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.

Thank you and welcome to Curis' fourth quarter and year-end [Indiscernible]. 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 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?

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 patient's lives. In the fourth quarter of 2021, we made significant strides towards that goal. To start, we are pleased to announce that our novel IRAK4 inhibitor CA-4948 will be adopting a new generic name emavusertib as well as introducing, take aim to our brand name for clinical trials moving forward with emavusertib. The taking them 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 cancer s. The first study taking leukemia is a Phase ½ 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 taking lymphoma is a Phase ½ 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 game leukemia study in targeted patients with relapsed refractory AML or MDS, whose disease is characterized by a spliceosome or FLT-3 mutations. The updated dataset supported the findings presented at EHA last year, further demonstrating encouraging anticancer activity, compared to standard of care therapies in an expanded set of patient data. As of December, we had enrolled 49 patients in monotherapy, 13 of which had genetically defined…

Thank you, Jim. Curis continues to operate from replace 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 the basic and diluted basis in 2020. With a 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 the 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 2020, and was comprised of the following: Cost of royalty revenues primarily amounts to the third party university patent license orders in connection with Genentech and Roche's Erivedge net sales were $0.5 billion for the years ended December 2021 and 2020. Cost of royalty revenues were $0.2 million 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 the same period, 2020. Settlement expenses were $10.8 million for the fourth quarter of 2021, as compared to $5.6…

We will now begin the question-and-answer session. [Operator Instructions] At this time, we will pause momentarily to assemble our roster. The first question is from Alethia Young with Cantor Fitzgerald. Please go ahead.

Thanks 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 talking about, how we're thinking about the trial designs. What's really vital versus what might not be viable? I know you've had this conversation with the FDA, but -- how you're thinking about what the expectation -- how you guys are framing up for what it should be on that front. And then, I 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? You'll be past the safety and efficacious doses? And how do you think about continuing monotherapy, or is there any option of potentially doing some -- more of a combination with those things?

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

Yeah, hey, Alethia, thanks for the question. The trial design we said we're breaking it down into high-risk MDS and AML. And I think you know currently the AML we believe is fairly straight forward. What we're trying to do is look both in parallel at a very rapid path to registration by with the FDA. And that could involve a single-arm study looking at surrogate endpoints like CR and CRh. Those endpoints are validated endpoints by the FDA and used also in conjunction with durability of response. A couple of drugs have been approved in this space and AML, including gets LiNiB and [Indiscernible] 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. Yet, In the data that we've presented some far, we've presented really very durable CR and CRh, and quite good effects on blood comps are 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.

Yeah, thanks, Bob. On the first question -- first, Alethia does that answer your question on trial design for CA-4948?

Yeah. That's helpful. Is there a distinction though in MDS is the what you might do versus AML, which obviously you can get a -- I can see the unmet need in the protocol and how we've gone forward with AML, but with MDS, like how you kind of think about a later stage trial design that [Indiscernible] comment on there?

Well, there's definitely --

[Indiscernible]

Go ahead, Bob.

Yes. So that's another population that is unique, although the historical evidence is that things don't work out so well up there. So we have seen, as you saw previously in that population, we've had very strong anticancer activity. So for example, 4 out of the 6 patients who had elevated blast counts at baseline normalized their blast count. So it's striking anticancer activity. And one of those patients even went on to a stem cell transplant, which is a potentially curative approach. So there we need to discuss with the FDA what type [Indiscernible] might be optimal for this patient population. Clearly the anti-cancer activity is one endpoints that we'll discuss. Also will be certain to think about our combination trial, and as those are coming that offers other opportunities for clinical trials and development moving forward there.

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 is clarity on the endpoints that the FDA is going to want to see. To Bob's point, there are several drugs that have looked at the CR to CRh rates as an endpoint. And it was actually not just for accelerated approval there, but full approval on those endpoints, so both emavusertib all got CR CRh rate. There seems to be broad agreement on what endpoints would make sense. And there's broad agreement that our data look great in those endpoints 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 look terrific compared to what else gets used. The lack of clarity is on what the endpoint 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 is 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 endpoints are clear in our data look good on those endpoints. In MDS, our data look 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 endpoints in that study. Hopefully that's helpful.

No, that's very helpful.

Okay. Great. Maybe I will go to your VISTA question.

Yeah

This year in 2021, the big check-the-box item will say [Indiscernible] we knew that to expect CRS side effects, we designed the study to expect that and to manage them effectively. 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 mics per kg, and the answer was we did, and we cleared 0.3 and we're now dosing a 0.6. 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're 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.

Just a quick -- another question I'll sneak in on low risk MDS. What's the update there with? I know it was an investigated trial but what's going on with that? That was a pretty interesting trial.

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 the European lead and 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 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.

At least from very helpful. Thank you very much.

Thank you. Alethia.

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

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 endpoints. How should we be thinking about the size of the study that you need? And when you can start a rolling after you talk to the FDA, would you be able to start by the end of this year or for the next year event. And then knowing what you know now about the pandemic, we've been dealing with it for two years, I just wanted to get your thoughts on what you think of involvement trans could be, how fast could you get the trial enrolled? Thanks.

Okay. Maybe I'll ask Bob to talk about the size of the study. First Bob.

Yeah, sure. The -- again, we can look at historical precedence 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 could have explored even lower numbers, but probably somewhere in that range for a trial that could have achieved 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 trials. In patients that we've already enrolled onto 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.

Yes. 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 's specifically median survival is 2.3 months. It was crazy. We would expect that given the efficacy we've seen so far, even though it's a small end so it's hard to talk about powering a 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 [Indiscernible]. 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 single-arm. And 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 say,s 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 the 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's grim for these patients. And the reason why survival's so grim is that nothing works. The number one genetic driver of disease in AML and MDS. It's not like for long expression. And I think part of the reason why survival so grim is that none of the treatments out there address that driver for nine for eight. 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?

Yeah, thanks Chairman. 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 awaiting more data, thanks?

There's no delay. This 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 timeline 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 will 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 groups so that we could get to the NDA timeline that much more quickly. That would be our hope, of course.

Great, thanks for taking my questions.

Sure, thanks, Ed.

The next question is from Yale Jen with Laidlaw and Company, please go ahead.

Good afternoon and thanks for taking my questions. I'm just going to tackle on the first or 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 ultimate total 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?

Yes, let me address the first one and I'll ask Bob to talk to the second one in duration. Thanks Yale for calling in. About the number of patients for AML and MDS, in both cases to be frank, the patient sample sizes are small. We already made the data public in the first week of January. [Indiscernible] -- no matter how we slice it, we're going to have a small dataset when we go talk to FDA. Is that enough patients for FDA's purposes? We'll find that 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 why 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 endpoint. And there's clarity that our data look really good in that endpoint 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 answer the follow up on duration?

So I think 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 endpoint. And often times the previous labels though the FDA is used a fixed month time-frame for that looking for certain number of patients to get beyond that point or to having events such as progression. So we would monitor those patients and the total number of patients that we enroll may actually be large enough such so that we hit that point even sooner than 6 months from the last patients enrolled. That'll be ultimately determined by our signal and the timing of the study.

Okay, great. One more question here regarding the VISTA. Do you start -- potentially starting the efficacy study later on this year. Is that that the two tumor considered as a [Indiscernible] cold tumor, and any impact at this point, or you probably will take all comers?

Yeah actually, we definitely like to enrich the patient population, So there's certain tumors that have relatively high expression of this stuff So in discussing with our investigators, we certainly encourage them to consider putting their patients that have those profiles onto the study. So for example, patients with mesothelioma have extremely high expression of this. Several of the gynecologic malignancies have extremely high expression of this, such as ovarian or uterine cancer. Some sense of non-small cell lung cancer and triple negative breast also have very high level of VISTA. You asked of hot versus cold. 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 are targeting VISTA in general can overcome some of the issues. For example, bringing a cold tumor into a -- lowering the threshold for activation of the immune system. So perhaps bringing cold tumors into a hot tumor setting.

Okay, great. That's very -- I'm sorry, go ahead.

That yellow a little bit. Go ahead, Bob.

No, please go ahead.

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're clearly [Indiscernible] try to enrich for those patients and 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 where knocking it down in monotherapy is sufficient in certain indications, but we also want to pursue a combination therapy. You've seen our pre -clinical dataset and it seems to be tremendously synergistic with PD1 and CTLA4 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 target is 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 concentration spooked in monotherapy in 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.

Thanks a lot and please enjoy.

Thanks, Yale.

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

Hi. This is Danya for Soumit Roy. Thank you for taking our questions and congrats on the updates. I would first like to ask about the AML MDS trial. Do you expect that with the click-off hold for the [Indiscernible] agents, are you expecting any [Indiscernible] uptick take from the AML MDS patients, especially for high-risk MDS?

I'm sure -- I think, the biggest issue with Magrolimab going on hold -- 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 study would benefit 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. I think our conversations with the physicians are more about if you're going to combine a drug with Nizatidine 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 are on clinical hold or not. 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.

Makes sense. As for the 8993, would you be collecting based on [Indiscernible] status? Or are we going to see [Indiscernible] in the next update? The expression levels?

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

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 other markers that -- As 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. And in specific, that 8993 is an excellent agent there that has not only great PK exposure, but more importantly, in patients are already seeing really dramatic pharmacodynamic affects that really affects the anticancer mechanisms directly. So we're really excited about our pharmacodynamic and biologic profile for this drug for our patients.

Great. Looking forward to the up dates. Thank you.

Thank you very much.

Again, [Operator Instructions] the next question is from Dane Leone with Raymond James, please go ahead.

Hi, guys. Thanks for taking the question. 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 displacing them cohort this year. And then when we could get first data out to the combination studies? And just any color again on -- if the clinical hold on magrolimab might accelerate potential enrollment into the combination studies with [Indiscernible], and what your general cadence of enrollment is expected or how it's been going so far. Thank you.

Sure. Thanks Dane and thanks for joining the call. 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 hold to 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, it's 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? You put them in the study that combines it with magrolimab or a study that combines it with emavusertib, formerly 4948. I think we can make up 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 to clinical hold should be helpful for us. We’ve seen a really exciting uptake and enrollment. You may remember that we had two splices on patients a year ago, we had three at EHA at June, and in -- for the January uptake we had 13. We're seeing a fairly dramatic uptake of physicians that are finding these patients and wanting to put them onto our study. My hope is that we can maintain that 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, FLT-3 patients in AML, combination therapy data with emavusertib and [Indiscernible], 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.

Is it, one follow-up on that, can you say that enrollment into the fan in is that combination cohorts are not they're not selected patients, right? So that's an all-comers regardless of mutational status?

That's right. So they're all-comers. But of course what we would look to do is replicate the experience that we had pre -clinically, which is -- pre -clinically, 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, pre -clinically. In all 3 cases, the data were significantly more compelling when you added emavusertib to it. Whether it was venetoclax monotherapy, azacitidine monotherapy, or the doublet. 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.

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

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

Okay. All right. Thanks.

Thank you.

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.

Thank you Gary and thank you everyone for participating in today's call. 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?

The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.