Good morning, and welcome to the Curis First Quarter 2023 Business Update Call. [Operator Instructions] Please note, this event is being recorded. I would now like to turn the conference over to Diantha Duvall, Curis' Chief Financial Officer. Ms. Diantha, please go ahead..

Thank you, and welcome to the Curis first quarter 2023 Business Update Call. Before we begin, I would like to encourage everyone to go to the Investors section of our website @www.curis.com to find our fourth quarter 2023 business update 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 Bob Martell, Chief Scientific Officer, and Jonathan Zung, our newly appointed Chief Development officer. We will also be available for a question-and-answer period at the end of the call. I'd like now to turn the call over to Jim..

Thank you, Diantha. Good afternoon, everyone, and welcome to Curis' First Quarter Business Update Call. . This past quarter, we made important progress with our lead clinical candidate, emavusertib.

As we mentioned in our March update, we completed enrolling the additional patients requested by FDA ahead of schedule, which we believe is indicative of both the clear unmet need in leukemia and the excitement among the clinical community for this novel agent.

We are collecting and analyzing data from these patients this quarter and expect to discuss these data with the FDA in the third quarter. We are optimistic that these data will be sufficient for the FDA to allow us to proceed with a Recommended Phase 2 Dose and move into the expansion phase of our take aim leukemia study.

We're also enrolling patients with Primary Central Nervous System Lymphoma or PCNSL, and treating them with Emavusertib in combination with the BTK inhibitor ibrutinib in our TakeAim Leukemia study.

We believe emavusertib in combination with ibrutinib has the potential to be an important new therapy in PCNSL, which is an orphan population of patients with high unmet need. I'm also pleased to announce the expansion of the Curis' executive team with the addition of Dr. Jonathan Zung as our Chief Development Officer. Dr.

Zung strengthens our executive team as a well-respected industry leader with a wealth of drug development experience in both biotech and large pharma.

In short, the CURES team continues to make significant progress in establishing our lead clinical candidate, Emavusertib, showing both clear single agent activity and broad potential and combination therapy as a potential cornerstone treatment in hematological malignancies.

And we look forward to sharing the results of our discussions with FDA in the quarter ahead.

With that, I'll turn the call back over to Diantha to review our financial results for the quarter, Diantha?.

Thank you, Jim. For the first quarter of 2023, Curis reported a net loss of $11.6 million or $0.12 per share, as compared to a net loss of $16.1 million or $0.18 per share for the same period in 2022. Revenues for the first quarter of 2023 were $2.3 million as compared to $2.1 million for the same period in 2022.

Research and development expenses were $9.1 million for the first quarter of 2023 as compared to $11.4 million for the same period in 2022. The decrease in research and development expenses for the quarter is primarily attributable to the timing of manufacturing costs and lower employee related costs due to a reduction in headcount.

General and administrative expenses were $4.8 million for the first quarter of 2023 as compared to $5.7 million for the same period in 2022. The decrease in general administrative expenses was driven primarily by lower employee related costs due to reduction in headcount.

For the first quarter of 2023, other income net was $0.1 million as compared to other expense net of 1 million for the same period in 2022. Other income expense net primarily consists of interest income partially offset by expense related to future royalty payments. As of as of March 30th, 2023.

Curis' cash, cash equivalent and investments totaled $71.8 million and there were approximately $96.6 million shares of common stock outstanding. We continue to be in a strong cash position and expect that our existing cash, cash equivalents and investments should enable us to maintain our planned operations into '25.

With that, I'd like to turn the call open the call for questions operator,.

[Operator instructions]. And our first question will come from Li Watsek with Cantor Fitzgerald. Please go ahead..

Hey, good afternoon. Thanks for taking out questions.

Jim, just curious, for the nine additional patients that you enroll in Q1, do you have a sense how the activity that you've seen so far compares to the higher dose of 300 meg? And do you have plan to maybe share the data prior to your meeting with FDA in Q3?.

So thank you very much for the question. So we're planning on having the discussion with FDA first and then we'll discuss the data more publicly later. Of course, that's the way the FDA would prefer it. And I think that's the best answer for us at this time.

I think what we can tell you that we've said in the past is, we answered all of the FDA's questions last year with one exception, and that was, we've got two doses, 200 milligrams, BID, and 300 milligrams, BID, both of which look safe, both of which have shown responses.

And the open question with the FDA is, which is the better of those two doses? So our view would be the data we had last year at this time, seemed to anticipate that both were good, both could lead to responses, both were safe. There seemed to be a slight preference for 300.

We have since added more patients at 200 to have a more fulsome analysis between the two. And my assumption is going to be that when we take these data to the FDA, they're going to look at the dataset and come out where, we are. And that is both doses are safe, both doses are effective.

If there's a preference for 300, that means the data were completely consistent with what we'd seen so far. If there's a preference for 200, that means the data at 200 look even better than they did last time.

Either of those outcomes is good, and I look forward to, to walking you through what these data look like after we have the conversation with FDA..

Okay. Maybe a follow….

Pretty long answer to the question. Hope that's helpful..

Yeah, sure.

Maybe a follow up question, when do you think you might be able to communicate to the three, with respect to the clinical hold after the meeting Q3 and I guess for this meeting, would you be able to discuss the registrational path with FDA as well?.

Yeah, I, I think our plan right now is that we hope to have this discussion with the FDA at the end of Q3. So we, of course, we would come out with the answers with that as, as soon as we have it that we're moving forward.

In terms of the next steps, I think we've been pretty clear in, in AML the design, the precedent for the design is fairly straightforward. We look at IDH1 one, IDH2, flip three, all of these studies, pivotal studies we're done with a single arm design with CR -- CRH is a primary endpoint duration of response and survival is secondary endpoints.

And we would assume that going forward, the FDA is going to be consistent with their past practice and have a similar design in MDs. It's a longer discussion. It's both in a good and bad thing.

The reason why it's a longer discussion is because there is no precedent for relapsed refractory treatment of MDS, and that's precisely because there are no drugs approved. So the the good news in that of course, is that it's a wide open space.

The more you know, uncertain news is of course, because it's a wide open space and because nothing is approved, it's going to take some dialogue with, with FDA. As with getting off clinical hold, I look forward to having those discussions with FDA. And of course, the minute we can, we will be very eager to discuss with you..

[Operator instructions].our next question will come from Yale Jen with Laidlaw & Company. Please go ahead..

Good afternoon, and thanks for taking the question. Thank you.

My first question is, my first question is that with the night patient you already enrolled, is there anything you can talk about the general characteristics of, of these patients?.

So yeah, we're going to, we're going to withhold talking about baseline characteristics and anything else that we're seeing until after we've had the discussion with FDA. We're not going to try and front run the FDA discussions.

But what we can say is that what you already know in this population, whether you're looking at relapse refractory AML or relapse refractory MDS, these patients all have a very poor prognosis. Median survival in the literature is anywhere from 2.3 to six months. It, it's just a, a very bleak prognosis.

So it's fair to say that any patients that have come into the study so far and any patients we're likely to see between now and NDA submission, those are going to be patients that are unfortunately in pretty tough shape..

Understood. appreciate that, and I respect that as well. You may also, my follow-up question here is that you mentioned about CCN test and could you give us a little bit background? How would you start this and what was the rationale behind it and where things are at this moment and what to anticipate in 609 months? And thanks..

Yeah. So the, the rationale for going into primary CNS lymphoma, so I, I can start and then I'll ask Bob to, to join in. So in general, in lymphoma, you remember we're treating lymphoma in combination with ibrutinib. The logic there is B-cell lymphoma today is treated really to down-regulate NF-κB activity.

And NF-κB in turn is driven by two biologic pathways, the BCR pathway where Btk lives and the toll-like receptor pathway where IRAK4 lives.

What we, what we discovered in our early scientific work that was then corroborated in the, in the lab and then of course later in the clinic, is that if you want to down-regulate NF-κB activity in these patients, the best thing to do isn't to shut down one pathway or the other. It's to shut down both.

So that's the logic behind going down lymphoma in general and in primary CNS lymphoma in particular, this is a type of cancer where it's particularly sensitive to the toll-like receptor side as opposed to the BCR side, and it's an orphan drug indication. So it should mean that we can get to an answer fairly quickly that hopefully works in our favor.

Bob, I don't know if you want to add any more colors to that..

Yeah, no, I think that was a good, good explanation. The, the majority of patients who have primary CNS lymphoma have MYD88 mutations. And is sort of, just to expand on what Jim said, this is a key driver of you know, IRAK4 and ultimately NF-κB activity.

And so the, the, the disease, the PCNSL disease seems to be weighted more towards the TLR pathway in terms of what's driving the actual disease. Now we have some really interesting data and there's some nice data published in the literature in particular with CNS lymphoma.

For example, we know that in preclinical models we get excellent exposure of emavusertib in these tumors and, and crossing the blood-brain barrier as well. So this is a nice feature of emavusertib in fact, getting levels in these preclinical models that are at therapeutic therapeutic ranges.

You know, that's been demonstrated not only for CNS lymphoma, but actually just as an aside for melanoma as well. So we think that this is a, a great area where there's not a lot of other drugs approved or, or used, and we think it's a, a great opportunity for us to you know, capture as a potential early indication..

And what type of expectation to be in terms of next six to nine months, should that be something occur after the FDA meetings and with the sort, the happy endings?.

Yeah, I think it's all too premature to talk about the timing of when we're going to have those data just yet. I'd say at this point we are in the, the, the phase of working with our sites to identify the patients, get them on drug, and then we'll follow them.

You know, just broadly, one of the reasons why most investors have been following leukemia more than they've been following lymphoma is that, you know, the bad news for the patients is that the leukemia disease sets tend to be a much worse prognosis.

The patients frankly don't survive very long, versus in lymphoma, their outcomes are a little bit better. So our view would be that all things being equal, we're likely to have data sets in the leukemia side sooner than we'll have data sets in the lymphoma side, but we are moving fast and furious on both fronts simultaneously..

I'll quickly add to I don't know if you remember our data that we presented last year. We had one patient who was resistant to ibrutinib, who continued ibrutinib. This is a patient with primary CNS lymphoma. They continued ibrutinib and added emavusertib and, and quickly went into a complete response. So, you know, we're really excited about that.

I think that's a nice proof of concept in patients..

Yeah. Underscores the idea as we said that NF-κB is really driving the disease and in turn what's driving NF-κB in these patients appears to be MYD88 going through the toll-like receptor side, which means they should be more amenable to our drug being added in combination.

And, and to Bob's point that one patient was only one patient, but it's obviously very exciting that it's consistent with what you might express..

Yeah. And a nice proof of concept that we can overcome ibrutinib resistance..

Exactly. Okay, great. That's very encouraging and again, thanks a lot and best luck for the meetings with the agency..

The next question will come from Dane Leon with Raymond James. Please go ahead..

Hey guys, this is Laura on for Dane. I have two questions.

First how long is the follow-up duration for the 200 milligram expansion cohort package to be taken to the FDA? And then also looking back at the Venetoclax combination that you guys disclosed at [indiscernible] last year are we going to be seeing any follow up data or more rep robust patient characteristics at any point this year? Thanks..

Sure. So let me address the, the first question first. So in terms of the follow up time, I think you can, you can glean that from the guidance that we gave on timing. So we opened the sites up in Q4. We recruited the patients in Q1, we're following them and getting them the, getting the data back in Q2.

And then we're filing and discussing data with FDA in Q3. So that's short of the timeline really in a nutshell. On Venetoclax, you may remember that when we were put on partial hold the FDA asked us to enroll only the monotherapy at 200 milligrams. So we don't really have further information to talk about in those combination patients.

Although of course, as you can imagine, as we look forward to lifting of the partial hold, we look forward to moving forward, not just with monotherapy, but with the combination therapy path. And look forward to having those discussions with you as soon as we can..

Yeah, and, and maybe I can add to that one of the exciting things about Venetoclax and is, as you recall the data you know, it looked like there was some really nice anti-cancer activity there. One of the key ways that you know, leukemia develop resistance to Venetoclax is actual up-regulation of other anti apop factors such as MCL1, BCLXL.

And these have been shown to, you know, be regulated through this exact pathway. And that's why we think you know, this drug emavusertib may be able to overcome resistance of venetoclax as well..

This concludes our question and answer session. I would like to turn the conference back over to the Company's President and Chief Executive Officer, Mr. James Dentzer for closing remarks. Please go ahead..

Thank you. And as always, thank you to the patients and families participating in our clinical trials, to our team at cures for their hard work and commitment, and to our partners at AURIGENE, ImmuNext and the NCI, for their ongoing help and support. We look forward to updating you again soon.

Operator?.

The conference is now concluded. Thank you again for your participation. You may now disconnect..