Kura Oncology, Inc. (NASDAQ:KURA) Q3 2023 Earnings Call Transcript

Kura Oncology, Inc. (NASDAQ:KURA) Q3 2023 Earnings Call Transcript November 3, 2023

Operator: Good afternoon, ladies and gentlemen, and welcome to the Third Quarter 2023 Kura Oncology Inc. Earnings Conference Call. At this time, all lines 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, November 2, 2023. I would now like to turn over the call to Pete De Spain, Head of Investor Relations. Please go ahead.

Pete De Spain: Thank you, Lester. Good afternoon, and welcome to Kura Oncology’s third quarter 2023 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. We believe our lead drug candidate ziftomenib is well positioned for market leadership with multibillion-dollar global revenue potential in acute leukemias and beyond. Our conviction is supported by a growing body of clinical data, as a monotherapy and more recently in combination with standards of care. A rapid pace of enrollment in our ongoing studies driven by strong clinical data and robust enthusiasm among investigators and patients, and a best-in-class safety and tolerability profile that we believe will enable ziftomenib to become a backbone of therapy across the continuum of care for AML patients. Ziftomenib is a once-daily oral drug candidate that targets the menin-KMT2A protein-protein interaction and has potential to address all patients for whom the menin-KMT2A pathway is a disease driver, representing up to 50% of patients with AML.

In our Phase 1 trial, ziftomenib demonstrated an impressive 35% CR rate and 45% overall response rate in 20 patients with NPM1-mutant AML treated at the recommended Phase 2 dose of 600 milligrams. Importantly, ziftomenib demonstrated a favorable safety profile and was well tolerated with no evidence of drug-induced QTc prolongation or myelosuppression, no patterns of toxicity and adverse events consistent with underlying disease. Building upon the strength of the data from our Phase 1 trial, we initiated a Phase 2 trial of ziftomenib in patients with NPM1-mutant relapsed or refractory AML earlier this year. The registration-directed trial is expected to enroll a total of 85 patients in the United States and Europe. We continue to be encouraged by the pace of enrollment in the trial, which in our view speaks to the size of the NPM1-mutant patient population in the relapsed and refractory setting as well as ziftomenib’s potentially meaningful advantages in safety profile and clinical activity relative to available therapies.

We expect to complete enrollment of all 85 patients in the Phase 2 registration-directed trial, no later than mid-2024. Increasingly, our clinical investigators refer to ziftomenib as a potentially transformational therapy. We believe their enthusiasm reflects not only their experience with it as a monotherapy, but the tremendous potential benefit to patients that could be realized by advanced ziftomenib to earlier lines of therapy and combining it with standards of care. Indeed, our vision for ziftomenib is that it can provide benefit to leukemia patients throughout the continuum of care, enabling deeper and more durable remissions in the frontline and relapsed/refractory populations in combination and is a potent monotherapy in the maintenance settings.

Clearly, as ziftomenib can do that it has potential to transform the treatment of AML and ultimately to transform the commercial market for anti-leukemic therapy. It is these transformations in the standards of care that have enabled meaningful advances for patients scenario such as CML, lymphoma and multiple myeloma with corresponding increases in market opportunity. Although AML has lagged behind these other areas due to the complexity, heterogeneity and aggressive nature of the disease, we believe ziftomenib may represent an inflection point for treatment of leukemia and potentially other diseases. As first steps towards realizing this vision, we’re evaluating ziftomenib combination studies, both in newly diagnosed and relapsed/refractory acute leukemia including NPM1 mutant and KMT2A-rearranged AML.

Our approach to combinations is to establish ziftomenib as a foundational therapy that can be combined safely with various commonly used regimens and then to prioritize those combinations that represent the largest unmet medical need and the greatest potential commercial value. Combination approaches also offer the potential to mitigate differentiation syndrome, particularly in the KMT2A rearranged population as has been previously demonstrated in the development of IDH inhibitors in combination with azacitidine. We began dosing patients in the first of our combination studies, which we call KOMET-007 in the middle of this year. KOMET-007 is a Phase 1 dose escalation study designed to assess safety, tolerability, and preliminary activity of ziftomenib in combination with either venetoclax and azacitidine in patients with relapsed/refractory NPM1 mutant and KMT2A rearranged AML or standard induction cytarabine daunorubicin chemotherapy commonly known as 7+3 in NPM1 mutant and KMT2A rearranged patients in the frontline setting.

We’re very pleased with the pace of enrollment in the KOMET-007 study, which currently includes patients with newly diagnosed and relapsed/refractory NPM1 mutant and KMT2A rearranged AML across the United States. At this rate, we anticipate being in position to share preliminary data with sufficient follow-up from 20 patients in KOMET-007 in early Q1 2024. We expect the data set to include safety and tolerability from NPM1 mutant and KMT2A rearranged patients treated with ziftomenib in both settings. We’re also working to initiate our KOMET-008 study of ziftomenib in combination with additional standards of care including the FLT3 inhibitor gilteritinib as well as our post-transplant maintenance program for ziftomenib, both of which are expected to begin in the first quarter of 2024.

Meanwhile, we continue to make progress toward a next-generation menin inhibitor, which we intend to direct to additional as yet undisclosed indications of high clinical, commercial, and strategic interest. As we continue to build the clinical data sets that we believe will support FDA registration and commercialization of ziftomenib, we recently enhanced our own commercial expertise with the addition of Brian Powl to our senior leadership team as our Chief Commercial Officer. Brian joined us over the summer with more than 20 years of experience in building commercial brands in hematology and oncology, with expertise in patient-focused strategies across sales, marketing, and market access for global biotech and pharmaceutical products. He’s already making an impact in the organization as we continue to realize the significant potential of ziftomenib as well as our rapidly emerging farnesyl transferase inhibitor programs.

We continue to unlock the substantial therapeutic and commercial value of farnesyl transferase inhibition and believe this novel mechanism is uniquely positioned to augment clinical benefit in multiple large solid tumor indications. Last month we presented positive results from our AIM-HN registration-directed trial of tipifarnib in patients with HRAS mutant head and neck squamous cell carcinoma. The results were featured during a late-breaking mini oral session at the European Society for Medical Oncology Congress in Madrid. Our AIM-HN data demonstrate that if one understands the proper biological context in which to use an FTI, it has the potential to drive meaningful clinical benefit for patients. We believe these data validate therapeutic value of farnesyl transferase inhibition as we look to advance beyond our initial strategy to target HRAS mutant tumors.

With our AIM-HN data in hand we continue to evaluate whether the combination of tipifarnib and alpelisib has potential to extend the clinical benefit observed in the AIM-HN trial to a broader set of HNSCC patients in our ongoing current HN study. We continue to evaluate patients in the dose escalation study to inform selection of the optimal biologically active dose to the combination. Once we determine OBAD, we’ll continue to evaluate whether the activity supports development and commercialization of the combination in HNSCC. One of the most important takeaways thus far from current HN is that tipifarnib demonstrates a favorable safety and tolerability profile at its full dose in combination with alpelisib. We believe this significantly derisks development of our next-generation, farnesyl transferase inhibitor KO-2806, as we look forward to evaluating it in combination with other targeted therapies.

With the success of targeted therapies such as KRAS inhibitors, tyrosine kinase inhibitors and EGFR inhibitors there’s now considerable focus on the development of companion therapeutics that have potential to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance. Last month, we presented exciting preclinical data at the triple meeting, supporting our rationale to combine KO-2806 with adagrasib in KRASG12C-mutated non-small cell lung cancer and with cabozantinib in clear cell renal cell carcinoma. A week later, we announced the first patient was dosed in the FIT-001 Phase 1 dose escalation trial of KO-2806. Concurrent with the dose escalation as a monotherapy in the FIT-001 trial, we also plan to evaluate KO-2806 in dose escalation combination cohorts, with adagrasib and cabozantinib.

Earlier today, we announced a clinical collaboration and supply agreement with Mirati Therapeutics to evaluate the combination of KO-2806 and adagrasib in patients with KRASG12C-mutated non-small cell lung cancer. Under the terms of the agreement, Kura will sponsor the Phase 1 study and Mirati will supply us with adagrasib for the study. This collaboration highlights the potential to address the urgent need for more durable and effective treatment options for patients with cancers driven by the KRASG12C-mutant oncogene. We look forward to collaborating with Mirati, an established leader in targeted oncology. We expect to begin dosing KO-2806 in combination with adagrasib in KRASG12C-mutated non-small cell lung cancer and in combination with cabozantinib in clear cell renal cell carcinoma by the middle of 2024.

If successful, we believe KO-2806 could become an ideal combination partner for multiple targeted therapies in large solid tumor indications. We look forward to sharing our continued progress in the months ahead. With that, I’ll now turn the call over to Tom, for a discussion of our financial results.

Tom Doyle: Thank you, Troy and good afternoon, everyone. I’m happy to provide a brief overview of our financial results for the third quarter of 2023. Research and development expenses for the third quarter of 2023 were $29.3 million compared to $25 million for the third quarter of 2022. The increase in R&D expenses was primarily due to the increase in clinical trial costs related to our ziftomenib and KO-2806 programs. General and administrative expenses for the third quarter of 2023 were $13.1 million compared to $11.6 million for the third quarter of 2022. Net loss for the third quarter of 2023 was $38.6 million compared to a net loss of $35.5 million for the third quarter of 2022. This includes non-cash share-based compensation expense of $7.1 million compared to $6.4 million for the same period of 2022.

As of September 30 2023, we had cash, cash equivalents and short-term investments of $452.6 million compared to $438 million as of December 31 2022. We believe that our cash, cash equivalents and short-term investments will be sufficient to fund our current operating plan to mid-2026. Today, we are filing a shelf registration statement and corresponding prospectus supplement for an at-the-market facility for our common stock. We are refreshing our shelf, which was set to expire next month along with an ATM in order to maintain good corporate housekeeping. With that, I’ll 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 milestones for the remainder of this year and next year. For ziftomenib, we report preliminary clinical data from 20 patients in the KOMET-007 trial in combination with ven/aza or 7+3 early in the first quarter of 2024. We dosed the first patients in the KOMET-008 trial in combination with additional standards of care including, the FLT3 inhibitor gilteritinib in the first quarter of 2024 initiate the post-transplant maintenance program in the first quarter of 2024 and complete enrollment of 85 patients in KOMET-001 registration-directed trial in NPM1 mutant AML by mid-2024. For tipifarnib, determine the optimum biologically active dose in combination with alpelisib and determine next steps for the program by mid-2024.

And for KO-2806, dosed the first patients in the FIT-001 dose escalation trial in combination with adagrasib in KRASG12C mutated non-small cell lung cancer and with cabozantinib in clear cell renal cell carcinoma by mid-2024. With that Lester, 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 Jason Zemansky from Bank of America. Your line is now open.

Jason Zemansky: Good afternoon, everyone. Thank you so much for our question and congrats on the quarter. Regarding the upcoming KOMET-007 update what do you think investors should be looking for from the data? What’s necessary before the community can start to feel confident about the potential for combinations and what are we looking for in safety and efficacy? And then a follow-up if I may.

Troy Wilson: Yes. Do you want to ask the follow-up now, Jason or you want to wait? Let me answer this one.

Jason Zemansky: Why don’t we go ahead?

Troy Wilson: So in terms of what investors should expect so 007 is a Phase 1 dose escalation study as I indicated. We are evaluating ziftomenib in combination with ven/aza in the relapsed setting and with 7+3 in the frontline setting. Importantly, we’re evaluating KMT2A and NPM1 mutant patients separately in separate cohorts. So there are six patients per cohort. So think of it as four cohorts and six patients each that’s 24 patients at a 200-milligram dose. And then as we dose escalate 24 patients at 424 patients at 600. In terms of what to look for, whether it’s our data or anyone else’s data, I think you start with safety and tolerability ability to combine drug-drug interactions do you have to discontinue doses do you have to dose reduce.

And then ultimately, of course there will be activity although of course in combination. I think Jason, we feel confident based on the monotherapy data that we’ve shared thus far from the 001 study. If you recall, we had among 20 patients with NPM1 mutant AML we had a 35% CR rate with full count recovery. Thus, we have no QTc prolongation, we have no drug-induced myelosuppression we have no predicted adverse drug-drug interactions we’re once daily we’re not a sensitive CYP3A4 substrate, all of those considerations will become important as you look to combine with these standards of care. This will be a preliminary look. We wanted to get it out there, so that investors could assess safety, tolerability, ability to combine and importantly ability to mitigate DS.

That was a question that, we were getting a lot as to why do you see a difference between KMT2A and NPM1. And we feel confident Jason that in early Q1 when we shared the data with you among those 20 patients we’ll be able to answer investors’ questions. We will of course hopefully continue dose escalation and look to reach a recommended Phase 2 dose in each of those two settings to then help inform the design of ultimate registration-enabling Phase 2/3 studies but one step at a time.

Jason Zemansky: Got it. And then in terms of the opportunities here how do you prioritize 7+3 versus ven/aza the frontline versus maintenance? And I guess, among those two is one better able to kind of give you a glimpse into how a combination with FLT3 would look?

Troy Wilson: Yeah. So, two good questions there. Let me take them kind of in order. If you look simply at the commercial opportunity venetoclax combinations and maintenance probably stand the tallest. Again, given some baseline assumptions probably more detail than we have time for right here. But ultimately, what we’d like to do and I think it will be important we look toward doing this eventually with someone right through some sort of partnership with a strategic partner you really want to be able to position ziftomenib in every combination setting. Why do I say that? You referenced specifically FLT3. FLT3 is half the NPM1 mutant combination. You now have quizartinib approved in the front line, you have gilteritinib approved in the relapsed refractory setting, that’s half of NPM1 is 15% of AML in the preclinical models that we and Syndax have both enabled through publications, that combination is curative in a preclinical setting.