Curis, Inc. (CRIS) Earnings Call Transcript & Summary

Good afternoon, and welcome to Curis TakeAim Leukemia Data Update Call. [Operator Instructions] 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 investors' 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 uncertainties, 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. T

Thanks, Diantha. Good afternoon, everyone, and welcome to Curis' TakeAim Leukemia Data 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 milligrams BID. Today we're reporting data for 25 new patients, expanding our total AML data set from 5 to 30 patients. Let's start with the splicing factor data. In July 2023, we disclosed data from 3 patients with relapsed/refractory AML with 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 4 of these 18 patients have achieved an objective response, one complete remission, or CR, 2 CRs with partial hematologic recovery or CRh and 1 morphologic leukemia-free state or MLFS. An additional 3 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 0. 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 3 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 shows 6 objective responses in these 11 patients, 3 CRs, 1 CRh and 2 MLFS. Of interest, all 3 of the patients who are naive to prior FLT3 treatment achieved objective responses. Even more encouraging, 3 of the 8 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 in 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 ema ven aza 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. [Operator Instructions] Your first question comes from the line of Bilal Jahangiri from Truist Securities.

I have a couple of questions. Is it fair to compare the 100% ORR and 66% CR/CRh rate in the 3 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?

Bill, this is Jim. Thank you for calling in, and thanks for the question. So I want to be careful to compare directly small data sets 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 the study where 87% of the patients were FLT3 naive. When we look at our study, only 3 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 preclinic, 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 data or what gilteritinib 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 were getting in naive patients. So 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.

The next question is from the line of Li Watsek from Cantor Fitzgerald.

Just a couple here. Maybe just comment a little bit on the duration of response that you've seen? And then for the 3 patients that are not response-evaluable, maybe just to expand a little bit on the reasons?

Yes. 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 could 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 3 patients who haven't yet achieved a response?

I think your question was actually the patients who are not response-evaluable -- so typically, patients who come on to the 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 -- the 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 neutrophils improvement, things like that. And as we mentioned in our press release, infection and sepsis is one of the top causes of death in these patients. And 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 an important parameter 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 spices on mutated cohort. Just wondering, will you think the FDA 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?

Actually, Bob, would you like to take a shot at that one first.

Yes. So that's a great question. I mean, ultimately, this would come down to a 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 precedents, 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.

Yes, 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 [ Hu ], 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 2 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 2 interesting dialogues to have with FDA. One, the traditional one on surrogate end duration and then the other one, simply on survival.

Could I add also -- 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 and we see that as a very good sort of lead into our other combination trial that Jim mentioned earlier.

Your next question is from the line of Ed White from H.C. Wainwright.

I might have missed this, but I was just wondering if you can tell us about the 2 patients that had the dual mutation FLT3 and [ NSF ].

Sure. So yes, you're exactly right. There were 2 patients in the population out of 30 that had dual mutation. Dual mutations are rare, a patient who has both the FLT3 and the splicing factor mutation. We did see one in the first data set, and we saw a second one in this new data set. 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 the -- did they respond?

So we haven't gone into the detail on a patient-by-patient basis. I think we're going to have more detail on the poster 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 is -- 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.

And on the -- 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?