Good morning, ladies and gentlemen, and welcome to the Curis Third Quarter 2024 Business Update Call. At this time, all lines are in a listen-only-mode. Following the presentation, we will conduct a question-and-answer session. [Operator Instructions] This call is being recorded on Thursday, November 14, 2024. I would now like to turn the conference over to Diantha Duvall, Curis's Chief Financial Officer. Please go ahead.

Thank you, and welcome to Curis' third quarter 2024 business 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 our third quarter 2024 business update press 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 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 Jonathan Zung, Chief Development Officer. 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.

Thank you, Diantha. Good morning, everyone, and welcome to Curis' third quarter business update call. Let's start with our TakeAim Leukemia Study, which is evaluating emavusertib in combination with ibrutinib in relapsed/refractory PCNSL patients that have failed after treatment with a BTK inhibitor. These patients are generally treated with a methotrexate-based regimen, which includes chemo or radiation in the frontline setting, followed by a BTK inhibitor when a patient's disease progresses. It's when this treatment fails in the salvage line setting that patients become eligible to enroll in our study and receive emavusertib in combination, excuse me, with ibrutinib. The thesis for this combination, which is supported by both preclinical data and our early clinical data, is that blocking both of the pathways driving NHL, blocking the TLR pathway with emavusertib and blocking the BCR pathway with ibrutinib can enable patients to achieve an objective response even after they've progressed on ibrutinib. In September, at the third annual IRAK4 symposium in Cancer, we released an update of our PCNSL data with 10 evaluable patients. These data showed 3 complete responses, CRs, 1 unconfirmed complete response, CRu, and 2 partial responses or PRs. The duration of response for 3 of the 4 patients with a CR or CRU was greater than 6 months. These data are very early, but also encouraging, especially given the high unmet need in this population. We continue to enroll patients in this study and are actively engaging with regulatory authorities to gain alignment on the registrational path. As a reminder, this study is being run in the U.S., Europe and Israel. It goes without saying that defining the registrational path to approval is a critical next step in emavusertib's development, and I'm pleased with the progress we're making. Now let's move on to our TakeAim Leukemia…

Thank you, Jim. Curis reported a net loss of $10.1 million or $1.70 per share for the third quarter of 2024 compared to a net loss of $12.2 million or $2.13 per share for the same period in 2023. Curis reported a net loss of $33.8 million or $5.77 per share for the 9 months ended September 30, 2024, compared to a net loss of $35.7 million or $6.96 per share for the same period in 2023. Research and development expenses were $9.7 million for the third quarter of 2024 compared to $10.4 million for the same period in 2023. The decrease was primarily attributable to lower consulting and employee-related costs. R&D expenses were $29.6 million for the 9 months ended September 30, 2024, compared to $29.5 million for the same period in 2023. General and administrative expenses were $3.8 million for the third quarter of 2024 compared to $4.8 million for the same period in 2023. The decrease was primarily attributable to lower legal and employee-related costs. G&A expenses were $13.4 million for the 9 months ended September 30, 2024, compared to $13.8 million for the same period in 2023. In October, we completed a registered direct offering and concurrent private placement of unregistered warrants with net proceeds of approximately $10.8 million. Including the impact of the October 2024 offerings, Curis' cash and cash equivalents totaled $31.6 million, and the company had approximately 8.5 million shares of common stock outstanding. Curis expects its existing cash and cash equivalents will enable its planned operations into mid-'25. With that, I'd like to turn the call over 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 Ed White from H.C. Wainwright. Your line is now open. Please ask your question.

Good morning. Thanks for taking my questions.

Good morning, Ed.

Good morning, Jim. So you had mentioned that you're working to gain alignment with the FDA in PCNSL. So that sort of implies that you're out of alignment. So what needs to be done right now to get into alignment? And what is the ideal pathway to approval in your mind?

Sure. So I wouldn't say we're out of alignment by any stretch. No, I'd just say we're engaging in the discussions. I think what we see, and we've said this in the past on calls, in the early days, earlier this year, as we started to get the first data in on these patients, we saw that we were seeing results in salvage line therapy that were, frankly, better than we expected and better than second line. And even though it was a small number of patients, we wanted to reach out directly to the FDA to see if we couldn't have an accelerated path for this drug. You know the normal path of approval is you complete a Phase I/II study, you run all the reports, you have an end-of-phase meeting with FDA and then talk with the FDA about what the registrational design looks like. We thought that given there's such a critical unmet need, no drugs are approved for this. And the salvage line data that we're getting look, frankly, terrific that we might have a faster path. So that's the discussion we're having right now of can we have an accelerated approval path? And if so, what does that look like? My hope is that, you know, with those discussions are, in my view, hopefully going to be in a position where we will have some clarity in Q1, but will remain to be seen. I think at this point, we're just excited by the data, and we're pleased that the FDA is engaged with us on identifying an accelerated or at least a faster path.

Great. Thanks, Jim. And Diantha, maybe a question for you. GA, general and administrative costs were down about $1 million quarter-over-quarter and R&D was down about $0.5 million. As you continue to advance in the clinic, how should we be thinking of expenses going forward, not only for the fourth quarter, but how should we be thinking of the cadence of expenses in 2025? I know it might be difficult as you're waiting for FDA guidance, but just wanted to get your initial thoughts on it.

Yes. Thanks, Ed, for the question. So our historical burn has really been in the, call it, $10 million to $12 million range. We did some cost modulation earlier in the year that has brought that burn down. But I would expect that the normal burn for Curis in 2025 should probably stay around that $10 million - that $10 million mark. It will vary due to some timing of manufacturing. But for the most part, I would sort of assume that sort of $10 million number.

Okay, great. Thanks for taking my questions.

You bet. Thanks. Ed.

Your next question comes from the line of Billal Jahangiri from Truist Securities. Your line is now open. Please ask your question.

Good morning. We had a question about Emma's [ph] potential in hrMDS given the abstract that was posted at ASH. These impressive responses in spliceosome mutants, which isn't surprising at this point given the data you all have shown. But what we want to know what the broader potential is given the specific impacts on gene signatures that you've seen. Like how representative are the mutations in the MDS patient population? Is it 10%, 15% or more? And given that VERONA hasn't read out, is pursuing a doublet without ven and hrMDS makes sense, are HMA and MOA synergistic or additive enough for that?

Yeah. Hi, Bill. Thanks for calling in. Great question. So first, yes, MDS is one of these things that not enough people are paying attention to. It's really exciting, and we're really looking forward to it. As you know, it's a challenging population. And until VERONA reads out, aza is standard of care. But once patients go through that, there's really nothing for those patients. So the opportunity is really terrific. So as you know, we've seen a lot of responses, more marrow CRs than CRs. We're seeing activity in patients with FLT3 mutation, patients with splicing mutations. And at this point, we're exploring the possibilities of different dosing regimens and also perhaps combining emavusertib with other agents. As you say, the VERONA readout is going to matter a lot of what that combination looks like. But I would say this is an evolving discussion. We're really looking forward to the data update that Dr. Garcia-Manero is going to provide at ASH. And hopefully, it should be a really exciting discussion going into 2025. But yes, thank you for paying attention to MDS, not as many people see that as we do.

Thank you.

Your next question comes from the line of Li Watsek of Cantor. Your line is now open. Please ask your question.

Hi, team. This is Daniel Bronder on for Lee. We have a question regarding the PCNSL trial and the contribution of parts. Do you think that the FDA might raise that as a question? And also, do you have any historical data on BTK responses that could help you answer that question?

Sure. Thank you for the question. Thanks for the call. Yeah, let me address the first question first, and then I'll go to the second one. So the short answer is discussions with FDA are evolving. So we'll have to see how they respond to that. But the design of the study is really meant to address that question implicitly. So we're taking patients in immediately after they have progressed on a BTK. So the logic would be, if you just progressed on a BTK inhibitor, retreating with that same inhibitor should have no effect. It should have a zero response rate, you just progressed. So by definition or by design, maybe more accurately, the benefit that you receive is much more likely to be due to the addition of emavusertib, either in its monotherapy capacity or in its synergistic effect, which we believe is at least the thesis suggests is powerful with the BTK inhibitor. So the first question is, yes, the FDA, we know, is likely to have that question, and we'll have that conversation with them and see how that plays into the registrational design. At the same time, we're benefiting from the design of the study that's currently in progress, which does, by definition or by design, highlight the comparative effect of the two agents. Now the second question or second part of the question you asked was about BTK and their efficacy. There's a lot of literature out there. The largest clinical study to date that was published was Carole Soussain [ph] study of ibrutinib in PCNSL. And you may remember in that study in second line, patients naive to a BTK were able to get a 19% CR rate and a 52% ORR. So I said earlier, we're very encouraged that our salvage line data are outperforming that, and they are. It's early days, to be fair. But we would not have expected that in any disease, a drug being studied in the salvage line setting would outperform second line. But I would say that's why we and why our clinicians are so excited about the possibility of this regimen.

Okay. Thank you so much. And if I may ask a follow-up or another question. We were just wondering, how are you going to go about the prioritization between your different programs, your PCNSL program versus the AML and MDS programs moving forward?

Yeah, that's a fantastic question. So if I tell you about all the high-class headaches we have at Curis, I am grateful that we are in the position that the drug works really where we would expect it to in a number of therapeutic areas. As you know, we're studying it in primary CNS lymphoma. We're studying it in AML. We're studying it in MDS. We've also got 5 ISTs going on in solid tumors that are reading out over the next 12 months. We have this embarrassment of investment opportunities and embarrassment of riches. And maybe the hardest part of the job for the management team at Curis is trying to figure out how to prioritize those. I would say, at this point in time, because we're in discussions with FDA on primary CNS lymphoma and what that registrational path looks like, I think by definition, given the clear unmet need and the data that we're seeing, that's got to be a very high priority for us. Coincidentally, it's a very attractive commercial market as well. Beyond that, expanding to the other 5 types of NHL where BTKs get used, that's a really compelling opportunity for us. AML and MDS, the data are about to read out at ASH. So I'd say with those data in hand, let's have that same discussion that we're having about NHL. What is the best path to approval and how do we engage the regulatory authorities in that discussion. And then shortly thereafter, we're going to start getting data in solid tumors. It's a great question. Today, we're prioritizing primary CNS lymphoma, but it is absolutely a high cost headache for us of how to prioritize all of these opportunities.

Okay. Thank you so much for taking my question.

You bet. Thank you.

Your next question comes from the line of Sean McCutcheon of Raymond James. Your line is now open. Please ask your question.

Hi, guys. Thanks for taking the questions. A couple from me. First, can you walk us through your current assessment of what you'll need as far as the data package for primary CNS lymphoma? In particular, what do you think will be the sufficient number of patients in the safety database as the go-forward combination with ibrutinib and Emma? And how many patients have you currently treated at or above that dose of Emma? Do you think 100 patients is kind of the rough threshold kind of based on precedent? And then secondly, can you speak to some of the challenges you've seen in enrolling the triplet study, whether that be disposition of the MRD-positive CR AML patients or just in general issues with aza/ven and timing of the treatment of patients with those agents? Thanks.

Thank you, Sean. So great questions. Let me start with the primary CNS lymphoma question, and then I'll go to the triplet study. So the primary CNS lymphoma study, to be honest, that's the whole point of the discussion we're having with FDA. As you know, the normal process for any drug going through studies is you run a Phase I/II, do dose escalation. When you get those data back, follow the patients, lock the database, produce all the reports, go to the FDA, have an end-of-phase meeting, talk about the registrational design and then you go into pivotal. I think given the data we have, we thought it should be - it was worth having a conversation with the FDA to see if they'd be interested in running a faster process. We're grateful that they agreed to take that call. We're now in discussions. In primary CNS lymphoma, there's not a lot of precedent, but we do know that there are two studies ongoing right now with a BTK inhibitor. So ibrutinib is the one that today is the standard of care for BTK inhibitors. But Ono Pharmaceuticals has a BTK inhibitor, tirabrutinib, which is approved in Japan for primary CNS lymphoma and is now in its study to get approval in the U.S. We know that for that study, it's second line, not salvage. Obviously, they're trying to displace ibrutinib. And they also have a frontline study that they're using tirabrutinib in combination with methotrexate-based regimens. In their study, the frontline study was N of 75 or is N of 75. The second-line study is N of 45. Presumably, salvage line setting wouldn't need 45. Now the question there is, of course, given our data from an efficacy perspective, that might make sense, but we need to recognize that tirabrutinib has a larger safety database simply because it's already approved in Japan. So I don't exactly know where the FDA is going to come out, but we think it's reasonable to suggest that if they're okay with granting us accelerated approval, that, that's a smaller study and that then we would have a larger study with perhaps a survival-based endpoint in a confirmatory trial. All of that's conjecture at this point. We need to finish these discussions and see how the FDA feels about that. But I think given the precedent that Ono has in their study sizes, it makes sense that in this ultra-rare indication, a small study would be appropriate. It's one of the reasons, of course, that we chose primary CNS lymphoma. Now on the triplet study, you had asked specifically about the design. What question were you looking to have about the design? The MRD...

Some of the -- yes, just some of the challenges you've seen in terms of enrollment and getting patients progressed on that study, whether that's just the disposition of the MRD-positive CR AML patients or it's more an issue kind of getting patients who are receiving - received aza/ven in the front line and are receiving it in the maintenance setting. Any reticence you've seen from docs in terms of adding additional agent to an aza/ven in that setting? And any insight on your strategy moving forward to kind of boost enrollment there?

Yes. No, I think you put your finger on it. It's not a reticence at all or a safety issue at all. It's just how do you find patients who are on aza/ven, who are in CR and still MRD positive and stable enough that they can go into our study into the triplet. At this point in time, what we really want to try and do is accentuate the safety. We - the long-term solution to finding all the patients is, of course, go from cycle 1, day 1 to get the patients the minute they're diagnosed and go to a lot of sites We are at a very small number of sites. We're simply looking to make sure that this combination of Emma, aza and ven aza is going to be safe and tolerable. As you know, aza and ven are a little tricky. No two sites dose them the same way. Anecdotally, half of all patients who go on aza/ven at some point have to come off for tolerability, not just efficacy. We want to make sure that the Emma aza/ven combination is tolerable first. So that's why we're going after these patients. So it won't take long. We just need a handful of patients and we just want to follow them to make sure we understand it. Once we do, then we frankly turbocharge the study. We go to cycle 1, day 1, we expand the number of sites. And at that point, once it's been shown to be safe and tolerable, no, I think the - you'll find the physician community is very eager to find something that will increase the potency of that aza/ven regimen.

Got it. Thank you.

Thank you. Thanks for the call.

We do not have further questions at this time. Jim Dentzer, please continue.

Thank you. And thank you, everyone, for joining us on today's call. And as always, a special 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, especially at Aurigene and the NCI and the academic community for their ongoing collaboration and support. We look forward to updating you again soon. Operator?

Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect.