Kura Oncology, Inc. (NASDAQ:KURA) Q1 2024 Earnings Call Transcript

Kura Oncology, Inc. (NASDAQ:KURA) Q1 2024 Earnings Call Transcript May 4, 2024

Kura Oncology, Inc. isn’t one of the 30 most popular stocks among hedge funds at the end of the third quarter (see the details here).

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.

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Q&A 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.