Kura Oncology, Inc. Q1 FY2024 Earnings Call

Good afternoon, ladies and gentlemen, and welcome to the Q1 2024 Kura Oncology Financial Results Conference Call. 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.

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.

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 endpoints 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 5 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 5 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 venetoclax/azacitidine 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 9 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 the 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 venetoclax/azacitidine 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 venetoclax/azacitidine 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 venetoclax/azacitidine in newly diagnosed NPM1-mutant or KMT2A-rearranged AML, venetoclax/azacitidine 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 2 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 physicochemical 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 4 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.

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 compensation 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.

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; identify 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; 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: dose the first patient with KO-2806 and adagrasib in KRAS G12C-mutated non-small cell lung cancer by mid-2024; complete enrollment of 2 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.

Operator Instructions Your first question comes from Jonathan Chang, Leerink Partners. Programs: dose the first patient with KO-2806 and adagrasib in KRAS G12C-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.

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 timeline for potential approval?

Yes, 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 in the NPM1 subset, which is by far and away the larger of the two subsets. In terms of timelines, 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 timelines. And we spelled out a couple of those, including rolling review and priority review. You basically 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 technique we can to accelerate timelines. 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 question.

Great. And just one more question for me. Can you provide any color on when we might see more ziftomenib clinical data over the course of the year?

Yes, sure. I'm sure this is a question on a lot of people's minds. So we have 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 moving quite quickly and quite aggressively through dose escalation. 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 the trend we saw in the first 20 patients in terms of safety, tolerability, combinability and clinical activity continue? 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 venetoclax/azacitidine and newly diagnosed 7+3 without the requirements for adverse risk. That will be 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 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 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.

Your next question comes from Jason Zemansky, Bank of America.

Congratulations on the progress thus far. I was hoping 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 who were not? Was it disease progression or something else? What dose were they being treated with?

Yes. Jason, thanks for the question. So maybe just to take a step back. Those numbers that I cited were as of the January 11 data cutoff. So I was basically restating the results from that data cut of the 20 patients. All of that data for those 20 patients was taken at a 200-milligram dose. 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 escalation is to determine what is the optimum dose in combination. In terms of what happened to the four patients, we didn't give a lot of granular detail at the time. We did call out that one patient crossed over from the frontline 7+3 to the relapsed/refractory venetoclax/azacitidine and had a CR in both arms. We had another patient who, unfortunately, had a small bowel obstruction before ever receiving ziftomenib. In these heavily pretreated, particularly relapsed/refractory patients, it's not that we're evidencing a high rate of progressive disease; it's more often that they have clinical sequelae associated with advanced leukemia. So that's the context of those numbers.

Got it. Maybe just to touch a little bit more on the KMT2A patients that dropped out of the trial. Was there homogeneity amongst that group? And does this read through to your expectations for ziftomenib within the entirety of the KMT2A population?

So again, staying on that 200-milligram data set of 20 patients, I think it's too small to draw any kind of firm conclusion. We did say and we do say 200 milligrams of ziftomenib is an active dose. There's no question. Is that the optimal dose? I would say stay tuned; we'll find out. Our view is if you can push the dose of monotherapy to 600 milligrams, you should. We've talked about the potential for whole-body exposure, and we think that's important for both getting patients into response and keeping them there. Whole-body exposure improves as you're able to go to higher doses. At the appropriate time, we'll walk you through the 200-milligram dose as well as the higher doses, and then we can draw conclusions on what we're seeing. What I can say, and you can tell it from enrollment, is we don't have any toxicities of significant concern and we don't have any real drug-drug interactions to speak of. That's part of why enrollment is going so quickly. Ziftomenib, once you've mitigated differentiation syndrome, is actually a very easy drug to work with in combination regimens. So we're looking forward to updating that data. I wouldn't over-interpret the 200-milligram data beyond the fact that the drug has manageable safety and tolerability and good early evidence of clinical activity.

Your next question comes from Roger Song, Jefferies.

Great. Congrats on the progress and, Troy, maybe start with one clarification question and one follow-up. For clarification, just to confirm, for the RP2D you're about to declare, is that in all of those four cohorts—first-line and relapsed/refractory in both venetoclax/azacitidine and the 7+3—but your Phase Ib expansion trial, you plan to do only in first-line venetoclax/azacitidine, is that correct?

Roger, I'm not sure I understand the second part of your question. Let me answer what I think is the first part. For the RP2D, each cohort is enrolling independently of the others. Remember, the protocol is written so we don't have to go back to the agency to initiate expansion cohorts. We need the Safety Monitoring Committee to determine 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 to the FDA to ask for permission. We will be validating that RP2D and gaining more experience in the expansion cohorts. As you move from escalation to expansion, you're actually going into patients who are relatively healthier; they still have AML, but they do not have adverse risk in the case of 7+3 or are frontline patients in the case of venetoclax/azacitidine. That helps clarify the profile of the drug so you can make appropriate considerations on registrational trials going forward, particularly for venetoclax/azacitidine where we're not yet in the frontline setting. Enrollment's going so fast that should be well underway after we reach the RP2D around midyear. The team is executing strongly. Did I answer your question?

Yes. I think you answered the first part. The second part is just to clarify what the Phase Ib expansion cohorts are, because you mentioned the first-line venetoclax/azacitidine combo, but how about the relapsed/refractory and the 7+3?

Okay, got it. The way to think about it is we will continue to evaluate the genotypes separately. You effectively have seven arms: frontline venetoclax/azacitidine for NPM1 and KMT2A; relapsed/refractory venetoclax/azacitidine for NPM1 and KMT2A; frontline 7+3 for NPM1 and KMT2A without the adverse-risk requirement; and one cohort of ziftomenib plus venetoclax only in the relapsed/refractory setting. There's interest from investigators on whether azacitidine is required with venetoclax in combination with a menin inhibitor, given menin inhibitors are epigenetic modifiers. We'll test that clinically and see. When you consider two genotypes times those arms plus the venetoclax-only combo, that gives seven arms. That's what we're describing as the Phase Ib. We will not necessarily move all of those into registrational studies; we're gathering safety and activity data and already working on what the first registration-enabling study will look like. We'll provide more color likely later this year.

Excellent. Okay. That's clear now. My follow-up is on the registration path. Can you give a bit of timeline guidance on when you will start to think about registration for either of those cohorts?

Yes. We're already thinking about it and are planning for it even as we continue to learn about ziftomenib during dose escalation. 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. But you can leave the dose in brackets and describe the trial pending dose confirmation. Our team is working intensely to map out what registration trials look like. We look at emerging data, the competitive landscape, what regulators look for in endpoints, and commercial considerations. So far, our belief is that ziftomenib has the potential to be the best-in-class menin inhibitor. We're not seeing anything thus far that dissuades that view in terms of safety, tolerability, combinability, absence of QTc issues and drug-drug interactions. We have a wealth of options. We won't do them all at once; we must prioritize. We'll likely give a view on design after getting input from health authorities to make sure they are appropriately engaged for registrational designs.

Your next question comes from Li Wang Watsek, Cantor Fitzgerald.

Congrats on the progress. Troy, can you provide any color on whether the FDA has seen additional data for the breakthrough designation potentially from the ongoing pivotal study as well?

Li, you may find this answer a bit unsatisfying. We can't give specifics on our engagement with the agency. Suffice it to say, they are very familiar with the benefit-risk profile for ziftomenib. They've been constructive partners from the beginning. We're in active discussions and are beginning to put pieces in place to make sure the NDA modules align with their expectations. I can't speak specifically to your question about what exact additional data they reviewed. They typically don't award BTD unless reasonably confident the drug can deliver. Of the drugs that receive BTD, many go on to approval; those that don't often have unrelated issues like manufacturing. We're thrilled by the designation, particularly as the first menin inhibitor to receive it.

Okay. For the 400-milligram dose that's been cleared, can you share any early indication whether you're seeing a dose response relative to the 200 milligrams? I understand patient populations differ, but any color would be helpful.

We cleared the 400-milligram dose; the situation is evolving in real time. What is encouraging is nothing concerning on safety, tolerability or drug-drug interactions. The monotherapy data clearly shows 600 milligrams is better than 200 milligrams. We didn't test 400 milligrams in monotherapy, but you would expect a similar relationship in combination settings. The key question is whether safety and tolerability are manageable at 600 milligrams in the combinations. If so, you would expect improved activity to carry through in both populations. I want to be careful not to get too far ahead of the data; we'll provide the proper context when we can.

Your next question comes from Brad Canino, Stifel.

Great. I 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?

Not really, Brad. Generally, the BTD process involves a presubmission exchange; if the agency wants a full application they will invite it. If they invite a full application, they typically respond in about 60 days. One question in the community was what exactly is the unmet need in NPM1-mutant AML. We were successful in convincing the agency that relapsed/refractory NPM1 has a similar unmet need to KMT2A. The FDA has been a constructive partner, and they see the promise of menin inhibitors. We've had a helpful dialogue dating back to resolving our partial clinical hold; they've been supportive.

Okay. As you're progressing through the combo dose escalation, have the enrollment rates across the different genotype cohorts come in line with expectations?

Yes. Enrollment has been strong and relatively even across cohorts, with week-to-week variability. Each arm enrolls roughly six patients per dose, but sometimes cohorts over-enroll when screening is complete but we're not ready to dose escalate. When all is said and done, escalation was planned for at least 72 patients; it'll be more than that given the enrollment pace. We began in July and compared to many comparables, enrollment has been rapid. The KMT2A frontline 7+3 cohort lags slightly, likely reflecting the lower incidence of KMT2A compared to NPM1; NPM1 is about 30% of AML and KMT2A is around 3% to 5% in AML. We expect to clear the 400-milligram cohort in KMT2A 7+3 imminently and expect that cohort to escalate to 600 milligrams as well.

Your next question comes from Peter Lawson, Barclays.

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?

It's early, Peter. The KMT2A patients are often younger and more likely to go to transplant; NPM1 patients tend to be older, median around 60, and may be less likely to proceed to transplant. From the 200-milligram data, even at a nonoptimized dose you saw meaningful clinical activity, better than many expected, and that gave us confidence to escalate. A big part of driving clinical benefit in KMT2A is whole-body exposure, which we think is critical to clearing extramedullary disease. Ziftomenib is highly tissue-penetrant and well tolerated with manageable differentiation syndrome when combined, so we're optimistic higher doses will benefit both patient groups.

Are you seeing anything in the side effect profile when you combine—any impact on duration of therapy or quirks from particular regimens?

If anything, ziftomenib is helping with backbones. In 7+3, chemo is about a week and then patients are on ziftomenib after that; you don't have to hit them with a sledgehammer when giving a potent differentiating agent. With venetoclax/azacitidine, investigators are open to moving patients off myelosuppressive regimens quickly. We're not seeing safety or tolerability concerns in combinations; if anything, ziftomenib's profile is best-in-class. Now that the differentiation syndrome question is largely addressed, ziftomenib can show what it can do.

Your next question comes from Phil Nadeau, TD Cowen.

This is Ernie Rodriguez for Phil. With competitors' menin inhibitors potentially launching later this year in another indication such as KMT2A, is there anything about their launch that you would be looking to? Are there metrics or aspects of their launch that would be useful or informative to your strategy?

This may surprise you, but if they get approval and reach market, we'll applaud and congratulate them. We all do this for patients, and KMT2A is a disease of high unmet need. Their progress would help educate physicians and the community as we advance what we believe is a better menin inhibitor. Whether you look at their combo data or ours, combo will be the way to go. We believe ziftomenib can be best-in-class in combination and maintenance, enabling a multibillion-dollar peak sales potential. We'll watch, cheer, and learn; while not all data will be directly comparable due to drug differences, their activity will be instructive about the utility of menin inhibitors. Enrollment patterns reflect that NPM1 is a larger population at about 30% of AML, and our rapid enrollment supports that view.

A quick one on the preclinical data in solid tumors you expect to disclose in H2: should we expect to determine which solid tumors are most amenable and likely to be pursued clinically, or is it more of a broad proof-of-concept across many solid tumors?

The preclinical work focuses on epigenetic regulation of oncogenes or potential oncogenes. Menin-MLL interactions play a critical role within and outside AML. When we present the nonclinical data, it will be clear where we're going first. We've taken our time and been data-driven in pursuing these opportunities. If the nonclinical work translates, it could be transformational for the disease types we target and expand the addressable market substantially.

Your next question comes from Ren (Reni) Benjamin, Citizens JMP.

Maybe I missed it, Troy, in your prepared remarks, but what's happening with the post-transplant program? Has that been initiated, and is it one of the upcoming milestones?

You did not miss it. The dedicated post-transplant program is an investigator-sponsored trial (IST). We've done everything as a company to support it and put it into investigators' hands; they're working through the last bits of start-up. Investigators control conduct, timing, and dissemination of data. The FDA has reviewed and cleared it; it's now in study startup under investigator control. We are assessing safety and tolerability of ziftomenib in the post-transplant maintenance context so we can discuss what a registration-enabling study would look like. While the dedicated IST is being started by investigators, our interventional trials permit physicians to put patients back on ziftomenib post-transplant in the monotherapy and combination settings. The IST is a dedicated study that would feed into a dedicated post-transplant maintenance study, enabling patients to move from front line through maintenance without interruption. That's the broader strategy.

Got it. Switching gears to KO-2806: with KCURRENT-HN and completion of two expansion cohorts and identifying an optimal biologically active dose by end of 2024, can we apply that timeline to KO-2806? Or is KO-2806 sufficiently different that combination studies and data could come faster?

I would hesitate to draw enrollment conclusions across trials. KCURRENT-HN is a small signal-seeking study to see if one plus one equals three. You don't expect strong responses from either tipifarnib or alpelisib alone in PIK3CA-mutant head and neck; the observations of activity at multiple doses are encouraging and derisk the path for KO-2806. KO-2806's primary focus right now is renal cell carcinoma and KRAS-driven tumors. If we can demonstrate a strong combination with adagrasib, we'll have the challenge of deciding which solid tumor indications to prioritize. The FIT-001 trial uses a dose-escalation design, and we've progressed quickly—dosing the first patient in combination with cabozantinib four months after entering clinic and aiming to dose adagrasib combination by midyear. We'll likely share FIT-001 data next year; it's probably too early to show FIT-001 data in 2024. We're encouraged by investigator interest and early signals, but it's early to define a full development strategy for KO-2806 versus tipifarnib.

Your next question comes from Justin Zelin, BTIG.

Troy, with KOMET-001 enrollment completion coming up, any thoughts on when we could see data from that study? Could that be a 2024 event or more likely 2025?

Let us complete enrollment. We've said we're very close. Once enrollment is complete we'll be in a better position to give guidance. The trial per protocol needs follow-up—often six months plus time to clean the data—so we'll be able to answer that better after full enrollment.

Great. That makes sense. On KO-2806, could we expect additional studies with other combination agents in the future, or are you comfortable with the current partnerships and combos?

There's a strong rationale to combine KO-2806 with other agents. The big takeaway from the current studies is we're driving activity by blocking wild-type HRAS and by blocking farnesylation of RHEB, which is critical to blunting innate and adaptive resistance to KRAS inhibitors. Defarnesylation of RHEB helps blunt PI3K pathway-driven escape mechanisms. If we can block RHEB farnesylation in combination with a KRAS inhibitor, we could potentially use FTIs in combination with many KRAS inhibitors. Mirati (now part of Bristol-Myers Squibb) has been a great collaborator; if we can demonstrate benefit with adagrasib, the biology is fundamental enough that an FTI could pair broadly with KRAS inhibitors. That's the highest-value application of an FTI.

Your next question comes from George Farmer, Scotiabank.

Two questions. First, what do you think the hurdles are for ziftomenib approval in NPM1 in the relapsed/refractory setting? Second, how do you think about resource allocation when developing ziftomenib in earlier lines of therapy combining with 7+3 or venetoclax/azacitidine?

For approval in relapsed/refractory NPM1 (and KMT2A), our view has consistently been you need about a 20% to 30% CR/CRh rate and roughly a four- to six-month median duration of response. You'd like to do better, but that's generally the bar for approval in the relapsed/refractory population. The Phase Ib data we reported, with a 35% CR/CRh in that initial dataset, coupled with the BTD award, gives confidence we're in the right vicinity for monotherapy approval. Regarding resource allocation, Kura could probably run one global pivotal trial on a go-alone basis. To maximize value and expand ziftomenib across frontline, maintenance, and potentially solid tumors, we may need partners or larger resources for multiple pivotal trials. Running global trials is facilitated with on-the-ground presence in countries. For now, we believe we can drive meaningful shareholder value by continuing to execute; we're actively evaluating efficient ways to take advantage of regulatory tools and design optimally prioritized registrational trials. We're working on the right balance of safety, tolerability, and activity data to guide registrational strategy.

There are no further questions at this time. I will now turn it back to Troy Wilson for closing remarks.

Great. 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.

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.