Curis Inc (CRIS) 2024 Q1 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Curis first quarter 2024 business update.

At this time, all lines are in listen only mode.

Following the presentation, we will conduct a question and answer session.

If at any time during this call you require immediate assistance, press star zero for the operator.

This call is being recorded on Tuesday, May seventh, 2024.

I would now like to turn the conference over to Diane said to Walt.

Yes, thank you, and welcome to QTS' First Quarter 2024 business update call before we begin, I would like to encourage everyone to go to the Investors section of our website at www.carrols.com to find our first quarter 2024 business update press release and related financial tables.

I would also like to remind everyone that during the call, we will be making forward-looking statements which are based on our current expectations and beliefs.

These statements are subject to certain risks and uncertainties, and actual results may differ materially.

For additional details.

Please see our SEC filings.

Joining me today on today's call are Jim Dentzer, President and Chief Executive Officer, Bob Martel, Chief Scientific Officer, and Jonathan zone, Chief Development Officer, 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.

Thanks, Dan, and good morning, everyone, and welcome to Curis' as Q1 business update call this quarter, we made significant progress in advancing M have asserted in our three key areas of focus.

First as a monotherapy in patients with relapsed refractory AML with a flip three or splicing factor mutation in our take in leukemia study, second as a doublet therapy for patients with relapsed refractory primary CNS lymphoma.

Combining Emma, who started with ibrutinib in our take game lymphoma study, and third, a triplet therapy in frontline AML for all comers, regardless of mutation status that combines MOVE started with a society and venetoclax next Tuesday in connection with the E hot conferences publication of accepted abstracts, we expect to provide a top line update of clinical data from our taking the Genius study.

Previously, we had disclosed data for five patients, three patients with a Flip three mutation and three patients with a splicing factor mutation, including one patient with both flit three and a splicing factor mutation who was included in both populations.

Our update.

Next week, we'll report data for 25 new patients, bringing the total to 30 relapsed refractory AML patients treated with M. of lucitanib as a monotherapy mutation status for these patients is 12 patients with a Flip three mutation and 20 patients with a splicing factor mutation, including two patients with both of flood three and a splicing factor mutation who are included in both populations.

We look forward to discussing the top line data for these patients on an investor call when the data are released, followed by more detailed presentations at the ASCO. and Y high medical conferences that more fully explore and with researchers potential to outperform as a single agent, the benchmarks for existing therapies in genetically targeted AML populations in the relapsed refractory Flip three population.

The benchmark for Flip three inhibition is gilteritinib, which is FDA label demonstrates can achieve a 21% CR CRh rate in patients who have failed frontline therapy with MOVA sort of our goal is to beat that benchmark.

We think this is possible even though the majority of patients in our study have failed prior treatment with a flit three inhibitor because unlike existing treatments and mobile search targets, both flit three and IRAC. for the Escape path for flit three, this is the central hypothesis of the molecule's design and is demonstrated in the preclinical data with 12 patients will be showing at Asco die hard.

We hope to further support that hypothesis, namely that Emma, who search it has the potential to establish a new and best in class benchmarks for the Phase three AML population as we move to the relapsed refractory splicing factor population.

We find that the benchmark is unfortunately for these patients far lower.

There are no drugs approved.

Expected survival is only a few months and existing treatments are ineffective.

The only study published for relapsed refractory AML patients with a splicing factor mutation was for patients treated with the AZ event double-up.

It was a very small study with only five patients and the response rate was zero.

This is especially notable as ACE event is standard of care in frontline AML for patients ineligible for intensive induction.

We hope MOD research novel mechanism can show clear single agent activity in this very challenging population.

Anything that shows have asserted can be 0% benchmark set by ACE events would be positive in our expanded dataset.

We'll be looking for blast count reductions, neutrophil increases, platelet increases, objective responses and ultimately, of course, extended survival.

As we turn to our team lymphoma study, we see significant progress there as well.

At the most recent ASH Conference, we presented data for five patients with relapsed refractory primary CNS lymphoma, who had failed prior treatment with a BTK inhibitor.

We expect to provide an update with additional data later this year, most likely at the ASH conference in December.

Previously, we have said we expected to report data on 10 to 15 patients.

Today.

We are pleased to refine that estimate to the high end of the range as we now expect to report data for approximately 15 relapsed refractory primary CNS lymphoma patients who have failed prior treatment with a BTK inhibitor.

We are also pleased to announce the advancement of our triplet study in all comers in frontline AML.

We have begun enrollment and expect to have preliminary safety data later this year.

Again, most likely at the ASH conference in December.

Excitement around this frontline study stems from the novel targeting of IRAK4 and builds upon the clear anti-cancer activity we are seeing in our monotherapy studies.

We know IRAC. four is an important target in AML and that neither is decided in North Canetic clocks addresses it.

The logical next step is to explore the MIA.'s event triplet and its potential to establish a new benchmark for frontline therapy in all comers in and now in summary, we're encouraged by our progress across the board in leukemia and lymphoma, and we look forward to reporting our updated leukemia data next week.

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

And I think again for the first quarter of 2024 Curis reported a net loss of $11.9 million or $2.5 per share as compared to a net loss of $11.6 million or $2.39 per share for the same period in 2023.

Research and development expenses were $9.6 million for the first quarter of 2024 as compared to $9.1 million for the same period in 2023.

The increase in research and development expenses were primarily attributable to higher employee-related costs.

General administrative expenses were $4.9 million for the first quarter of 2024 as compared to $4.8 million for the same period in 2023.

As of March 31, 2024 Curis has cash cash equivalents and investments totaled $40.7 million and there are approximately 5.9 million shares of common stock outstanding.

We continue to be in a solid cash position and expect that our existing cash, cash equivalents and investments should enable us to maintain our planned operations into 2025.

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

Operator.

Thank you.

Ladies and gentlemen, we will now begin the question and answer session.

Should you have a question, please press the star followed by one on your touchtone phone.

You will hear it from that your hand has been should you wish to decline from the polling process, please press the star followed by two.

If you are using a speakerphone, please lift the handset before pressing One moment please, for your first question.

Your first question comes from Summit gross.

We've joint research.

Scott, we wanted to congratulations on progress on multiple fronts.

Really really clearly presented a couple of questions on the data expected data next week.

I don't know if I missed it.

Are you going to present data for both the free three mutant and lysosome mutants in the relapsed refractory setting?

And what kind of details could we expect?

Are you going to give us fair details around baseline blast count levels?

How much percentage reduction and response rate, neutrophil recovery, et cetera?

Hi, Sumit, thanks for joining on.

So yes, we are absolutely going to be presenting data for both the Flip three and the splicing factor mutation populations, and it is going to be a top line review of data.

Obviously, we need to be a little sensitive to the conference.

We can talk to the abstract.

And but of course, we're going to need to wait for the poster to come up to have the more detailed discussion.

So we think there's some exciting news next week.

We're looking forward to talking about it, and we look forward to having the conversations at both Vasconia and a more detailed and granular level.

Totally understandable.

My last question is around the path forward for these spaces, a mutant patient population, the relapsed refractory setting.

So the flit three arm population, I think the registration path is much clearer on the spliceosome mutation.

How are you planning to go forward?

Are you going to develop, um, on any companion diagnostic or is it included a fairly routinely screen for that mutation?

If you can give us any color.

Sure.

So we need to we need, of course, to have a discussion with FDA.

So I want to be a bit careful here that we're giving you our thoughts, but it's going to really depend on how the conversation with FDA goes.

The complicating factor here, I would say at the highest level when we think about the design of the study is we need to put into context, nothing is approved because nothing works.

This is the first drug that shown single-agent activity in this population.

So whether or not the FDA looks for something like an objective response rate, whether they look for survival, whether they want a single arm study or whether it would be comparing to something else all of these questions are great questions, and we've got some thoughts on those, but it's really going to depend upon a conversation with FDA.

So I'm going to have to hold off on that one a little bit.

And if we go forward and we think about any new genetically driven population, I think it's fair to assume that we're going to need a companion diagnostic.

And again, that will depend on the conversation with FDA of what the timing is for that and how that how that gets incorporated into a pivotal study.

But I'd say stay tuned.

But I and if I may sneak in one last question is around the above bar to beat for the relapsed refractory Phase three.

You mentioned military, gilteritinib CR rate of 21 ish percent, but those won't Flip three experiences patients.

So in our mind, the rest for the bar to beat was more more like 11, 12% response rate.

Is that fair or are you setting up a high bar for yourself?

Yes, actually, and Bob's may be the best person to talk to that.

Bob, would you mind Gentlemen?

Yes.

Thanks, Jim.

I agree, Sumit.

See the bar in terms of what we might expect from a new drug in targeting Phase three in this area would be much lower than 21% because obviously these patients have demonstrated resistance to flit three inhibition.

And that's exactly where it will research.

It is so critical because targeting IRC. four is key.

The TLR pathway, as you know, is strongly upregulated following flit three inhibition.

In fact, TLR signaling through IRAC. four is a resistance mechanism, and that's why we think even though a patient has had resistance to put three inhibition, we can rescue that with this combination.

So 21%, we don't know what the FDA will require as as the hurdle for this, we presented that as a prior precedent for approval of gilteritinib in the earlier line of therapy.

It may be that they would accept lower than that and so that really, as Jim mentioned, will require some discussions with them.

Thank you for taking all the questions and looking forward to the data next week.

Thank you.

Your next question comes from the line of BladderChek with Cantor Fitzgerald.

Your line is open.

Good morning and congrats on the progress on.

Just a couple of questions here.

Should we expect additional started data at a conference relative to the abstract data cuts and then maybe comment on whether we're going to see some MRD. data and what will be the median follow-up, and thank you, Lee, and I appreciate the questions.

So yes, there certainly will be additional detail at both conferences compared to what's in the abstracts.

So similar to my answer to Shannon's question.

We are going to have a discussion about top line detail next week, and we're really looking forward to that.

But it's going to be limited to data that are in the abstract.

There is by definition, as you can, as you can imagine, there's going to be much more detail that comes and at the posters and in the presentation, to ask Tony, how Okay.

And the median follow-up, and let's let's wait and have a discussion about the data when the data are released, if that's all right.

At their data.

And if I recall correctly, these patients have less than two prior lines of therapy.

Maybe just I'll expand a little bit on what these treatments are for both 43 and by zone and patients enrolled on the study?

And how should we think about the impact of prior lines on the response to John?

Yes.

Thank you.

So it's actually less than three prior lines and a coming into the study.

And so yes, typically in AML or actually, you know what, Bob, maybe you are the better person to talk about the lines of therapy that typical typically happen in these patients in AML.

And so, right?

So oftentimes, patients with a Flip three mutation may get some cytotoxic intensive chemotherapy upfront or a lesser intensive, but generally they will have had prior Flip three inhibitors like we were just discussing a bit ago.

And patients who are very fit ineligible for intensive induction, oftentimes will get that therapy.

But those patients once they fail would go on to either then therapy.

And then all of the patients who really are not eligible for intensive induction will get events.

So as you may know, patients who fail or progress on AEs have been or are resistant to that of extremely poor outcomes.

There's been a couple of studies that have looked at outcomes following failure of events.

And the survival in both of those studies is about two to three months across the board on those patients.

So really a difficult population to treat and our data should be viewed in that perspective as well, which we're really excited about.

Thank you.

Your next question comes from the line of Yale Jen with Laidlaw Your line is now open of.

Good morning and thanks for taking the questions.

But just on a step on the last question, just ask, you mentioned that the Asia event is the I guess that's their lifeblood, but three inhibitor patients.

So you've mentioned about the survival, what about the often because I think that probably will be a benchmark actually, you might have compared to us.

Well, yes.

Actually, again, Bobby, you're probably better to take that one.

So the response rate sort of so there's not a lot of data on a slicing factor mutation post Jose's event, there is one really interesting study looking at first line treatments with AML that demonstrate splicing factor mutation have an extremely low response rate.

So patients who don't have a splicing factor mutation have approximately 80% response rate and only maybe 20% who can achieve that, whereas almost 80% of the patients with a splicing factor mutation are unable to achieve a CR in the first line, it's dramatically dramatically reduced in terms of a flit three subset of population that is roughly similar, although there aren't as detailed data on that.

Does that answer your question?

Yes.

And that was frontline the whale.

And so of course, in relapsed refractory, it gets far worse across the board.

Right.

So it's one of the reasons why we're excited about the populations that we're going after is that they're so underserved and the hurdle to show something is lower, and we're excited to talk about the the agent activity that we're seeing in that population.

Again, it's relapsed refractory, in our case, not frontline, even though in both settings, there's a dramatic drop-off in performance for existing therapies.

Right?

And that getting shifting it cost us to think whether these patients will be I mean, in these major population, would you anticipate potentially accelerated approval pathway if the data was robust.

So it's interesting that you say that the we looked at the precedents in AML, specifically for gilteritinib for IDH one and for IDH two in all three cases, the FDA approved those drugs on four trials that were single-arm studies based on a CR CRh endpoint.

And that led to full approval, not even accelerated approval.

So we can't of course, put words in the FDA's mouth.

We need to have the discussion with the FDA both, but we believe that those precedents reflect an understanding and FDA these diseases are really underserved by existing therapies.

And these patients are in need of new therapies.

So our hope would be that if we can bring a dataset to FDA that can show that we can we can see single-agent activity and pair it with early, but still indications of survival that the FDA will hopefully be in a position to agree to a registration path that can get these drugs in the hands of physicians and patients as quickly as possible.

Maybe last question here again, delivery forward-looking type of precise, which is that in terms of booked three patients.

Would you consider any if the data is robust, would you consider a combination and or in other words, we'll move up to the first line instead of in the refractory patients at this stage of development?

Yes.

So in fact, the answer is we've already started that right?

And it's not just for flit three.

It's for all comers, whether you have a Flip three mutation or not.

And the reason for that, of course, is that our our drug and start to target does target plus three, but it also targets IRAK4 It targets the CLKSCRK. one two and four targets, Dirk, I mean this is a multi-targeted drug that hits a number of targets of interest in the context of AML.

So and that is precisely why we've already started the frontline study, the triplet study of MR in combination with these events.

So our hope would be with this initial study that we can show safety.

And with those safety data in hand, by the time we get to year end, we'll be in a position to have the drug be what I would call partner ready.

We'll have a mature dataset in splicing factor patients and Flit three patients as a monotherapy.

And we will have shown a hopefully by the time we get to ASH in the even though it's just in a handful of patients that adding Emma to the event doublet in Frontline is safe.

And if we can do that.

I think we can make the case with the regulatory authorities that we are prepared to go simultaneously in the relapsed refractory setting as a monotherapy and the front-line setting in combination.

And I think we'll be in a position to have a conversation with partners to get access to obviously non-dilutive financing, but access to a broader clinical infrastructure.

So that we can accelerate the pace of clinical development and increase our ability to maximize commercial launch.

So all of those things are part of our thinking at this point in time.

Okay.

Great.

That's very helpful.

And we'll look forward to see the data next week in Congress.

Thank you very much.

Appreciate it.

Your next question comes from the line of Bill January with Cary, your line is open and congratulations on the progress.

I have a couple of questions here.

Your split for three and spliceosome patients inside the study is that representative of the real world.

And then also I'm going to move on over to the triplet study.

Is there a way, too, I don't know when we pick a subgroup of patients to derisk on the safety side because in the first time we'll be seeing this triplet on.

And I guess.

Yes, a question on Mentor PCNSL., are you still enrolling BTKBTK. naive patients as well so that we can compare and contrast those two data sets between experienced and later this year.

Yes.

Thank you.

I appreciate it, Phil, and thanks for joining us.

So let me trying to knock off those three questions in a row.

So first on the split on Flip three patients versus spliceosome patients.

So this one is really, really interesting, and I think it reflects the unmet need in AML.

Both of these studies are recruiting quickly.

And as you may recall, we came off our partial clinical hold midyear last year, got our sites up and running and them.

And we're seeing really strong enrollment rates across the board at our sites.

There's a there's a real pent-up demand in AML for a novel target on in particular, as you know, the the pace of spliceosome has been really interesting.

So Flip three constitutes roughly a third of AML, one-third of AML patients have a Flip three mutation patients with a splicing factor mutation make up a much smaller portion of that community, maybe 10% of AML patients have a splicing factor mutation and yet that has outpaced enrollment in Phase three.

And I think it's precisely what we said.

There are no drugs available.

Not only there's nothing approved nothing works for these patients.

This is the first time people are seeing activity and to see that kind of activity with a single agent is is really compelling.

So we look forward to sharing our results with you next week in those two populations.

And we look forward and having the discussions with FDA as well, we are we've got to our dataset in 20 patients with spliceosome.

We're going to add another couple of Phase three and follow these patients and take those data to the FDA and begin the discussions on registrational design and we're looking forward to that.

And the second question was about triplet safety.

So and so the design of this study, as you may remember, I think, is really interesting and it's all about, as I mentioned, to Gail, ensuring that that our leukemia program is partner ready.

So we will have, by year end, mature datasets in two distinct genetically driven populations and Flit three and splicing factor mutation.

The study we just started in triplet is a study that enrolls patients who are currently on event in the frontline setting who have achieved CR, but are still MRD-positive.

We are going to then take those patients into the study and add MOVE certain to their therapy.

Turning the doublet into a triplet, of course, what we're hoping is that we can see efficacy and get those patients to MRD negativity.

But the key is that we will have been able to isolate the safety effect of adding MOVA assertive to that event doublet to the to the current standard of care.

So that by the time we get to year end, obviously, we're always hoping to see signs of efficacy.

But what we really want to be able to say is we've got a drug that that's hitting a novel target indirect for that novel target.

Clearly matters because we're seeing single agent activity.

We know that the existing standard of care of AIDS event doesn't hit it.

And then we hope to add to the discussion by year end, we can add a drug, and we've researched it to that doublet that allows the current standard of care to address this new novel target of IRAC. four, and we would hope of course, that we would then see in the clinic in that setting what we saw in the preclinical data, which is we have the potential to establish a new benchmark and establish a new standard of care in frontline therapy in AML across the board, all comers, but three mutation or not.

Then your third question was on BTK naive patients in the study in lymphoma.

So just as a reminder, we have tested the combination of MOVA asserted and with ibrutinib in multiple indications within a NHL and specifically with primary CNS lymphoma in BTK naive patients as well as BTK experienced patients.

The underlying logic of the drug is that patients who are on ibrutinib or NHL patients who are on ibrutinib are on it precisely because it allows them to downregulate NF-kappa B overactivity by blocking the BCR pathway.

There are two pathways that are driving NF-kappa B over activity in these patients.

There are a lot of BTK inhibitors.

Today, there's only one drug that blocks TLR pathway that second pathway driving NF-kappa-B overactivity and that some have asserted.

So our view would be blocking both of those pathways that are driving NF-kappa B, which is driving disease in NHL blocking both pathways is always going to be better than blocking either one alone.

So if we can, if we can then take that mechanistic logic into the preclinical setting and see the hypothesis is supported, which we've already done and now go into the clinic and compare and contrast as you say BTK naive and BTK experienced patients being able to show both is good and we already have, but we think it's even more powerful.

If we if all we had were BTK naive patients.

Someone might wonder whether the efficacy was coming from the BTK inhibitor.

But because we know these patients are on a BTK and then and then fail either relapsed or refractory, you would, of course, expect not to immediately rechallenge them with ibrutinib.

Yet again, the response rate is probably going to be zero.

So if we can show that we can get activity in those patients, even though they've just failed BTK, then it's obviously either the performance of Emerald was sort of a loan or MODUs circuits, synergistic combination with BTK and its ability to resensitize patients to BTK that is driving that.

And so we think that's a really powerful thing to do.

And thank you for asking that question.

I guess that was pretty long.

I hope and I hope it answered your question thoroughly.

It did it did I just one more on the on the comparison front back in the triplet.

I know it's meant to be safety, but I guess just for those of us because our job, right, so I wouldn't be unethical view to, um, not give them as we start to do some of these patients for the sake of comparison rates as are there any historical benchmarks that you can point to?

So no shortcuts to get phases and then have MRD positivity and how they fare off just so that we have something to compare to when that time comes.

Yes, actually within leukemia setting, Bob, maybe you're a better person to talk to that?

Yes, I don't have the details right in front of me, but I'm clearly there is a major problem for IAML. and induction because if a patient continues to have molecular evidence of disease, that implies that the disease has has not been taken care of.

So a significant portion of patients are able to get to MRD negative.

But there's also, I'd say, a significant majority of patients who can't achieve that, maybe they achieve a CR or a CRA.s. But when we do in a minute, a molecular analysis.

It is not MRD-negative, and that correlates very strongly with that with relapse.

And so that's what we ultimately would be looking to achieve in this early study.

Like Jim said, we're looking mainly for safety.

And so we don't have that as a goal for this particular study.

But ultimately, that would be the long term and go ultimately in earlier sort of upfront, it's a situation where we would start out the the study in combination with Asia them from the beginning.

Thanks.

Appreciate it.

Your next question comes from the line of Shawn McCutcheon of Raymond James.

Your line is open.

Hey, guys.

Thanks for taking the question and definitely look forward to the top line next week.

But correct me if I'm wrong, but you've said previously that the potential pivotal cohort in the relapsed refractory AML setting, you're probably going to end up having to go after either for three or spliceosome in a single study with the commutations maybe going into the same bucket.

So first, is this consistent with your current understanding where your current plan?

I can you walk us through the decision between flit three and slices of in that context, what factors you're considering, obviously, flit three a bit more well established in terms of the scale and scope of the data set that that you'll need?

Yes.

No, thank you, Sean, and thanks for the question.

So yes, you're right.

In the past, we have certainly said that.

And I would say the same thing today with the very significant caveat that we need guidance from FDA on this issue.

And our expectation is that it's very clear for patients that have a Flip three mutation only or a splicing factor mutation only.

They're going to go into their respective studies.

And as we've talked about, it's roughly one-third of the population in ML. has a Phase three population and roughly 10% have a splicing factor mutation.

And there are a small number of patients, and we've seen it in our in our 30 patients, we've got two.

And so there are going to be a small number of patients who would qualify for both studies.

And I suspect and again, we haven't had that conversation with FDA.

But I suspect what they're going to ask is that we put patients with dual mutation in one study and not in both studies, but we need to have that conversation with them to make sure that that's what they'd like to see how you how you decide which one they go in.

That's again, that's going to be a subject of discussion with FDA, but those patients would presumably be eligible and for both populations.

Thanks.

And just a quick point of clarification.

Sorry if I missed this, but will the the E Han, the Asco dataset see the same data?

Yes, is the short answer that question.

It's the same data cut for both populations.

We'll talk about that more next week when the data come out.

But absolutely the there's going to be different presenters at both conferences and sort of the behind the scenes story of working at a biotech company and managing a novel target is that you high-class headache, you get a lot of physicians on both sides of the pond that want to present your data.

And so we're going to have different people at different conferences, but the data set, the data cutoff is the same.

Thank you.

If there are no further questions at this time, I'll turn the call over to Jim Dexter.

Please continue.

Thank you, operator.

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 and the NCI for their ongoing help and support.

We look forward to updating you again soon.

Operator?

Ladies and gentlemen, this concludes today's conference call thank you for your participation.

You may now disconnect.