Curis, Inc.

Good morning, ladies and gentlemen, and welcome to the Curious Provides First Quarter 2025 Business Update Conference Call. At this time, all lines are in listen-only mode. Following the presentation, we will conduct a question and answer session. If at any time during this call you require immediate assistance, please press star zero for the operator. This call is being recorded on Tuesday, May 6, 2025. I would now like to turn the conference over to Diantha Duvall. Please go ahead.

Thank you, and welcome to the Curious First Quarter 2025 Business Update Call. Before we begin, I would like to encourage everyone to go to the Investor section of our website at .curious.com to find our First Quarter 2025 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 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 Denzer, President and Chief Executive Officer, Jonathan Zung, Chief Development Officer, and Dr. Ahmed Hamdi, joining us today as our new Chief Medical Officer. We will also be available for a question and answer period at the end of the call. I would now like to turn the call over to Jim.

Thanks, Diantha. Good morning, everyone, and welcome to Curious' First Quarter Business Update Call. I would like to start this quarter's call by welcoming Dr. Ahmed Hamdi to the Curious Executive Team. Dr. Hamdi is a well-known and respected leader in the industry and brings a wealth of experience as the CMO of Pharmacyclics, founder and CMO of Aserta, and founder and CEO of VinxRx. Ahmed, welcome. Thank you,

Jim. It's a great pleasure to be here. I'm excited to join the Curious Team at this very critical time to advance EMA-Vuserta towards regulatory filings in primary CNS lymphoma in both U.S. and Europe. I also look forward to expand its use beyond primary CNS into additional indications like NHL, AML, and solid tumors. Given my experience in both Ibrutinib and Calibrutinib, I have a special appreciation for the potential of EMA-Vuserta in combination with BTK inhibition in NHL. I look forward to working with the team here at Curious to bring novel therapies to patients. Thanks, Ahmed.

In addition to strengthening our leadership team with Dr. Hamdi, we continue to make steady progress in our Take-Aim Lymphoma Study, which is evaluating EMA-Vuserta in combination with Ibrutinib in PC and SL patients. As a reminder, the Take-Aim Lymphoma Study is a single-arms study with an ORR endpoint in patients with PC and SL who have progressed on BTK eye treatment. And after collaborative discussions with FDA and EMA over the last year, we expect the study to support accelerated submissions in both the U.S. and Europe. As of January 2nd, 2025, the most recent data cutoff date, 27 patients with relapsed refractory PC and SL have been treated with the EMA-Vuserta and Ibrutinib combination, including 7 BTK eye-naive patients and 20 BTK eye-experienced patients. Among 13 of the 20 BTK eye-experienced patients for whom change in tumor burden data were available, 9 patients demonstrated a reduction in tumor burden, including 6 objective responses, 2 partial responses, and 4 complete responses, with 3 of the 4 CRs lasting more than 6 months and 1 patient who's been in complete remission for almost 2 years and is still on study. Among 6 of 7 BTK eye-naive patients for whom change in tumor burden data were available, 5 patients demonstrated a reduction in tumor burden, including 5 objective responses, 4 partial responses, and 1 complete response. We expect to have additional data from the Take-Aim Lymphoma Study at ASH later this year. In addition, over the next 12 to 18 months, we'll be focused on enrolling 30 to 40 additional patients we'll need for the NDA's submission, and we'd like to see 6 to 8 responses in that

data set. Now let's turn to AML. As you'll recall,

at the ASH conference in December, Dr. Eric Weiner from Dana-Farber presented data for 21 patients with a FLIT3 mutation who had received fewer than 3 lines of prior therapy and were treated with M. of usurtib as monotherapy at the RP2D of 300 mg BID. These data show a 38% composite CR rate in the salvage line setting, with 10 objective responses in 19 response-available patients and 7 of the 10 responses reported at the first assessment. To put these data into context, Gilteritinib, the leading FLIT3 inhibitor in relapsed refractory AML, was approved with a composite CR rate of 21% in a patient population where only 13% of patients had been previously treated with a FLIT3 inhibitor. In the M. of usurtib study, over 80% of the patients had been previously treated with a FLIT3 inhibitor. We believe the reason the M. of usurtib data are so compelling is its novel mechanism of action. It blocks both IRC-4 and FLIT3. For several years, it has been suggested in the literature that blocking IRC-4 can enable patients to overcome adaptive resistance to FLIT3 inhibition. These

clinical data clearly support that thesis. Finally, I'd like to provide an update on our progress with the Triplet study

in Frontline AML. As a reminder, we initiated a Phase I study last year of M. of usurtib as an add-on agent to Venetoclax N-Azocytidine in Frontline AML. This study is assessing safety and tolerability where M. of usurtib is added to a patient's 7, 14, and 21-day dosing regimens after they have achieved a CR in Venetia but are still positive for minimal residual disease. We have successfully completed the 7-day dosing cohort, and enrollment of the 14-day cohort is currently ongoing. As you can see, we've had a very exciting and productive quarter. We look forward to providing additional updates as the year progresses. With that, I'll turn the call back to Diantha for a financial update. Diantha?

Thank you, Jim. CURE has reported a net loss of $10.6 million or $1.25 per share for the first quarter of 2025 compared to a net loss of $11.9 million or $2.05 per share for the same period in 2024. Research and development expenses were $8.5 million for the first quarter of 2025 as compared to $9.6 million for the same period in 2024. The decrease was primarily attributable to lower employee-related costs. General and administrative expenses were $4.0 million for the first quarter of 2025 as compared to $4.9 million for the same period in 2024. The decrease was primarily attributable to lower employee-related costs, professional, legal, and consulting costs. In March, we've completed a registered direct financing and concurrent private placement with net proceeds of approximately $8.8 million. CURE's cash and cash equivalents totaled $20.3 million as of March 31, 2025, and the company had approximately $10.5 million shares of common stock outstanding. CURE expects its existing cash and cash equivalents will enable its planned operations into the next quarter of 2025. With that, I'd like to open the call up for questions. Operator?

Thank you so much. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by one on your touchtone phone. You will hear a prompt that your hand has been raised. Should you wish to remove your hand from the question and answer process, please press star followed by two. If you're using a speakerphone, please lift the handset before pressing any keys. One moment for

your first question. And your first question comes from Lee Watts with Cantor.

Please go ahead.

Hi. Good morning, guys. I wanted to welcome Dr. Handy to the team. Maybe just a couple of questions from us. I guess big picture on your positioning of lymphoma versus AML. Just given you have a relatively straightforward path to approval in terms of lymphoma, you might need a large setting for AML. I guess the question is,

number

one, how much data do you want to generate in front line of AML to either move forward or maybe pause and focus on the lymphoma opportunity? And the second is what are the things you're doing or could be doing to potentially accelerate the enrollment of the lymphoma study?

Thank you, Lee. So let me address this briefly, lymphoma versus AML, and then I'll ask Dr. Zung to talk about things we're doing on enrollment. So in lymphoma versus AML, we are moving ahead with both simultaneously. Now, more resources, of course, are dedicated to the PC and SL study. It's farther along, many more sites, many more patients, of course. So our focus in lymphoma is in primary CNS lymphoma and enrolling as many patients as we can towards that 30 to 40 target we need to get to NDA submission. On the AML side, the spend is a little lighter because it's earlier stage, but we're focused on our front line study, getting through that safety study. So we're trying to evaluate, as you know, M of assertive in combination with Venasa in the front line setting. And while we think that has a long-term, very strong potential, in the short term, our focus is really just enrolling a small number of patients to clear those initial regimens for safety. So it's a relatively small use of our resources, but it's absolutely just as strong a focus for us as the primary CNS lymphoma side. With that, maybe, Jonathan, if you'd like to chime in on the enrollment.

In terms of the enrollment in the lymphoma program, we've got 37 sites that are currently open. We're at the major centers of excellence in the U.S., Europe, and Israel where the patients are seen and treated. We have regular site engagement outreaches with the investigators and the coordinators. So we're doing everything that's normally done in a clinical trial to sort of drive engagement to result in enrollment.

Oh, good morning, Lee. This is Ahmed. Obviously, there's quite a bit of thinking that's going on right now as far as the NHL indications and the AML. So there's more discussions that will be coming down the road on how do we prioritize and when do we prioritize. Obviously, we'll keep everybody posted.

Yeah, and as you can imagine, Lee, obviously, we're all thrilled to get Dr. Hamdi here on board as part of the team. And as we not just push ahead aggressively towards PC and SL, but look to expand across NHL and AML to make the most of this drug wherever it provides utility. Obviously, we're very eager to work with the team and really look forward to our progress. Thank you.

Thank you, guys. Thank you. Your next question comes from Creepa Devarakonda with Truist. Please go ahead.

Hey, guys. Thank you so much for taking my question and congratulations on bringing Dr. Hamdi aboard. So a couple of questions. One for the lymphoma, you noted you have 37 sites open. I think previously you had mentioned 30. Just wondering if this is the final or you're planning to add more sites and are you still on track to complete enrollment in the timeframe that you had mentioned I think last time you had said 12 to 18 months? And have you had any additional conversations with the FDA? I just, given all the changes to the FDA, just was wondering if there's any concern that the agreement that you came to with the FDA will continue to be respected with all the changes that are happening. Thank you.

So, Jim, this is Jonathan. So on the enrollment side, there are no real changes there. We're constantly looking at the sites that we have opened. We opened, as we had mentioned in previous calls, additional sites last year. So that's where we are. On

the FDA side, Kripa, I don't think we have any concerns at all that there will be a change. I think we're grateful to be blunt that we were able to get to the FDA to get the collaboration that we needed last quarter before this current turmoil started. I worry about the industry and about companies who have to reach out to gain similar effort from the FDA in this climate. But I think for Curus's perspective, we were very fortunate in our timing. We're grateful to have their support, and we're pushing ahead. So, yeah, we share your concern for the industry as a whole, but I think from Curus's perspective, we're pleased about where we are.

Great. Thank you so much for the call.

Your next question comes from Sumit Roy with Jones Research. Please go ahead.

Hi. Thank you for taking my question. This is Danya for Sumit Roy. I have a question about your ASCO presentation. Can you give any color and what type of mutations might affect responses? And I have another question for the AML. Are there any updates on potential development steps for EMA in the relapser factory AML? Thank you.

Yeah. So why don't I take the first one and then actually ask Jonathan to chime in on the second one. So on the first one, I think it's a little too early to talk about mutations and their impact. I think the primary impact that we see with M of assertive is really driven by the mechanism of action more broadly. So as we know, the way to treat NHL is to downregulate the overactivity of -kappa-B. Historically, at least for the last 10 years, paved by pharmacics, the way to do that is with a BDK inhibitor. It blocks the BCR pathway, which is one of the two pathways that drives -kappa-B. We have the only drug that blocks the other pathway, the TLR pathway. And our thesis, which panned out in the lab and we now see in the clinical data, it's panning out as well, is that when you block both pathways that are driving -kappa-B, you can maximize the downregulation of -kappa-B activity, and that's what's driving the benefit to patients. So it's less about any particular genetic mutation, and it's more about blocking the fundamental drivers of that oncologic activity. And Jonathan, maybe if you could chime in on the second one. Yeah, so on

the AML development side, obviously, once we complete the ongoing triplet study, the safety study, along with the data that we've presented, Eric Weiner, Dana Farber presented, we'll come back and talk about what the forward plans are on the AML side, whether it's frontline relapse, refractory, and or both. And I

would close also in saying one of the things that should be very clear to everyone on the call, and certainly very clear to us on the team, is one of the biggest advantages of having Dr. Handy join the team, is now that we've got a solid path on primary CNS lymphoma, we're looking to expand across NHL to everywhere where BTK inhibitors provide benefit. Because the BTK inhibitor provides benefit in an NHL indication, whether it's PCNSL, CLL, Woldenstroms, any of the indications where a BTK inhibitor gets used, that's going to be an opportunity where blocking the second pathway could provide benefit. It's exactly what we see in our first indications. It's exactly what we saw in the lab, and it's precisely why we've asked Dr. Handy to come on board. So I look forward to reporting out that progress.

Okay, great. Thank you.

Thank you so much. As a reminder, if you would like to ask a question, please press star

1.

And at this time, there are no further questions. I would now like to pass the call over to Jim Dempster for closing remarks.

Thank you, Operator. And thank you, everyone, for joining today's call. And 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 Orogyne, the NCI, and the academic community for their ongoing collaboration and support. We look forward to updating you again soon. Operator?

Ladies and gentlemen, this concludes today's conference call. Thank you so much for your participation. You may now disconnect.