Q1 2024 Curis Inc Earnings Call & Business Update
Yeah.
Speaker Change: Good morning, ladies and gentlemen, and welcome to the Carey's first quarter 2020 for a business update at this time all lines are in listen only mode. Following the presentation well conduct a question and answer session. If at any time during this call you require immediate assistance.
Please press star zero for the operator this call is being recorded on Tuesday May seven 2024, I would now like to turn the conference over to Dan said Duval. Please go ahead.
Yeah.
Thank you and welcome to curious as 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 dot terrorists dot com to find our first quarter 2024 business update press release and related financial tables.
Speaker Change: 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.
Speaker Change: Joining me today on today's call are Jim Dentzer, President and Chief Executive Officer.
Speaker Change: Bob Martell, Chief Scientific Officer, and Jonathan Zhang Chief Development Officer will also be available for a question and answer period at the end of the call.
James E. Dentzer: Now like to turn the call over to Jim.
James E. Dentzer: Thank you Dan.
James E. Dentzer: Good morning, everyone and welcome to curious as Q1 business update call.
James E. Dentzer: This quarter, we made significant progress in advancing <unk>, who started in our three key areas of focus.
James E. Dentzer: First as a monotherapy in patients with relapsed refractory AML with a flip three or splicing factor mutation in our T game leukemia study.
James E. Dentzer: Second as a doublet therapy.
James E. Dentzer: For patients with relapsed refractory primary CNS lymphoma, combining <unk> with Ibrutinib and our T game lymphoma study.
James E. Dentzer: And third as a triplet therapy in frontline AML for all comers, regardless of mutation status that combines <unk>, who started with azacitidine and vanilla clocks.
James E. Dentzer: Next Tuesday in connection with the Ehow conferences publication of accepted abstracts, we expect to provide a top line update with clinical data from our taking leukemia study.
James E. Dentzer: Previously we have disclosed data for five patients.
James E. Dentzer: Three patients with a flip three mutation and three patients with a splicing factor mutation include.
James E. Dentzer: Including one patient with both a flip three and displacing factor mutation who was included in both populations.
James E. Dentzer: Our update next week, we will report data for 25 new patients.
James E. Dentzer: Bringing the total to 30 relapsed refractory AML patients treated with <unk>, who started as a monotherapy.
James E. Dentzer: The 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 a flip three and a splicing factor mutation who are included in both populations.
James E. Dentzer: We look forward to discussing the topline data for these patients on an investor call. When the data are released followed by more detailed presentations at the <unk> and <unk> medical conferences that more fully explore <unk> potential to outperform as a single agent the benchmarks for existing therapies in <unk>.
James E. Dentzer: Medically targeted AML populations.
James E. Dentzer: In the relapsed refractory flit three population.
James E. Dentzer: Benchmark for flip three inhibition is guilty written it.
James E. Dentzer: Which is FDA label demonstrates can achieve a 21% CR cri rate in patients who have failed frontline therapy.
James E. Dentzer: With Emma who sort of our goal is to beat that benchmark.
James E. Dentzer: We think this is possible even though the majority of patients in our study have failed prior treatment with a flip three inhibitor.
James E. Dentzer: Because unlike existing treatments and muscle certain targets, both flipped three and Iraq for the escape paths for flip three.
James E. Dentzer: This is the central hypothesis of the molecules design and as demonstrated in the preclinical data.
James E. Dentzer: With 12 patients will be showing it as co D. Hot we hope to further support that hypothesis, namely that Emma who search it has the potential to establish a new and best in class benchmark for the flip three AML population.
James E. Dentzer: As we move to the relapsed refractory splicing factor population.
James E. Dentzer: We find that the benchmark is unfortunately for these patients far lower.
James E. Dentzer: There are no drugs approved.
James E. Dentzer: Expected survival is only a few months.
James E. Dentzer: And existing treatments are ineffective.
James E. Dentzer: The only study published for relapsed refractory AML patients with a slicing factor mutation.
James E. Dentzer: It was for patients treated with the ease of N doublet.
James E. Dentzer: It was a very small study with only five patients.
James E. Dentzer: And the response rate was zero.
James E. Dentzer: This is especially notable as as event is standard of care in frontline AML for patients ineligible for intensive induction.
James E. Dentzer: We hope <unk> novel mechanism can show clear single agent activity in this very challenging population.
James E. Dentzer: Anything that shows <unk> can be zero percent benchmark set by his event would be positive.
James E. Dentzer: In our expanded dataset, we'll be looking for blast count reductions neutrophil increases platelet increases objective responses and ultimately of course extended survival.
James E. Dentzer: As we turn to our taking lymphoma study we.
James E. Dentzer: We see significant progress there as well.
James E. Dentzer: 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 PTK inhibitor.
James E. Dentzer: We expect to provide an update with additional data later this year.
James E. Dentzer: Most likely at the Ash conference in December.
James E. Dentzer: Previously we had said we expected to report data on 10 to 15 patients.
James E. Dentzer: 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 PTK inhibitor.
James E. Dentzer: We are also pleased to announce the advancement of our triplet study in all comers in frontline AML.
James E. Dentzer: We have begun enrollment and expect to have preliminary safety data later this year again, most likely at the Ash conference in December.
James E. Dentzer: The excitement around this frontline study.
James E. Dentzer: <unk> from the novel targeting of Iraq for and builds upon the clear anticancer activity, we are seeing in our monotherapy studies.
James E. Dentzer: We know Iraq for is an important target in AML and that neither is decided in nor venetic clocks addresses it.
James E. Dentzer: So the logical next step is to explore the AMA is even triplet and its potential.
James E. Dentzer: Central to establish a new benchmark for frontline therapy in all comers in AML.
James E. Dentzer: 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.
James E. Dentzer: With that I'll turn the call back over to Anthony to review, our financial results for the quarter anthem.
James E. Dentzer: Panther.
Anthony: Thank you Jim for the first quarter of 2024 curious reported a net loss of $11 9 million or $2 five per share as compared to a net loss of $11 6 million or $2.39 per share for the same period in 2023.
Anthony: Search 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.
Anthony: General and administrative expenses were $4 9 million for the first quarter of 2024 as compared to $4 8 million for the same period in 2023.
James E. Dentzer: As of March 31, 2024 curious as cash cash equivalents and investments totaled $40 7 million and they were 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.
James E. Dentzer: Our planned operations into 2025.
Speaker Change: With that I'd like to open the call for questions operator.
Speaker Change: Thank you, ladies and gentlemen, who 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 raised should you wish to decline from the appalling process refreshed.
Speaker Change: The star followed by chance.
Speaker Change: You are using a speaker phone please lift the handset before pressing any Keith one moment. Please for your first question.
Speaker Change: Okay.
Speaker Change: Yeah.
Speaker Change: Okay.
Speaker Change: Okay.
James E. Dentzer: Your first question comes from summit ROI with the joint research.
Soumit Roy: Please go ahead.
Soumit Roy: Everyone and congratulations on progress on multiple fronts really really clearly presented.
Soumit Roy: Couple of questions on the data expected data next week.
Soumit Roy: I don't know if I missed it are you going to present data for both the <unk> mutant and places them mutants in the relapsed refractory setting.
Soumit Roy: And what kind of details could we expect or are you going to give us further details around baseline <unk> current levels, how much per cent reduction and.
Soumit Roy: The response rate neutrophil.
Soumit Roy: Recovery et cetera.
Speaker Change: Yeah, Hi, Sumit, thanks for joining.
Speaker Change: So yes, we are absolutely going to be presenting data for both the flit three and the splicing factor mutation populations.
Speaker Change: It is going to be a topline reeves.
Speaker Change: Review of data, obviously, we need to be a little sensitive to the conference we can talk to the abstract.
Speaker Change: 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 theres. Some exciting news next week, we are looking forward to talking about it.
Speaker Change: And we look forward to having the conversations with both <unk> and <unk> and a more detailed and granular level.
Speaker Change: Totally understandable.
Speaker Change: My last question is around.
Speaker Change: That forward for these spaces are mutant patient population in the relapsed refractory setting. So the three three population I think the registration path is much clearer.
Speaker Change: On the spliceosome mutation.
Speaker Change: Are you planning to go forward or are you going to develop.
Speaker Change: Yeah.
Speaker Change: Any companion diagnostic or is it included a fairly routinely screened for that mutation. If you can give us any color sure. So we need we need of course to have a discussion with FDA. So I want to be careful here that we're giving you our thoughts, but it's going to really depend on how the conversation with FDA goes the.
Speaker Change: The complicating factor here I would say at the highest level when we think about the design of the study.
Speaker Change: Is we need to put into context nothing is approved.
Speaker Change: Because nothing works.
Speaker Change: This is the first drug that shown single agent activity in this population.
Speaker Change: So whether or not the F D a.
Speaker Change: Looks for something like an objective response rate.
Speaker Change: Whether they look for survival.
Speaker Change: 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 our conversation with FDA. So I'm going to have to hold off on that one a little bit.
Speaker Change: If we go forward.
Speaker Change: 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.
Speaker Change: Again that will depend on the conversation with FDA of what the timing is for that and how that.
Speaker Change: How that gets incorporated into a pivotal study, but I'd say stay tuned.
Speaker Change: Got it and if I may sneak in one last question is around the <unk>.
Speaker Change: But to beat for the relapsed refractory phase III, you mentioned Kilroy at neighborhood CR rate of 21 ish percent, but those weren't flip three experienced patient so.
Speaker Change: In our mind, the reservoir or the bar to beat was more.
Speaker Change: More like 11%, 12% response rate is that fair or are you setting up a high bar for yourself.
Speaker Change: Yeah actually bobs may be the best person to talk to that Bob would you mind jumping in.
Bob Martell: Yes, Thanks, Jim.
Bob Martell: I agree.
Bob Martell: The bar in terms of.
Bob Martell: What we might expect.
Bob Martell: New drug targeting <unk> three in this area would be much lower than 21% because obviously these patients have demonstrated.
Bob Martell: Distance to flit, three inhibition and Thats exactly where Amazon is.
Bob Martell: It is so critical because targeting IraQ4 alright is key.
Bob Martell: LR pathway as you know is strongly up regulated following three inhibition in fact CLR signaling through Iraq for is a resistance mechanism and that's why we think even though a patient has had resistance to <unk> inhibition.
Bob Martell: Can rescue that with this combination the 21%.
Bob Martell: We don't know what the FDA will require as.
Bob Martell: As the hurdle for this we presented that as a prior precedent for approval of guilty written it in the earlier line of therapy.
Bob Martell: It may be that they would accept lower than that.
Bob Martell: And so that really as Jim mentioned will require some discussions with them.
Speaker Change: Thank you for taking all the questions and looking forward to the data next week. Thank you.
Leak Bloodsack: Your next question comes from the line of leak blood sack with Cantor Fitzgerald. Your line is open.
Leak Bloodsack: Hey, good morning, Congrats on the progress.
Leak Bloodsack: Just a couple of questions here should we expect additional data.
Speaker Change: Data at <unk> conference relative to the abstract data cuts.
Speaker Change: And maybe comment on whether we're going to see some M. R. D data and what will be the median follow up.
Speaker Change: Thank you Lee and I appreciate the question.
Lee: So yes, there is certainly will be additional detail at both conferences compared to what's in the abstract so similar to my answer to assume it's question, we're going to have a discussion about topline 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.
Lee: By definition as you can as you can imagine there's going to be much more detailed it comes.
Bob Martell: The posters and presentations at Astro anyhow.
Bob Martell: Okay.
Bob Martell: And the median follow up.
Speaker Change: Let's let's wait and have a discussion about the data when the data are released if that's all right. Okay. That's fair.
Speaker Change: And then.
Speaker Change: If I recall correctly these patients have less than two prior <unk>.
Bob Martell: Lines of therapy, maybe just.
Bob Martell: Expand a little bit on what these treatments are for both.
Bob Martell: Three and spices on.
Speaker Change: Patients enrolled in the study and how should we think about the impact of prior lines on the response to yeah. Yeah. Thank you so it's actually less than three prior lines.
Bob Martell:
Speaker Change: Coming into the study.
Bob Martell: So yeah typically in AML, well 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 and AML.
Bob Martell: Perfect.
Bob Martell: Alright, so oftentimes patients with a flit three mutation may get some cytotoxic intensive chemotherapy upfront or.
Bob Martell: After intensive but generally they will have had prior <unk> inhibitor like we were just discussing.
Bob Martell: A bit ago.
Bob Martell: Patients, who are really fit ineligible for intensive induction oftentimes, we'll get that therapy, but those patients once they fail.
Bob Martell: Onto either then therapy.
Bob Martell: And then all of the patients who really are not eligible for intensive induction will get as they've been.
Bob Martell: So as you may know page.
Bob Martell: Patients who fail.
Bob Martell: Our progress is a van or are resistant to that have extremely poor outcomes.
Bob Martell: Okay.
Bob Martell: It's been a couple of studies that have looked at outcomes following a failure.
Bob Martell: The ban 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.
Bob Martell: Our data should be viewed in that perspective, as well, which are which we're really excited about it.
Speaker Change: Thank you.
Bob Martell: Your next your next question comes from the line of Neil Jen with Laidlaw.
Neil Jen: Your line is now open.
Neil Jen: Good morning, and thanks for taking the questions.
Neil Jen: Uh huh.
Neil Jen: On the last question.
Neil Jen: As though what you mentioned the Ada van is the.
Neil Jen: I guess that's their lifeblood.
Neil Jen: <unk> three inhibitor patients so you've mentioned about the survival.
Neil Jen: What about the.
Neil Jen: Or off because I think that probably will be.
Neil Jen: Benchmark actually even by half compared to as well.
Speaker Change: Yes, actually again, Bob Youre, probably better to take that one.
Bob Martell: So the response rate.
Bob Martell: So there's not a lot of.
Bob Martell: As data.
Bob Martell: On lighting factory mutation post.
Bob: Post days event. There is one really interesting study looking at first line treatment.
Bob Martell: With AML.
Bob Martell: Demonstrates splicing factor mutations have an extremely low response rate for patients who don't have a splicing factor mutation.
Bob Martell: Approximately 80% response rates.
Bob Martell: 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 flip III subset of population.
Bob Martell: That is.
Bob Martell: Roughly.
Speaker Change: Similar although there arent as detailed data on that does that answer your question yes.
Speaker Change: And that was the frontline by the way ill.
Speaker Change: 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 there is so underserved.
Speaker Change: 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.
Speaker Change: Right.
Speaker Change: It's just a.
Speaker Change: One of these patients.
Speaker Change: In this patient population would you anticipate potentially et.
Speaker Change: Celebrate pathway if the data was robust.
Speaker Change: So it's interesting that you say that the <unk>.
Speaker Change: We look at the precedence.
Speaker Change: Ml spin.
Speaker Change: Specifically for Gil to retina.
Speaker Change: D H, one and for ADH too.
Speaker Change: In all three cases.
Speaker Change: The FDA approved those drugs for trials that were single arm studies.
Speaker Change: Based on our see our CRH endpoint.
Speaker Change: And that led to a full approval not even accelerated approval.
Speaker Change: So we can't of course put words in the Fda's mouth, we need to have the discussion with the FDA.
Speaker Change: But we believe that those precedence reflect an understanding at FDA that these diseases are.
Speaker Change: Really underserved by existing therapies and these patients are in need of new therapies.
Speaker Change: So our hope would be that if we can bring a dataset to F D. A.
Speaker Change: They can show that we can we can see single agent activity and pair it with.
Speaker Change: Early but still indications of survival.
Speaker Change: That the FDA will hopefully.
Speaker Change: Be in a position to to agree to a registration path that can get these drugs in the hands of physicians and patients as quickly as possible.
Speaker Change: Maybe last question here again, there will be forward looking.
Speaker Change: Type of thoughts, which is in terms of the.
Speaker Change: Three patients.
Speaker Change: We will do because I mean, if the data is robust, but would you consider a combination or in other words, we'll move up to the first line instead of.
Speaker Change: In the refractory patients.
Speaker Change: At this stage of development.
Speaker Change: Yeah. So in fact, the answer is we've already started that right and it's not just for <unk> for all commerce, whether you have a split three mutation or not and the reason for that of course is that you know.
Speaker Change: Our our drug and when we start to target does target flit three but it also targets Iraq for a targets the Clk's CLK, 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.
Speaker Change: And that is precisely why we've already started the frontline study the triplet study of <unk> in combination with as event.
Speaker Change: So our hope would be with this initial study that we can show safety.
Speaker Change: And with those safety data in hand by the time, we get to year end, we'll be in a position.
Speaker Change: To have the drug be what I would call partner ready.
Speaker Change: We'll have a mature dataset in.
Speaker Change: In splicing factor patients and flit three patients as a monotherapy and.
Speaker Change: And we will have shown a hopefully by the time, we get to ash.
Speaker Change: And even though it's just in a handful of patients that adding <unk> to the <unk> doublet in frontline is safe.
Speaker Change: And if we can do that.
Speaker Change: 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 in frontline setting in combination.
Speaker Change: And I think we'll be in a position.
Speaker Change: To have a conversation with partners.
Speaker Change: To get access to obviously non dilutive financing.
Speaker Change: 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.
Speaker Change: So all of those things are part of our thinking at this point in time.
Speaker Change: Okay great.
Speaker Change: Very helpful.
Speaker Change: Sure.
Speaker Change: See the data next week and congrats thank you very much I appreciate it.
Speaker Change: Your next question comes from the line of Bill January with Macquarie. Your line is open.
Bill January: Hi, congratulations on all progress.
Bill January: A couple of questions here your split for three and spliceosome.
Bill January: Patients inside the study is that representative of the real world.
Bill January: And then also I'm going to move on over to the triplet study is there a way to I don't know maybe pick a subgroup of patients to derisk on the safety agencies in the first time will be savings strictly.
Bill January: And.
Bill January: I guess my question on NIM for <unk> are you guys still enrolling PTK became naive patients as well.
Bill January: So that we can compare and contrast, those two datasets between experience.
Bill January: Later this year.
Speaker Change: Yeah. Thank you I appreciate it Phil and thanks for joining us So let me try and knock off those three questions in a row. So first.
Speaker Change: Split on flit three patients versus spliceosome patients. So this one is really really interesting and I think it reflects the unmet need.
Speaker Change: In AML both of these studies are recruiting quickly.
Speaker Change: As you May recall, we came off our partial clinical holds mid year last year got our sites up and running and.
Speaker Change: Yeah.
Speaker Change: 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.
Speaker Change: In particular as you know the.
Speaker Change: The peso spliceosome has been.
Speaker Change: Really interesting so put three.
Speaker Change: Constitutes roughly a third of AML, one third of AML patients have a <unk> three mutation.
Speaker Change: Patients with a splicing factor mutation make up a much smaller portion of that community, maybe 10% of AML patients have a spicing factor mutation.
Speaker Change: And yet that has outpaced enrollment and flit three and I think it is 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.
Speaker Change: 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.
Speaker Change: Yeah.
Speaker Change: We've got to our dataset in 20 patients with splices home, we're going to add another couple in foot 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.
Speaker Change: The second question was about triplet safety so.
Speaker Change: So the design of this study as you May remember I think is really interesting and it's all about as I mentioned to Yale.
Speaker Change: Ensuring that that our leukemia program as partner ready.
Speaker Change: So we will have by yearend mature dataset in two distinct genetically driven populations and flit three and splicing factor mutation. This.
Speaker Change: The study, we just started and triplet.
Speaker Change: Is a study that enrolls patients who are currently on is even in the frontline setting.
Speaker Change: Who have achieved CR.
Speaker Change: But are still positive.
Speaker Change: We're going to then take those patients into the study.
Speaker Change: And add <unk> to their therapy, turning the doublet into a triplet.
Speaker Change: Of course, what we're hoping is that we can.
Speaker Change: See efficacy and get those patients to <unk> negativity.
Speaker Change: But the key is that we will have been able to isolate the safety effect.
Speaker Change: Adding <unk> to that as events doublet to the to the current standard of care.
Speaker Change: 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.
Speaker Change: We've got a drug.
Speaker Change: It's hitting a novel target.
Speaker Change: IRAK four.
Speaker Change: That novel target.
Speaker Change: Clearly matters, because we're seen single agent activity.
Speaker Change: We know that the existing standard of care of as even doesn't hit it.
Speaker Change: And then we hope to add to the discussion by year end, we can add a drug <unk>.
Speaker Change: To that doublet.
Speaker Change: Allows the current standard of care to address this new novel target of Iraq for and we would hope of course that we would then see in the clinic in that setting what we saw in the in the preclinical data.
Speaker Change: Which is we have the potential to establish a new benchmark and establish a new standard of care in frontline therapy in ml across the board all comers flit three mutation or not.
Speaker Change: Then your third question was on PTK naive patients in the study.
Speaker Change: In lymphoma, so just as a reminder.
Speaker Change: We have tested the combination of <unk> asserted.
Speaker Change: With Ibrutinib.
Speaker Change: In multiple indications within the NHL and specifically with primary CNS lymphoma, <unk> naive patients as well as <unk> experienced patients.
Speaker Change: The underlying logic of the drug.
Speaker Change: Is that.
Speaker Change: Patients who are on a bruton nib or NHL patients who are on ibrutinib.
Speaker Change: Iran. It precisely because.
Speaker Change: It allows them to down regulate Nf Kappa b over activity by blocking the VCR pathway.
Speaker Change: There are two pathways that are driving Nf Kappa b over activity in these patients.
Speaker Change: There are a lot of <unk> inhibitors today.
Speaker Change: There's only one drug that blocks CLR pathway that second pathway driving of Nf Kappa b over activity and that's <unk>.
Speaker Change: So our view would be blocking both of those pathways that are driving Nf Kappa B, which is driving disease in NHL.
Speaker Change: Blocking both pathways is always going to be better than blocking the either one alone.
Speaker Change: So if we can if we can then take that mechanistic logic.
Speaker Change: Into the preclinical setting and see the hypothesis is supported which we've already done.
Speaker Change: And now go into the clinic and compare and contrast, as you say be teekay naive and <unk> experienced patients being able to show both is good and we already have.
Speaker Change: But we think it's even more powerful.
Speaker Change: If all we had were be teekay naive patients someone might wonder whether the efficacy was coming from the <unk> inhibitor.
Speaker Change: But because we know these patients are on <unk>, and then and then fail.
Speaker Change: Either relapsed or refractory.
Speaker Change: You would of course expect that.
Speaker Change: To immediately re challenged them with Ibrutinib, yet again the.
Speaker Change: This rate is probably going to be zero.
Speaker Change: So if we can show that we can get activity in those patients even though they have just failed PTK.
Speaker Change: Then it's obviously either.
Speaker Change: The performance of <unk> alone or <unk> synergistic combination with PTK and its ability to re sensitize patients to <unk> that is driving that.
Speaker Change: And so we think that's a really powerful thing to do.
Speaker Change: Thank you for asking that question.
Speaker Change: I guess that was pretty long I hope, it's I hope it answered your question thoroughly.
Speaker Change: It did I had just one more on the on the comparison from back in the triplet.
Speaker Change: It's meant to be safety, but.
Speaker Change: I guess just for those of us whose.
Speaker Change: John right so it.
Speaker Change: It would be unethical to.
Speaker Change: Not good certainty some of these patients for the sake of comparison rates are there any historical benchmarks that you can point to for assurance, who get as even and then have MLD positivity and how they fare offs. Just so that we have something to compare to in that time gums, yeah actually within the leukemia setting Bob maybe you bet.
Speaker Change: Person to talk to that.
Bob: Yeah, I don't have the details right in front of me, but <unk>.
Speaker Change: Clearly there are more.
Speaker Change: Major problem for AML induction because.
Speaker Change: If a patient continues to have molecular evidence of disease that implies that the disease has not been taken care of so.
Speaker Change: A significant portion of patients are able to get to MRV negative, but theres also.
Speaker Change: I'd say the significant majority of patients who can achieve that.
Speaker Change: Maybe they achieve a CR or a CRH, but when we do in our molecular analysis.
Speaker Change: It is not <unk> negative and that correlates very strongly with.
Speaker Change: Relapse and so that's what we're ultimately we'd 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.
Speaker Change: Goal for this particular study, but ultimately that would be the long term.
Speaker Change: Go ultimately.
Speaker Change: Earlier sort of upfront situation.
Speaker Change: Situation, where we would start out.
Speaker Change: Study in combination with either then from the beginning.
Speaker Change: Thanks I appreciate it.
Speaker Change: Your next question comes from the line of Sean.
Sean: Mccutcheon of Raymond James Your line is open.
Sean McCutcheon: Hey, guys. Thanks for taking the question and definitely look forward to the top line next week.
Speaker Change:
Sean McCutcheon: Correct me, if I'm wrong, but you said previously that the potential pivotal cohort in relapsed refractory AML setting, you're probably going to end up having to go after either three or slices.
Speaker Change: And a single study.
Speaker Change: With no co mutations maybe going into the same bucket.
Speaker Change: So first of all this.
Speaker Change: Assistant with your current understanding or your current plan Alright can you walk us through the decision between four three and spices.
Speaker Change: In that context, what factors, you're considering obviously, but three EBIT more well established in terms of the scale and scope of the dataset that youll need. Thanks.
Speaker Change: Yeah, no. Thank you Sean and thanks for the question.
Speaker Change: Yes.
Speaker Change: So, yes youre right.
Speaker Change: In the past, we have certainly said that and I would say the same thing today.
Speaker Change: The very significant caveat that we need guidance from FDA on this issue.
Speaker Change: Our expectation is that.
Speaker Change: It's very clear for patients that have a flit three mutation only or a splicing factor mutation only there.
Speaker Change: We're going to go into their respective studies.
Speaker Change:
Speaker Change: And as we've talked about it's roughly one third of the population in AML has a flip three population and roughly 10% have a splicing factor mutation.
Speaker Change: There are a small number of patients and we've seen it.
Speaker Change: Our in our 30 patients we've got too.
Speaker Change: So there are going to be a small number of patients who would qualify for both studies and I suspect.
Speaker Change: Again, we havent had that conversation with FDA, but I suspect what theyre going to ask is that we put patients with duo 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.
Speaker Change: That's again, that's going to be a subject of discussion with FDA, but those patients would presumably be eligible.
Speaker Change: For both populations.
Speaker Change: Yeah, Thanks, and just a quick point of clarification.
Speaker Change: Sorry, if I missed this but.
Speaker Change: <unk> dataset.
Speaker Change: The same data.
Speaker Change: Yes.
Speaker Change: Is the short answer that question. It's the same data cut for both populations. We will talk about that more next week when the data come out but absolutely.
Speaker Change: They're going to be different presenters at both conferences.
Speaker Change: You know sort of the behind the scenes story of working at a biotech company in 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.
Speaker Change: So we're going to have different people at different conferences, but the dataset. The data cutoff is the same.
Speaker Change: Okay. Thank you.
Speaker Change: Okay.
Speaker Change: There are no further question at this time I'll turn the call over to Jim <unk>. Please continue.
James E. Dentzer: Thank you operator, and as always thank you to the patients and families participating in our clinical trials.
James E. Dentzer: So our team at curious for their hard work and commitment.
James E. Dentzer: And to our partners at origin and the NCI for their ongoing help and support we look forward to updating you again soon.
James E. Dentzer: Operator.
Speaker Change: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.
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Speaker Change: Thanks.
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