globally. It would take forever. We estimate something like 7+ years. That's just not a feasible study. So the discussion will be the use of a surrogate endpoint. Primarily.
My follow-up is, is sort of, like, tangential to that. You have a cash runway for BioXcel for over a year. You know, what are you thinking about as far as potential for monetizing this drug or partnering this drug to make sure that it can be developed quickly, and then for the big picture for the company?
It seems like something you could monetize in some way to help the company in case the FDA comes back and says you have to run 1 million trials.
Good morning, Robyn, this is Vimal. I will take that question. You're absolutely right. This asset is adding value to our business, and now we have the complete data set, and we will start the process, as you mentioned, looking for partnership or potential M&A to monetize and extend our cash runway. So this asset can add to that. But having this data in our hand, it will allow us now to start those discussions in a meaningful manner with potential partners. We have seen some early interest, and we will pursue on that path.
Great. Thank you, guys.
Thank you.
Thank you. Next question is coming from Greg Harrison from Bank of America. Your line is now live.
Hey, guys. Good morning. Congrats on the data, and thanks for taking our question. I wanted to ask about the Avelumab historical control you used here. Can you help us understand how this study was chosen and why it's a fair comparator for this indication and for your trial?
Yeah, so in essence, Greg, morning. We believe, I mean, it's the best comparator because it's the only comparator, right? This is the only published series with a checkpoint in this disease, to our knowledge, and we've looked, and our investigators agree with that. So there are differences. We've said sample size a bit smaller. Probably the most important one is that not all of their patients were histologically confirmed. But if you look at the differences between the studies, arguably they make the case that the Avelumab group should possibly be doing better. In other words, we have worse prognostic factors. So I think all these points say this is a reasonable comparator, and ultimately, it's really the only one that we could have used.
Got it. Thanks again.
Thank you.
Thank you. Next question is coming from Colin Bristow from UBS. Your line is now live.
Hey, good morning, and congrats on the data. Just a couple from my side. Bigger picture to start, I, I guess after the prior updates on this asset, you, you had said a couple of times that you the data with FDA. I'm just curious, did this happen? And if so, just, you know, what was the outcome of those discussions? And then secondly, can you just describe the intellectual property, sort of portfolio for BXCL701 so we can, think about that, especially in terms of, monetizing this? Thanks.
Sure. Morning, Colin. Yeah, so we previously said that we would have FDA interactions, second half of this year. It's now October. We did hold back in making the FDA meeting request until we had these data in hand. I think that probably made sense. The request has gone in. The briefing book will follow very shortly, and we will be having the conversations that we've been describing, between now and the turn of the year. So that's essentially the update.
Good morning, Colin. This is Vimal. I will take your intellectual property question. We earlier this year, in January, we got the patent issued for BXCL701 combination with checkpoint inhibitors, so it's already issued patent that has a potential expiry until 2036. In addition to that, BXCL701 is a new chemical entity. We get 5 years of data exclusivity, plus whatever time is required, like, you know, another 30 months. In addition, we have filed patent related to the formulation of this drug. Initially, this was a refrigerated the way the current formulation that has been tested. Now we have developed a formulation for room temperature, so that will provide additional IP.
We believe we have very strong IP position with patent and data exclusivity to maintain our market exclusivity for the indication for BXCL701.
Great. Thanks.
Thank you. Next question is coming from Sumant Kulkarni from Canaccord Genuity. Your line is now live.
Morning, thanks for taking my question. It's a, it's a two-parter. You've put these results into context with the avelumab dataset, but could you give us a sense of where exactly an innate immunity activator like BXCL701 lies in the competitive landscape for neuroendocrine prostate cancer and what that might mean for next steps, specifically in terms of potential competition for patients for a phase II-B trial? How much time would a typical phase II-B trial take for this kind of indication?
Sure. Morning, Sumant. So in terms of competitive landscape and where we fit in, and clearly the oncolytics are active here in the innate space, and there's been data relatively recently there. Without naming the company, I'm sure we both know what it is, Boston-based. The issue there, of course, is that that asset has to be injected intratumorally, and there are obviously considerations there. It does look as though, again, this may be just my personal view, but it does look as though the field has kind of migrated towards NK cells, either activation by antibody or indeed cell therapy. I mean, BXCL701's an oral agent. We have published detailed mechanism work, which does demonstrate that we pull into the microenvironment, both T-cells and NK cells.
I think if you can do that with an oral small molecule, arguably that has advantages over the other approaches. So that would be my take on the landscape. And the second question was?
You mentioned the timeline for a potentially infeasible trial, but what would a feasible phase II-B look like?
Sure. If we use as a, as a straw man, the, the phase II-B that we previously described, right? For example, at, at, at the KOL Day, we think, we believe we can bring that study in within 24 months. That, that was the, the estimate that, that we presented. That would be a sub-100, N of 100 patient trial. Obviously, if that were to increase, then the, the duration of the study would be, would be longer.
Got it. Thank you.
Thank you. As a reminder, that's star one to be placed into question queue. Our next question today is coming from Corinne Jenkins from Goldman Sachs. Your line is now live.
Yeah, good morning. Can you just remind us if there's been any sort of single agent study of Pembro in this context? And then kind of following from that, what do you expect to need to demonstrate from a component contribution perspective, and do you think that the FDA will require additional studies from that perspective?
Yeah. So in terms of Pembro or KEYTRUDA, I mean, most of that work has been in the Adeno space. And I think you, you'll know as well, probably better than I, five or six failed large randomized phase III studies. I think I believe at this point, Merck has pulled out of adenocarcinoma. They are interested in small cell neuroendocrine. I think it's generally accepted in the field that single agent checkpoint in microsatellite stable, small cell prostate, it is just not active. And I don't believe there are any data out there that says otherwise or contradicts that.
Your point in terms of what would the FDA expect in terms of comparator, I mean, again, we previously argued, with strong backup from our, our KOLs and our investigators, that it may actually be unethical to expose patients to, to Pembro, given the data that's, Pembro in, in this indication, small cell prostate, just given the data that's out there. MSS is not expected to respond. Again, it's never a good thing to, to second guess what the FDA is going to say, but let's, let's brainstorm and say they feel very strongly that Pembro should be tested here. That would certainly not be the end of the world, because we could close that arm based on a response rate endpoint, probably fairly quickly.
I don't see how Pembro could be active when all the data say otherwise in this patient population.
Okay. And then just I feel like we've, you know, been looking for a strategic exit for this program for some time now. Is there any other gating factor beyond these data that you see in terms of realizing the value for the asset? And then, yeah, maybe I'll just stop there.
Hi, Corinne. Good morning. This is Vimal. I think we have never gone out and looked for a partner proactively. It has been more through scientific conferences, where there was interaction among the scientists. So those conversations always continued, and people wanted to see complete data set. Now we have complete data set in our hand. Now will be the time to make a concerted effort around potential partnering, M&A, or potential financing, what would be the optimal to move this asset forward?
Is the IPO off the table at this point?
I would say nothing is off the table, but we want to be very practical, what is a reasonable solution within a short amount of time.
Okay.
Corinne, can I just add, in terms of data, the only other data set, I mean, we've clearly presented multiple data cuts and interim analyses and so on. The only other dataset coming from this study, the phase II-A study, would be a biomarker update, and we have had an abstract accepted for SITC on exactly that.
Okay, thank you.
Thank you. Next question is coming from Richard Nguyen from Mizuho. Your line is now live.
Good morning, and congratulations to the team. This is Richard Nguyen on for Graig Suvannavejh. Just a couple questions for us. When can we expect to see, you know, full data from this study? It seems like we're getting, you know, small drops here and there, and I just wanted to know when, you know, fuller or the completed data from this set. Also, if you can remind us about what percent of your cash runway is dedicated to BXCL701? Thanks.
Sure. So I'll take the first part of that. So just to clarify, what we did present the primary endpoint in full at ASCO GU this year, and these are the time to event analyses. Beyond that, as I mentioned, there will be a biomarker readout at SITC. To your point, it doesn't make any sense to then present further data or cuts of it at meetings. We will proceed directly to the manuscript. So the manuscript will obviously have, you know, all the data. Because it's N of 28 and it's not a huge study, you will see individual patient data as well. So that's the definitive answer.
Hi, Richard, this is Vimal. In terms of the cash, we are not dedicating any more capital to BXCL701. We're just closing out the studies that are ongoing. Our cash, I would say, is fully dedicated to our lead program, BXCL501, for which we have two upcoming FDA meetings and an, we will be very excited to share the outcomes from those meetings in next couple of months.
Thank you. Next question is coming from Samir Devani from Rx Securities. Your line is now live.
Hi, guys. Thanks for taking my questions. I guess I got two. Just wanted to double-check. When, when patients progressed in this study, were they able to go on to another trial? I guess that's the, the first question. And then I guess the second question is the six patients, the six patients that had adverse events that were, that discontinued, do you know the outcomes in terms of survival for those six patients? Thanks.
Yeah. So first question was, again, when they progress, are they allowed to go on to other therapies and/or other studies? Short answer is yes. A follow-up question, which you didn't ask, but I'll answer, is did we then capture that data? So we don't know what they subsequently had. Just bear in mind, three prior lines of therapy, and the range 1-8, they've had quite a lot of treatment to date. But yes, they were certainly permitted to proceed to other therapies. What that was, it's not that common to capture that information. We don't know what they subsequently got. And most patients obviously had tried platinum, so platinum is the most impactful agent in this disease, obviously.
Just on the second question about the six that discontinued due to AE, what happened to them?
Yeah, yeah, yeah. Yeah, let me answer the, your question, because we can talk individually about the, the six discons. If you look at the safety database, N of 34, versus the efficacy database, N of 28, there's an N of 6. They're not all discons due to AEs. If we add those six pa- so all of those patients were alive at last follow-up. That's an important point. If you add those six patients in, this will obviously be in the manuscript, the Kaplan-Meier doesn't look any different. Median survival looks essentially the same. That's good news. It shows again that the data are fairly robust.
Okay, great. Thanks very much.
Thank you. We've reached the end of our question- and- answer session. I'd like to turn the floor back over to management for any further or closing comments.
Thank you very much for joining us today, and have a great day.
Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time.