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

Good morning, and welcome to Curis' Emavusertib Update Call. [Operator Instructions] Please note this event is being recorded. And 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 Curis' Emavusertib 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 Curis announces positive emavusertib update press release. I would also like to remind everyone that during our 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 Dentzer, President and Chief Executive Officer; Dr. Ahmed Hamdy, Chief Medical Officer; and Dr. 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' Emavusertib Update Call. We're excited to report updated data from the TakeAim lymphoma study in primary CNS lymphoma, one of the most rare and most difficult to treat of the NHL subtypes. As a reminder, the TakeAim lymphoma study is a 3-part study of emavusertib in combination with ibrutinib in patients with relapsed/refractory PCNSL. Part A, the dose escalation part of the study is complete. Part B is the single-arm study in BTKi-experienced patients and Part C is the randomized study in BTKi-naive patients. As you may recall, we reported data for patients treated in Parts A and B of the study last year with a May 1, 2025 data cutoff. At that time, we reported a 71% overall response rate in BTKi-naive patients with 5 of 7 patients achieving a response. We're pleased to report that as of the July 1, 2026 data cutoff, the ORR is now 86% with 6 of 7 BTKi-naive patients achieving a response. When we focus on evaluable patients, those patients who were able to complete at least 1 cycle of treatment, the response rate increases to 100% or 5 of 5 BTKi-naive patients. For context, it is important to note that published studies of BTK inhibitors in PCNSL have generally shown response rates of 40% to 70%. Clearly, the combination of emavusertib plus a BTK inhibitor appears to be better than BTKi alone. For BTK-experienced patients, those patients whose disease has progressed while taking a BTK inhibitor, the results look arguably even more impressive. Last May, we reported a 27% response rate with 7 of 26 patients responding. A year later, we have increased the patient data set by 50%. We now have 39 patients, and the response rate has remained consistent with a 26% ORR and 10 of 39 patients responding. When we focus on evaluable patients, again, those patients who were able to complete at least 1 cycle of treatment, the response rate increases to 33% or 10 of 30 BTKi-experienced patients. For context on this population, patients who have failed both frontline therapy and BTKi have a very poor prognosis with many patients proceeding directly to hospice or best supportive care. That emavusertib is helping patients change that story and reverse their disease is very encouraging. In short, the updated data in both BTKi-naive and BTKi-experienced patients continue to show strong activity and continue to support the potential for accelerated approval submissions in both the U.S. and Europe. As the study continues to advance with strong support from clinical investigators and key opinion leaders in the PCNSL community, we look forward to completing full enrollment in the registrational data set on schedule in 2027. Now let's turn to CLL. As you recall, last year, we engaged with a number of KOLs who are excited about expanding our emavusertib studies into additional NHL subtypes. They were especially interested in exploring emavusertib's potential to fundamentally change the treatment paradigm for CLL patients, where the current standard of care is BTK inhibitors. Over the last decade, BTK inhibitors have become standard of care in CLL and NHL because of their ability to block the BCR pathway and help patients achieve objective responses. However, these responses are typically partial responses, not complete remission. The result is that patients treated with a BTK inhibitor end up having to stay on it in chronic treatment for the rest of their lives. Additionally, because they never achieve complete remission, many of these patients develop BTKi-resistant mutations and ultimately, their disease progresses. We are looking to improve upon the current standard of care by adding emavusertib to a patient's BTKi regimen, applying a dual blockade to the 2 biologic pathways driving CLL. This dual blockade with BTKi blocking the BCR pathway and emavusertib blocking the TLR pathway and enable patients whose NHL subtype partially responds to a BTK inhibitor to achieve deeper responses with the combination, including the ability to achieve complete remission or undetectable disease and the potential for time-limited treatment. If we are successful, adding emavusertib to BTKi could change the treatment paradigm in CLL, reducing the risk of developing a treatment-resistant mutation and improving a patient's overall quality of life. The first step in testing this hypothesis in CLL is our proof-of-concept study in patients currently on BTKi monotherapy who have achieved partial remission but have been unable to achieve complete remission or undetectable MRD. Enrollment in the CLL study continues to gain momentum. Just a few weeks ago, we announced that we had 11 clinical sites activated and that we had consented our first 6 patients. Since then, we have consented 4 more patients, bringing the total to 10 patients consented. With that strong momentum, we are pleased to reiterate our guidance that we expect to dose the first 5 patients by the end of this month, and we are raising our guidance for clinical data from 5 patients to 5 to 10 patients by year-end. It's been a terrific year so far with updated PCNSL data, reinforcing the regulatory strategy for our first NHL submission and demand for CLL enrollment exceeding our expectations, reflecting both the clear unmet need in CLL and the support from the clinical community that emavusertib has the potential to address that need. We look forward to providing additional updates as the year progresses. With that, I'd like to open the call for questions. Operator?

[Operator Instructions] And your first question comes from the line of Kripa Devarakonda from Truist.

Congratulations on the progress. I was wondering if you can remind me what the specific number of BTKi-experienced patients required for the registrational data set is? And is there a floor ORR the FDA expects to see for this patient population? And I know you didn't -- I don't think you mentioned it, but just was wondering if there is -- if you have any sense of median duration of response for these responders that you talked about today?

Yes. Thank you, Kripa. I appreciate the questions, and thank you for joining. So just as a reminder, when we went back and had our discussions with FDA, one of the reasons we selected PCNSL in this salvage-line setting is because the alternatives are so grim. So patients post BTK, once they failed not just chemo and methotrexate in frontline, but then they've gone on a BTK inhibitor and their disease has progressed after that, they have no options. There's nothing approved. There is no consistent guideline. And many of those patients are frankly too frail to even take another round of chemo. So oftentimes, these patients end up going to best supportive care or hospice. So the ORR in that population is really zero. Nobody publishes results for that population because nothing works. When we had the discussions with the regulatory authorities, what we said is, look, we all understand that the real-world response rate is zero. Let's just suggest a statistical lower bound of 10%. And if we can get more than 10% responses statistically p-value less than 0.05, would that be sufficient? And then the answer from both the EMA and FDA says, yes, there's nothing for these patients. If you can show that you can exceed that lower bound, that would work. So now we had a discussion about the stats. And if we see a response rate of 20% or higher, in order to achieve a p-value of 0.05, we would need somewhere in the range of 45 to 60 patients. So then the question to EMA and FDA was, would that size of data set be sufficient, knowing that we need to address safety as well as efficacy. And our conversations were very successful. Both agencies thought that was reasonable. And so that's where we're headed. And that's why we expect to have that data set fully enrolled by next year. And then the follow-on question that you asked about duration was, well, what sort of duration do we expect to see? Well, in this population, as I said, nothing works. So any duration would be terrific. The largest study ever done in this population was the iLOC study by Carole Soussain in Paris. And that study, as a reminder, showed the progression-free survival in BTKi patients is 2 months. So we've shown so far that we can get to 4 to 6 months. In fact, some of our patients have been on drug now for over 2 years, approaching 3 years. I suspect we're going to have a very strong story to tell, assuming that the data hold between now and full enrollment. Our response rate and our duration are better than we were expecting. So thank you for those questions.

And your next question comes from the line of Yale Jen from Laidlaw & Company.

Congrats on the great data. My first question is that given for the PCNSL that the both patient -- BTK naive and BTK experienced patients show very compelling data, would you also consider filing for the first line as well as for second line? And what might be the additional work needed for potentially achieve both -- sort of both paths? And then I have a follow-up.

Yes. So thank you, Yale, first and foremost, for the questions and also for dialing in today. We appreciate it. Yes, I mean you raised a very exciting prospect. So we are looking at an oral-oral combination of patients that in the evaluable population has a response rate of 100%. And those are patients that are second line. They've already been through chemo and methotrexate, right? Chemo and methotrexate is frontline therapy. But the published reports for chemo and methotrexate are that the response rate is 80%. We're looking at a response rate in second line with an oral-oral, so a far easier regimen to tolerate than frontline with chemo and methotrexate. Now I'm not prepared to suggest that with our small data set, we only have 5 evaluable patients, 7 ITT, right? It's a very small data set. I don't know that I want to take that next step and say that we think we can leapfrog into frontline therapy in these patients. I think that's premature. But I would say we feel very confident that the drug is active. It's clearly adding efficacy to a BTKi regimen. And we think that the prospects for gaining our first label, first in the salvage line and then with full approval in combination with BTKi. Our overall thesis is, there's a $12 billion market for patients with NHL who take a BTK inhibitor. Our view would be we are going to go into all 5 of those indications, PCNSL first, but then CLL, Waldenstrom's, mantle cell, marginal zone, wherever a patient takes a BTKi inhibitor today, those patients tomorrow if these data hold suggest they should be taking BTKi plus ema. And that's a really exciting place for us to be. Thank you that...

Okay. Great. And maybe just a follow-up. With this data at this moment, would you thinking of schedule a meeting with the FDA or you will wait until, for example, end of the year to have this data -- to have a meeting with FDA, maybe even accelerate the process further instead of waiting for the completion of the enrollment in next year for the salvage line. And at the time also in terms of the BTK naive, if you have more data there, again, the same question, whether you will have a conversation with the agency to discuss all the possibilities.

Thank you again, great question. So on the regulatory strategy, I'd say we've got a really good dialogue going with FDA. They greatly appreciate. And we should remind everyone, when we went to the FDA, we brought with us 2 key opinion leaders, right? The Head of Primary CNS lymphoma for Sloan Kettering and the Deputy Chair of Lymphoma for Mayo Clinic in Rochester, and the support from the community and then the support that we gained from FDA and the EMA was really encouraging. At this point, the dialogue is terrific. They're glad that companies like Curis are pioneering novel molecules in areas of clear unmet need where patients really do need access to a therapy that can extend the quality of their life. And so far, the data seem to support that enthusiasm. I'd say right now, we plan as the data come in to reach out to the FDA and EMA where appropriate to take advantage of any opportunity we can for accelerated treatment or favorable regulatory action that could be beneficial to getting this drug to patients as fast as possible. So as I said, right now, we are continuing to look at a drug that is performing really well in this first indication. And the second one, CLL, the much larger indication, the enthusiasm from the community is really exciting for us. And I look forward to both better data as we move forward in CLL as well as PCNSL, but also an ongoing discussion with regulatory authorities. So I'd say stay tuned.

And your next question comes from the line of Sara Nik from H.C. Wainwright.