Good afternoon and welcome to Curis' TakeAim Leukemia Data Update 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 the number one on your touch-tone phone. To withdraw your question, please press star then the number two. Please note this event is being recorded. I would now like to turn the conference over to Diantha Duvall, Curis' Chief Financial Officer. Diantha, please go ahead. Thank you, and welcome to the Curis TakeAim Leukemia Data Update Call. Before we begin, I would like to encourage everyone to go to the investor section of our website at www.curis.com to find the press release titled "Curis Announces Additional Data from Patients with Target Mutations in the TakeAim Leukemia Study." I would also like to remind everyone that during the call we will be making forward-looking statements, which are based upon our current expectations and beliefs. These statements are subject to certain risks and uncertainty, and actual results may differ materially. For additional details, please see our SEC filings. Joining me on today's call are Jim Dentzer, President and Chief Executive Officer, and Dr. Bob Martell, Chief Scientific Officer. We will also be available for a question-and-answer session at the end of the call. I'd like to now turn the call over to Jim. Thanks, Diantha. Good afternoon, everyone, and welcome to Curis' TakeAim Leukemia Update Call. As you saw in the press release we issued 30 minutes ago, we're pleased to announce updated data from our TakeAim Leukemia Study for relapsed refractory AML patients with a FLT3 or splicing factor mutation. This is an ongoing phase I/II study evaluating emavusertib as a monotherapy at the recommended phase II dose of 300 mg b.i.d. Today we're reporting data for 25 new patients, expanding our total AML dataset from five to 30 patients. Let's start with the splicing factor data. In July 2023, we disclosed data from three patients with relapsed refractory AML with a U2AF1 or SF3B1 mutation. In today's update, we're reporting data for 20 patients with a splicing factor mutation, 18 of whom are response evaluable. Preliminary data show four of these 18 patients have achieved an objective response: one complete remission, or CR, two CRs with partial hematologic recovery, or CRh, and one morphologic leukemia-free state, or MLFS. An additional three patients are ongoing and have shown increases in neutrophils, an important measurement for assessing the effectiveness of an AML therapy. We're especially encouraged by these data given the grim prognosis facing AML patients with a splicing factor mutation. From the moment they're diagnosed, their expectation for survival is on median only a few months. There are no approved therapies, and currently available treatments are ineffective. The only study published for relapsed refractory patients with a splicing factor mutation was for patients treated with the combination of azacitidine and venetoclax. This combination is a standard of care in the frontline setting, but when it was studied in relapsed refractory patients with a splicing factor mutation, the response rate was zero. We believe the reason emavusertib is outperforming that benchmark is because emavusertib blocks IRAK4, a key driver of disease in AML that is especially impactful in patients with a splicing factor mutation and which is not addressed by either azacitidine or venetoclax. Now let's turn to the FLT3 data. In July 2023, we disclosed data from three patients with relapsed refractory AML with a FLT3 mutation. In today's update, we're reporting on 12 patients with a FLT3 mutation, 11 of whom are response evaluable. Preliminary data show six objective responses in these 11 patients: three CRs, one CRh, and two MLFS. Of interest, all three of the patients who were naive to prior FLT3 treatment achieved objective responses. Even more encouraging, three of the eight patients who had progressed on or following prior treatment with a FLT3 inhibitor were able to achieve objective responses when treated with emavusertib. The benchmark for FLT3 inhibition is currently gilteritinib, which in its FDA label shows a 21% CR/CRh rate in relapsed refractory patients. This is despite the fact that most of the patients in that study had never been treated with a FLT3 inhibitor before. We believe the reason emavusertib is outperforming that benchmark, even though most of the patients in our study had been previously treated with a FLT3 inhibitor and progressed, is because emavusertib blocks both FLT3 and IRAK4, the escape mechanism for FLT3 inhibition. Emavusertib's activity is consistent with its molecular design and consistent with what we saw in the lab. We're encouraged to see emavusertib continue to demonstrate its potential to be the best-in-class therapy for AML patients with a FLT3 mutation. In summary, we're very pleased with the progress emavusertib has made in the 10 months since the FDA's partial clinical hold was removed. The study has enrolled more quickly than expected, and emavusertib continues to outperform the benchmarks for monotherapy in relapsed refractory AML, even in the most challenging patient populations and in patients who have progressed following treatment with venetoclax and HMA. The anticancer activity we're seeing in our monotherapy studies is both exciting on its own and exciting for the signal it represents as we begin our frontline triplet study. We know IRAK4 is an important target in AML, and we know that neither venetoclax nor azacitidine addresses it. So the logical next step is to explore the emavusertib triplet and its potential to establish a new benchmark for frontline therapy in all comers in AML. We look forward to sharing initial safety data from that study with you later this year. With that, I'd like to open the call for questions. Operator? Thank you, ladies and gentlemen. We will now begin the question-and-answer session. Should you have a question, please press star followed by the number one on your touch-tone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press star followed by the number two. If you are using a speakerphone, please lift the handset before pressing any keys. Your first question comes from the line of Bilal Janggiri from Truist Securities. Your line is now open. Hi guys, congrats on the data. I have a couple questions. Is it fair to compare the 100% ORR and 66% CR/CRh rate in the FLT3 naive patients to the 21% benchmark in gilteritinib directly? And then I was wondering if you saw any more patients convert from an MLFS into a CR or CRh. Thanks. Hi Bill, this is Jim. Thank you for calling in and thanks for the question. So I want to be careful to compare directly small datasets that aren't in the same study. I think what is fair is to understand the context in which the patient populations are sitting where the drugs are addressed. In the case of gilteritinib, that 21% CR/CRh rate, that was in a study where 87% of the patients were FLT3 naive. When we look at our study, only three of the patients were FLT3 naive, and we saw responses in all of them. Now, I'm not going to suggest that we're going to get a 100% response rate in all patients that are FLT3 naive. Of course not. What I am going to suggest is that we expected, given the mechanism of action for emavusertib and the data that we saw in the preclinical, we do believe that emavusertib has the potential to be best-in-class. And the limited data we have so far support that thesis. In the naive patient population, which is where gilteritinib's data or what gilteritinib's data represent, in that population we appear to be competitive and with the potential to be best-in-class. And then when we look at the patients who went on a FLT3 and progressed, well, those are patients who shouldn't be responding, and yet we're getting better data in that population than the FLT3 inhibitors we're getting in naive patients. I would say we're always a little cautious in early data and comparing data from multiple studies, but I would say these data are a pretty powerful next step in supporting the thesis that this could be the best-in-class therapy for these patients. Thank you. Yep. Any other questions? Next question from you both? Oh, sorry. I'm sorry. Thank you. Next question is from the line of Li Watsek from Cantor Fitzgerald. Please go ahead. Hey, thank you for taking our questions. Just a couple here. Maybe just a comment a little bit on the duration of response that you've seen. Then for the three patients that are not response evaluable, maybe just expand a little bit on the reasons. Yeah, why don't I take the first one, and I'll ask Bob to chime in on the second one. On the duration of response, I think, I mean, to be honest, it's a little too soon to talk about duration. So we just got off hold 10 months ago, got our sites up and running, got these patients enrolled, and I mean, we're thrilled that we're already seeing a signal in responses. But I think we need to follow these patients for a longer period of time before we can have a discussion on where the duration sits and especially where it sits within the context of other available therapies. But I'd say for now, we are seeing what we'd like to see. Bob, would you like to comment on the three patients who haven't yet achieved a response? Bob, you may be on mute. Yes, I was. Sorry. That's all right. So I think your question was actually the patients who are not response evaluable. So typically, patients who come on to study in order to be response evaluable, they need a baseline evaluation as well as an on-study evaluation. And so those patients did not achieve that for various reasons. And reasons could include progressive disease or coming off study for some other reason. It's difficult to tell for sure. That's why we highlight the overall number of patients as well as the subset of patients who actually did have responses. We also note several patients who, as Jim mentioned, this is an ongoing study in several patients who have not achieved a response at this point but are continuing on study and showing signs of clinical improvement such as neutrophil improvement, things like that. As we mentioned in our press release, infection and sepsis is one of the top causes of death in these patients. So we see this maybe not as a specific direct endpoint per se, but as we're thinking about looking forward to future studies, in fact, pivotal studies with survival as the endpoint, these could be important parameters to help give us a view as to the broader benefit of the drug across the patient population since improving neutrophil counts reduces risk for developing sepsis and infection. And then just another question for the splicing factor mutated cohort. Just wondering, do you think the FDA's regulatory bar for the CR/CRh might be in this population? Do you think the benchmark here is 0% like you alluded to earlier or maybe around 10% as we've seen with other AML studies but with other mutations? And then in terms of the next steps for the regulatory steps, maybe just remind us what are you going to do? Yeah, actually, Bob, would you like to take a shot at that one first? Yeah, so that's a great question. I mean, ultimately, this would come down to discussion with the FDA. I'd like to sort of point out a couple of aspects of this. One is the striking single-agent activity of the drug where we're achieving some of these responses despite prior HMA and prior venetoclax. This has been very impressive. If we think about the prior precedence, we see that oftentimes the FDA looks at the response rate, but they also look at the lower bound of the confidence interval. We believe that in a population where the response rate published so far is really 0%, having a lower bound above 10% is not unreasonable. But obviously, that is something that we need to discuss with the agency. Yeah, I'd like to expand on that as well. Thank you, Li, for the question. So I would say first, the traditional design in AML where you look at an endpoint, you follow the patients, you look at duration, and to see how that compares is certainly a valid approach and a valid path worth exploring with FDA. There may be another one in this population. And when we think about the patients with a splicing factor mutation, one of the reasons why it's not just no drugs work, but there really aren't any studies in this population is because the patients, frankly, don't live long enough to be studied. There was a really interesting paper in Oncotarget by WHO where they described that the prognosis for survival for patients once they're diagnosed with AML, if they don't have a splicing factor mutation, their expectation on median is 29 months, about 2.5 years. If the patients do have a splicing factor mutation, that 29 months drops to two months. Once the patients are diagnosed, they have to go through frontline therapy. As you can imagine, the clock is ticking. There's not a whole lot of time once they've gone through frontline therapy and progressed for anything to work or, frankly, for that population to be studied. So one opportunity to have a discussion with the FDA about path is, of course, the traditional one, which is more surrogate endpoint-driven and duration-driven. But another one might be survival. To Bob's point, this is the first time that a single agent has shown activity in this population. I mean, we're getting decreased blast counts, increased heme counts. We're getting CRs. But most importantly, patients are staying alive and on study. That could be something of real interest with the agency. I don't want to commit to anything, of course, because that's something that we need to have a conversation about. But I think in this population, unlike FLT3 or any other subpopulation within the landscape of AML, there may be two interesting dialogues to have with FDA. One, the traditional one on surrogate and duration, and then the other one simply on survival. Can I add also that I think a really important aspect of this is single-agent activity by itself is, in my view, very predictive, ultimately, of potential for combination efficacy. We see that as a very good sort of lead into our other combination trial that Jim mentioned earlier. Thank you, Li. Do you have any other questions? Your next question is from the line of Ed White from H.C. Wainwright. Please go ahead. Hi, can you hear me okay? We can. Hi, Ed. Hi, Jim. I might have missed this, but I was just wondering if you can tell us about the two patients that had the dual mutation, FLT3 and SF? Sure. So yeah, you're exactly right. There were two patients in the population out of 30 that had dual mutation. Dual mutations are rare. A patient who has both a FLT3 and a splicing factor mutation. We did see one in the first dataset, and we saw a second one in this new dataset. So what would you like to know about them exactly? Their prognosis is, as you can imagine, tough because they have the splicing factor mutation. I was just wondering, did they respond? Oh, so we haven't gone into detail on a patient-by-patient basis. I think we're going to have more detail on the post hoc when we get to the conferences. But I would suggest, just as a frame of reference, that patients with a splicing factor mutation, no matter what other mutations they have, FLT3, RUNX1, whatever that might be, their prognosis, it's going to be pretty tough. But we will be very interested in having a more detailed discussion when the posters come out at ASCO and EHA. Okay. Thanks. Okay. Yeah, thank you. One quick question on the data you gave us some data on patients that had MLFS response. Is that really a response that the FDA is interested in? Don't they typically focus on CR/CRh? I'm just trying to think of how we should be viewing these patients that responded like that. Or are you thinking that they could turn to CR or CRh responses? Yeah, Bob's probably the best person to talk to that one. Bob? Yeah. So well, MLFS is basically a complete normalization of the malignant blast count in the bone marrow. So on the surface, it's a very strong sign of anti-cancer activity. In fact, the loss of the visible excessive blast in the bone marrow. And it's recognized as part of guidelines for AML. In terms of the FDA, so the FDA is obviously they've traditionally used CR and CRh, but clearly, they're interested in other endpoints as standalone endpoints such as minimal residual disease, MRD, and potentially MLFS. One of the things I think that's extremely important here, and it's the same point that I made about the neutrophil count, and that is that this is a clear sign of sort of anti-cancer activity. As that relates to thinking about our broader studies that ultimately go towards survival, demonstrating that we can control the cancer in this way is, I think, a good predictor of potential outcomes for future long-term survival studies. Yeah. And I would add to that, Ed, the way we think about MLFS is really twofold. To Bob's point, it's an indicator that the drug's working because what our drug does, as you can imagine, in AML, what's happening is the bone marrow is packed with malignant blasts, and that's crowding out the body's ability to generate the neutrophils and platelets that it needs. So the first step is, of course, to address the blasts. And that's what our drug does. It reduces the blast count in the bone marrow. And then if the bone marrow is healthy enough, we hope to see it, of course, recover the capability to generate neutrophils and platelets. But step one in that process is you see the blast counts drop, hopefully all the way to achieve MLFS. So as you started your question, is that an indicator that the patients are on their way to CRh, CRi, or full CR? And I would suggest that in the time course of events, yeah, it's a necessary precursor. We have no guarantee that they'll continue to get on that road towards CRh or full CR. But that is, of course, where they would start heading as they're going in a good direction. And then the second point to Bob's comment, simply addressing the cancer in these patients is the whole point of the drug. And that is a really important sign for us. We've got very clear, very strong single-agent activity. And we think in certain patient populations, single-agent activity is enough. It certainly seems to be compelling compared to other therapies that are out there. It's even more compelling when we think about going frontline. Knowing what we're seeing in the single-agent activity tells us IRAK4 is an important target, that we're hitting it. And since we know frontline therapy doesn't do that, we should see in the clinic what we saw in the lab, which was synergy with AZA and VEN. And that could potentially establish a new benchmark. That's why we've just started that study, and these data reinforce our optimism. Okay. Thanks, Jim. Thanks, Bob. You bet. Thanks, Ed. Your next question is from the line of Soumit Roy from Jones Research. Please go ahead. Hi, everyone. Jim, if I may get a little bit of broad color from the strategic point of view, would you be pushing forward in the relapsed refractory setting, FLT3, or splicing factor mutation, even if FDA gives some kind of guideline? Or would you conserve resources and focus purely on the frontline, AZA, VEN, emavusertib, triple combo? Yeah, it's a great question. Thank you, Soumit. So I'd say first and foremost, we need to have a dataset ready to go talk to FDA. And as you've heard us say in the past, we believe roughly 20 patients is the right-sized dataset to go have that conversation. So we think as we get those patients and we go to the FDA, in the case of FLT3, a monotherapy path would likely involve a CR/CRh endpoint with some element of duration, of course. And I would say today, we're not quite at that 20-patient bar, but we're getting close, and the data are supportive of that path. In the splicing factor, I think we've got 20 patients. We need to keep following them. We've got eight patients ongoing at the data cutoff. We need to follow them and see how they do. But we may have the very first drug that works in that setting. And as I said earlier, in response to Li's question, there may be two paths available in that setting. We need to have a conversation with FDA. In the background, we have the frontline study started. So we certainly need to understand what is the most capital-efficient path for the company. But we also want to make sure that we have a drug with a novel target that we think has the potential to really change the game for patients with AML. And I look forward to having a dialogue with FDA and trying to work through what is the best path forward of these three paths: monotherapy, FLT3, monotherapy, splicing factor, and, of course, frontline in all comers. If you decide to still move forward on a splicing factor angle, you would have to develop a compelling diagnostic. With a larger dataset of like 80-100 patients, your response rate is probably going to pull back further. Thinking through that, you still want to go ahead on that? Yeah, I think that's clearly one of the considerations that we're going to have as we go through that process with FDA. You're exactly right. Nobody's addressed this population before, so there isn't an approved companion diagnostic for splicing factor patients. There are gene panels that look for these mutations, and they're standard: the FoundationOne panel, the Illumina panel. Places like MD Anderson have proprietary panels. But we would have to have a discussion with FDA that talked about, "We seem to have a drug that is active in this population." If that means we need to have a companion diagnostic, which is extra time and cost, that's going to have to be part of the calculus in figuring out, from a Curis perspective, what makes the most sense in addressing that population with a new therapeutic. Okay. A little bit of a question, a few questions on the data itself. Could you give us maybe some sense on the baseline blast percent, where this started, or at least a range, and why more patients are not undergoing stem cell transplantation, the CR patients, and the sick? Yeah, probably. I'm sorry, Soumit. Go ahead. Sorry. One last question is, the kinetics of the blast reduction, do you expect you would see further deepening except for one or two patients? This is pretty much it, the response rate. Yeah, thank you. Actually, Bob's probably the best person to answer that one. Bob? Well, thanks, Soumit, for those great questions. So the blast count of baseline, by definition, for AML, that needs to be above 20%. And so these patients had blast counts in the range of 20 up to I don't know what the highest was. I think it was in the range of 80 or so. So very high percentage blast. As Jim mentioned, many of these, if not most of the patients, their bone marrow was full of blast. And so the reduction that we see is pretty striking. Now, for the FLT3 population, as we mentioned in the press release, these tended to occur very rapid drops in blast, which is quite impressive and very advantageous for those patients. Five out of the six responses were seen within the first 28 days of being on study on the first bone marrow evaluation. We've seen rapid drops as well in the splicing factor mutated disease in those patients as well. But as Jim mentioned, a number of those patients are still on. We have seen, over time, deepening of responses as well. We'll be giving more detailed data on those at the presentation itself. That's really helpful. Thank you and congrats on the data again. Excellent. Thank you, Soumit. Your next question comes from the line of Sean McCutcheon from Raymond James. Your line is now open. Hi, guys. Thanks for taking the questions. There's a couple on my end. First, what do you think the bar is post-FLT3 inhibitor? So in the Admiral Study, the CR rate post-FLT3 TKI was 19%, and they got a CRc rate of close to 50%, 48%. You're seeing a CRc rate of about three out of eight, and you're getting a two out of eight for the CR/CRh. So just curious what you're thinking in terms of what the bar will be post-FLT3 TKI, given that that's likely the initial approval setting. And then second, notice that a previously disclosed patient, the CR patient with an SRSF2 and a DNMT3A co-mutation, was previously listed in the ASH 2023 disclosure as one prior line of therapy. And it looks like in the abstract today in the table, it was listed as two prior lines of therapy. Just curious if you can provide some clarification on the baseline disposition of that patient. Thanks. Thanks, Sean. Thanks for calling in. I might ask Bob to take a first shot at that one, and then I've got some thoughts as well. Bob? Yeah. So I think, in general, for single-agent post-FLT3, we believe that a targeted response rate in the low 20%, in a single-arm study, is sufficient based on the precedence of gilteritinib and initial approval. I think the Admiral Study provides a little bit of a different context than this. So I think we'll wait to see, and we'll have this discussion with the agency. And again, would also project forward to subsequent combination studies as well. So not only in the mutated splicing factor population, but also in the FLT3 population, combinations is something that we'll be evaluating going forward. Yeah. And so I'd like to add to that too. So when we look at the data for gilteritinib and just to make sure that we're all looking at the same database, gilteritinib was approved on 138 patients. They got a CR in 16 of those patients, so an 11.6% CR rate. CRh rate was 9.4%. So the CR/CRh rate that led to the approval of gilteritinib was 21.0%, 29 CR/CRhs out of 138 patients. When they later did a follow-on to that study, that CR rate did increase from the 11.6%, I believe, to 14.2%. So there was a modest increase as they followed those patients for longer periods of time, just like our study, which is ongoing. If you follow those studies for a longer period of time, hopefully, some of those patients who had just started on drug or are already at MLFS will convert into CRs. So I expect we would see the same kind of thing. I think what we can say, without being overly aggressive about comparing data from different studies, is that the reason why our CR/CRh rate is higher than theirs, even though we're in, as I said, in response to an earlier question, even though we're in primarily patients who have failed prior FLT3 as opposed to naive patients, which is the case in the gilteritinib Admiral study, I would say it's because gilteritinib, like midostaurin, like quizartinib, they only hit FLT3. They're not hitting FLT3 and the escape mechanism. So I think there is clearly, I'd say, optimism on our part or encouragement on our part, based on the data we've seen to date, that if these data hold in larger datasets, we should get as friendly a reception from FDA as we're getting from our investigators, who are, of course, eager to put the patients onto our study. And we're glad that the patients seem to be responding. I hope that was helpful. Yeah, thanks. Just on that one patient that was, and correct me if I'm wrong if it's not the same patient, but a prior patient that was listed as one prior line of or one prior line of therapy. The abstract release today is listed as two prior lines of therapy, the SRSF2 patient. Yeah. Bob, do you want to speak to that patient? Well, actually, let me take that back. Let's be real careful, Bob, about responding on a patient-by-patient question because I know what's in the poster. So yeah, I think maybe, Sean, if that's all right, what I'd like to defer is detailed questions going on a patient-by-patient basis. And I don't want to risk incurring the ire of the organizers of ASCO and EHA. So I think I'm very happy talking about the summary of data that's being released. But of course, the detail that's going to show up in the poster is happy to take that question. But why don't we do that in Chicago when we're at ASCO or in Madrid at EHA, if that's okay? Yep, got it. Thanks, guys. Yeah, I think I just made my general counsel and my head of regulatory happy, or at least head of the conference is happy with that. Thank you. This concludes our question-and-answer session. I would now like to turn the conference back over to the company's President and Chief Executive Officer, Jim Dentzer, for any closing comments. Thank you, operator. As always, thank you to the patients and families participating in our clinical trials, to our team at Curis for their hard work and commitment, and to our partners at Aurigene and at the NCI for their ongoing help and support. We look forward to updating you again soon and hope to see all of you at ASCO and EHA. Thanks so much. Ladies and gentlemen, this concludes today's conference call. Thank you very much for your participation. You may now disconnect.