Curis (CRIS) Q4 2021 Earnings Call Transcript

Curis (CRIS 4.35%)
Q4 2021 Earnings Call
Feb 24, 2022, 4:30 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good afternoon, and welcome to Curis' fourth quarter and year-end 2021 earnings call. [Operator instructions] Please note, this event is being recorded. I would now like to turn the conference over to the company's chief financial officer and chief administrative officer, Bill Steinkrauss. Please go ahead.

Bill Steinkrauss -- Chief Financial Officer

Thank you, and welcome to Curis' fourth quarter and year-end 2021 [Audio gap] Before we begin, I would encourage everyone to go to the investors section of our website at www.curis.com to find our fourth quarter and year-end 2021 and earnings 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, head of R&D. 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. Jim?

Jim Dentzer -- President and Chief Executive Officer

Thanks, Bill. Good afternoon, everyone. It's my pleasure to welcome you to Curis' fourth quarter and year-end earnings call. At Curis, we are driven by our mission to develop the next generation of transformative cancer therapies that meaningfully improve and extend patients' lives.

In the fourth quarter of 2021, we made significant strides toward that goal. To start, we're pleased to announce that our novel IRAK4 inhibitor, CA-4948, will be adopting a new generic name, emavusertib, as well as introducing TakeAim, our brand name for clinical trials moving forward with emavusertib. The TakeAim branding was selected to highlight the targeted design of emavusertib as the first-in-class IRAK4 inhibitor in oncology. As a reminder, emavusertib is currently being evaluated in nine distinct patient populations across three clinical studies in AML, MDS and B-cell cancers.

The first study, TakeAim Leukemia, is a phase 1/2 study with both monotherapy and combination arms for patients with relapsed or refractory acute myeloid leukemia, or AML, and high-risk myelodysplastic syndromes or MDS. The second study, TakeAim Lymphoma, is a phase 1/2 combination study with ibrutinib for patients with relapsed or refractory NHL or other hematologic malignancies. The third study is the phase 2 LUCAS study evaluating emavusertib in patients with lower-risk MDS, being led by Dr. Uwe Platzbecker of the University of Leipzig.

In early January, we announced positive updated data from the TakeAim Leukemia study in targeted patients with relapsed/refractory AML or MDS whose disease is characterized by a spliceosome or FLT3 mutation. The updated dataset supported the findings presented at EHA last year, further demonstrating encouraging anti-cancer activity compared to standard-of-care therapies in an expanded set of patient data. As of December, we have enrolled 49 patients in monotherapy, 13 of which had genetically defined diseases, either spliceosome mutation or FLT3 mutation, and were evaluable for efficacy. We plan to discuss data from this ongoing study with the FDA in the first half of this year with the goal of clarifying the regulatory path for bringing this novel therapy to patients in critical need.

We will provide an update on that discussion later this year. Additionally, enrollment is proceeding well for the combination arm exploring emavusertib plus azacitidine for patients naive to HMA and emavusertib plus venetoclax for patients naive to venetoclax. We expect to have initial data from these combinations in the second half of this year. I'd like to briefly touch on the ongoing phase 2 LUCAS IST for patients with lower-risk MDS being led by Dr.

Uwe Platzbecker, the co-chairman of EHA's Scientific Working Group on MDS. Demonstration of safety and efficacy in low-risk MDS could lead to a potential breakthrough in the MDS field. While the current standard of care with EPO-stimulating agents can be effective for patients with lower-risk MDS, who have low-serum EPO, the effect is often transient. It is not disease modifying, and it does not prevent the progression of MDS to AML.

We believe that emavusertib, with its direct targeting of IRAK4, could be a transformative disease-modifying alternative, allowing the potential to treat these patients in a much earlier stage of disease. While physicians can give leukemia patients transfusions and they have drugs that can stimulate blood cell growth, at Curis, we're developing drugs that have potential to stop the cancer. In these early days of clinical testing, our data have demonstrated the potential to do just that even in patients with spliceosome mutation for whom existing therapies don't work. Now let's move on to our B-cell cancer program and the TakeAim Lymphoma study.

We initiated the combination study, evaluating emavusertib with ibrutinib last year after seeing clear efficacy with this novel monotherapy agent and seeing that the efficacy was durable over such an extended period of time for these extremely sick patients. The dose escalation portion of this study is expected to enroll approximately 18 patients in a 3+3 design with emavusertib doses starting at 200 and escalating to 300 milligrams BID. Ibrutinib dosing will be whatever is appropriate for the patient's respective NHL subtype. We expect to report initial data from this study in the first half of this year.

Moving on to our second asset in the clinic, our first-in-class monoclonal anti-VISTA antibody, CI-8993, and a novel immune checkpoint inhibitor we're developing in collaboration with ImmuNext for the treatment of patients with relapsed or refractory solid tumors. We were excited to present clinical data on our phase 1 dose escalation study of CI-8993 in January, demonstrating a promising safety profile and highlighting the potential of CI-8993 to activate multiple anticancer mechanisms. CI-8993 is a monoclonal antibody designed to antagonize VISTA-mediated immune suppression through myeloid and T-cell mechanisms. We believe CI-8993 is the most advanced anti-VISTA antibody currently in clinical development and has the potential to be a game-changing cancer therapy.

The role of VISTA may go beyond other checkpoint inhibitors, as we believe VISTA inhibition has the potential for broad application in many tumor types, both in monotherapy and in combination with existing checkpoint inhibitors. Because of VISTA's localization on a variety of immune cells, targeting it affects numerous cancer immune mechanisms, many of which are not addressed by targeting PD-1, CTLA-4 or other checkpoints. Our phase 1 dose escalation study has shown to date that CI-8993 has a safe and well-tolerated safety profile. Initially, we started dosing at 0.15 milligrams per kilogram, which was the highest dose cleared in the Janssen study.

We then escalated dosing to 0.3 milligrams per kilogram and most recently to 0.6 milligrams per kilogram. We're encouraged by our initial safety data as they appear to demonstrate the effectiveness of the procedures we implemented to manage expected CRS effects. The pharmacokinetic profile of CI-8993 demonstrates the ability to overcome a PK sink effect and achieve meaningful drug exposure. This fact is exemplified by our observation of clear pharmacodynamic effects in CI-8993 with early signs that CI-8993 is activating multiple anticancer mechanisms in patients tested to date.

For these reasons, we believe that therapeutic targeting of VISTA with CI-8993 and has the potential to be a critical addition to the immune-oncology arsenal. We look forward to sharing more data on this in the second half of 2022. In summary, we're pleased with the progress we've made in 2021, and we look forward to further progress in 2022. With that, I'll turn the call over to Bill to review our financial results for the quarter.

Bill?

Bill Steinkrauss -- Chief Financial Officer

Thank you, Jim. Curis continues to operate from a place of financial strength. For the year ended December 31, 2021, Curis reported a net loss of $45.4 million or $0.50 per share on both a basic and diluted basis, as compared to a net loss of $29.9 million or $0.61 per share on both a basic and diluted basis in 2020. For the fourth quarter of 2021, Curis reported a net loss of $13.6 million or $0.15 per share on both a basic and diluted basis, as compared to a net loss of $7.5 million or $0.11 per share on both a basic and diluted basis for the same period in 2020.

Revenues for the year ended December 31, 2021, were $10.6 million, as compared to $10.8 million for the same period in 2020. Revenues for both periods comprised primarily of royalty revenues recorded on Genentech and Roche's net sales of Erivedge. Revenues for the fourth quarters of 2021 and 2020 were $3.1 million and $3 million, respectively. Operating expenses for the year ended December 31, 2021, were $52.7 million, as compared to $35.7 million for the same period in 2020.

Operating expenses for the fourth quarter of 2021 were $15.7 million, as compared to $9.3 million for the same period in 2020 and comprised of the following. Cost of royalty revenues, primarily amounts due to third-party university patent licensors in connection with Genentech and Roche's Erivedge net sales, were $0.5 million for the years ended December 31, 2021 and 2020. Cost of royalty revenues were $0.2 million [Audio gap] of 2021 and 2020. Research and development expenses were $34.9 million for the year ended December 31, 2021, as compared to $23.1 million for the same period 2020.

[Audio gap] development expenses were $10.8 million for the fourth quarter of 2021, as compared to $5.6 million for the same period in 2020. This increase was primarily attributable to increased clinical and manufacturing costs for our programs and higher personnel spending as a result of additional headcount. General and administrative expenses were $17.3 million for the year ended December 31, 2021, as compared to $12.1 million for the same period in 2020. General and administrative expenses were $4.8 million for the fourth quarter of 2021, as compared to $3.5 million for the same period in 2020.

The increase in general and administrative expense was driven primarily by higher costs for stock-based compensation, professional consulting services, personnel and insurance as compared to the prior year. Net other expense was $3.4 million for the year ended December 31, 2021, as compared to $5 million for the same period in 2020. For the fourth quarter of 2021 and 2020, net other expense was $1.1 million and $1.2 million, respectively. Net other expense primarily consisted of imputed interest expense related to royalty payments.

As of December 31, 2021, Curis' cash, cash equivalents and investments totaled $139.8 million, and there were approximately 91.6 million shares of common stock outstanding. Curis expects that its existing cash, cash equivalents and investments should enable it to maintain its planned operations into 2024. With that, I'd like to open the call for questions. Operator?

Questions & Answers:

Operator

[Operator instructions] The first question is from Alethia Young with Cantor Fitzgerald. Please go ahead.

Alethia Young -- Cantor Fitzgerald -- Analyst

Hey, guys, thanks for taking my question, and congrats on the progress that you guys are making over the past couple of months. I just wanted to drill a little bit down into maybe talking about how we're thinking about kind of the trial design. What's really viable versus what might not be viable and into kind of -- I know you've had this conversation with the FDA. But just how are you thinking about what's the expectation or how you guys are framing up for what it should be on that front? And then I just also wanted to ask on VISTA.

Do you guys feel as if you will be in a position to potentially achieve proof of concept by the time we get to the end of the year? I mean like you'll kind of be past the safety and to kind of efficacious doses. And do you think -- how do you think about kind of continuing monotherapy? Or is there any kind of option to potentially do something more of a combination dose as well? Thanks.

Jim Dentzer -- President and Chief Executive Officer

Thank you, Alethia. Thanks for joining as well. Bob, you're probably the first -- the best person to talk to the trial design for 4948. Then we can address the VISTA one in a second.

Bob Martell -- Head of R&D -- Analyst

Yeah. Hey, Alethia, thanks for the question. So the trial design, if we sort of break it down into high-risk MDS and AML, and I think currently, the AML, we believe, is fairly straightforward. What we're trying to do is look both in parallel at a very rapid path to registration with the FDA.

And that could involve a single-arm study looking at surrogate end points like CR and CRh. Those end points are validated end points by the FDA and used also in conjunction with durability of response. A couple of drugs have been approved in this space in AML, including gilteritinib and ivosidenib both with response rates in the low 20% range. So we think that this is a pretty viable approach, and we also have a population here that historically has been quite challenging to get these types of responses.

In the data that we've presented so far, we've presented a really very durable CR and CRh and quite good effects on the blood count to those patients in a very difficult-to-treat population. And so I think that's our main focus for the clinical trial for AML, and we'll discuss that with the FDA coming up.

Jim Dentzer -- President and Chief Executive Officer

Yeah. Thanks, Bob. So on the VISTA question -- look, first, Alethia, does that answer your question on trial design for 4948?

Alethia Young -- Cantor Fitzgerald -- Analyst

Yeah. That's helpful. I mean I guess is there a distinction, though, in MDS as to what you might do versus AML, which I mean, obviously, I can see the kind of the unmet need in the protocol, I mean kind of how we've gone forward in AML, but with MDS, like how do you kind of think about a later-stage trial design that have more momentum there?

Bob Martell -- Head of R&D -- Analyst

Well, there's definitely more --

Jim Dentzer -- President and Chief Executive Officer

Go ahead, Bob.

Bob Martell -- Head of R&D -- Analyst

Yeah. So that's another population that is unique, although the historical evidence is that things don't work quite so well there. So we have seen clearly, as you saw previously, in that population, we've had very strong anticancer activity. So for example, four out of the six patients who had elevated blast count at baseline normalized their blast counts, so striking anticancer activity.

And one of those patients even went on to stem cell transplant, which is a potentially curative approach. So there, we need to discuss with the FDA what type of surrogate might be optimal for this patient population. Clearly, the anticancer activity is one end point that we'll discuss. Also, we'll be starting to think about our combination trials; and as those come in, that offers other opportunities for clinical trial development moving forward there.

Jim Dentzer -- President and Chief Executive Officer

Yeah. Maybe if I were to summarize that as well to emphasize a little bit of those -- some of those points, Alethia, I'd say that, in AML, there's clarity on the end points that the FDA is going to want to see. To Bob's point, there are several drugs that have looked at the CR and CRh rate as an end point. And it was actually not just for accelerated approval there, full approval on those end points, so gilteritinib, ivosidenib and enasidenib all got CR, CRh rates.

So there seems to be broad agreement on what sort of end points would make sense, and there's broad agreement that our data look great in those end points compared to anything else used in relapsed/refractory setting. In MDS, in those same two points, I'd say everybody seems very comfortable that our data looked terrific compared to what else gets used. The lack of clarity is on what the end point is going to be, and that's where there's a lot of discussion. Certainly, we get a lot of questions about that because the fact of the matter is there are no drugs approved in relapsed/refractory MDS.

Given that there are no drugs approved and there are no drugs approved because nothing's worked, it's not clear where the FDA will come out on that. So I think the AML path is, of course, much more clear. We just need to go make that case to the FDA and get them comfortable that we're ready to go to the pivotal design on this. But the end points are clear, and our data look good on those end points.

In MDS, our data looked good certainly compared to chemo, which gets used more than half the time in these patients. But the lack of clarity is simply because there are no drugs approved. So we will be trotting new ground with FDA on the primary end points in that study. Hopefully, that's helpful.

Alethia Young -- Cantor Fitzgerald -- Analyst

No, that's very helpful.

Jim Dentzer -- President and Chief Executive Officer

OK. Great. So maybe I will go to your VISTA question. So yeah, so VISTA in 2021, the big check-the-box item was, say, we knew that to expect CRS side effects.

We designed the study to expect that and to manage them effectively. And so we needed to go out and prove that we could, to make it short, we could succeed where Janssen failed. Could we clear 0.15 mg per kg? And the answer was we did, and we cleared 0.3, and we're now dosing at 0.6. So the check the box on safety so far has been a terrific win for 2021.

Now for 2022, the goal changes. Now we're on the hunt for efficacy. We don't know exactly which dose level will lead to the type of concentrations of drug that will lead to tumor shrinkage, but that's what we're hunting for. So we are looking to, in monotherapy, dose escalate and explore to try and find what is the right dose to expand on the exciting pharmacodynamic findings that we've seen so far and hopefully see evidence of tumor shrinkage.

At the same time, you mentioned, are we also thinking about combination therapy, and the answer to that is yes. We will be moving forward and stay tuned on that discussion with an approach, where we're going to study both monotherapy and combination therapy in the clinic in 2022.

Alethia Young -- Cantor Fitzgerald -- Analyst

And just a quick -- just another question I was making on low-risk MDS. What's kind of the update there with -- I know it was an investigator trial. But just kind of what's going on with that? Thought it was a pretty interesting trial.

Jim Dentzer -- President and Chief Executive Officer

Yeah, it's a really interesting trial. As I mentioned in my comments, it's just because it's an IST, we don't have a whole lot of visibility to that. My expectation is I know that Dr. Platzbecker, who's -- he's the European lead in MDS.

He's the head of the EHA Working Group on MDS. He's got 17 sites in that study. So my hope is -- and I say it's a hope. I can't promise, of course, since we don't run it.

But my hope would be that we'll have data from that study at some point this year. But having a small molecule with our safety profile that's disease modifying to use in that setting is something that, obviously, not just we're excited about, but obviously, Dr. Platzbecker and his team are very excited about as well. So we look forward to hopefully seeing results from that study later this year.

Alethia Young -- Cantor Fitzgerald -- Analyst

That's very helpful, thanks.

Jim Dentzer -- President and Chief Executive Officer

Yup. Thank you.

Alethia Young -- Cantor Fitzgerald -- Analyst

Thank you very much.

Jim Dentzer -- President and Chief Executive Officer

Thank you, Alethia.

Operator

The next question is from Ed White with H.C. Wainwright. Please go ahead.

Ed White -- H.C. Wainwright and Company -- Analyst

Good afternoon. Thanks for taking my questions. So just to dive down a little bit more in AML, as you said, you have a clarity of end points. How should we be thinking about the size of the study that you need? And when you can start enrolling after you talk to the FDA, would you be able to start by the end of this year? Or is it a next year event? And then knowing what you know now about the pandemic, we've been dealing with it for two years, just wanted to get your thoughts on what you think enrollment trends could be.

How fast could you get the trial enrolled? Thanks.

Jim Dentzer -- President and Chief Executive Officer

OK. Maybe I'll ask Bob to talk about the size of the study first. Bob?

Bob Martell -- Head of R&D -- Analyst

Yeah. So again, we can look at historical precedents in the studies that Jim and I mentioned that achieved approval with single-arm studies. They all enrolled somewhere between 100 and 200 patients. Given the very poor outcome in this population, we couldn't explore even lower numbers, but probably somewhere in that range for a trial that could achieve approval.

What we're hoping to do is -- and we'll discuss this aspect with the FDA as well in terms of the study enrollment, considering potentially expanding our current trial, so patients that we've already enrolled on to the trial, we'll capture the data that would be relevant there and then continue potentially enrolling that versus starting a new study. So those are a couple of options that we would discuss with the FDA.

Jim Dentzer -- President and Chief Executive Officer

Yeah. And so Ed, I would echo what Bob said and especially when you look at the other studies that have been done historically. Bear in mind that the survival, once you're post HMA in this setting, is two to six months. Post HMA specifically, median survival is 2.3 months, which is crazy.

So we would expect that given the efficacy we've seen so far, even though it's a small end, so it's kind of hard to talk about powering the study for statistical purposes, it seems reasonable to say that we would be in the range of other studies that have gone after pivotal design in AML. Whether or not we can start in 2022 or 2023 is going to depend a little bit on the design that FDA accepts. Of course, what we would hope for is a single-arm study, in which case we're ready to go now. We've already been testing patients on a single arm.

And so of course, we would leverage those data and just keep steaming forward with the existing sites and recruiting from those and adding new ones. If, on the other hand, of course, the FDA comes back and says they want a controlled study that's -- now you've got to get that protocol out and now you're talking more of a 2023 start. But our hope would be that they'll follow precedent and go with a single-arm study. And then the last question you had about how fast could it enroll, we've been really pleased at the rate of enrollment.

I think it's the consequence of the unfortunate fact that survival is so grim for these patients. And the reason why survival's so grim is that nothing works. The No.1 genetic driver of disease in AML and MDS is IRAK4 long expression, and I think part of the reason why survival's so grim is that none of the treatments out there address that driver. 4948, now emavusertib, does.

So our hope would be that the excitement we've seen among the investigators so far would continue as we add more sites into the pivotal study. Is that helpful, Ed?

Ed White -- H.C. Wainwright and Company -- Analyst

Yup. Thank you. And just one last question on that regarding the discussion with the FDA, do you have all the data in hand now to speak with the data -- with the FDA that you want? Or is there any delay as you are awaiting more data?

Jim Dentzer -- President and Chief Executive Officer

No, there's no delay. It is an ongoing study. So we're going to continue to have more data in hand with every day and week that progresses. I think our time line is unchanged.

We expect to have a discussion with FDA in Q2. That's what we're certainly going to ask for. We can't control when they schedule it, but we believe we'll have sufficient data at task for that meeting, and we think it'll be a good discussion. But in terms of how much data we have at any given point, the study is ongoing, so we continue to enroll through the process.

And our hope would be, if it's a single-arm study, as we've been enrolling patients the whole time, we'll just keep adding those patients into the pivotal group so that we could get to the NDA time line that much more quickly. That would be our hope of course.

Ed White -- H.C. Wainwright and Company -- Analyst

Great. Thanks for taking my questions.

Jim Dentzer -- President and Chief Executive Officer

Thanks, Ed.

Operator

The next question is from Yale Jen with Laidlaw Company. Please go ahead.

Yale Jen -- Laidlaw Company -- Analyst

Good afternoon, and thanks for taking my questions. I'm just going to tag on the first -- the earlier question in terms of the FDA meetings. In terms of the patient, do you see -- so by the time you talk to the FDA, do you have sufficient MDS versus AML patients? Or how do you see that? And the second question to that is that what do you anticipate augment, sort of follow-up FDA would require you to assess for the duration of response? Would that be roughly 12 months, whether that will be for the current study or for the future studies?

Jim Dentzer -- President and Chief Executive Officer

Yeah. So let me address the first one, and I'll ask Bob to talk to the second one in duration. Thanks, Yale, for calling in. So about the number of patients for AML and MDS, in both cases, to be frank, the patient sample size is small.

We already made the data public in the first week of January. We [Audio gap] no matter how we slice it, we're going to have a small data set when we go talk to FDA. Is that enough patients for FDA's purposes, we'll find out when we have the discussion. We think so.

We think that the data are clear, that the drug is active. It's active as a single agent, and it's active in a population where nothing else works. I think that's a strong fact pattern to take to the FDA. Now will we have more patients over time? Of course.

That's exactly the way we want to go talk to them. We think this drug merits a pivotal study, and we're willing to put the resources to work to increase the patient size to be able to demonstrate whether or not this really does merit approval. So that's the point of the discussion. Whether or not they differentiate how many patients we need for AML versus MDS, that's not clear.

We'll find out over time. As I said in response to Alethia's question, I think the points that everyone agrees on are that there seems to be a really clear discussion for AML. There's clarity in the end point, and there's clarity that our data looked really good in that end point compared to existing therapies. In MDS, everybody is excited about how our data look compared to existing therapy, but there's not a whole lot of clarity on end point.

And so I think those will be the key items for discussion with FDA. Bob, could you do -- answer the follow-up on duration?

Bob Martell -- Head of R&D -- Analyst

Yeah, definitely. Yale, so I think what you're asking is how long after we enroll x number of patients do we need to wait to get the duration of response for the FDA. And so that really depends on ultimately the number of patients getting to a certain end point and oftentimes, the -- in previous labels that the FDA has used, kind of a six-month time frame for that kind of looking for a certain number of patients to get beyond that point or to have an event such as progression. So we would monitor those patients, and the total number of patients that we enroll may actually be large enough such that we hit that point even sooner than six months from the last patients enrolled.

So that will be ultimately determined by our signal and the timing of the study.

Yale Jen -- Laidlaw Company -- Analyst

OK. Great. Maybe just one more question here regarding the VISTA. You started -- potentially starting the efficacy study later on this year.

Is the sort of [Audio gap] considered as a hot [Audio gap] cold tumor? And any impact at this point? Or you probably will take all [Audio gap]

Jim Dentzer -- President and Chief Executive Officer

Yeah. Actually [Audio gap]

Bob Martell -- Head of R&D -- Analyst

Yeah, we definitely like to enrich the patient population. So there are certain tumors that have relatively high expression of VISTA. So in discussing with our investigators, we certainly encourage them to consider putting their patients that have those profiles on to the study. So for example, patients with mesothelioma have extremely high expression of VISTA.

Several of the gynecologic malignancies have extremely high expression of VISTA such as ovarian or uterine cancer. Subsets of non-small cell lung cancer and triple-negative breast also have very high level of VISTA. You asked [Inaudible] of hot versus cold. So certainly, in our preclinical models, certain hot tumors are quite responsive to this drug; but also, we've had some clear evidence that this antibody or targeting VISTA, in general, can overcome some of the issues, for example, bringing a cold tumor into a -- basically lowering the threshold for activation of the immune system, so perhaps bringing cold tumors into a hot tumor setting.

Yale Jen -- Laidlaw Company -- Analyst

OK. Great. That's very -- go ahead. I'm sorry, go ahead.

Jim Dentzer -- President and Chief Executive Officer

No. Yale, I -- go ahead, bob.

Bob Martell -- Head of R&D -- Analyst

No, please go ahead.

Jim Dentzer -- President and Chief Executive Officer

Right. So I would add to that a little bit. I'd say that in VISTA, to be fair, this is part of the challenge and also the exciting part of going after a novel target. We know that in The Cancer Genome Atlas, there are certain indications, as Bob mentioned, that are associated with high VISTA expression.

They're clearly correlated with high VISTA expression. We don't know if it's correlation or causation. We are clearly going to try to enrich for those patients in all the indications Bob mentioned; and hopefully, we'll see efficacy in monotherapy in those patients. But we don't know.

That will be part of the exploration. Is VISTA a target? We're knocking it down in monotherapy is sufficient in certain indications. But we also want to pursue combination therapy. You've seen our preclinical dataset, and it seems to be tremendously synergistic with PD-1 and CTLA-4 for all the reasons that the literature suggests.

It's just never been tested in patients before. I think the idea that we are hitting the target and the targets having effect is suggested by not just the CRS symptoms that we have seen but also by the PD data that we have published in patients. And I think as we increase drug concentrations both in monotherapy and targeted patient -- in targeted indications and also in combination, we hope to see that the findings that we saw in the lab show up in the clinic as well. But that's -- as I say, that's part of the fun of pursuing a new target that no one's ever gone after before.

So stay tuned.

Yale Jen -- Laidlaw Company -- Analyst

Thanks a lot, and please enjoy.

Jim Dentzer -- President and Chief Executive Officer

Thanks, Yale.

Operator

The next question is from Soumit Roy with JonesTrading. Please go ahead.

Danya Ben-Hail -- JonesTrading -- Analyst

Hi, this is Danya for Soumit Roy. Thank you for taking our question, and congrats on the updates. I would first like to ask about the AML/MDS trials. Do you expect that with the clinical hold of the anti-CD47 agents, are you expecting any specific uptake from the AML/MDS patients, especially for high-risk MDS?

Jim Dentzer -- President and Chief Executive Officer

Sure. So I think the biggest issue with magrolimab going on hold, yeah, all things being equal, anybody else that's got a study going in AML and MDS, those patients need to go somewhere. So all other trials in the study would benefit just in enrollment, all things being equal. I would think the bigger question for us when a physician considers which trial to go into, is it a magrolimab combination study or is it an emavusertib combination study.

They want to think about what's the best thing for patients. Now there's clearly a larger dataset for magrolimab than there is for emavusertib, but both patients were studied in monotherapy. And you may remember that the monotherapy data for magrolimab didn't look anywhere near as good as the monotherapy data for emavusertib. So I think our conversations with the physicians are more about if you're going to combine the drug with azacitidine, which drug do you want to combine with.

And we think we've got a pretty compelling case that the drug you want to choose in that case is emavusertib whether they're on clinical hold or not. So yeah, all things being equal, I think that should help other drugs that are being studied in the space. But I think for us, in particular, having the only drug in the clinic that targets the driver of disease or at least the largest driver of disease is really the more important factor.

Danya Ben-Hail -- JonesTrading -- Analyst

Makes sense. And as for the 8993, would you be collecting baseline VISTA status? Or are we going to see [Inaudible] in your next update on expression levels?

Jim Dentzer -- President and Chief Executive Officer

Yeah. Actually, Bob, do you want to talk to that?

Bob Martell -- Head of R&D -- Analyst

Yeah, we're capturing a lot of aspects, including baseline information from patients. Although to be clear, we're not selecting patients specifically for high VISTA, but we'll be monitoring that and ultimately, correlating that as well as [Audio gap] so -- and you saw some of the data that we presented in January. We have a pretty robust biologic and pharmacodynamic program going on for that molecule. And we think that that's going to provide a great perspective on VISTA in general as a target in specific that 8993 is an excellent agent there that has not only great PK exposure but more importantly, in patients we're already seeing really dramatic pharmacodynamic effects that really affect anticancer mechanisms directly.

So we're really excited about our pharmacodynamic and biologic profile of this drug for our patients.

Danya Ben-Hail -- JonesTrading -- Analyst

Great. Looking forward to the update. Thank you.

Jim Dentzer -- President and Chief Executive Officer

Thank you very much.

Operator

[Operator instructions] The next question is from Dane Leone with Raymond James. Please go ahead.

Dane Leone -- Raymond James -- Analyst

Hi guys, thanks for taking the question. Yes. Any color you can give in terms of how you view the cadence of enrollment, continued enrollment for 4948 and what that provides you with in terms of a line of sight for setting expectations for clinical updates on the spliceosome cohort this year and then when we could get first data out to maybe the combination studies? And just any color again on if the clinical hold on magrolimab might accelerate potential enrollment into the combination studies with ven/aza and what your general cadence of enrollment is expected or how that's been going so far? Thank you.

Jim Dentzer -- President and Chief Executive Officer

Sure. Thanks, Dane, and thanks for joining the call. So I think my comments on magrolimab and the impact on their clinical hold on our enrollment pace, I think I answered a few minutes ago. As I said, I think all things being equal, the halt of the magrolimab study should help us and anybody else that wants to run a clinical study in AML and MDS.

I think the bigger factor, though, for us versus magrolimab is going to be what's best for the patient. And if you have two studies to choose from as a clinician, as an investigator to combine with azacitidine, which drug do you pick? Do you put them in a study that combines it with magrolimab or a study that combines it with emavusertib, formerly 4948? I think we can make a very strong case that you want to put it in azacitidine plus emavusertib based on the single-agent activity that we showed versus magrolimab. But that said, I think you're right. All things being equal, the clinical hold should be helpful for us.

We've seen a really exciting uptick in enrollment. You may remember that we had two spliceosome patients a year ago. We had three at EHA at June. And for the January update, we had 13.

So we're seeing a fairly dramatic uptick of physicians that are finding these patients and wanting to put them on to our study. So my hope is that we can maintain that kind of excitement level and that we will be producing data that we can report out on later this year on a whole host of fronts. So we've got monotherapy data with spliceosome patients in AML, spliceosome patients in MDS, FLT3 patients in AML, combination therapy data with emavusertib and azacitidine, also emavusertib plus venetoclax. We've got the IST going in low risk or lower risk MDS.

And we've also got combination with ibrutinib data. So we've got a whole host of clinical activity going on simultaneously. And my hope is that we're going to have a raft of data across the board. And my hope would be, of course, that it will be just as exciting in 2022 as it was in 2021.

Dane Leone -- Raymond James -- Analyst

Is it -- one follow-up on that. Can you -- so the enrollment into the ven and aza combination cohorts are not -- they're not selected patients, right? So that's an all-comers regardless of mutational status.

Jim Dentzer -- President and Chief Executive Officer

That's right. So they're all-comers. But of course, what we would look to do is replicate the experience that we had preclinically, which is preclinically, we showed terrific synergy or at least terrific additive effect that the patients who were going to go on azacitidine or venetoclax or the doublet, for that matter, preclinically, in all three cases, the data were significantly more compelling when you added emavusertib to it, whether it was venetoclax monotherapy, azacitidine monotherapy or the doublet. So what we're looking to do in the clinic is to replicate that.

We want to get combination with venetoclax, combination with azacitidine. And then assuming that that goes well, we'd love to pursue a triplet as well.

Dane Leone -- Raymond James -- Analyst

And can you give an update on just how many patients you've enrolled into the combination arms --

Jim Dentzer -- President and Chief Executive Officer

We haven't given an update on that yet, but that would be part of the update that we're going to give later this year.

Dane Leone -- Raymond James -- Analyst

OK. All right. Thanks.

Jim Dentzer -- President and Chief Executive Officer

Thank you.

Operator

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, James Dentzer, for any closing remarks.

Jim Dentzer -- President and Chief Executive Officer

Thank you, Gary, and thank you, everyone, for participating in 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, ImmuNext and the NCI for their ongoing help and support. We look forward to updating you again soon. Operator?

Operator

[Operator signoff]

Duration: 51 minutes

Call participants:

Bill Steinkrauss -- Chief Financial Officer

Jim Dentzer -- President and Chief Executive Officer

Alethia Young -- Cantor Fitzgerald -- Analyst

Bob Martell -- Head of R&D -- Analyst

Ed White -- H.C. Wainwright and Company -- Analyst

Yale Jen -- Laidlaw Company -- Analyst

Danya Ben-Hail -- JonesTrading -- Analyst

Dane Leone -- Raymond James -- Analyst

More CRIS analysis

All earnings call transcripts