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

Thanks, everyone, and welcome to the business update call for Curis covering the first quarter of 2024. To start, I'd ask you all to visit the investor portion of our site, www.curis.com, where the press release for our Q1 2024 business update is posted along with the accompanying financial tables. I also want to note that forward-looking statements will be made on this call, and those reflect what we currently expect and believe. Such statements carry specific risks and uncertainties, and what actually happens could be materially different. For more on that, please refer to our SEC filings. With me on the call today are Jim Dentzer, our President and Chief Executive Officer, Bob Martell, our Chief Scientific Officer, and Jonathan Zung, our Chief Development Officer. A question and answer session will also be held at the end of the call. At this point, I'll hand things over to Jim.

Appreciate it, Diantha. Morning, everybody, and thanks for joining Curis's Q1 business update call. During this quarter, we achieved meaningful headway in moving emavusertib forward across our three main focus areas. To start, as a monotherapy for relapsed refractory AML patients who carry a FLT3 or splicing factor mutation, within our TakeAim Leukemia study. Then, as a doublet for relapsed refractory primary CNS lymphoma patients, pairing emavusertib with ibrutinib in our TakeAim Lymphoma study. And finally, as a triplet in frontline AML for all comers, no matter their mutation status, which combines emavusertib with azacitidine and venetoclax. This coming Tuesday, alongside the EHA conference's release of accepted abstracts, we anticipate giving a top-line update on clinical data from our TakeAim Leukemia study. In the past, we reported data on five patients, three carrying a FLT3 mutation and three carrying a splicing factor mutation, among them one patient with both a FLT3 and a splicing factor mutation, counted in both populations. Our update next week will cover data on 25 new patients, which raises the total to 30 relapsed refractory AML patients given emavusertib as a monotherapy. Mutation status across these patients breaks down as 12 with a FLT3 mutation and 20 with a splicing factor mutation, among them two patients with both a FLT3 and a splicing factor mutation, counted in both populations. We're eager to talk through the top-line data on these patients during an investor call once the data come out, with fuller presentations to follow at the ASCO and EHA medical conferences that dig deeper into emavusertib's potential to beat, as a single agent, the benchmarks set by current therapies in genetically targeted AML populations; within the relapsed refractory FLT3 population, the benchmark for FLT3 inhibition is gilteritinib, and its FDA label shows it can reach a 21% CR/CRh rate among patients who have failed frontline therapy. With emavusertib, our aim is to surpass that benchmark. We believe this is achievable, even with most patients in our study having failed earlier treatment with a FLT3 inhibitor. That's because, unlike current treatments, emavusertib goes after both FLT3 and IRAK4, which is the escape path for FLT3. This sits at the core of the molecule's design hypothesis and shows up in the preclinical data. Using the 12 patients we'll present at ASCO and EHA, we hope to lend further support to that hypothesis, specifically that emavusertib could set a new and best-in-class benchmark for the FLT3 AML population. Turning to the relapsed refractory splicing factor population, we see the benchmark is, sadly for these patients, much lower. No drugs are approved, expected survival is just a few months, and current treatments don't work. The sole published study for relapsed refractory AML patients with a splicing factor mutation involved patients treated with the Azaven doublet. That was a very small study of only five patients, and the response rate came in at zero. The fact that Azaven serves as the standard of care for frontline AML patients who can't receive intensive induction makes this particularly noteworthy. Our hope is that emavusertib's novel mechanism of action may demonstrate clear single-agent activity within this highly challenging population. Any result showing emavusertib surpassing the 0% benchmark established by Azaven would count as positive. Within our expanded data set, we will be examining reductions in blast counts, rises in neutrophils, increases in platelets, objective responses and, ultimately of course, prolonged survival. Turning now to our TakeAim Lymphoma study, we observe substantial progress on that front too. During the most recent ASH conference, we shared data covering five patients suffering from relapsed refractory primary CNS lymphoma who had previously failed treatment with a BTK inhibitor. We anticipate giving an update containing additional data before this year ends, in all likelihood at December's ASH conference. In the past, we stated that we anticipated reporting data covering 10 to 15 patients. Today we are glad to narrow that projection toward the upper portion of the range, since we now anticipate reporting data covering roughly 15 relapsed refractory primary CNS lymphoma patients who have previously failed treatment with a BTK inhibitor. We are likewise glad to disclose the advancement of our triplet study involving all comers in frontline AML. Enrollment has started, and we anticipate having preliminary safety data before this year ends. Once again, in all likelihood at December's ASH conference. The enthusiasm surrounding this frontline study comes from the novel targeting of IRAK4 and rests upon the obvious anticancer activity we observe in our monotherapy studies. We recognize that IRAK4 is a significant target in AML and that neither azacitidine nor venetoclax tackles it; therefore the sensible subsequent step involves investigating the ema-aza-ven triplet along with its capacity to set a fresh benchmark for frontline therapy among all comers in AML. To sum up, we feel encouraged by our progress throughout leukemia and lymphoma, and we anticipate reporting our updated leukemia data next week. Having said that, I'll hand the call back to Diantha so she can go over our financial results for the quarter. Diantha?

Thanks, Jim. Curis posted a net loss of $11.9 million for Q1 2024, which works out to $2.05 per share. That compares with a net loss of $11.6 million, or $2.39 per share, during the same quarter in 2023. R&D costs came to $9.6 million in the first quarter of 2024, versus $9.1 million a year earlier in 2023. Those higher research and development expenses largely stemmed from greater costs tied to employees. G&A expenses reached $4.9 million in Q1 2024, compared with $4.8 million for the equivalent period in 2023. As of March 31, 2024, cash, cash equivalents, and investments at Curis came to $40.7 million, with roughly 5.9 million shares of common stock outstanding. Our cash position remains solid, and we anticipate that the cash, cash equivalents, and investments we currently hold ought to let us keep our planned operations running into 2025. Having said that, I'd like to turn the call over to questions. Operator?

Hi everyone, and congrats on the advances you've made on several fronts. The presentation was genuinely, genuinely clear. A few questions regarding the data — the expected data coming next week. I'm not sure whether I missed this, but will you be showing results for both the FLT3 mutant group and the splicing mutants in the relapsed refractory setting? And what sort of specifics should we anticipate? Will you provide us solid specifics regarding baseline blast count levels, the percentage reduction, response rate, neutrophil recovery, and so on?

Hello, Soumit. Appreciate you being here; so yes, we will definitely be presenting data covering both the FLT3 and the splicing factor mutation populations. It's going to be a top line review of the data. Clearly, we have to be somewhat mindful of the conference. We can discuss the abstract, but naturally, we'll have to hold off until the poster is available before we can get into the more detailed discussion; so, we believe there's some exciting news coming next week. We're eager to talk about it, and we're eager to have those conversations at both ASCO and EHA at a level that's more detailed and granular.

That makes complete sense. For my final question, I'd like to ask about what lies ahead for patients with splicing mutations in the relapsed refractory setting. With the FLT3 group, the registration pathway seems considerably more straightforward, I believe. Regarding the splicing mutation, what's your strategy moving forward? Do you intend to create a companion diagnostic, or is that mutation already part of standard screening and therefore covered? Any insight would be appreciated.

Of course. Naturally, we have to talk things over with FDA. So I want to be cautious and note that what we're sharing reflects our own thinking, though ultimately it will hinge on how that FDA discussion unfolds. The trickiest element, I'd say, broadly speaking, as we consider how to design the trial, is that we must factor in the reality that no therapies are approved... Since none of them work. Ours is the initial agent demonstrating single agent activity within this group. So whether FDA seeks something along the lines of an objective response rate, or whether they're looking at survival, or whether a single arm study is what they want, or whether a comparison against another option would be required — those are all excellent questions, and we do have certain views about them, yet the answer truly rests on our conversation with FDA. So I'll need to refrain from answering that one for now. Should we proceed, and should we consider any newly identified genetically driven population, it seems reasonable to expect that a companion diagnostic will be necessary. Once more, the timing for that and the way it fits into a pivotal study will be determined by our discussion with FDA; but I'd suggest keeping an eye out.

Understood — and if I could fit in a final question, regarding the threshold to beat for relapsed refractory FLT3, you brought up gilteritinib having a CR rate around 21%, though those individuals hadn't been exposed to FLT3 drugs; so from our perspective, the hurdle was closer to an 11% to 12% response rate. Is that accurate, or are you creating a tough standard for yourselves?

Yes, honestly, Bob might be the ideal individual to address that. Bob, could you please chime in?

Yes, thank you, Jim. Sumit, I'm with you on that. The threshold for what we'd anticipate from a novel agent aimed at FLT3 in this setting, you know, ought to be considerably beneath 21%, since these individuals clearly have shown they're resistant to FLT3 inhibition. That is precisely the point where emavusertib becomes so essential, given that going after IRAK4 is crucial. As you're aware, the TLR pathway gets significantly upregulated once FLT3 is inhibited. Indeed, signaling through TLR via IRAK4 functions as a resistance mechanism, which is why we believe that despite a patient having developed resistance to FLT3 inhibition, this combination can rescue them. Regarding that 21%, we have no idea what hurdle the FDA is going to demand here; we put that forward as an earlier precedent, the approval of gilteritinib in a prior line of therapy; perhaps they'd be willing to take something below it. So that, as Jim pointed out, is going to call for certain conversations with them.

I appreciate you fielding all of these questions. I'm eager to see the data that comes out next week.

Thanks.

Hi there, morning. Nice work on the advances. I have a few things to ask. Will there be another dataset presented at the EHA conference beyond what appears in the abstract data cuts? Also, could you say something about whether MRD data is coming, and what the median follow-up will be?

Thanks, Lee, I appreciate that. Yes, at both conferences there will definitely be more detail than what the abstract contains. So, as I said when answering Sumit, next week we'll talk through top-line detail, and we're eager for that, though it will be confined to data included in the abstract. Naturally, as you might expect, far more detail is coming in the posters and presentations at ASCO and EHA.

All right. And what about that median follow-up period?

If it's okay with you, let's hold off and talk through the data once they come out.

Okay, that's fair.

Great.

Then, assuming my memory serves, those individuals had undergone fewer than 2 earlier regimens. Could you perhaps elaborate somewhat regarding the purpose of those therapies for the FL patients as well as the FLT3 and splicing ones who joined the trial, and what way ought we consider how the number of previous treatments affects the reaction to this?

Yes. Yes, I appreciate that; in fact, it is fewer than 3 earlier regimens upon entry into the study.

All right.

Yeah, so usually with AML... Actually, hold on. Bob, you might be the right one to explain the treatment phases these patients generally go through when they have AML.

Okay, so, um, frequently, a patient who has a FLT3 mutation might receive cytotoxic intensive chemotherapy as a first treatment, or something less intensive — but usually they've already been given a FLT3 inhibitor, as we talked about a little while ago. Those who are quite fit and can undergo intensive induction often receive that, yet once such patients don't respond, they'd move on to Azacitidine therapy. After that, every patient who truly cannot have intensive induction will be given Azacitidine. So, as you probably are aware, people who don't respond or whose disease worsens while on Azacitidine, or who are resistant to it, do extremely badly. A few studies have examined what happens after Azacitidine fails, and in each of those studies survival comes out at roughly two to three months, uniformly across those patients. So it's genuinely a hard group to treat. And, you know, our findings ought to be seen within that context too, which is something we're quite enthusiastic about.

Thanks.

Morning, and I appreciate you answering our questions. I'd like to follow up on what was just asked — specifically, you said Azaven is, I believe, the third line for patients on FLT3 inhibitors. You brought up survival. But what about the ORR? I think that's likely a benchmark you'd need to measure against too.

Yeah. Honestly, once again, Bob, you're probably the better person to handle that one.

Regarding the response rate — data on splicing factor mutation following post-Azaven treatment is quite limited. One particularly interesting study of first-line AML therapies shows that splicing factor mutations come with an extremely low response rate. Patients without such a mutation have response rates of about 80%, and only perhaps 20% of them can reach that, while nearly 80% of patients who do carry a splicing factor mutation cannot achieve a CR in the first line. That's a dramatically, dramatically lowered figure. As for the FLT3 subset of the population, it looks roughly comparable, though the data there aren't as detailed. Does that address your question?

Yeah, and that was frontline, by the way, Yale.

Mm-hmm.

Um, so-