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spk06: Good afternoon and welcome to QRIS's fourth quarter and year-end 2021 earnings call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After the company's prepared remarks, call participants will have an opportunity to ask questions. To ask a question, you may press star then one on your touchtone phone. To withdraw your question, please press star, then two. Please note, this event is being recorded. I would now like to turn the conference over to the company's Chief Financial Officer and Chief Administrative Officer, Bill Steinkraus. Please go ahead.
spk02: Thank you, and welcome to QRIS's fourth quarter and year-end 2020. Before we begin, I would encourage everyone to go to the investor section of our website, at www.curis.com to find our fourth quarter and year end 2021 earnings release and related financial tables. I would also like to remind everyone that during the call, we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. For additional details, please see our SEC filings. Joining me on today's call are Jim Denser, President and Chief Executive Officer, and Bob Martel, Head of R&D. We will also be available for a question and answer period at the end of the call. I'd now like to turn the call over to Jim. Jim? Thanks, Bill. Good afternoon, everyone.
spk05: It's my pleasure to welcome you to QRIS's fourth quarter and year-end earnings call. At QRIS, we're driven by our mission to develop the next generation of transformative cancer therapies that meaningfully improve and extend patients' lives. In the fourth quarter of 2021, we made significant strides towards that goal. To start, we're pleased to announce that our novel IRAC4 inhibitor, CA4948, will be adopting a new generic name, emavucirtib, as well as introducing Take Aim, our brand name for clinical trials moving forward with emavucirtib. The Take Aim branding was selected to highlight the targeted design of emavucirtib as the first in class IRAC4 inhibitor in oncology. As a reminder, emavucirtib is currently being evaluated in nine distinct patient populations across three clinical studies in AML, MDS, and B-cell cancers. The first study, Take Aim Leukemia, is a Phase I-II study with both monotherapy and combination arms for patients with relapsed or refractory acute myeloid leukemia, or AML, and high-risk myelodysplastic syndromes, or MDS. The second study, Take Aim Lymphoma is a Phase I-II combination study with ibrutinib for patients with relapsed or refractory NHL or other hematologic malignancies. The third study is the Phase II Lucas study, evaluating amavucirtib in patients with lower-risk MDS, being led by Dr. Uwe Platzbecker of the University of Leipzig. In early January, we announced positive updated data from the Take Aim Leukemia Study in targeted patients with relapsed refractory AML or MDS whose disease is characterized by a spliceosome or FLT3 mutation. The updated data set supported the findings presented at EHA last year, further demonstrating encouraging anti-cancer activity compared to standard of care therapies in an expanded set of patient data. As of December, we had enrolled 49 patients in monotherapy, 13 of which had genetically defined diseases, either spliceosome mutation or FLT3 mutation, and were evaluable for efficacy. We plan to discuss data from this ongoing study with the FDA in the first half of this year with the goal of clarifying the regulatory path for bringing this novel therapy to patients in critical need. We will provide an update on that discussion later this year. Additionally, enrollment is proceeding well for the combination arm exploring amavucirtib plus azacitidine for patients naive to HMA and amavucirtib plus venetoclax for patients naive to venetoclax. We expect to have initial data from these combinations in the second half of this year. I'd like to briefly touch on the ongoing Phase II Lucas IST for patients with lower-risk MDS being led by Dr. Uwe Platzbecker, the co-chairman of EHA's scientific working group on MDS. Demonstration of safety and efficacy in low-risk MDS could lead to a potential breakthrough in the MDS field. While the current standard of care with EPO-stimulating agents can be effective for patients with lower-risk MDS who have low serum EPO, the effect is often transient. It is not disease-modifying, and it does not prevent the progression of MDS to AML. We believe that emavucirtib, with its direct targeting of IRAC4, could be a transformative disease-modifying alternative, allowing the potential to treat these patients in a much earlier stage of disease. While physicians can give leukemia patients transfusions, and they have drugs that can stimulate blood cell growth, at Curus, we're developing drugs that have potential to stop the cancer. In these early days of clinical testing, our data have demonstrated the potential to do just that, even in patients with spliceosome mutation for whom existing therapies don't work. Now let's move on to our B-cell cancer program and the TAKE-AIM lymphoma study. We initiated the combination study, evaluating emavucirtib with ibrutinib last year, after seeing clear efficacy with this novel monotherapy agent and seeing that the efficacy was durable over such an extended period of time for these extremely sick patients. The dose escalation portion of this study is expected to enroll approximately 18 patients in a 3 plus 3 design with emavucirtib doses starting at 200 and escalating to 300 milligrams BID. Ibrutinib dosing will be whatever is appropriate for the patient's respective NHL subtype. We expect to report initial data from this study in the first half of this year. Moving on to our second asset in the clinic, our first-in-class monoclonal anti-VISTA antibody, CI8993, a novel immune checkpoint inhibitor we're developing in collaboration with Immunext for the treatment of patients with relapsed or refractory solid tumors. We were excited to present clinical data on our phase one dose escalation study of CI8993 in January, demonstrating a promising safety profile and highlighting the potential of CI8993 to activate multiple anti-cancer mechanisms. CI8993 is a monoclonal antibody designed to antagonize VISTA-mediated immune suppression through myeloid and T-cell mechanisms. We believe CI8993 is the most advanced anti-VISTA antibody currently in clinical development and has the potential to be a game-changing cancer therapy. The role of VISTA may go beyond other checkpoint inhibitors, as we believe VISTA inhibition has the potential for broad application in many tumor types, both in monotherapy and in combination with existing checkpoint inhibitors. Because of VISTA's localization on a variety of immune cells, targeting it affects numerous cancer immune mechanisms, many of which are not addressed by targeting PD-1, CTLA-4, or other checkpoints. Our Phase I dose escalation study has shown to date that CI8993 has a safe and well-tolerated safety profile. Initially, we started dosing at 0.15 milligrams per kilogram, which was the highest dose cleared in the Janssen study. We then escalated dosing to 0.3 milligrams per kilogram, and most recently to 0.6 milligrams per kilogram. We're encouraged by our initial safety data as they appear to demonstrate the effectiveness of the procedures we implemented to manage expected CRS effects. The pharmacokinetic profile of CI8993 demonstrates the ability to overcome a PK-SYNC effect and achieve meaningful drug exposure. This fact is exemplified by our observation of clear pharmacodynamic effects in CI8993 with early signs that CI8993 is activating multiple anti-cancer mechanisms in patients tested to date. For these reasons, we believe that therapeutic targeting of VISTA with CI8993 has the potential to be a critical addition to the immune oncology arsenal. We look forward to sharing more data on this in the second half of 2022. In summary, we're pleased with the progress we've made in 2021. And we look forward to further progress in 2022. With that, I'll turn the call over to Bill to review our financial results for the quarter. Bill?
spk02: Thank you, Jim. QRIS continues to operate from a place of financial strength. For the year ended December 31, 2021, QRIS reported a net loss of $45.4 million, or 50 cents per share, on both a basic and diluted basis. as compared to a net loss of $29.9 million or 61 cents per share on both a basic and diluted basis in 2020. For the fourth quarter of 2021, Securus reported a net loss of $13.6 million or 15 cents per share on both a basic and diluted basis as compared to a net loss of $7.5 million or $0.11 per share on both a basic and diluted basis for the same period in 2020. Revenues for the year ended December 31, 2021, were $10.6 million as compared to $10.8 million for the same period in 2020. Revenues for both periods comprised primarily of royalty revenues recorded on Genentech and Roche's net sales of AeroVeg, Revenues for the fourth quarters of 2021 and 2020 were $3.1 million and $3 million, respectively. Operating expenses for the year ended December 31, 2021 were $52.7 million, as compared to $35.7 million for the same period in 2020. Operating expenses for the fourth quarter of 2021 $15.7 million as compared to $9.3 million for the same period, 2020, and comprised of the following. Cost of royalty revenues primarily amounts due to third-party university patent licensors in connection with Genentech and Roche's AeroVegNet sales. $0.5 million for the years ended December 31, 2021, and 2020. Cost of royalty revenues were $0.2 million of 2021 and 2020. Research and development expenses were $34.9 million for the year ended December 31, 2021, as compared to $23.1 million for the same period, 2020. Development expenses were $10.8 million for the fourth quarter of 2021 as compared to $5.6 million for the same period, 2020. This increase was primarily attributable to increased clinical and manufacturing costs for our programs and higher personnel spending as a result of additional headcount. General and administrative expenses were $17.3 million for the year ended December 31, 2021, as compared to $12.1 million for the same period in 2020. General and administrative expenses were $4.8 million for the fourth quarter of 2021 as compared to $3.5 million for the same period in 2020. The increase in general and administrative expense was driven primarily by higher costs for stock-based compensation, professional consulting services, personnel, and insurance as compared to the prior year. Net other expense was $3.4 million for the year ended December 31, 2021, as compared to $5 million for the same period, 2020. For the fourth quarter of 2021 and 2020, net other expense was $1.1 million and $1.2 million, respectively. Net other expense primarily consisted of imputed interest expense related to royalty payments. As of December 31, 2021, QRIS's cash, cash equivalents, and investments totaled $139.8 million, and there were approximately 91.6 million shares of common stock outstanding. QRIS expects that its existing cash, cash equivalents, and investments should enable it to maintain its planned operations into 2024. With that, I'd like to open the call for questions.
spk06: Operator, we will now begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then 2. At this time, we will pause momentarily to assemble our roster. The first question is from Alicia Young with Cantor Fitzgerald. Please go ahead.
spk01: Hey, guys. Thanks for taking my question, and congrats on the progress that you guys are making over the past, you know, couple months. I just wanted to drill a little bit down into, you know, maybe talking about how we're thinking about kind of the trial design, you know, what's really viable versus what might not be viable, and to kind of, I know you haven't had this conversation with the FDA, but just, you know, how you're thinking about what the expectation or how you guys are framing up for what it should be. on that front. And then I just also wanted to ask on VISTA, do you guys feel as if, you know, you will be in a position to potentially achieve proof of concept, you know, by the time we get to the end of the year? I mean, like, you know, you'll kind of be past the safety and the, you know, kind of efficacious doses. And do you think, how do you think about kind of continuing monotherapy or is there any kind of option to potentially do something more of a combination with VISTA as well? Thanks.
spk05: Thank you, Alicia. Thanks for joining as well. Bob, you're probably the first, the best person to talk to the trial design for 4948, and we can address the VISTA one second.
spk09: Yeah. Hey, Alicia. Thanks for the question. So the trial design, you know, we sort of break it down into high-risk MDS and AML. And I think, you know, currently the AML, we believe, is fairly straightforward. What we're trying to do is look both in parallel at a very rapid path to registration with the FDA. And that could involve a single arm study looking at surrogate endpoints like CR and CRH. Those endpoints are validated endpoints by the FDA and used also in conjunction with durability of response. A couple of drugs have been approved in this space in AML. including giltaritinib and ivacidinib, both with response rates in the low 20% range. So we think that this is a pretty viable approach. And we also have a population here that historically has been quite challenging to get these types of responses, yet in the data that we've presented so far, You know, we've presented a really very durable CR and CRH and quite good effects on the blood counts for those patients in very difficult to treat populations. And so I think that's our main focus for the clinical trial for AML, and we'll discuss that with the FDA coming up.
spk05: Yeah, thanks, Bob. So on the VISTA question, well, first, Alethea, does that answer your question on trial design for 4948?
spk01: Yeah, that's helpful. I mean, I guess, you know, is there a distinction, though, in MDS as to what you might do versus AML, which, I mean, obviously, you know, I can see the kind of unmet need in the protocol. I mean, kind of how we've gone forward in AML, but with MDS, like, how do you kind of think about, you know, a later stage trial design that could have, you know, momentum there?
spk05: Well, there's definitely... Go ahead, Bob.
spk09: Yeah, so that's another population that is unique, although the... historical evidence is that things don't work quite so well there. So we have seen clearly, as you saw previously, in that population, we've had very strong anti-cancer activity. So, for example, four out of the six patients who had elevated blast count at baseline normalized their blast count. So striking anti-cancer activity. And one of those patients even went on to stem cell transplant, which is a potentially curative approach. So there we need to discuss with the FDA what type of surrogates might be optimal for this patient population. Clearly, the anti-cancer activity is one endpoint that we'll discuss, you know, also will be you know, starting to think about our combination trials. And as those come in, that offers other opportunities for clinical trial development moving forward there.
spk05: Yeah, maybe if I were to summarize that as well to emphasize a little bit of some of those points, Alethea, I'd say that in AML, there's clarity on the endpoints that the FDA is going to want to see. To Bob's point, There are several drugs that have looked at the CR and CRH rate as an endpoint, and it was actually not just for accelerated approval. They got full approval on those endpoints. So giltaritinib, ibacidinib, and inacidinib all got CR, CRH rate. So there seems to be broad agreement on what sort of endpoints would make sense, and there's broad agreement that our data look great in those endpoints compared to anything else used in relapsed or factory setting. In MDS... In those same two points, I'd say everybody seems very comfortable that our data looked terrific compared to what else gets used. The lack of clarity is on what the endpoint is going to be. And that's where there's a lot of discussion. Certainly, we get a lot of questions about that because the fact of the matter is there are no drugs approved in relapsed refractory MDS. Given that there are no drugs approved, and there are no drugs approved because nothing's worked, it's not clear where the FDA will come out on that. So I think the AML path is, of course, much more clear. We just need to go make that case to the FDA and get them comfortable that we're ready to go to the pivotal design on this. But the endpoints are clear, and our data look good on those endpoints. In MDS, our data look good, certainly compared to chemo, which gets used more than half the time in these patients. but the lack of clarity is simply because there are no drugs approved. So we will be trotting new ground with FDA on the primary endpoints in that study. Hopefully that's helpful.
spk01: No, that's very helpful.
spk05: Okay, great. So maybe I will go to your VISTA question. So, yeah, so VISTA in 2021, the big check the box item was safety. We knew to expect CRS side effects. We designed the study. to expect that and to manage them effectively. And so we needed to go out and prove that we could, to make it short, we could succeed where Janssen failed. Could we clear 0.15 mgs per kg? And the answer was we did, and we cleared 0.3, and we're now dosing at 0.6. So the check the box on safety so far has been a terrific win for 2021. Now for 2022, the goal changes. Now we're on the hunt for efficacy. We don't know exactly which dose level will lead to the type of concentrations of drug that will lead to tumor shrinkage, but that's what we're hunting for. So we are looking to, in monotherapy, dose escalate and explore to try and find what is the right dose to expand on the exciting pharmacodynamic findings that we've seen so far and hopefully see evidence of tumor shrinkage. At the same time, You mentioned, you know, are we also thinking about combination therapy? And the answer to that is yes. We will be moving forward and stay tuned on that discussion with an approach where we're going to study both monotherapy and combination therapy in the clinic in 2022.
spk01: Just another question I want to sneak in. On low-risk MDS, what's kind of the update there? I know it was an investigative trial, but just kind of what's going on with that? I thought it was a pretty interesting trial.
spk05: Yeah, it's a really interesting trial. As I mentioned in my comments, it's just because it's an IST, we don't have a whole lot of visibility to that. My expectation is I know that Dr. Platzbecker, who's, you know, he's the European lead in MDS. He's the head of the EHA working group on MDS. He's got 17 sites in that study. So my hope is, and I say it's a hope. I can't promise, of course, since we don't run it. But my hope would be that we'll have data from that study at some point this year. But having a small molecule with our safety profile that's disease-modifying to use in that setting is something that obviously not just we're excited about, but obviously Dr. Plotzbecker and his team are very excited about as well. So we look forward to hopefully seeing results from that study later this year.
spk01: That's very helpful. Thanks.
spk05: Yep.
spk01: Thank you, Cross. Thank you very much.
spk05: Thank you, Alethea.
spk06: The next question is from Ed White with HC Wainwright. Please go ahead.
spk04: Good afternoon. Thanks for taking my question. So just to dive down a little bit more in AML, as you said, you have a clarity of endpoints. How should we be thinking about the size of the study that you need? And when you can start enrolling after you talk to the FDA, would you be able to start by the end of this year or is it a next year event? And then knowing what you know now about the pandemic, we've been dealing with it for two years, just wanted to get your thoughts on what you think enrollment trends could be. How fast could you get the trial enrolled? Thanks. Okay.
spk05: Maybe I'll ask Bob to talk about the size of the study first. Bob?
spk09: Yeah, so sure the, you know, again, we can look at historical precedents in the studies that Jim and I mentioned that achieved approval with single arm studies. They all enrolled somewhere between 100 and 200 patients, you know, given the very poor outcome in this population. You know, we could explore even lower numbers, but, you know, probably somewhere in that range for a trial that could achieve approval. You know, what we're hoping to do is, and we'll discuss this aspect with the FDA as well in terms of the study enrollment, you know, considering potentially expanding our current trial. So patients that we've already enrolled onto the trial, you know, we'll capture the data that would be relevant there and then continue potentially enrolling that versus starting a new study. So those are a couple of options that we would discuss with the FDA.
spk05: Yeah, and so, Ed, I would echo what Bob said, and especially when you look at the other studies that have been done historically, bear in mind that The survival, once you're post-HMA in this setting, is two to six months. Post-HMA, specifically, median survival is 2.3 months, which is crazy. So we would expect that given the efficacy we've seen so far, even though it's a small end, so it's kind of hard to talk about powering a study for statistical purposes, it seems reasonable to say that we would be in the range of other studies that have gone after pivotal design in AML. Whether or not we can start in 2022 or 2023 is going to depend a little bit on the design that FDA accepts. Of course, what we would hope for is a single-arm study, in which case we're ready to go now. We've already been testing patients on single-arm. And so, of course, we would leverage those data and just keep steaming forward with the existing sites and recruiting from those and adding new ones. If, on the other hand, of course, the FDA comes back and says they want a controlled study, that's, you know, now you've got to get that protocol out, and now you're talking more of a 2023 start. But our hope would be that they'll follow precedent and go with a single-arm study. And then the last question you had about how fast could it enroll, you know, we've been really pleased at the rate of enrollment. I think it's the consequence of the unfortunate fact that survival is so grim for these patients. And the reason why survival is so grim is that nothing works. The number one genetic driver of disease in AML and MDS is IRAC4 long expression. And I think part of the reason why survival is so grim is that none of the treatments out there address that driver. 4948, now Emma Vucerta, does. So our hope would be that the excitement we've seen among the investigators so far would continue as we add more sites into the pivotal study. Is that helpful, Ed?
spk04: Yep. Thanks, Jim. And just one last question on that regarding the discussion with the FDA. Do you have all the data in hand now? to speak with the FDA that you want, or is there any delay as you are awaiting more data?
spk05: No, there's no delay. It is an ongoing study, so we're going to continue to have more data in hand with every day and week that progresses. I think our timeline is unchanged. We expect to have a discussion with FDA in Q2. That's what we're certainly going to ask for. We can't control when they schedule it, but we believe we'll have sufficient data to ask for that meeting, and we think it'll be a good discussion. But in terms of how much data we have at any given point, the study is ongoing, so we continue to enroll through the process. And our hope would be, if it's a single-arm study, as we've been enrolling patients the whole time, we'll just keep adding those patients into the pivotal group so that we could get to the NDA timeline that much more quickly. That would be our hope, of course.
spk04: Great. Thanks for taking my question. Sure. Thanks, Ed.
spk06: The next question is from Yale Jen with Laidlaw & Company. Please go ahead.
spk07: Good afternoon, and thanks for taking my questions. I'm just going to tackle on the earlier question in terms of the FDA meetings. In terms of the patient, do you see, by the time you talk to the FDA, do you have sufficient MDS versus AML patients, or how do you see that? And the second question to that is that what do you anticipate the ultimate sort of follow-up FDA will require you to assess for the duration of response? Would that be roughly 12 months, whether that would be for the current study or for the future studies?
spk05: Yeah, so let me address the first one, and I'll ask Bob to talk to the second one in duration. Thanks, Yael, for calling in. So about the number of patients for AML and MDS, in both cases, to be frank, the patient sample size is small. You know, we already made the data public in the first week of January. No matter how we slice it, we're going to have a small data set when we go talk to FDA. Is that enough patients for FDA's purposes? We'll find out when we have the discussion. We think so. We think that the data are clear, that the drug is active, it's active as a single agent, and it's active in a population where nothing else works. I think that's a strong fact pattern to take to the FDA. Now, will we have more patients over time? Of course. That's exactly why we want to go talk to them. We think this drug merits a pivotal study. And we're willing to put the resources to work to increase the patient size to be able to demonstrate whether or not this really does merit approval. So that's the point of the discussion. Whether or not they differentiate how many patients we need for AML versus MDS, that's not clear. We'll find out over time. As I said in response to Alethea's question, I think the points that everyone agrees on are that there seems to be a really clear discussion for AML. There's clarity in the endpoint, and there's clarity that our data look really good in that endpoint compared to existing therapies. In MDS, everybody's excited about how our data look compared to existing therapy, but there's not a whole lot of clarity on endpoint. And so I think those will be the key items for discussion with FDA. Bob, could you answer the follow-up on duration?
spk09: Yeah. So I think what you're asking is how long after we enroll, you know, X number of patients do we need to wait, you know, to get the duration of response for the FDA. And so that really depends on ultimately the number of patients getting to a certain endpoint. And oftentimes, you know, in previous labels, the FDA has used kind of a six-month timeframe for that, kind of looking for a certain number of patients to get beyond that point or to, you know, have an event such as progression. So we would, you know, we would monitor those patients and the total number of patients that we enroll may actually be large enough such that we you know, hit that point even sooner than six months from the last patient's enrolled. So that'll be ultimately, you know, determined by our signal and the timing of the study.
spk07: Okay, great. Maybe just one more question here regarding the VISTA. You started potentially starting the efficacy study later on this year. Is that the sort of tumor... So there is a cold tumor and any impact at this point, or you probably will take all comers.
spk05: Yeah, actually.
spk09: Yeah, we definitely like to enrich the patient population. So there's certain tumors that have relatively high expression of VISTA. So, you know, in discussing with our investigators, we certainly encourage them to consider putting their patients that have those profiles onto the study. So for example, patients with mesothelioma have extremely high expression of VISTA. Several of the gynecologic malignancies have extremely high expression of VISTA, such as ovarian or uterine cancer. Subsets of non-small cell lung cancer and triple negative breast also have very high levels of VISTA. You asked, you know, of hot versus cold, so certainly, In our preclinical models, certain hot tumors are quite responsive to this drug, but also we've had some clear evidence that this antibody or targeting VISTA in general can overcome some of the issues, for example, bringing a cold tumor into a, basically lowering the threshold for activation of the immune system. perhaps bringing cold tumors into a hot tumor setting.
spk07: Okay, great. Go ahead. I'm sorry.
spk05: Go ahead. Go ahead, Bob.
spk09: No, please go ahead.
spk05: So I would add to that a little bit. I'd say that, you know, in VISTA, to be fair, this is part of the challenge and also the exciting part of going after a novel target. We know that in the Cancer Genome Atlas, there are certain indications, as Bob mentioned, that are associated with high VISTA expression. They're clearly correlated with high VISTA expression. We don't know if it's correlation or causation. We're clearly going to try to enrich for those patients and all the indications Bob mentioned, and hopefully we'll see efficacy in monotherapy in those patients, but we don't know. That'll be part of the exploration. Is VISTA a target where knocking it down in monotherapy is sufficient in certain indications? But we also want to pursue combination therapy. You've seen our preclinical data set and it seems to be tremendously synergistic with PD-1 and CTLA-4 for all the reasons that the literature suggests. It's just never been tested in patients before. I think the idea that we are hitting the target and the target's having effect is suggested by not just the CRS symptoms that we have seen, but also by the PD data that we have published in patients. And I think as we increase drug concentrations both in monotherapy and targeted indications and also in combination, we hope to see that the findings that we saw in the lab show up in the clinic as well. But that's, as I say, that's part of the fun of pursuing a new target that no one's ever gone after before. So stay tuned.
spk07: Well, thanks a lot, and please enjoy it. Sure.
spk06: Thanks, Yale. The next question is from Samat Roy with Jones Trading. Please go ahead. Hi.
spk03: This is Dania for Samat Roy. Thank you for taking our questions and congrats on the updates. I would first like to ask about the AML-MDS trials. Do you expect that with the clinical hold for the anti-CD47 agents, are you expecting any specific uptakes from the AML-MDS patients, especially for high-risk MDS?
spk05: Sure. So I think the biggest issue With Megrolimab going on hold, yeah, all things being equal, anybody else that's got a study going in AML and MDS, those patients need to go somewhere. So all other trials and study would benefit in enrollment, all things being equal. I would think the bigger question for us when a physician considers which trial to go into, is it a Megrolimab combination study or is it an emavucirtib combination study, they want to think about what's the best thing for patients. Now there's clearly a larger data set for migrolimab than there is for emavucirtib. But both patients were studied in monotherapy. And you may remember that the monotherapy data for migrolimab didn't look anywhere near as good as the monotherapy data for emavucirtib. So I think our conversations with the physicians are more about if you're going to combine a drug with azacitidine, which drug do you want to combine with? And we think we've got a pretty compelling case that the drug you want to choose in that case is emfucirtin, whether they're on clinical hold or not. So yeah, all things being equal, I think that should help other drugs that are being studied in the space. But I think for us in particular, having the only drug in the clinic that targets the driver of disease, or at least the largest driver of disease, is really the more important factor.
spk03: Makes sense. And as for the 8993, would you be collecting baseline VISTA status? Are we going to see stratification in the next update, the expression level?
spk05: Yeah, actually, Bob, do you want to talk to that?
spk03: Yeah, we're capturing a lot of aspects, including...
spk09: baseline information from patients, although to be clear, we're not selecting patients specifically for HyVista, but we'll be monitoring that and ultimately correlating that as well as other markers with HyVista. So, as you saw, some of the data that we presented in January, we have a pretty robust, you know, biologic and pharmacodynamic program going on for that molecule, and we think that that's going to... you know, provide a great perspective on VISTA in general as a target, and in specific that 8993 is an excellent agent there that, you know, has not only great PK exposure, but more importantly, in patients, we're already seeing really dramatic pharmacodynamic effects that really affect anti-cancer mechanisms directly. So, you know, we're really excited about our pharmacodynamic and biologic profile of this drug. for our patients.
spk03: Great. Looking forward to the updates. Thank you.
spk06: Thank you very much. Again, if you have a question, then one. The next question is from Dane Leone with Raymond James. Please go ahead. Hi, guys.
spk08: Thanks for taking the question. Any color you can give in terms of how you view the cadence of enrollment continued enrollment for 4948 and what that provides you with in terms of a line at site for setting expectations for clinical updates on the spliceosome cohort this year and then when we could get first data out to maybe the combination studies and just any color again on if the clinical hold on mcgrollamab might accelerate potential enrollment into the combination studies with veneza and what your general cadence of enrollment is expected or how that's been going so far thank you sure thanks dane and thanks for joining the call um
spk05: So I think my comments on Mgrulamab and the impact on their clinical hold on our enrollment pace, I think I answered a few minutes ago. As I said, I think all things being equal, the halt of the Mgrulamab study should help us and anybody else that wants to run a clinical study in AML and MDS. I think the bigger factor, though, for us versus migrolimab is going to be what's best for the patient. And if you have two studies to choose from as a clinician, as an investigator, to combine with azazitidine, which drug do you pick? Do you put them in a study that combines it with migrolimab or a study that combines it with emofusertib, formerly 4948? I think we can make a very strong case that you want to put it in azazitidine plus emofusertib. based on the single agent activity that we showed versus Megrolimab. But that said, I think you're right. All things being equal, the clinical hold should be helpful for us. We've seen a really exciting uptick in enrollment. You may remember that we had two spliceosome patients a year ago. We had three at EHA in June. And for the January update, we had 13. So we're seeing a fairly dramatic uptick of physicians that are finding these patients and wanting to put them onto our study. So my hope is that we can maintain that kind of excitement level and that we will be producing data that we can report out on later this year on a whole host of fronts. So we've got monotherapy data with spliceosome patients in AML, spliceosome patients in MDS, FLT3 patients in AML, combination therapy data with emavucirtib and azacitidine, also emavucirtib plus venetoclax. We've got the IST going in low-risk or lower-risk MDS. And we've also got combination with ibrutinib data. So we've got a whole host of clinical activity going on simultaneously. And my hope is that we're going to have a raft of data across the board. And my hope would be, of course, that it will be just as exciting in 2022 as it was in 2021.
spk08: Just one follow-up on that. So the enrollment into the FEN and AZA combination cohorts, are not selected patients, right? So that's an all-comers regardless of mutational status?
spk05: That's right. So they're all-comers. But, of course, what we would look to do is replicate the experience that we had preclinically, which is preclinically we showed terrific synergy or at least terrific additive effect that the patients who were going to go on azacitidine or venetoclax or the doublet, for that matter, preclinically, in all three cases, the data were significantly more compelling when you added imoblucertib to it, whether it was venetoclax monotherapy, azazitidine monotherapy, or the doublet. So what we're looking to do in the clinic is replicate that. We want to get combination with venetoclax, combination with azazitidine, and then assuming that that goes well, we'd love to pursue a triplet as well.
spk08: And Can you give an update on how many patients you've enrolled into the combination arms?
spk05: We haven't given an update on that yet, but that will be part of the update that we're going to give later this year.
spk08: Okay. All right. Thanks.
spk05: Thank you.
spk06: This concludes our question and answer session. I would like to turn the conference back over to the company's president and chief executive officer, James Denser, for any closing remarks.
spk05: Thank you, Gary, and thank you, everyone, for participating in today's call. And as always, thank you to the patients and families participating in our clinical trials, to our team at QRIS for their hard work and commitment, and to our partners at Origen, Immunext, and the NCI for their ongoing help and support. We look forward to updating you again soon. Operator?
spk06: The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.
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