Good afternoon and welcome to the Curis Third Quarter 2021 Earnings Call. All participants will be in a listen-only mode. [Operator instructions] After the company's prepared remarks, call participants will have an opportunity to ask questions. [Operator Instructions] Please also note this event is being recorded. I would now like to turn the conference call over to Curis’ Vice-President of Investor Relations and Corporate Communications, Elif McDonald. Please go ahead.

Thank you Garry. Welcome to Curis' third quarter 2021 earnings call. Before we begin, I would encourage everyone to go to the Investors section of our website at www.curis.com to find our third quarter 2021 earnings release and related financial tables. I would also like to remind everyone that during the call, management 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; Bill Steinkrauss, Chief Financial Officer and Bob Martell, Head of Research & Development. 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?

Thank you, Elif. Good afternoon everyone. It’s my pleasure to welcome you to Curis’ this third quarter earnings call. As we look back on the year, we have come so far as a Company making important progress with both of our lead clinical programs, CA-4948, and CI-8993. Every day at Curis, we strive to develop the next-generation of transformative cancer therapies that meaningfully improve and extend patient's lives. In the third quarter, we made significant progress towards that goal. To start, let me review our lead asset, our novel small molecule IRAK4 inhibitor CA-4948. CA-4948 is the most advanced of IRAK4 inhibitor in clinical development for cancer, and is currently being evaluated in nine distinct patient populations across AML, MDS and B cell cancers. There is a critical unmet need for safe fast acting treatments for patients with AML, the leading cause of leukemia deaths in the United States. In MDS, the need may be even more critical, as so many patients are left with only supportive care as their best option for treatment. We are excited that the original scientific rationale for CA-4948 and IRAK4 inhibiton has been followed by consistent and encouraging results in the lab and so far consistent and encouraging results in the clinic. In both our B cell cancer and AMM and MDS studies, CA-4948 has continually demonstrated a well-tolerated safety profile, and the ability to demonstrate improved efficacy over multiple cycles of treatment. These findings were most recently presented at the EHA meeting in June, where we shared data from the monotherapy arm of our Phase 1/2 AML MDS study demonstrating clear efficacy, with no dose-limiting myelosuppression, a potentially key differentiating factor that may allow even extremely sick patients with low thresholds for drug tolerability to be treated with CA-4948. Our second lead program…

Thank you, Jim. For the third quarter 2021, we reported a net loss of $11.1 million or $0.12 per share on both the basic and diluted basis, as compared to a net loss of $6 million or $0.11 per share on both the basic and diluted basis for the same period in 2020. For the nine months ended December 30 2021, we reported a net loss of $31.8 million or $0.35 per share, as compared to a net loss $22.4 million or $0.52 per share for the same period 2020. Revenues for the third quarter 2021 and 2020 were $3 million and $2.7 million, respectively. Revenues for the nine months ended September 30, 2021 were $7.5 million as compared to $7.8 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. Operating expenses for the third quarter of 2021 were $13.1 million as compared to $7.5 million for the same period 2020. Operating expenses for the nine months ended September 30 2021 were $37 million as compared to $26.4 million for the same period 2020. And we're comprised of the following; cost of royalty revenues, primarily announced due to third party University patent license orders in connection with Genentech and Roche's Erivedge net sales. We’re $0.2 million for the third quarter of 2021 as compared $2.1 million to the same period in 2020. Cost of royalty revenues were $0.4 million for both the nine months ended September 30 2021 and 2020. Research and Development expenses were $8.6 million for the third quarter of 2021 as compared to $4.7 million for the same period in 2020. The increase in direct research and development expenses for the quarter is primarily attributable to increased clinical and manufacturing costs…

Ladies and gentlemen, at this time we'll begin the question-and-answer session. [Operator Instructions] Our first question is from Alethia Young with Cantor. Please go ahead.

Hey, guys, thanks for taking my questions. Just a couple. One, I wanted to start with, maybe the kind of I don't know, if you're ready to kind of give this granularity. But should we be thinking that kind of the FDA conversation probably would happen, after kind of the second more robust update? So maybe perhaps like a little bit later in the first half of 2021. I guess my this kind of leads into my second question, which is, I guess with 10 to 20 people like do you think that's going to be sufficient? Do you have safety and other stuff from other studies? But just do you think that's what's your competence, everyone that being that kind of enough to trigger a conversation that can inform potential pivotal strategy even though I know it's a much smaller population? And then my third question was, you mentioned, I guess, you mentioned the complete the complete response, which existed, but then you mentioned potential for another complete response. So I just wanted to confirm that that's not been seen yet. It's just what you hope to see? Thanks.

Yes, thankfully, this is Jim. So let me start with that last one, because I know that's of high interest. It's what we're hoping to see this; obviously, it's not a call where we're discussing the data that we have seen. We've got a couple months for the data to mature. But we when we think about what we're hoping to see with this drug, this drug has shown a really unique ability as a monotherapy to reduce cancer burden across the spectrum. With a majority of these patients are getting their blast counts all the way back down to the normal range. That's what we want to see. We've already seen one CR, we'd love to see another one. We want to give that update in January. We don't have all those data yet. But of course, if you ask for what we were hoping for, that was sort of our guidance. In terms of the FDA meeting, we have always planned and we've been very clear about this all year. We have always been planning to get the concentration focus on spliceosome patients in FLT-3 patients. When we saw that the data we had at EHA was so compelling, we really ramped up our efforts to get patients on drug. Our regulatory consultants had given us guidance that in order to meet with the FDA, we probably need 10 to 20 patients. And that's our goal is to get 20 patients, 10 to 20 patients on drug by December 31. Whether or not the FDA agrees with those consultants and takes our meeting and has the discussion we hoped for, of course, we don't have any control over. But the general consensus seems to be that if we can get 10 to 20 patients and the data look consistent, then we should have a good shot at having a successful discussion with the FDA. The reason for the new update that we're offering in January is of course, we're very pleased with what we said. We don't have all the data yet, but the data that we have, we think do look compelling and consistent with what we've been. And we think that if we can make that cut off to have 8 to 10 patients at year-end and with spliceosome mutations, and another three with FLT-3, that does go a long way to giving everybody our investigators, the KOL community and investors a very good sense of where are the data trending? We've only seen three patients so far. Where are the data trending, so that we have a good sense of how that discussion with the FDA might go. That's the point of that update. So we're very happy with where we sit but of course we've got more data internally and we'd like to make it public so that January plan is to make all of that public.

And then just maybe it's the follow on and the safety would the ibrutinib combination that you mentioned, you haven't seen anything like related to rhabdo or anything, so I think you said there was no deal to you? So I just want to confirm that.

Yes, actually, Bob, would you mind talking about that?

Yes. So we've obviously continued to dose patients with our 300 dose level in the monotherapy study that's going along? Well, as Jim said, we'll update the safety on that. We probably won't be giving an update on the combination study at that point. But yes, there were no dose limiting issues at that initial dose level, so it was quite well tolerated, which, which is really exciting. Because, as you know, now we're able to dose escalate up to the full dose of both, both drugs.

Great, thank you.

The next question is from Dane Leone with Raymond James. Please go ahead.

Hi, thank you for taking the questions and congratulations on the progress. I guess, in light of the announcement that you're going to host an update call in January. Now, maybe, given this isn't going to be the full dataset of what you hope to have in spliceosome and FLT-3, could you maybe just clarify how to set expectations? I guess the worry is, if you're giving this update in January, everyone tries to interpret it in terms of a data set that you'd actually walk into the FDA with, maybe something akin to the men [ph] and inhibitor class. But it seems like from your commentary, you're trying to give more of an anecdotal update. So maybe you can just provide some caveats to what this data analysis is actually going to look like. And the context that you're trying to hope to pull out of updating people publicly, without maybe the full datasets here for the spliceosome group.

Sure, we’re not making an initial comment on that now let's start to expand as well. So I think the thought process is, of course, we gave a terrific update of three patients, but it was only three patients at EHA with a spliceosome mutation. And in fact, one FLT-3 patient, FLT-3 patients did exactly what we hoped, exactly what the literature would suggest, that patients that did not respond to other FLT-3 inhibitors coming onto our study. And within two cycles, not only getting a response, but seeing complete eradication and mutation. I mean both datasets, the first three and the one look terrific. And we then moved fast and furious to have a discussion with the FDA. And I think what we're just trying to respond to is it's a long time between EHA, in that discussion with the FDA, we have a lot of confidence. And we are seeing terrific progress in that study. And we wanted to give everybody else a chance to see what we're seeing. So it's not the full update that we'll have in, six months from now. But we think the data that we have now and the data we're going to have by year end is a nice update, and it gives us a significant upgrade, just five months after EHA we're going to triple the dataset. We think that's going to be I think a very robust discussion. It's not anecdotal. And it's not, it's not the complete total of all patients that will ever be on the drug. But it's a significant increase of the data size, and really should give everyone a chance to share our enthusiasm for the progress of the study. Bob, would you like to add to that?

I think you described it. Well, Jim. So basically, as we've said, we've been so excited about the disease modifying aspect of this drug really, especially in this population seems to have a really potent effect on, limiting blast growth and reducing blast. And we think that this is a therapy that that the FDA will be very interested in, in a population where no other drugs are approved. And so based on our EHA data, we sought to really build our case around that and really focus on the FDA, with our goal being we would like to update the community publicly along the way with data when we have relevant updates. And so that's the goal here in January. This isn't going to be the exact datasets that we take to the FDA, but it will be, as Jim said, a tripling of the number of patients that we've presented publicly so far, and we think it should give the community a lot more confidence about the drug and the anti-cancer activity of the drug going into that hope, potential discussion with the FDA.

Great, sorry, just clarify one thing. What at what point of follow up for the cohort of spliceosome mutations? Are you going to go to the FDA? Are you looking to have that fully enrolled with clinical follow up for all those patients to properly evaluate efficacy before having that discussion with FDA? Are you doing that before you have a more mature dataset and that cohort?

Well, there obviously, when we do go, there will be a range of patients in terms of duration on study. We'd obviously like to have a minimum duration for all the patients that we present to them. It's an on-going process. And even the data that we present to them will be interim data to some extent, but we think, by the first half, and so we've committed to considering that as a possibility in the first half of 2022, and we believe that we'll have enough data that's mature enough at that point to speak with them, or at least we'll request to speak with them.

Okay. So just to be clear, you won't actually have feedback from the FDA when you give the update in January, correct?

That's right.

Okay, understood…

Yeah, yeah, no, no we should be really clear Dane. We haven't already spoken to the FDA that the plan has not right. We are planning a meeting with the FDA in the first half of 2022, this is just a chance to give everybody a snapshot to see all of the data that we are now seeing, triple the size of the data they've seen so far, to give them a greater confidence that we really do have something. The skepticism that you get into developing a new drug in this space should be high. In monotherapy, there is nothing approved for these patients, because nothing works is the data that we've seen so far remarkable, but it's small, NF-3 and NF-1. So I think being able to provide people a greater sense of competence, that this really is something that nobody has seen before, that we really do have a drug in monotherapy that can address cancer in these patients I think is tremendously exciting. And so we're very interested in in providing that update.

Okay, thank you.

The next question is from Justin Walsh with B. Riley Securities. Please go ahead.

Hi, thanks for taking the question. Maybe you give us some color on what we should be looking for in that the B-cell cancer combo data. I believe that you have a Simon 2-stage design to help explore signals and the expansion portion. But maybe you could remind us what response rates do you think would be meaningful and the various lymphoma indications you're looking at?

Yes, it's better question for Bob. Bob?

Yes, so obviously started that. That's a combination with ibrutinib and just to recount, ibrutinib hits the other primary pathway that activates NF-kappaB, so and other BTK inhibitors inhibit that pathway. 4948 is really the only drug that's targeting the other primary pathway, activating NF-kappaB in these malignancies. And that's, TLR signaling through the myddosome and that drives the combination that we're putting in here. Right now, clinically, we've seen activity with our drug as a monotherapy targeting this pathway. Obviously, ibrutinib and other BTKs have monotherapy activity there. What we would like to do is enhance that activity as part of this combination. And in the study that you mentioned, really has four different cohorts. Each, each of which is a, what we consider a low hanging fruit for targeting or IRAK4. These are indications where there's a high incidence of MYD88 mutation, which is a key part of the myddosome and strong signaling through NF-kappaB via that pathway. And it's also indications where we think there's a straightforward registrational path as well. And so we'll be expanding in each of these, we'll be looking to gain estimates of the efficacy of these combinations. As one example, the fourth cohort is a cohort where we're looking at adaptive resistance. And that's where a patient has experienced progression on ibrutinib. In this case, we add 4948s, and so to address your question, any efficacy that we see there suggests, sort of proof-of-concept of adding 4948 to ibrutinib as part of that combination. Ultimately, once we get those estimates of efficacy, we'll discuss with the FDA, what, what we think is a relative relevant target, or a pivotal study going forward from that. But we haven't, we haven't put a stake in the ground, specifically, for a target response rate. We would obviously hope to get a reasonable percentage of patients having durable responses, and hopefully deep responses and in many cases deeper than what we would expect with the BTK inhibitor by itself.

Got it. Do you have a sense of roughly how many patients we can expect -- that that readout, and if those include patients from those four specific cohorts of interest?

Yes, so just to reiterate the four cohorts. I already mentioned one, which is the adaptive resistance, and that can be any patient across any indication who's had a root node. The other three include primary CNS lymphoma, this is a very deadly and difficult to treat disease that actually has a very high incidence of mid-88 mutation. Myddosome lymphoma is another one that has a high activation of NF-kappaB through this pathway. And so, with those, we, we hope that we'll see, strong efficacy there.

Got it. Thanks for taking the questions.

[Operator Instructions] The next question is from Soumit Roy with Jones Trading. Please go ahead.

Hello, everyone. Thanks for taking the question. If you could rewind us a little bit on the natural history of progression of the MDS from low risk to high risk, do we see an increase stimulation [ph] of these spliceosome mutation. And what would the standard of care response rates look like? Some kind of benchmark to look at?

Yes, hi, Soumit. Thanks for your call. Bob, would you mind commenting on that? I know, this is more your area of expertise.

Yes, so the natural history, it's interesting, these spliceosome mutations occur extremely early in the natural history of the disease. As you may know, they've been known for quite a while and correlating oftentimes with one of the first mutations found in a disease. And it wasn't until about a year and a half or two years ago that it was even known what the spliceosome mutation did in terms of their oncogenic role. And it was it was some work by Amit Verma and Dan Starczynowski, who determined that it's actually this alternate splicing of IRAK4-L. And so, as I mentioned, it's a pilot what some people call a founder mutation. These splices are mutations. And they tend to persist throughout the disease. So normally, a patient may start out with low risk MDS with one of these spliceosome mutations, and over time, their disease starts to accumulate other changes and ultimately becomes more aggressive. And unfortunately, some patients die along the way because the complications of the disease such as neutropenia, and low platelet count, thrombocytopenia. But in general, these spliceosome mutations persist if the patient does evolve their disease and ultimately can transform into leukemia AML. And again, during that transformation, most of the patients still retain that IRAK or the spliceosome mutation, suggesting that this is a really critical component that's important for the survival of the disease itself. And that's why we think that this drug has a very important role for all stages and exactly why we're going after the low risk disease as part of the Uwe Platzbecker collaboration, as well as these later lines, with the high risk MDS and ultimately the AML. And the response rates and information that you look for in terms of endpoints across the spectrum ranging from…

Yes. Thank you all for the really detailed color really, a lot to look forward to in January and beyond. Last question is, can you remind us if you're switching mutant patient, can they be FLT-3 inhibitor experienced or they have to be naïve?

They can be FLT-3 inhibitor experienced. In fact, the patient we actually presented at EHA was FLT-3 inhibitor experienced. So that patient had been treated with ibrutinib and had absolutely no response to ibrutinib, which is one of the primary FLT-3 inhibitors that are approved by the FDA. And then they came on to this study and had a dramatic reduction in the bone marrow and blast achieved a PR and done quite well. So, I think the important point to note here is that for patients who are on FLT-3 inhibitors, it's been demonstrated that one of the primary mechanisms of resistance to those inhibitors is in fact, signaling through TLR pathways and specifically through IRAK4. So, the suggestion in the literature is combine an IRAK4 inhibitor with a FLT-3 inhibitor. Well, fortunately 4948 is the perfect drug in this case, because we hit both IRAK4 and FLT-3. So yes, we'll definitely be open to both of those possibilities.

Got it. So you will continue to enroll FLT-3 experienced? Okay, thank you so much for taking the questions and congrats on the progress.

Thank you very much.

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 on-going 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.