Kura Oncology, Inc. (NASDAQ:KURA) Q1 2024 Earnings Conference Call May 2, 2024 4:30 PM ET
Company Participants
Pete De Spain – EVP, IR
Troy Wilson – President & CEO
Thomas Doyle – SVP of Finance & Accounting
Conference Call Participants
Jonathan Chang – Leerink Partners
Jason Zemansky – Bank of America
Roger Song – Jefferies
Li Watsek – Cantor Fitzgerald
Bradley Canino – Stifel
Peter Lawson – Barclays
Reni Benjamin – Citizens JMP
Justin Zelin – BTIG
George Farmer – Scotiabank
Operator
Good afternoon, ladies and gentlemen, and welcome to the Q1 2024 Kura Oncology Financial Results Conference Call. At this time, all participants are in listen-only mode. Following the presentation, we will conduct a question-and-answer session. [Operator Instructions] This call is being recorded on Thursday, May 2, 2024.
I would now like to turn the conference over to Pete De Spain, Head of Investor Relations. Please go ahead.
Pete De Spain
Thanks, Chris. Good afternoon, and welcome to Kura Oncology’s First Quarter 2024 Conference Call. Joining me on the call are Dr. Troy Wilson, our President and Chief Executive Officer; and Tom Doyle, our Senior Vice President of Finance and Accounting.
Before I turn the call over to Dr. Wilson, I’d like to remind you that today’s call will include forward-looking statements based on current expectations. Such statements represent management’s judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Kura’s filings with the SEC, which are available from the SEC or on the Kura Oncology website for information concerning risk factors that could affect the company.
With that, I’ll now turn the call over to Troy.
Troy Wilson
Thank you, Pete, and thank you all for joining us. Let’s jump right in. Last week, we were proud to announce that ziftomenib is the first investigational treatment to be granted breakthrough therapy designation for the treatment of NPM1-mutant AML. The FDA granted BTD for Ziftomenib based on data from our ongoing KOMET-001 clinical trial in patients with relapsed refractory NPM1-mutant AML. NPM1-mutant AML is a disease of significant unmet need for which there is no approved targeted therapy, and it represents approximately 30% of new AML cases annually.
BTD is awarded for a drug that treats a serious or life-threatening condition and may demonstrate substantial improvement on one or more clinically significant end points over available therapies. The designation is intended to expedite development and review of drugs, including an organizational commitment by FDA senior managers and experienced review staff as well as eligibility for rolling review and priority review.
We’re highly encouraged by FDA’s decision to grant Breakthrough Therapy Designation for ziftomenib, recognizing its potential as an innovative medicine for patients with NPM1-mutant AML. We look forward to working even more closely with FDA to bring ziftomenib to patients in urgent need of effective treatments as quickly as possible.
Meanwhile, we’re on track to complete enrollment of 85 patients in our ongoing KOMET-001 registration directed trial of ziftomenib in relapsed/refractory NPM1-mutant AML by the middle of this year. Ziftomenib is also being evaluated in combination with current standards of care, including venetoclax/azacitidine or cytarabine plus daunorubicin, commonly known as 7+3, in patients with NPM1-mutant or KMT2A-rearranged AML.
In January, we reported preliminary clinical data from the first 20 patients in the dose escalation portion of the KOMET-007 trial, including five newly diagnosed patients with adverse risk AML and 15 patients with relapsed/refractory AML. Ziftomenib demonstrated an encouraging safety and tolerability profile in combination with 7+3 and with venetoclax plus azacitidine, enabling continuous administration of ziftomenib while effectively mitigating the risk of differentiation syndrome.
Notably, no differentiation syndrome events of any grade were reported among the first 20 patients. Furthermore, no dose-limiting toxicities, QTC prolongation, drug-drug interactions or additive myelosuppression were observed. As of the January 11 data cutoff, all five newly diagnosed patients with adverse risk NPM1-mutant or KMT2A-rearranged AML treated with ziftomenib and 7+3, achieved a complete remission with full count recovery for a CR rate of 100%.
The overall response rate among the 15 relapsed refractory patients treated with ziftomenib and ven/aza was 53%, including a 40% ORR among the 10 patients who had received prior venetoclax, a setting with very limited effective treatment options. The CR/CRh rate among the nine relapsed/refractory patients who were menin inhibitor naive was 56%. As of the data cutoff, 16 of the first 20 patients remained on trial, including all 11 NPM1-mutant patients.
Continuous daily dosing of ziftomenib at 200 milligrams QD was well tolerated and safety profile was consistent with features of underlying disease and backbone therapies. I’m very pleased to say that our team continues to demonstrate outstanding execution. The 400-milligram dose of ziftomenib has now been cleared for both the NPM1-mutant and KMT2A-rearranged relapsed/refractory ven/aza cohorts and enrollment for both of those subsets at the 600-milligram dose is ongoing.
We’ve also cleared the 400-milligram dose of ziftomenib in the frontline adverse risk NPM1-mutant 7+3 cohort and have escalated to the 600-milligram dose. Enrollment of the 400-milligram dose in the frontline KMT2A-rearranged 7+3 cohort is ongoing, and we anticipate clearing that dose cohort shortly. At this rate, we expect to identify the recommended Phase II dose for ziftomenib in combination with ven/aza and in combination with 7+3 by the middle of this year.
Concurrently, we plan to initiate a Phase Ib expansion study with a number of combination cohorts, including ven/aza in newly diagnosed NPM1-mutant or KMT2A-rearranged AML, ven/aza in relapsed-refractory NPM1-mutant or KMT2A rearranged AML, venetoclax in relapsed-refractory NPM1-mutant AML and 7+3 in newly diagnosed NPM1-mutant or KMT2A-rearranged AML, removing the qualifications for high-risk disease.
Each Phase Ib combination cohort is expected to enroll independently with approximately 20 patients per cohort. In the meantime, we continue dosing patients in our KOMET-008 study of ziftomenib in combination with additional standards of care, including the FLT3 inhibitor gilteritinib, FLAG-IDA or a low-dose AraC for treatment of relapsed-refractory NPM1-mutant or KMT2A-rearranged AML. Roughly half of all patients with relapsed-refractory NPM1-mutant AML have co-occurring FLT3 mutations and the prognosis for these patients is poor.
Preclinical data for ziftomenib in combination with FLT3 inhibitors demonstrate strong synergistic effects compared to either single agent alone. We believe a best-in-class safety and efficacy profile as well as optimal pharmaceutical properties will enable ziftomenib to become a cornerstone of therapy for patients with acute leukemias. This belief is backed by increasing investigator enthusiasm as evidenced by rapid enrollment across all of our ongoing ziftomenib studies and further bolstered by Breakthrough Therapy Designation by FDA.
Ultimately, our mission is to develop ziftomenib across the continuum of care for all patients with acute leukemias whose disease is driven by the menin pathway. We also have a growing body of preclinical data that supports attractive opportunities for menin inhibitors beyond acute leukemias. Based on internal preclinical data, we believe there may be a role for ziftomenib in the treatment of certain solid tumors and we’re working towards submission of an investigational new drug application for the first of these solid tumor indications in the second half of this year.
We look forward to sharing some of the preclinical data that support this opportunity at a scientific or medical meeting later this year. Meanwhile, we continue to make progress toward a next-generation menin inhibitor, which we intend to direct toward an additional soon-to-be disclosed indication. And we remain in a strong financial position, enabling us to invest in research, development and precommercial activities to maximize the value of ziftomenib and support our other pipeline assets.
Now let’s turn our attention to our farnesyl transferase inhibitor programs. We continue to build upon the impressive clinical benefit we’ve demonstrated with tipifarnib as a monotherapy in patients with recurrent and metastatic head and neck cancer. We have been evaluating the combination of tipifarnib with the targeted therapy alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma in a Phase I dose escalation study that we call KURRENT-HN.
We remain pleased by the manageable safety and tolerability profile of tipifarnib in combination with alpelisib and we are encouraged by the clinical activity observed at multiple dose levels. We expect to complete enrollment of two dose expansion cohorts to help inform selection of the optimum biologically active dose for the combination by the end of 2024 and we look forward to presenting preliminary clinical data from the KURRENT-HN trial of tipifarnib and alpelisib at a medical meeting in the first half of 2025.
We believe the manageable safety and tolerability we’ve observed with the combination of tipifarnib and alpelisib, also significantly derisks development of our next-generation farnesyl transferase inhibitor KO-2806 as we begin to evaluate it in combination with other targeted therapies. Despite the success of targeted therapies such as tyrosine kinase inhibitors and KRAS inhibitors, a considerable need remains to drive enhanced antitumor activity while addressing mechanisms of innate and adaptive resistance.
We are developing our next-generation farnesyl transferase inhibitor KO-2806 to address this need. KO-2806 was designed to improve upon the potency, pharmacokinetic and physical chemical properties of tipifarnib. Last year, we presented compelling preclinical data supporting the rationale for combining KO-2806 with distinct classes of targeted therapies, including tyrosine kinase inhibitors and KRAS inhibitors.
In October, we began dosing patients with KO-2806 as a monotherapy in a Phase I dose escalation trial that we call FIT-001. That trial uses an innovative design that enables us to begin dose escalation of KO-2806 in combination cohorts very early on in the study while continuing to dose escalate concurrently as a monotherapy.
In fact, we dosed the first patient with KO-2806 in combination with cabozantinib in clear cell renal cell carcinoma in February, just four months after KO-2806 entered the clinic. And we are on track to dose the first patient in combination with adagrasib in KRAS G12C mutated non-small cell lung cancer by the middle of this year.
As a reminder, the study of KO-2806 and adagrasib is supported by a clinical collaboration and supply agreement with Mirati now part of Bristol-Myers Squibb. While our focus with KO-2806 remains on renal cell carcinoma and KRAS-driven tumors, its rapid development progress provides us with further flexibility as we consider potential development paths forward in head and neck squamous cell carcinoma. If successful, we believe KO-2806 could become the ideal combination partner for multiple targeted therapies in large solid tumor indications.
With that, I’ll now turn the call over to Tom for a discussion of our financial results.
Thomas Doyle
Thank you, Troy, and good afternoon, everyone. I’m happy to provide a brief overview of our financial results for the first quarter of 2024. Research and development expenses for the first quarter of 2024 were $36.3 million compared to $25.2 million for the first quarter of 2023. The increase in R&D expenses was primarily due to increases in clinical trial costs related to our ziftomenib and KO-2806 programs.
General and administrative expenses for the first quarter of 2024 were $18.2 million compared to $11.4 million for the first quarter of 2023. Net loss for the first quarter of 2024 was $49.5 million compared to a net loss of $34.1 million for the first quarter of 2023. This included noncash share-based comp expense of $8.5 million compared to $6.8 million for the same period in 2023.
As of March 31, 2024, we had cash, cash equivalents and short-term investments of $527 million compared to $424 million as of December 31, 2023. This includes net proceeds of approximately $145.8 million from our private placement in January of 2024. We believe that our cash, cash equivalents and short-term investments will be sufficient to fund our current operating plan into 2027.
With that, I now turn the call back over to Troy.
Troy Wilson
Thank you, Tom. Before we jump into the question-and-answer session, let me lay out our anticipated upcoming milestones. For our menin inhibitor programs, complete enrollment of 85 patients in the KOMET-001 registration-directed trial of ziftomenib in NPM1-mutant AML by mid-2024, identified a recommended Phase II dose of ziftomenib in combination with venetoclax and azacitidine by mid-2024, identify the recommended Phase II dose of ziftomenib in combination with 7+3 by mid-2024 and initiate a Phase Ib expansion study of ziftomenib in combination with standards of care including venetoclax/azacitidine in newly diagnosed NPM1-mutant or KMT2A-rearranged AML in the second half of 2024 and submit an investigational new drug application for ziftomenib in a solid tumor indication and present preclinical data at a medical meeting in the second half of 2024.
And for our farnesyl transferase inhibitor programs dosed the first patients with KO-2806 and adagrasib and KRASG12C-mutated non-small cell lung cancer by mid-2024. Complete enrollment of two expansion cohorts in KURRENT-HN and identify the optimal biologically active dose of tipifarnib and alpelisib by the end of 2024 and present data from the KURRENT-HN trial of tipifarnib in combination with alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma in the first half of 2025.
With that, operator, we’re now ready for questions.
Question-and-Answer Session
Operator
Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. [Operator Instructions] Your first question comes from Jonathan Chang, Leerink Partners. Jonathan, please go ahead.
Jonathan Chang
Hi, guys. Congrats on the progress and thanks for taking my questions. First question, how should we be thinking about the implications of ziftomenib getting Breakthrough Therapy Designation on the likelihood of success of KOMET-001 and the time line for potential approval?
Troy Wilson
Yeah, Jonathan. Thanks for the question. So in terms of the implications for approval, there was a question out there in the ether whether NPM1-mutant AML was actually of the same magnitude as KMT2A-rearranged AML in terms of unmet need. And as we indicated in the prepared remarks, this is the agency saying, not only is that a significant unmet need, but this is a therapy that represents the potential for substantial improvement over the standard of care. Now we haven’t commented specifically on our specific engagements with the FDA other than to say across our various studies, we’re engaged with the agency on a regular basis across different studies.
And as we look forward to an eventual NDA submission, I think you have to believe that not only is this a validation of ziftomenib in terms of this patient population but it’s certainly a derisking event as we think about the submission and ultimately an application for marketing approval. That’s certainly the way that we view it. It is, after all, the first and only BTD and the NPM1 subset, which is by far and away the larger of the two subsets. In terms of time lines, again, we’ve said consistently, what matters is that you get it at or ideally just before you complete enrollment because what it really does is several things.
It recruits the A team from the agency which is important at a time when the agency has a lot going on, right? A lot of sponsors vying for attention, you get their priority and their expert review. They work with you very collaboratively and they basically open up other possibilities to accelerate time lines. And we spelled out a couple of those, including rolling review, priority review. You basically — you get on the short list of priority programs at the agency. So we intend — we’ve said consistently, we intend to take advantage of every tool and trick and technique we can to accelerate time lines. This is the latest one.
I think it puts us in a solid position. We are exactly where we want to be in terms of enrollment. As we say in the heading to the sub-bullet, enrollment is nearing a close and now we’re looking forward to letting the data mature and then all the work that goes into the submission and then looking forward beyond that. So Hopefully, that answers your questions.
Jonathan Chang
Great. Thank you. And just one more question for me. Can you provide any color on when we might see more of ziftomenib clinical data over the course of the year?
Troy Wilson
Yeah. Sure. I’m sure this is a question on a lot of people’s minds. So we have kind of multiple things to be looking at. The last update, again, as we alluded to in the prepared remarks, was the January disclosure where we showed data from the first 20 patients enrolled in the KOMET-007 study. Clearly, we can give an update on those patients. We are just really moving quite quickly and quite aggressively through dose escalation.
It’ll — I think a lot of people are looking toward what is the recommended Phase II dose for the different combinations and in the different populations? And then what does that data look like? Does it — does the trend — we saw, we think, pretty encouraging data from the first 20 patients in terms of safety, tolerability, combinability and clinical activity, does that trend continue, right? Are there — does everything look good?
And then as we alluded to, obviously, you turn the corner, you move into the expansion cohorts which will take us into newly diagnosed frontline ven/aza, newly diagnosed 7+3 without the requirements for adverse risk. That will be sort of another tranche of data. We haven’t, Jonathan, to this point been more specific. We’re keeping our options open. People are looking toward EHA. We’re not even yet to the late-breaking abstract deadline.
We’ve used corporate events quite successfully. There’s always ASH at the end of the year. We may take advantage of one or several of those. And when we have more specific guidance that we can give you, we’ll say something. But that’s the way we’re looking at it. We know — we think we know what our audience, our analysts and investors are looking for, and we’re going to try to come at the right times with the right data that will help give everyone confidence that we’re going in the right direction.
Jonathan Chang
Got it. Thanks for taking the questions.
Troy Wilson
Sure.
Operator
Thank you. Your next question comes from Jason Zemansky, Bank of America. Jason, please go ahead.
Jason Zemansky
Good afternoon. Thank you so much for taking our questions and congratulations on the progress thus far. I was hoping maybe you could shed some light into the patients who have remained on the trial. You mentioned 16 of 20 patients, including all 11 NPM1 patients are still in the study. What happened with the four, did — was it disease progression or something else? What dose were they being treated with?
Troy Wilson
Yeah. Jason, thanks for the question. So maybe just to take a step back. Those numbers that I cited to you were as of the January 11 data cutoff. So I was basically restating the results from that data cut of the 20 patients. We had — as we said, we had all five patients in the newly diagnosed 7+3 cohort respond. We had a significant number in the relapsed/refractory. We are just to sort of set everybody’s expectations that all of that data for those 20 patients was taken at a 200-milligram dose.
And I think it was an open question in many people’s minds as to what to expect at a 200-milligram dose. I had more than one investor say to me, well, it wasn’t really active at 200, I hope you get to 600. It’s actually active at all the doses. We did determine that the 600-milligram dose is the optimal dose of monotherapy. And the point of this experiment, this escalation is to determine what is the optimum dose in combination.
In terms of — I don’t know that we that we gave a lot of detail at the time, Jason, of that data cut. We did have — I just — something that we did call out at the time. We have one patient who crossed over from the frontline 7+3 to the relapsed/refractory ven/aza had a CR actually in both arms.
We had another patient who — Mollie, I think, at that time, cited, who had — unfortunately had a small bowel obstruction before the patient ever even got on zifto. So in these heavily pretreated, particularly relapsed/refractory it’s not evidencing a high rate of progressive disease. It’s more often that they have, unfortunately, Jason, some clinical sequelae that just are associated with having advanced leukemia.
Jason Zemansky
Got it. Well, maybe just to kind of touch a little bit more on the KMT2A patients that dropped out of the trial. Was there a homogeneity amongst the group? And does this read through to your expectations for zifto within the, I guess, entirety of the KMT2A population?
Troy Wilson
I — so I wouldn’t — so again, staying on that 200-milligram data set, of 20 patients, I think it’s too small to draw any kind of conclusion. We do — we did say and we do say 200 milligrams of zifto is an active dose. There’s no question. Is that the optimal dose? I would say stay tuned, right? We’ll find out.
Our view is if you can push the dose of monotherapy to 600, you should, something that we are — that we’ve talked about is the potential for whole body exposure. And we think that’s important in terms of both getting patients into response, Jason, and keeping them there. And obviously, that improves as you’re able to go to higher doses. You get higher whole body exposure.
We’ll — at the appropriate time, we’ll be able to walk you through the 200 dose as well as the higher doses, and then we can draw some conclusions as to what we’re seeing. What I can say to you, and you can just tell it from enrollment is, we don’t have any toxicities. We don’t have any real DDIs to speak of. That’s part of we think why enrollment is going so quickly.
Zifto is, once you’ve mitigated a differentiation syndrome, it’s actually a very easy drug to work with, with these various combination regimens. So we’re looking forward to updating that data. I wouldn’t — other than the drug is this has manageable safety and tolerability and good early evidence of clinical activity. I’m not sure I would over-interpret that 200-milligram data.
Jason Zemansky
Got it. Perfect. Thanks for the color.
Troy Wilson
Sure.
Operator
Thank you. Your next question comes from Roger Song, Jefferies. Roger, please go ahead.
Roger Song
Great. Congrats for the progress and thank you for taking the question, Troy. Maybe start with the one clarification question and one follow-up question. For clarification, just to confirm, for the RP2D you’re about to declare that is in all of those four cohorts first-line and relapsed/refractory in both ven/aza and the 7+3, but your Phase Ib trial or the Phase Ib expansion trial, you plan to do only in first-line ven/aza, is that correct?
Troy Wilson
Roger, I’m not sure I understand the second part of your question. What — let me answer what I think is the first part, and then you can ask me the second part again. For the RP2D, each cohort is enrolling independently of the others. And so — and remember, for everybody’s sake, the way the protocol is written, we don’t have to go back to the agency to initiate the expansion cohorts.
We need the Safety Monitoring Committee to make a determination that our recommended Phase II dose has appropriate safety and tolerability to move forward into an expansion cohort. We don’t have to go back, in other words, to the FDA and ask for permission. We will — and so — and those cohorts are — they’re roughly all enrolling at the same rate, but there’s a little bit of variability, as you can tell. The KMT2A 7+3 cohort is lagging just a little bit behind the other three. We will be validating that RP2D and gaining more experience in the expansion cohorts.
And you’re really — as I said, again, the — as you move from escalation to expansion, you’re actually going into “healthier patients”, they still have AML, but patients who do not have adverse risk, for example, in the case of 7+3 or frontline patients in the case of ven/aza, you’d like to understand the profile of the drug in that set so that you can then make the appropriate considerations and decisions on registrational trials going forward, particularly in ven/aza, we’re not yet in the front line.
We need to get there. So that will help us clarify safety, tolerability, combinability and activity. And enrollment’s going so fast, Roger, that that’s not going to be — that should be well underway here after we reach the RP2D around midyear. The team is just crushing it in terms of enrollment. Did I answer your questions?
Roger Song
Yeah. I think you answered the first part. The second part really is just to clarify what is the Phase Ib expansion cohort because you mentioned the first line ven/aza combo, but how about the relapsed/refractory and the 7+3? Thank you.
Troy Wilson
I see. Okay. Got it. Yes. So the way to think about it is we will continue to evaluate the genotypes separately. So you have effectively seven arms. You have ven/aza, frontline ven/aza, NPM1 and KMT2A, you have relapsed/refractory, again, NPM1 and KMT2A. Same thing with 7+3 front line now no longer adverse risk. And then one cohort you might have picked up on, which is ziftomenib plus venetoclax, only venetoclax in the relapsed/refractory setting.
And that’s one where we get a lot of interest from investigators asking the question, do you really need azacitidine? And you clearly need ven, but do you need azacitidine given that menin inhibitors are epigenetic. Their mechanism is an epigenetic modifier. We’ll test that in the clinic and see. So when you consider each of two genotypes times those two essentially three plus the ven/zifto combo, that gives you seven arms.
That’s what we’re describing, Roger, as the Phase Ib. We will not necessarily move forward with all of those into registrational. We’re gathering the safety data, the — we’ve activity data. We’re already working on what do — what is the first registration-enabling study look like, the second, etc. We’ll provide more color on that likely later this year.
Roger Song
Excellent. Okay. So that’s clear now. Actually, you already partially answered my last question, follow-up question is the registration path. Maybe can you give us a little bit in terms of time line guidance when you will start to think about the registration for either of those cohorts?
Troy Wilson
Yeah. So we’re already thinking about it. We’re already planning for it. Even though we’re learning — we’re continuing to learn about zifto as we dose escalate. And to some extent, what you’re waiting for is you need to be able to say to health authorities, this is the dose in the combination, and this is the data that supports that dose selection. That’s the point of this exercise. But you can leave that dose, Roger, in brackets and say this is what the design of the trial looks like. pending this dose. And our team is working quite intensely already to map out what do those registration trials look like?
And obviously, you look at our emerging data, you look at the competitive landscape, you look at what are the regulators looking for in terms of endpoints, you do the commercial considerations all of that gets folded in. What I can say to you is, so far, our belief is that ziftomenib has the potential to be the best-in-class menin inhibitor. And there’s nothing we’re seeing thus far that takes us off of that view in terms of safety, tolerability, combinability, absence of toxicities, QTc, drug-drug interactions, everything is looking good.
So at this point, we have a wealth of options. We clearly won’t do them all or won’t do them all at the same time. We need to prioritize. And we’re doing that important work now, Roger. We’ll talk more about the design. We’ll probably give you a view on the design after we’ve gotten some input from the health authorities because we want to make sure that we bring them along as is appropriate when you’re considering registrational studies.
Roger Song
Excellent. Thank you, Troy for all the comments. That’s it from us.
Troy Wilson
Thank you.
Operator
Thank you. Your next question comes from Li Watsek, Cantor Fitzgerald. Li, please go ahead.
Li Watsek
Hey, good afternoon. Congrats on the progress. Just a couple of questions from me. Troy, I wonder if you can provide any color on whether the FDA has seen additional data for the breakthrough definition potentially from the ongoing pivotal study as well?
Troy Wilson
Yeah, Li. So you may find this answer unsatisfying. And for that, I apologize. We can’t really give you specifics on our engagement with the agency. Suffice it to say, they are very familiar with the benefit risk for ziftomenib. I mean they’ve been great partners with us from the beginning. As I say, we are in active discussions with them, already beginning to put the pieces in place to make sure that the modules of the NDA are lining up with their expectations.
I can’t speak specifically to your question. I think they don’t frequently award a BTD unless they’re reasonably confident that the drug is actually going to deliver. Of the drugs that get Breakthrough Therapy designation, 90% of them go on to get approval. The ones that don’t, it’s typically like a manufacturing issue or something else, which obviously won’t be the case of a small molecule. That gives you some guardrails. But we’re obviously thrilled by the BTD designation and particularly to be the first menin inhibitor and maybe the only ones to actually get it.
Li Watsek
Okay. Thanks. And then for the 400 mg dose, it sounds like it’s being cleared. So I wonder if you can share any maybe early indication whether you’re seeing a dose response here relative to the 200 mg. I understand the patient population is slightly different, but any color there would be helpful.
Troy Wilson
Yeah. I can’t really — so we cleared it for those of you who listen regularly, the last time we had — I had the microphone in a Reg FD-compliant setting, I said that one of the three cohorts was open at 600 mg. Here we are, I think it’s two weeks later or 10 days later, now three of the four are open. My point Li in telling you that is this data is evolving in real time.
What is encouraging is, again, nothing really to be concerned about in terms of safety, tolerability, drug-drug interactions. I want to be careful not to get too far ahead of the data. The monotherapy data, Li, clearly says 600 mg is better than 200 mg. We didn’t test 400 mg, obviously, but 600 mg was clearly better than 200 mg. You would expect, Li, that same relationship to apply in the combination setting.
And so the real question is, can you actually — is the safety and tolerability manageable at 600 mg. If that’s the case, then you would expect improved activity to pull through in both populations. But I’ll answer you that — the question that way rather than sort of trying to give you an early peak at the 400 milligram cohort.
Li Watsek
Okay. Thank you.
Troy Wilson
Sure.
Operator
Thank you. Your next question comes from Brad Canino, Stifel. Brad, please go ahead.
Bradley Canino
Great. Thank you, and it’s nice to be able to focus on just your call this evening. I just wanted to check in on the BTD. Can you help me understand when you submitted for that designation? And why it ended up at that submission date?
Troy Wilson
Yeah. So, not really Brad. You — just to answer the question in a general sense, in our experience the way the BTD works is you have a pre-submission if the agency wants you to put in a full application, they’ll indicate it at that time, otherwise, they might indicate that they’d like to see you answer questions or provide additional data. If they invite you to submit the full application, they typically get back to you in about 60 days. That’s — again, that’s the general course.
One of the questions that I think was out there in the community was what exactly is the unmet need in NPM1-mutant AML. And we — I think we were very successful in convincing the agency of the view of many of the docs, which is if particularly once you’re in the relapsed/refractory setting, there’s no difference in unmet need between KMT2A and NPM1.
So we’ve had a very constructive dialogue with the agency all the way back to — I hate to say it, but the agency was very helpful in terms of our navigating our partial clinical hold. They have been great partners ever since. I think they see the promise of menin inhibitors. I think they’re quite — I don’t want to speak for them, but they have been a great partner to work with.
Bradley Canino
Okay. And maybe if I can ask one more. As you’re progressing through the combo dose escalation, have the enrollment rate across the different cohort mutations come in line with your expectations headed into the trial? Thank you.
Troy Wilson
Yeah. So the enrollment has actually been pretty even across the cohorts. It ebbs and flows. As you go week to week, it — I’m not sure, Brad, we had really — I’m not sure what our expectations necessarily were going in. Certainly, we are seeing very, very strong engagement. I’ll just remind everybody that for each of these arms, if you will, it’s six patients per dose. Now some of these doses are actually over enrolling because sometimes you have patients who have cleared screening and — but you’re not yet ready to put them in the next highest dose.
So there may be rather than six, we may have seven or eight or even more at a given dose. But at a minimum, when all is said and done and the escalation was at least 72 patients. And I’m telling you now, it will be more than 72. Think about how fast that enrollment is gone. We started in July and look at it relative to other comparables out there, there’s just been incredibly strong engagement. The lag in the KMT2A frontline 7+3, Brad, is probably just reflective of the difference in the incidence.
Again, NPM1 is 30% and KMT2A is probably 5% — it’s 10% if you include all of leukemia. It’s probably 3% to 5% in AML. That’s probably what you’re seeing. But it’s — again, it’s lagging behind only very, very briefly. We should — as we said, we should be clearing the 400-milligram cohort in the 7+3 KMT2A here imminently, and we expect that, that one will go to 600 mg as well.
Bradley Canino
Thank you.
Troy Wilson
You’re welcome.
Operator
Thank you. Your next question comes from Peter Lawson, Barclays. Peter, please go ahead.
Peter Lawson
Hey. Thanks for the taking the questions. Just around the 200-milligram dose in combination, are there any trends emerging from the duration on therapy between the KMT2A versus the NPM1 patients, Troy?
Troy Wilson
It’s early, Peter. It’s early — I mean, the — maybe just to take a step back, it’s too early. If you look at these patients in general though, Peter, the KMT2A are often younger, more typically more frequently go to transplant. The NPM1s, the median age is like 60. So they — and they — oftentimes, they’re older, a little bit more frail. They perhaps don’t go to transplant as readily as the KMT2A. I think it’s too early to say.
What we saw from the 200-milligram data, Peter, was even at that dose, which, again, in our view, was a nonoptimized dose, you saw meaningful clinical activity, I think better than many people expected. And it certainly gave us confidence to continue escalating. A big part of the KMT2A, Peter, of driving clinical benefit there is going to be this concept of whole body exposure. We think that’s critically important.
We think it gives the patients the best chance of really differentiating all of the extramedullary disease. And that’s the advantage that zifto has as we look out across the competitive landscape. It’s highly tissue penetrant. It’s extremely well tolerated. It doesn’t have any other toxicities. And in combination, the DS is very well managed, very well mitigated.
So I think we’re optimistic, Peter, that as we go higher in dose, that may be — that may provide a benefit to both sets of patients and whether those patients go on to transplant or not. Obviously, we’ll be able to say a lot more when we show you the next data installment here.
Peter Lawson
Got you. And then are you seeing anything in the side effect profile when you combine, is there anything that would be impacting duration of therapy or any quirks from particular regimens?
Troy Wilson
If anything, Peter, I think it’s actually helping with the backbones. Zifto is so active in these populations that people think about — if you think about how do you use this, in the case of 7+3, they’re on for about a week, right, on chemo and then they’re on zifto after that. You don’t have to hit them with a sledgehammer when you’re giving them a potent differentiating agent, and that’s both populations. With ven/aza, the protocol follows ven/aza as it’s labeled, but there’s an openness among investigators to move patients off of these myelosuppressive regimens as quickly as possible.
You may actually see better results. We’ll see when you combine with zifto. It’s early days. But Peter, we’re not seeing anything in terms of safety, tolerability, side effect profiles, combinability. We’re not seeing anything that’s giving us any concern. In fact, if anything, it’s telling us — we use these best-in-class language. We mean it when we say it, zifto. Now that we’ve put the DS question largely to bed, I think zifto is really going to be able to show you what it can do.
Peter Lawson
Great. Thank you so much. Thanks for taking the questions.
Troy Wilson
Pleasure.
Operator
Thank you. Your next question comes from Phil Nadeau, TD Cowen. Phil, please go ahead.
Unidentified Participant
Thank you. This is Ernie Rodriguez for Phil. Thanks for taking our questions. We have one. With the competitors many inhibitors launching, even though it’s in another indication, the KMT2A, is there anything — they’re likely launching soon in this year — later this year, is there anything on that launch that you would be looking to or any metrics or any other aspects that you would expect will be useful or informative to your strategy?
Troy Wilson
Yeah. This may surprise you, but let me take off my Kura CEO hat for a second and just say, if they’re able to get approval and get to market, we’re going to applaud. We’re going to congratulate that. Because at the end of the day, we all do this for patients. And KMT2A, which is the indication you’re talking about is a disease of high unmet need. I think that — and I’ll let them speak to their process and where they are. It is — KMT2A is a much smaller opportunity, but it’s a good indicator of the utility of menin inhibition.
We’d certainly be happy that they’re out educating physicians and educating the community when we’re coming along with what we believe is a better menin inhibitor. And whether you look at their combo data or our combo data, you have to believe that combo is the way to go here. So while we believe that ultimately, when we get to market in NPM1-mutant AML, we will be best-in-class. We also think it sets the stage for us to be best-in-class in combination and in maintenance.
And that’s how you drive a multibillion dollar peak sales potential. So we’ll be paying — playing — excuse me, we will be paying careful attention, watching, cheering, learning, not necessarily tracking their key performance indicators because the drugs are very different, but it will be instructive of the utility of menin inhibitors. What is clear to us is that there is — 30% of AML patients are NPM1. We’re seeing that in terms of enrollment. It’s going like gangbusters. And the fact that we’re seeing such strong KMT2A enrollment in the combo, I think really speaks to the potential of those regimens to drive activity. Hopefully that answers your question.
Unidentified Participant
It does. And another quick one on the preclinical data in solid tumors that you expect to disclose in H2. What should we expect on that — are we going to be able to determine like what — which kind of solid tumors would be most amenable — or you will be pursuing on the clinical side or is it more like a broad proof of concept in a broader range of solid tumors.
Troy Wilson
It’s — yes. So it — what we’re talking about really is epigenetic regulator — epigenetic regulation of oncogenes or potential oncogenes, right? That’s what you should be looking for. Are there going to be multiple opportunities? We think so. But each of them is sort of — we’re all still learning about epigenetic regulation. What’s clear to us is that menin, the menin MLL interaction appears to play a critical role both within and outside of AML.
When you see this nonclinical data, and we’ve been working on this internally for quite some time, looking not only with zifto, but with other menin inhibitors as well. You’ll know — it will be very obvious to you, the first place that we’re going. Beyond that, I think we have to continue to be data-driven. We’ve been very good about putting non-clinical data out there and letting that guide the development.
We’re going to continue to do that. So we’ve really taken our time, gone to school, done the work and quite excited to share that data with you here in the second half of the year. It will if it works the way it works non-clinically, it’s potentially transformational for that disease type and can only then drive the TAM that much larger.
Unidentified Participant
Got it. Thank you. That’s helpful. Thanks for taking our questions.
Troy Wilson
Sure.
Operator
Thank you. Your next question comes from Ren Benjamin, Citizens JMP. Ren, please go ahead.
Reni Benjamin
Hey, good afternoon, guys. Thanks for taking the questions. Maybe I missed it, Troy, in your prepared remarks, but what’s happening with the post-transplant program? Has that been initiated, maybe I missed it, is one of the upcoming milestones. Just wanted to know how you’re thinking about that.
Troy Wilson
Yeah. Thanks for asking, Ren. You did not miss it. What I can tell you is in contrast to 001 — KOMET-001 and KOMET-007 and KOMET-008, that trial is an investigator-sponsored trial. We’ve done everything as sponsor — or not as sponsor, but as the drug sponsor, if you will, as a company, we’ve done everything we can. We’ve put it into the investigator’s hands. They’re working through the last few bits of red tape. They have everything they need. As with any investigator-sponsored study, it’s their study.
They control the conduct, they control the timing, they control the dissemination of data. What I can tell you, Ren, is that the FDA has reviewed it, cleared it. It’s really now just in study startup, but it is in the hands of the investigators. So we’re not — we’re probably not going to be in a position to guide you on enrollment there, and we’re going to have to rely on them to speak about the trial. But it’s going in the right direction.
And let me go one step further. It’s just to remind everybody, we are assessing the safety and tolerability of ziftomenib in the post-transplant maintenance context so that we can have the appropriate discussions with health authorities about what a registration-enabling study would look like. Because we can’t do everything at the same time, we’ve chosen to — we’ve actually accepted a proposal to do it as an IST. And at this point, Ren, they’re just, I think, put — dotting the I’s and crossing the T’s.
I will — one other thing — yes, one other thing, Ren, I’ll say is, of course, and this — we do get this question, which is why I wanted to add to it. We do have patients in post-transplant maintenance, both in the monotherapy and in the combination setting. So as — the way we’re doing this is, our studies now permit physicians to put their patients back on ziftomenib post-transplant, if they’re in the various studies.
The IST that I referenced is a dedicated study that would be a lead into a dedicated post-transplant maintenance study, which would be independent and essentially agnostic to where those patients come from. Those two strategies would then marry up to make sure that you can take patients from the front line all the way through to the maintenance setting without interruption. That’s our — that’s the bigger picture strategy.
Reni Benjamin
Got it. Thank you for that added clarity. Just switching gears a little quick to 2806. When I look at KURRENT-HN and the potential to complete enrollment in the two expansion cohorts, and still identify the optimal biologically active dose in — by the end of 2024. Is — can I take that kind of a time line and apply it to 2806 or is 2806 such a unique molecule and very different from tipi that maybe that entire enrollment of the combination studies is going to be a lot quicker, we might see data a lot faster than we’re seeing in KURRENT-HN.
Troy Wilson
Sure. Yeah. So I would be hesitant to draw conclusions across trials about enrollment. The KURRENT-HN trial, the one you’re referring to is it’s a handful of size. It’s a signal-seeking study really intended to answer the question is one plus one equal to three. Tipifarnib 1, alpelisib 1, do you get better activity than either drug as monotherapy. I’ll remind everybody, you don’t expect to see really responses from either tipifarnib or alpelisib in PIK3CA-mutant head and neck.
The work that’s been done with alpelisib largely resulted in stable disease, and you wouldn’t expect tipifarnib to have activity in that genotype in head and neck. So the fact that we’re seeing activity at multiple doses and that we have manageable safety, tolerability and activity to justify some dose optimization, I think, is a good — it says we may be able to extend beyond the work that we did with tipi as a monotherapy and open up that patient population.
But it’s also, I think, highly derisking of what you should expect with 2806. Because if you can combine with alpelisib, it gives you confidence that you can combine with whether it’s adagrasib, cabozantinib or something else, it’s giving us confidence that you want 2806 to be a new and improved tipifarnib.
The final thing, Ren, is we don’t want to go too fast. I know that sounds counterintuitive. It’s actually a very good question. If there’s an opportunity in head and neck, do you go with tipi or do you go with 2806. And I would say our primary focus with 2806 right now is renal cell carcinoma and KRAS-driven tumors. There are — I don’t even know how many KRAS inhibitors either in the clinic or steaming into the clinic, they will all have the same issue.
They will all have innate and adaptive resistance. We’re trying to come up with an approach that basically cuts that off at the needs. And if we can demonstrate with adagrasib, then we’re going to have the high-class problem of which of these solid tumor indications do we pursue. We’ve been, Ren, very data-driven with current and just letting the patient experience sort of guide us on where to go. We’re encouraged, the physicians are encouraged, the response rate in that setting is like 20% in second line, it’s 5% or less in third line. It is as bad as pancreatic cancer. So the fact that we’re seeing, I think, encouraging clinical activity is a good thing.
It’s just too early, Ren to say what’s the development strategy? Is it 2806? Is it tipifarnib? It’s — I think it does go away toward derisking the overall program. And again, if we can pull this off, you’re talking about some big solid tumors. The 2806 trial is a dose-escalation study. And those always have their own challenges.
But again, I wouldn’t draw conclusions of one disease type to the other. Our clin-ops team has been exceptional across the board from zifto to 2806, to KURRENT. They’re making good progress with the FIT-001 trial. We’ll likely share data next year on that study. I think it’s probably a little too early to show anything on FIT here in ‘24.
Reni Benjamin
Excellent. Thanks for taking the questions.
Troy Wilson
Sure.
Operator
Thank you. Your next question comes from Justin Zelin, BTIG. Justin, please go ahead.
Justin Zelin
Thanks for taking the questions. Troy, just with the KOMET-001 enrollment completion coming up here. Any thoughts on when we could see data from that study? Could that be a 2024 event or in 2025?
Troy Wilson
Yeah. Justin, let us — I know this is going to be a bit unsatisfying, let us complete enrollment. We’ve said we’re very close. Let us complete that, and then we can give you guidance on kind of what to expect. I want to make sure we do this in the right time and the right place. We obviously want to give the trial per protocol needs six months plus the time to clean the data. I think we’ll be able to answer that question better coming on the back of full enrollment.
Justin Zelin
Great. That makes sense to me. And just on 2806, could we expect additional studies with other combination agents in the future or are you pretty comfortable with what you have right now? Thanks.
Troy Wilson
Yeah. There’s certainly a rationale, Justin, to combine with other drug candidates. I think what we want to do is — and I’m going to just — for 30 seconds, just go a level deeper. The big takeaway from the current study is that you’re driving activity in that setting, both by blocking wild-type HRAS and we think by blocking farnesylation of RHEB. RHEB stands for Ras homolog expressed in brain.
Why do I call that out? I called that out because that — if you look at the posters that we’ve presented, RHEB — defarnesylation or removal of the farnesyl group from RHEB is critical to blunting the innate and adaptive resistance that arises to KRAS inhibitors. And as I said, if you inhibit KRAS, the tumor is going to do a number of different things to try to escape.
One of them is to upregulate PI3 kinase signaling through that pathway, blocking RHEB farnesylation is critical to blunting that effect. So if we can block RHEB in current with one combination, it gives us confidence that we’re going to be able to block it in a different context with a KRAS inhibitor.
If that’s true, and we see activity and I will tell you, initially, Mirati, now Bristol have been great clinical collaborators on this study. They’ve been very supportive. They’ve given us great input. You could imagine, Justin, using an FTI in combination with almost any KRAS inhibitor. That’s how fundamental that biology is. It’s on par with SHIP2 with SOS1, that’s how you think about it. And it’s taken us a number of years to get there, but that’s the highest — probably the highest best use, most valuable application of an FTI.
Justin Zelin
Great. Thanks for taking my questions.
Operator
Thank you. Your next question comes from George Farmer, Scotiabank. George, please go ahead.
George Farmer
Hi. Thanks for taking my question. I have two. Troy, could you address what you think the hurdles are for zifto approval in NPM1 in relapsed/refractory setting. It’s the first question. The second question is how you think about resource allocation when developing zifto in earlier lines of therapy combining with 7+3 or ven/aza?
Troy Wilson
Yeah. Can you ask the first part of the question again? I just want to make sure I’ve got — the second part is resource allocation. The first part was the hurdle rate or is that right?
George Farmer
Yeah. What do you think the hurdles are for FDA approval of zifto, refractory?
Troy Wilson
Sure. Yeah. So I think — we think that the hurdle rate for the NPM1 cohort, the same is true for KMT2A, by the way. We’ve consistently said for approval, our view is you need 20% to 30% CR/CRH four months to six months median duration of response. Would you like to do better? Yes. But we’ve never — we and I think our competitors have consistently said in our view, that’s the bar for approval in the relapsed/refractory population. It’s going to be different in combination.
And one of the things that we expect in combination is that we expect the duration for both populations, particularly the KMT2A to improve as we go to higher doses. But when we talk about the combinations, we’re going to set the bar a little bit differently. But the fact that we had a 35% CR/CRH rate in the Phase Ib, again, don’t get emotionally attached to 35%. That’s great. You need to be 20% to 30%. But that Phase Ib data, coupled with the BTD award, I think, gives you confidence that we’re in the right ZIP code for being able to secure an approval for monotherapy.
In terms of your question around resource allocation, we can do — we, Kura, on a go-alone basis, can probably pretty readily do one global pivotal trial. Now if we want to really blow out zifto and maximize the value, you’re talking about potentially multiple pivotal trials, including frontline, including maintenance, potentially solid tumors. We’ve said all along, they’re very likely will come a time when we need the resources, both financial and operational of a party larger than we are.
Running global pivotal trials is facilitated if you have people on the ground in all those different countries. But at the moment, we think we can drive really meaningful value for shareholders by just continuing to execute as we have. One of the things you want to understand is what’s the safety, tolerability, activity and some view into durability, both for NPM1 and KMT2A as you go to frontline because the longer that is, both — whether patients go to transplant or not, that’s going to help inform the commercial models. And really, we think, drive the value.
So you’ll see us — we’re already actively evaluating what are different — how can we be clever. How can we take advantage of everything the health authorities have to offer, be efficient about the first combination pivotal trial, I think, we’re providing a really good foundation that will inspire physicians to have confidence that zifto can be used readily with these different combinations, right? And that’s the starting point is you give them comfort that they can use it safely. It can be given orally once a day. There’s no other complications and then you just let the efficacy and the clinical activity speak for itself.
George Farmer
Okay. Thank you.
Operator
Thank you. There are no further questions at this time. I will now turn it back to Troy Wilson for closing remarks.
Troy Wilson
Great. Thank you. Thank you all once again for joining the call today. We’ll be participating in the Bank of America Healthcare Conference in a couple of weeks, and we look forward to seeing many of you there. In the meantime, if you have any additional questions, please feel free to contact Pete, Tom or me. Thank you, and have a good evening, everyone.
Operator
Thank you. Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.
