Good morning, ladies and gentlemen. And welcome to the Curis Provides Second Quarter 2024 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. [Operator Instructions] This call is being recorded on Thursday, August 1, 2024.

I would now like to turn the conference over to Diantha Duvall. Please go ahead..

Thank you and welcome to Curis’ second quarter 2024 business update call. Before we begin, I would like to encourage everyone to go to the Investor section of our website at www.curis.com to find our second 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 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; 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’ second quarter business update call. Let’s start with our TakeAim Lymphoma 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 have generally seen methotrexate chemo and radiation in the front-line setting, followed by ibrutinib in the second line. As patients progress on ibrutinib, they’re eligible to enroll into our study where we add emavusertib to their ibrutinib regimen.

The scientific thesis for this combination is that blocking both of the pathways driving NHL, the TLR pathway with emavusertib and the BCR pathway with ibrutinib, can enable patients to achieve an objective response even after they have progressed on ibrutinib in monotherapy.

We presented data for the first five patients in this study at the ASH conference last December, where we reported an objective response rate over 50%. These data were early but very encouraging, especially given the high unmet need in this population.

We’ve continued to enroll patients in this study, and as we noted in our press release this morning, have recently initiated discussions with regulatory authorities to gain alignment on the registrational path for emavusertib in combination with ibrutinib in primary CNSL.

It goes without saying that defining the registrational path is a critical next step in emavusertib’s development, and I’m pleased with our most recent engagement with FDA. I look forward to communicating the outcome of these discussions at the appropriate time.

Discussions are also progressing in Europe, where we’re pleased to report that emavusertib has been granted orphan drug designation for primary CNS lymphoma by the European Commission.

This designation provides several benefits, including 10 years of market exclusivity, reduced fees for protocol and scientific assistance, as well as marketing authorization applications, and a central application process for marketing authorization with the European Medicines Agency.

While these regulatory discussions are ongoing, we continue to make excellent progress on the operational front as well, and expect to reach our target number of 30 clinical sites in the U.S. and Europe, and have initial data for 15 to 20 patients by year end.

Now let’s move to our TakeAim Leukemia study, which is evaluating emavusertib in monotherapy in patients with relapsed/refractory AML. At ASCO and EHA earlier this year, we provided updated data for two patient populations in this study, patients with a splicing factor mutation and patients with a FLT3 mutation.

In the splicing factor mutation, four of 18 evaluable patients achieved an objective response, including one complete remission or CR, two CRs with partial hematologic recovery, or CRh, and one morphologic leukemia-free state or MLFS.

In the FLT3 population, six of 11 evaluable patients achieved an objective response, including three CRs, one CRh, and two MLFSs. Also of note, three of the patients were naïve to treatment with a FLT3 inhibitor.

All three of these patients achieved objective responses, and three of the remaining eight patients, those who had failed prior treatment with a FLT3 inhibitor, were able to achieve an objective response with emavusertib.

We believe these data support emavusertib’s novel mechanism and its potential as a treatment for patients with relapsed/refractory AML. In the frontline setting, you may remember that preclinical data demonstrate a synergistic effect when emavusertib is combined with azacitidine and venetoclax, the standard-of-care in frontline AML.

We recently initiated a study of this triple combination, that is emavusertib in combination with azacitidine and venetoclax in frontline AML. We expect to have initial safety data from this study later this year.

Overall, I’m very pleased with the progress in both our TakeAim Leukemia and TakeAim Lymphoma studies, and I look forward to providing additional updates as the year progresses. With that, I’ll turn the call over to Diantha for the financial update..

Thank you, Jim. Curis reported a net loss of $11.8 million or $2.03 per share, as compared to a net loss of $12 million or $2.47 per share, for the same period in 2023. Curis reported a net loss of $23.7 million or $4.08 per share for the six-month ended June 30, 2024, as compared to a net loss of $23.5 million or $4.87 per share for the same in 2023.

Research and development expenses were $10.3 million for the second quarter of 2024, as compared to $10 million for the same period in 2023. Research and development expenses were $19.9 million for the six-month ended June 30, 2024, as compared to $19.2 million for the same period in 2023.

General and administrative expenses were $4.8 million for the second quarter of 2024, as compared to $4.2 million for the same period in 2023. General and administrative expenses were $9.7 million for the six-month ended June 30, 2024, as compared to $9 million for the same period in 2023.

The increases in both research and development and general and administrative expenses are primarily attributable to higher employee-related costs. Curis’ cash, cash equivalents and investments totaled $28.4 million, and there were approximately 5.9 million shares of common stock outstanding.

We expect that our existing cash, cash equivalents and investments should enable us to maintain our planned operations into the first quarter of 2025. With that, I’d like to open the call for questions.

Operator?.

Thank you. [Operator Instructions] Your first question comes from the line of Yale Jen of Laidlaw. Please go ahead..

Good morning and thanks for taking the question and congrats on all the progress. I’ve got two here. The first one is that in terms of the PCNSL readout toward the end of the year, what do you consider to be the bar for advancing the program forward? In other words, what would be the guidepost that you were looking for? Then I have a follow-up..

So just as a reminder, Yale. Thank you, by the way, for calling in for the question. As a reminder, we’re looking to treat patients who have failed the BTK inhibitor. So let’s put this into perspective. They failed first-line treatment. They failed the BTK inhibitor.

If we retreated them with the BTK inhibitor, which is really that same choice over again, of course, they wouldn’t respond. What we’re looking to see is if we can get objective responses, period.

Now, I realize the data have been a lot better than that so far, but I think the bar for patients is, can we show that the thesis holds, that even if you’ve failed on a BTK inhibitor, adding emavusertib to it fundamentally changes the efficacy of that regimen. That’s what we’re really looking for..

Okay. And….

And of course, in a larger number of patients, right? Of course..

Absolutely.

And you anticipate about maybe at least 15 patients roughly at a time when you report the data?.

That’s right..

Okay. And maybe the follow-up question here is that in terms of the leukemia, congrats on all the data that the positive data reported earlier. And I believe you mentioned there’s different options you can pursue going forward, obviously, depending on the data to be reported in the near future.

Some of the options in terms of plus three, you could have either for the naïve patient or extremely experienced patients, or as well as for the FFM [ph], you would obviously have experienced the patients on that only.

How would you consider different optionality or maybe you want to take it all heading to 2025?.

Sure. So, as you know, in leukemia, there’s more optionality and that’s a fortunate consequence of the design of the molecule, right? Because the molecule hits IRAK4, which is expressed in nearly every patient..

Hello? Hello..

Ladies and gentlemen, I would like to inform you that the speaker has been disconnected. Please wait a while. Thank you..

Operator, this is Jonathan Zung from Curis. Jim is trying to dial back in..

We’re back in, Jonathan..

Okay..

Thank you very much..

Not sure what happened. We got disconnected from the call. So I was answering Yale Jen’s question.

Yale, perhaps, you can help me with where I got cut off?.

Sure. Not a problem. The second question is that for the leukemia, you have different options to contemplate in terms of whether for FLT3, you will treat targeting either the naïve treatment -- naïve or treatment-experienced, as well as for the FFM that you would treat, obviously, only the treatment-experienced. So among the three options….

Okay..

… I guess whether you want to, one, two or all?.

Yeah. So a couple of thoughts. So let’s first talk about frontline therapy, which would be combination and then separately monotherapy with FLT3, and then within FLT3, of course, breaking it out into the separate groups for naïve and for experienced..

Sure..

So as you know, one of the things that makes the molecule more attractive in the leukemia setting is that it hits IRAK4 and FLT3, IRAK4 being expressed in nearly all patients with AML, and then also FLT3, where the FLT3 mutation we know is present in roughly a third of the population.

So because it has that unique targeting, we think it could have a monotherapy application in leukemia, as opposed to frontline, where we think it will be available to all comers in combination with azacitidine and venetoclax, and of course in non-Hodgkin’s lymphoma when it combines with ibrutinib.

In the FLT3 subpopulation, as we look at monotherapy, you’re exactly right. It could be appropriate for both naïve patients and experienced patients. It would be ideal, of course, with infinite resources to chase after all of those populations.

I think one of the discussions we’re going to have at year-end, as we report a more full reading of the data set at ASH, is of course, which of these populations are we going to prioritize for moving forward most aggressively. So, I would say stay tuned for that discussion, but all of those opportunities are in front of us..

Okay. Great. That’s very helpful.

And maybe just quickly make it one more, which is in terms of IRAK4 composing, what might be the highlight for the upcoming one in effect?.

Yeah. I think the IRAK4 symposium, we’re very pleased to be doing that again this year. As you know, the level of interest in IRAK4 as a whole has gone up in the academic community every year since we first started publishing about IRAK4’s utility on oncology.

We’ve got, I think, a really great cross-section of people involved this year, looking at leukemia experts, lymphoma experts, and also highlighting work in solid tumors. So the clinical data that Curis has been focused on today, and in our public forums, is really in leukemia and lymphoma, because that’s where our clinical data are.

But we’ve also got five ISTs ongoing in solid tumors, and there is a wealth of really interesting preclinical data, and several of them are initiating studies now into patients as well. So I expect in the months, quarters, and years to come, that’s going to become an increasingly important and interesting part of the story..

Okay. Great. That’s very helpful and congrats on the progress. I look forward to ASH for more details..

Thank you very much..

Thank you. Your next question comes from the line of Ed White of H.C. Wainwright. Please go ahead..

Good morning. Thanks for taking my question. Jim, you mentioned when you were discussing TakeAim Lymphoma that you recently met with the FDA to discuss those registrational paths. Just wanted to know your thoughts on what your ideal regulatory path would be? Thanks..

Well, I think we would like to move as expeditiously as we can, of course. The typical path in drug development is to conclude your Phase I, II study and have an end-of-phase meeting, and then talk about with the FDA how do you design the pivotal study.

I think in this case, because the unmet need is so clear, obviously the data that we put out last December looked very compelling, and I think, we thought it was appropriate to initiate these discussions a little ahead of schedule, and we are grateful that the regulatory authorities were amenable to having those discussions.

So we’re in the middle of them now, and of course I can’t comment on ongoing discussions, but we would look forward to working with both FDA and EMA on the most expeditious path to get this drug available to patients who sorely need it..

Okay, Jim. Thanks for taking my question..

You bet. Thank you.

Operator?.

Thank you for that. Our next question comes from the line of Soumit Roy. Please go ahead..

Hi. Good morning, Jim and everyone. Sorry, I was a little delayed and missed the first few minutes of your prepared remarks.

Is the -- are you still pursuing the relapsed/refractory path for FLT3 or spliceosome with ema monotherapy going forward? Is that the FDA conversation about?.

Yes. So there was a similar question from Yale, from Yale Jen of Laidlaw about that. Thank you, Soumit. So as you know, we’ve got opportunities in leukemia in both monotherapy and combination, and of course, the combination opportunity in NHL.

The NHL1 is probably in the foremost of people’s minds because that appears to be the one that’s farthest along. As I say, we’re already in discussions with regulatory authorities on what that registrational design ought to be. I think with EMA, FLT3 and spliceosome as monotherapy, those data look really interesting.

We’re going to have a readout of that data set of roughly 20 patients in each group by year end. And then, of course, the combination, which we would expect, if it does mirror what we saw in the lab, we would expect this could be a really interesting add to frontline, to current standard of care in that setting.

I think for FLT3 and spliceosome, as we see those mature data, we’ll have that conversation at that time when it comes out. And of course, the initial readout, even though it’s just a safety readout, there are a lot of people interested in that as well.

We’re going to have a high fast headache in front of ourselves to prioritize which of these studies we focus on first and fastest, but hold that thought..

Okay.

So is it fair to expect these FDA meetings would be held post-ASH, maybe first quarter of 2025?.

For NHL….

Or….

Those discussions are already in process. For FLT3, we would wait to see what the data looked like before we would reach out to FDA. I think in AML, the landscape is more crowded. In primary CNS lymphoma, as you know, there are no drugs approved.

In the third-line setting, I realize our data are early, but it’s showing the kind of results that there isn’t a comparable result in that setting for these patients.

So I think given the clear unmet need and given the data that we’ve seen to-date, we think there’s an opportunity to get a treatment to patients that appears to be in these early days, very promising. So we want to move on that as aggressively as we can.

And as I said, we’re grateful that the regulatory authorities agreed to pick up that discussion earlier than we would normally do it..

Got it.

By NHL, you mean the PCNS?.

Yes..

Okay..

Yes. Yeah..

And are you seeing any specific, when you’re approaching the physicians for the enrollment, are you seeing any specific comments, like are they reluctant or there is no other options for these patients, so it’s an easy pitch to use ema in this setting?.

No. Unfortunately for the patients, but fortunately for the study, I think the unmet need in this population is, well, frankly, it’s horrible for those patients. There are no drugs approved. Frontline, as you know, it’s really high-dose methotrexate, chemo, and whole brain radiation.

Once they progress on that, they typically go on ibrutinib, and then after that, there really is nothing. We hope to be part of a solution for these patients that in bringing this new treatment, it looks as though early days, early data, but it has the potential to be very promising. And so as I say, we continue to enroll.

We have a lot of enthusiasm among the community. I know when you went to the conference, you were able to catch up with several of the investigators yourself. Enthusiasm is really quite high. Early days, we know. I always want to be careful to mention that. But I have to say we’re very excited by what we’re seeing. Our physicians are very excited.

And we’re glad that the regulatory authorities were interested in entertaining the discussions a little ahead of schedule, which was, of course, very encouraging for us..

Right. As we saw with Gilead’s CAR-T also in PCNSL, it’s a fairly high ICANS event. So small molecule on your safety profile certainly allows it.

Another question, maybe a little bit aside from the blood cancer, in the solid tumor, do we have any visibility if the bladder cancer trial, when it will start recruiting, I don’t know if this is an investigator-run trial with KEYTRUDA and emavusertib. Any thoughts would be appreciated..

Sure. So as you know, we’ve got five investigator-sponsored trials going on right now in solid tumors. We’ve been focusing on the NHL study, and of course, the leukemia study, because those are the ones that are company-sponsored and those are the ones where we’ve got clinical data.

But we’ve got studies going on in pancreatic and gastroesophageal, melanoma, urothelial bladder cancer and colorectal as well. All of those studies have really nice preclinical data that have been published at various conferences over the last 12 months to 24 months.

And we’re now at the point where they’re moving into the clinic, which is really exciting. I hope we’ll be in a position to see results from some of these studies in 2025. But again, these are ISTs. They’re investigator-sponsored trials. They’re not company-sponsored.

So, of course, we don’t actually have control over either the enrollment or the reporting of data from those studies. But we’re watching them with great interest, and of course, very appreciative of the collaboration with each of these study sponsors..

Thank you again for taking all the questions and congrats on the progress..

Thank you very much..

Your next question comes from the line of Li Watsek from Cantor. Please go ahead..

Good morning, guys. Sorry if I missed it earlier, but Jim, maybe just a digital question in terms of how you view the opportunity in lymphoma versus AML. It sounds like the unmet need there in lymphoma is a little bit higher and maybe less competitive.

So, how are you thinking about maybe prioritize lymphoma versus AML? Are you waiting for some maybe regulatory input to make a decision?.

Yeah. Thank you, Li. Thanks for calling in. Thanks for the question. So, in NHL versus AML, there are a couple of ways to answer that question. Of course, I think the interest in NHL is partially because that’s the most recent data and that’s the one where we’re in discussions, of course, with regulatory agencies.

Across the landscape of NHL, it’s obviously a much larger market as well. So, BTK inhibitors in 2023 had revenue of $11 billion. It’s a massive space that hasn’t had any novel drugs enter into it, excuse me, in recent years. And if our recent data hold, we, of course, would look to move very aggressively in primary CNS lymphoma.

And then with those data in hand and those processes underway, we would go across NHL to all of those other indications. I think that’s really building the excitement from investors and why we focus on that more.

In leukemia, I think the excitement is, while it is a more competitive space, as you note, the molecule really seems to be fortuitously designed for an AML setting. I mean, it was obviously deliberately designed as an IRAK4 inhibitor, and as you know, we deliberately designed key oncology targets of interest.

But because it hits IRAK4 and FIT3, it really has the ability to offer an unusual benefit, a unique and independent targeted benefit for patients in that setting. So, yes, I think the excitement on NHL is partially because of the advanced state of the data within the context of the unmet need and the regulatory progress.

But AML also very, certainly very high on our radar screen..

Okay. And then -- yes, I appreciate the color. And then maybe a question on the frontline AML combo strategy.

Just curious if there’s a plan to maybe stratify by IRAK4 long discussion and maybe have a step plan built around that, as well as for all comers?.

Yeah. So, thank you. I think we’re thinking in leukemia, as you note, or certainly as you’re implying, that there is a separate strategy for monotherapy versus combination.

So, with FLT3 as an additional target, I think that offers the ability, given that the drug targets both IRAK4 and FLT3, offers the potential for best-in-class therapy among the FLT3 inhibitors, which is a third of the population in AML.

And again, I know you know this, but for the benefit of others on the call, the research that we’re pointing to originally published with the Melgar paper [ph] showed that the reason why patients on a FLT3 inhibitor don’t do better than you might expect on a FLT3 inhibitor is the escape path is IRAK4.

It’s specifically toll-like receptor path signaling through IRAK4. So, by blocking both FLT3 and IRAK4, we’re blocking both the primary driver -- primary path of the disease and its escape path. And that really, in our view, even though the data are early, it explains why the data look to be better than other FLT3 inhibitors.

So, monotherapy there, I think, is a really exciting alternative. In frontline, we just started that study, so we need to see whether or not it’ll pan out, but the preclinical data are clear. IRAK4 is expressed in nearly every patient with AML, all comers. And we know azacitidine and venetoclax, which is the current standard-of-care, don’t hit it.

So, the preclinical data showed that when you added emavusertib to standards-of-care, when you added ema to the aza-ven doublet, there was a significant increase in efficacy. Now, we hope to see that in patients, and we’ve just started that study, but stay tuned. I hope that helps..

Thanks..

Yeah..

[Operator Instructions] There are no further questions at this time. I’d now like to turn the call back over to Jim. Please go ahead..

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 Aurigene, 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 our conference call for today. We thank you for participating and ask that you please disconnect your lines..