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Edited Transcript of KURA earnings conference call or presentation 25-Feb-20 9:30pm GMT

Q4 2019 Kura Oncology Inc Earnings Call

LA JOLLA Mar 10, 2020 (Thomson StreetEvents) -- Edited Transcript of Kura Oncology Inc earnings conference call or presentation Tuesday, February 25, 2020 at 9:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Bridget A. Martell

Kura Oncology, Inc. - Acting Chief Medical Officer

* Marc Grasso

Kura Oncology, Inc. - CFO & Chief Business Officer

* Pete De Spain

Kura Oncology, Inc. - VP of IR & Corporate Communications

* Troy Edward Wilson

Kura Oncology, Inc. - Chairman, CEO & President

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Conference Call Participants

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* Chris Shibutani

Cowen and Company, LLC, Research Division - MD & Senior Research Analyst

* David Simms Ruch

SVB Leerink LLC, Research Division - Associate

* Jay Olson

Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst

* Pasquale Sansone

H.C. Wainwright & Co, LLC, Research Division - Research Analyst

* Tyler Martin Van Buren

Piper Sandler & Co., Research Division - Principal & Senior Biotech Analyst

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Presentation

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Operator [1]

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Ladies and gentlemen, thank you for standing by. And welcome to the Fourth Quarter 2019 Kura Oncology Earnings Call. (Operator Instructions) Please be advised that today's conference is being recorded. (Operator Instructions)

I would now like to hand the conference over to your speaker, Pete De Spain, Kura's Vice President of Investor Relations. Please go ahead.

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Pete De Spain, Kura Oncology, Inc. - VP of IR & Corporate Communications [2]

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Thank you, Sidney. Good afternoon. And welcome to Kura Oncology's fourth quarter and full year 2019 conference call. Joining me on the call from Kura are Dr. Troy Wilson, our President and Chief Executive Officer; Dr. Marc Grasso, our Chief Financial Officer and Chief Business Officer; and Dr. Bridget Martell, our acting Chief Medical Officer.

Before I turn the call over to Dr. Wilson, I would 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 Dr. Troy Wilson, President and CEO of Kura Oncology.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [3]

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Thank you, Pete. And thank you all for joining us this afternoon. Our mission at Kura is to realize the promise of precision medicines to help patients with cancer lead better, longer lives. Over the past 5 years, we've made significant strides toward achieving that mission. We've advanced 3 wholly owned drug candidates into the clinic.

We've achieved clinical proof-of-concept in 4 separate indications, with our lead candidate tipifarnib. We've initiated our first registration-directed trial of tipifarnib, and we're now actively preparing for a second. And we continue to make progress with our 2 emerging pipeline programs, our ERK inhibitor KO-947 and our menin inhibitor, KO-539.

Recently, we've also taken a number of steps to better position the company for our next phase of growth. This includes an increasing investment in precommercial activities, expansion of our team of medical science liaisons and importantly, the appointment of our Chief Commercial Officer, Kirsten Flowers.

Kirsten joined us last month from Array BioPharma, where she built and led the commercial organization that delivered the impressive launch of Braftovi+ Mektovi for patients with BRAF-mutant melanoma in the United States. Previously, she held several commercial leadership roles at Pfizer, including U.S. commercial lead for the launches of Ibrance in breast cancer and in Inlyta in renal cell carcinoma. Although Kirsten has been onboard only for a short time, she's already proven to be a valuable addition to our executive leadership team as we refine our market insights and begin to build the capabilities and expertise required for commercial success and long-term growth.

Last month, we also announced that Antonio Gualberto had stepped down as Chief Medical Officer. We want to thank him for his contributions and wish him success in his future endeavors.

With this transition, comes an opportunity to sharpen our focus on operational execution across our pipeline. To that end, we're very fortunate to have Bridget Martell, who previously served as our Vice President of Clinical Development and is now stepped up to lead our clinical development organization. Bridget is a proven leader with broad experience in drug development and a track record of success. She has deep familiarity with our organization and pipeline, having served as the clinical lead for our menin-MLL program over the past 2 years. Her impact has already been felt on the leadership team, and I'm excited to be working together more closely. I'm also personally gratified to see how our leadership team and company have pulled together during this transition, and I firmly believe we are stronger and more aligned as a result.

Now, let me bring you up to speed on each of our programs, beginning with tipifarnib and HRAS mutant solid tumors. Execution of our registration-directed trial of tipifarnib in HRAS mutant head and neck squamous cell carcinoma remains our highest priority. The global multi-center trial, AIM-HN, is designed to enroll at least 59 evaluable HNSCC patients with high HRAS mutant variant allele frequency, who've received prior platinum-based therapy. We anticipate AIM-HN will complete enrollment in the first quarter of 2021.

As a reminder, we presented data from our Phase II trial of tipifarnib in HNSCC patients with high HRAS mutant variant allele frequency at the triple meeting in October. The interim results of the Phase II RUN-HN trial showed an objective response rate of approximately 50%, with a median progression-free survival of approximately 6 months.

In comparison, the overall response rates for the 3 therapies approved for treatment of HNSCC in the second line, pembrolizumab, nivolumab and cetuximab range from 13% to 16%, with progression-free survival of approximately 2 months.

In December, the FDA granted fast track designation to tipifarnib for the treatment of patients with HRAS mutant HNSCC after progression on platinum therapy. Fast track designation highlights the potential for tipifarnib to address the unmet need for patients with this devastating disease. The designation offers the opportunity for frequent interactions with the FDA to discuss the drug's development plan, to support drug approval as well as eligibility for rolling submission of a new drug application.

Our primary goal for the program is to generate a data package sufficient to support a first application for marketing approval in HRAS mutant HNSCC. We also continue to explore options to broaden the market opportunity to other HRAS mutant solid tumor indications.

In September last year, we reported that an investigator-sponsored trial of tipifarnib in HRAS mutant urothelial carcinomas, met its primary efficacy endpoint. In addition, a number of patients with HRAS mutant salivary gland cancer were treated with tipifarnib during the conduct of our Phase II trial, several of whom experienced tumor shrinkage and prolonged disease stabilization. Further analysis of both studies are ongoing, and we anticipate data will be presented at an upcoming medical meeting.

In addition to the opportunity in HRAS mutant cancers, the discovery of CXCL12 pathway biomarkers offers the potential to expand the opportunity for tipifarnib to additional hematologic malignancies and solid tumors. For more on our program in advanced T-cell lymphomas, I'll turn the call over to Dr. Bridget Martell.

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Bridget A. Martell, Kura Oncology, Inc. - Acting Chief Medical Officer [4]

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Thank you, Troy. In December, we reported updated clinical data at the American Society of Hematology Annual Meeting in Orlando, showing robust and durable activity from tipifarnib as a monotherapy in relapsed or refractory angioimmunoblastic T-cell lymphoma, or AITL. Our data presented by Dr. Thomas Witzig, a Hematologist at the Mayo Clinic and a principal investigator in the trial, demonstrated an objective response rate of approximately 50% in a heavily pretreated patient population with a median of 3 prior regimens.

Additionally, enhanced antitumor activity was observed in the 10 clinical trial patients who carried mutations in the killer cell immunoglobulin-like receptor or KIR, a CXCL pathway associated biomarker. These patients had an overall response rate of 70% and a complete response rate of 40%. We believe our data, coupled with the high unmet medical need for these patients, support our efforts to expand the development of tipifarnib beyond our initial focus in HRAS mutant solid tumors.

As a reminder, peripheral T-cell lymphomas comprise up to 20% of all aggressive non-Hodgkin's lymphomas and consist of many different subtypes of fast-growing lymphomas. Outcomes for these patients are poor, 5-year survival is approximately 30%. Although several drugs have been approved in the relapsed and/or refractory setting, none has led to survival benefit. In addition, the national comprehensive cancer network guidelines currently recommend clinical trials for these patients.

On another note, before we continue, significant advances in the genetic landscape of T-cell lymphomas have led to a revision of the World Health Organization classification and the introduction of new terminology. As such, we have modernized our terminology going forward in an effort to align with the latest WHO classification. For instance, instead of AITL and AITL-like lymphomas, you'll hear us refer to more comprehensive classification of advanced nodal lymphomas, of T follicular helper, or TFH phenotype, which includes AITL.

Following positive feedback from our end of Phase II meeting with the FDA, we are now preparing to initiate a registration-directed trial of tipifarnib in advanced nodal lymphomas of TFH origin, including AITL. This single-arm trial will target enrollment of approximately 128 patients who are relapsed or refractory to at least one prior systemic cytotoxic therapy. Here, we will investigate 2 independent primary objectives: objective response rate in all patients enrolled and objective response rate in patients who carry a KIR mutation.

Patients will be enrolled on the basis of a pathologic diagnosis of disease, KIR mutational status will be determined retrospectively. Each of the 2 primary objectives has a null hypothesis of 9%, and each can be met independently. We believe the feedback from our end of Phase II meeting with the FDA indicates that the trial, as designed, could support an NDA seeking accelerated approval for tipifarnib, monotherapy in lymphomas of TFH origin and/or lymphomas of TFH origin with KIR mutations.

We are concurrently conducting start-up activities and expect to initiate the registration-directed trial in the second half of the year.

With that, I'll turn the call back over to Troy.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [5]

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Thank you, Bridget. We believe that CXCL12 pathway biomarkers may have the potential to unlock the therapeutic value of farnesyl transferase inhibitors across a range of hematologic and solid tumor indications. One of the indications of particularly high interest is pancreatic cancer. The currently reported 5-year survival rate for pancreatic cancer remains at a dismal 10%. And there's an urgent need to identify new molecular mechanisms to drive antitumor activity and improved survival.

Recall a year ago, we reported a retrospective analysis of prior clinical data that appears to identify a potential association between CXCL12 expression and clinical benefit from tipifarnib in patients with pancreatic cancer. Since then, we've continued to conduct additional preclinical work to validate tipifarnib in CXCL12-high subpopulation of pancreatic cancer patients. Recently, we generated preclinical data showing that tipifarnib can block production of CXCL12 by activated pancreatic stellate cells.

In addition, we've observed the potential for synergy between tipifarnib and chemotherapy in preclinical models of pancreatic cancer. These data bolster our retrospective analysis for the prior clinical data and further support our decision to conduct a proof-of-concept trial of tipifarnib in combination with chemotherapy in the second-line setting for the treatment of advanced pancreatic cancer. Preparations are underway to initiate this trial in the second half of 2020. We're very encouraged by the high level of clinical activity observed thus far in both solid tumors and hem malignancies. With 4 positive Phase II studies now achieved, we believe farnesyl transferase inhibition has the potential to deliver multiple expansion opportunities and long-term growth.

Now, let's turn our attention to our emerging pipeline programs, beginning with our ERK inhibitor, KO-947. KO-947 is a potent and selective small molecule inhibitor of ERK, a protein kinase that represents a central node on the mitogen-activated protein kinase, or MAPK pathway, a well-established pathway in human cancers. We have been evaluating KO-947 in a Phase I dose-escalation study and believe we have identified a recommended Phase II dose for KO-947 as a monotherapy.

Recently, however, we observed a dose-limiting serious adverse drug reaction in a single patient enrolled on the study. Although patients were permitted to remain on therapy, we voluntarily paused enrollment. We also met with FDA to discuss the safety observation and consistent with our actions, the trial was placed on a partial clinical hold. However, based on our assessment of the available pharmacovigilance data, we believe we have a path forward to resume the trial with additional safety monitoring in place. We're working to lift the hold and resume the study at the recommended Phase II dose of KO-947 as a monotherapy.

Upon FDA agreement, we plan to initiate an expansion cohort to evaluate KO-947 in HNSCC in esophageal squamous cell carcinoma patients with 11q13 amplifications, genetically defined populations identified as particularly sensitive to KO-947 monotherapy in preclinical models.

Our other emerging drug candidate is KO-539, a first-in-class potent and selective small molecule inhibitor of the menin-MLL protein-protein interaction. Preclinical data support the potential for potent antitumor activity in genetically defined subsets such as MLL fusions and rearrangements as well as NPM1 mutations.

Despite a number of advancements in the treatment of patients with AML, the 5-year survival rate for people 20 years and older with AML is less than 25%. KO-539 has received orphan drug designation from the FDA for the treatment of acute myeloid leukemia, recognizing its potential to address the population of patients with high unmet need. We dosed the first patient in our Phase I/II clinical trial of KO-539 in relapsed and refractory AML in September 2019, and the trial continues in dose escalation.

Our goal is to reach a recommended Phase II dose or a maximum tolerated dose and with the potential to enrich in NPM1 mutant AML and MLL rearranged genetically defined subgroups later this year. We continue to believe that KO-539 represents a differentiated approach to the treatment of patients with AML. We remain enthusiastic about its potential and look forward to sharing updates with you in the months ahead.

With that, I'll now turn the call over to Marc Grasso for a discussion of our financial results for the fourth quarter and full year 2019.

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Marc Grasso, Kura Oncology, Inc. - CFO & Chief Business Officer [6]

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Thank you, Troy, and good afternoon, everyone. I'll provide a brief overview of our financial results here on the call and invite you to review our 10-K filed today for a more detailed discussion.

Research and development expenses for the fourth quarter of 2019 were $13.5 million compared to $12.1 million for the fourth quarter of 2018. R&D expenses for the full year 2019 were $47.8 million compared to $46.8 million for the prior year. The increases in R&D expenses for the year was primarily due to an increase in clinical development activities related to our registration-directed trial, tipifarnib, offset by decreases in preclinical development for KO-539, companion diagnostics and clinical supply manufacturing activities for tipifarnib and noncash share-based compensation.

General and administrative expenses for the fourth quarter of 2019 were $5.5 million compared to $4.6 million for the fourth quarter of 2018. G&A expenses for the full year 2019 were $19.7 million compared to $16.1 million for the prior year. The increase in G&A expenses was primarily due to increases in noncash share-based compensation and personnel costs.

Net loss for the fourth quarter of 2019 was $17.9 million compared to a net loss of $16.1 million for the fourth quarter of 2018. Net loss for the full year 2019 was $63.1 million compared to a net loss of $60.4 million for the prior year. Net loss for the fourth quarter and full year 2019 included non-cash share-based compensation expense of $2.4 million and $9.4 million compared to $1.7 million and $8.7 million for the same periods in 2018.

Our cash, cash equivalents and short-term investments were $236.9 million as of December 31, 2019, compared with $179 million as of December 31, 2018.

Post receipt of regulatory feedback regarding our proposed registration-directed trial in advanced T-cell lymphomas, we are updating our cash guidance. We believe our cash, cash equivalents and short-term investments will be sufficient to fund our operating expenses and capital expenditure requirements into 2022.

With that, I will now turn the call back over to Troy.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [7]

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Thanks, Marc. Before we jump into the Q&A session, let me lay out our anticipated milestones for the year ahead. For tipifarnib, additional Phase II data in HRAS mutant solid tumors, including HRAS mutant urothelial carcinoma in 2020; initiation of a registration-directed trial in advanced T-cell lymphoma in the second half of 2020; initiation of a proof-of-concept study in pancreatic cancer in the second half of 2020; additional Phase II data in chronic myelomonocytic leukemia in 2020; and the potential for full enrollment in AIM-HN in the first quarter of 2021.

For KO-947, open an expansion cohort of HNSCC and esophageal squamous cell carcinoma patients with 11q13 amplifications in 2020; and for KO-539, achievement of a recommended Phase II dose by the end of 2020.

With that, operator, we're now ready for questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from Jonathan Chang with SVB Leerink.

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David Simms Ruch, SVB Leerink LLC, Research Division - Associate [2]

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This is David Ruch on for Jonathan. I guess, first, could you provide any additional color on the partial clinical hold and the SAE that was observed? Just kind of any color on what that was? And does this impact the condition -- like what are the conditions of the hold, I guess?

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Bridget A. Martell, Kura Oncology, Inc. - Acting Chief Medical Officer [3]

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Sure. Thank you for the question. This is Bridget. As with any clinical trial, we don't really discuss clinical trial data outcomes, whether it's safety or efficacy. But suffice it to say, we're confident that this will be an iterative and collaborative discussions with the FDA, and we are confident that we'll move into our expansion cohort shortly.

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David Simms Ruch, SVB Leerink LLC, Research Division - Associate [4]

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Okay. Could you talk a little bit in general on how this impacts the development strategy overall? And how you might be potentially thinking about combination studies down the road?

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Bridget A. Martell, Kura Oncology, Inc. - Acting Chief Medical Officer [5]

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So from a monotherapy perspective, before I get to the combination, I think the goal in any Phase I trial is studying a new chemical entity as a monotherapy and reaching a recommended Phase II dose, oftentimes by virtue of a dose-limiting toxicity. And so based on that, we know that we have achieved that, and we can now look to combination therapies that would be in concert with the mechanism of this drug and both benefit patients and have a sufficient safety profile.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [6]

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I think, David -- this is Troy. Just to add to that. I don't think it changes at all our strategy from a development perspective, we've been consistent that we see an opportunity to evaluate KO-947 at a recommended Phase II dose in these 11q13 amplified patients. That is -- those patients were suggested by the extensive preclinical modeling that we did, that we've spoken to over the past several years. As Bridget mentioned, we need to work internally and with FDA to lift this clinical hold, and then we look forward to moving forward into those populations. But it doesn't change the development strategy really in any way. It is -- the goal is to identify a recommended Phase II dose, and we've done that. We do need to work through this though with FDA.

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David Simms Ruch, SVB Leerink LLC, Research Division - Associate [7]

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Got it. Understood. I guess moving on from that, could you talk about if the AIM-HN study is positive, what are the next steps for tipifarnib in squamous cell head and neck? And what are the opportunities for frontline expansion and kind of other expansion opportunities beyond SCCHN?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [8]

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Sure. It's a good question. And I think we're guided by 3 different things. We're guided by what we've seen clinically both in RUN-HN and AIM-HN. We're guided by the evolving landscape of standard of care. And then we're guided by our preclinical data. Clearly, they're -- I think, one has to acknowledge that immune therapy and combinations with chemotherapy are moving to the front line. We've talked in the past about evaluating tipifarnib in combination with various agents, including chemotherapy, targeted therapy and potentially immune therapy. We're not yet at a point where I think we can articulate to you exactly what the clinical studies would look like, but it is something of interest to us.

And as I mentioned in the prepared remarks, what we are also encouraged by is that we see a level of clinical activity as we look across solid tumors, whether it may be head and neck, urothelial, salivary. And so we also want to be mindful of that. And this is going to be an evolution with the research and development group as well as Kirsten's group, the commercial group to plot out the next steps.

So I think we'll have more to say about that perhaps later in the year. At this point, though, we do definitely see an opportunity to move to additional indications into -- earlier in the treatment paradigm, if and when AIM-HN is successful.

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Operator [9]

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And our next question comes from Chris Shibutani with Cowen.

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Chris Shibutani, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [10]

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Thank you very much, two questions. On the reclassification, the new WHO terminology for the lymphoma genetic landscape T-cell there, should we think that, that reclassification, possibly, at all changes the potential denominator of patients that you might be thinking would be eligible for your therapies? Or is that just true, true, not related, and again, your sort of biomarker-guarded strategy still gives you the same scope of patients when you think about the ultimate either clinical trial or commercial opportunity?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [11]

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Yes. Chris, thanks for the question. So the literature references suggests that there are 3,500 to 4,000 patients per year in the U.S. with PTCL, equivalent numbers in ex U.S. territories. Our best estimate of the eligible patient population under the new classification, the nodal T-cell lymphomas of the T-follicular helper phenotype, is approximately 30% of that population. It may be a little higher outside the U.S. But it probably doesn't change what we've been guiding to in terms of the eligible population. It's just the physicians and the KOLs who treat this disease are very active at, as you know, challenging for new therapies, new biomarkers, new ways of classifying patients.

And so this -- in our way of thinking, this actually probably helps us. Because, again, it's -- the entry criteria onto the study is a pathological diagnosis that's consistent with the WHO criteria, then with a retrospective analysis of the biomarker. In that way, it's different than the AIM-HN study. Does that help answer your question?

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Chris Shibutani, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [12]

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Yes. No, it does seem to be a little bit more of a classification difference. I just didn't know whether or not it had any implications for how we should be thinking about the opportunity, and we'll certainly continue to follow that. If I could ask a follow-up question. AIM-HN and enrollment, you have some clear goals for the patient numbers at a minimum and the time lines, which I think you've reiterated now to be first quarter of 2021.

You also mentioned that you have some additional fresh eyes on potentially the situation, particularly with Bridget and Kirsten, with Kirsten's pedigree coming from Array certainly is something that I think with a commercial viewpoint, could be potentially valuable.

Can you tell us about any of the new insights or strategies that you're perhaps putting into place that continue to perhaps give you confidence in being able to meet those time lines? I think in the past, you talked about kind of trying to figure out how patients who are either in the Phase II versus the Phase III study, often there were questions of perhaps sicker patients, whether they were eligible or not. How are you balancing those factors, particularly with the new voices at the table that you have?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [13]

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Yes. Thanks for the question. So maybe to take the questions in reverse. So we are delighted to have Bridget in this expanded role, partnering with -- not only with Kirsten but with Kathy Ford, our Chief Operating Officer. And we are -- I said it in the prepared remarks, and I'll reiterate it, it is our highest priority at the company. And we are focused on a number of aspects of that study, including numbers of patients screened. Given that we are screening in the front line, we have to be mindful of the impact of kind of the evolving treatment landscape in the front line. And it's very much -- it's the #1 thing we talk about at the company.

At this point, I'm not sure I can give you a lot more clarity. We are -- we're at a point now where nearly every site is open that is going to be open. There may be a straggler or two. We continue to try to get more out of our sites in terms of screening patients and to doing the best we can to deliver on the time line that we've articulated. But I can't get much more into the specifics at this point.

I do think, and again, I said this in the prepared remarks, and I'll emphasize it, it's been, I think, terrific to have Bridget come in and have the team really come together, and not only look at AIM-HN but across the entire pipeline. We have lots of ways of creating value, lots of kind of interesting inflection points throughout the year. And I've been just -- as CEO, just really gratified to see the extent to which the team has pulled together, to say, how can we do better, do different and better if needed. So I think we'll be in a stronger position going forward through the rest of this year and into next year.

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Chris Shibutani, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [14]

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It's great to see the bench strength improve and we'll keep an eye on that trial enrollment.

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Operator [15]

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Our next question comes from Tyler Van Buren with Piper Sandler.

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Tyler Martin Van Buren, Piper Sandler & Co., Research Division - Principal & Senior Biotech Analyst [16]

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I had another one on AIM-HN, especially with the encouraging updates on enrollment and precommercial activities. So can you just confirm that it's still 15 responses required to reject the null hypothesis? And if the 15th response comes tomorrow, can you start the NDA -- the rolling NDA submission immediately? Are you guys in a situation where you can do that? And how long would that take in terms of time lines? And specifically, you also mentioned eligibility for NDA rolling submission. How is that determined?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [17]

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Right. So Tyler, thanks for the question. You've got a few things kind of packed in there. So you're correct, 15 confirmed responses are what are needed to reject the null hypothesis. Those have to be centrally adjudicated and reviewed by the Data Safety Monitoring Committee. So if and when that happens, we are assuming that the DSMB will notify the company, that the company has to both notify the agency and the investigators on the study. We would then anticipate that we would make that information public. I think it's -- let me just say, it's premature, I think, to talk about the timing of the submission. We are -- we were gratified to get the fast track designation.

I think that's a recognition by FDA of the unmet medical need and the clinical activity that was demonstrated in Phase II. We continue to push to take advantage of any sort of regulatory advantage that would be available, not only in head and neck but now you'll see in T-cell lymphoma. That's a bit of a work in progress. But I don't want to look too far into the future. Our focus at the moment is on that execution point that you mentioned, and we'll keep it there. We are trying to set the company up for success if and when AIM-HN is positive.

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Tyler Martin Van Buren, Piper Sandler & Co., Research Division - Principal & Senior Biotech Analyst [18]

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Okay. That's helpful. And maybe just a quick second one. On menin-MLL, can you just give us any sort of color where you are in terms of the dose ranging? Or what dose cohort you're at? And also, if you expect any responses or significant clinical benefit in this initial non-enriched patient population?

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Bridget A. Martell, Kura Oncology, Inc. - Acting Chief Medical Officer [19]

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Tyler, this is Bridget. I can address that question for you. So we are in dose escalation in the Phase I portion of the trial. It is an all-comer, AML, as we have stated before. However, investigators do know that we are targeting a certain population, so they will choose their patients as appropriate on to the dose-escalation trial. We don't disclose currently where we are in that dose escalation. We can just say that it is progressing as planned.

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Operator [20]

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And our next question comes from Jay Olson with Oppenheimer.

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Jay Olson, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [21]

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Congrats on all the progress and new additions to your leadership team. I wanted to follow-up on the positive feedback from FDA at your end of Phase II meeting and comments they made about the registrational study in AITL. Was there any color provided in terms of the 2 primary endpoints, as to what the benchmark would be for either the ORR in patients who carry the KIR mutation or the ORR in all patients in the study?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [22]

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Sure, Jay. This is Troy. Thanks for the question. The -- so we now refer to that trial as the trial formerly known as AITL. Because the T follicular helper phenotype, including AITL, is a bit of a mouthful. We'll come up with an appropriate name for the trial in the future.

But as we mentioned, so the design of that trial is consistent with what has been used for other agents that have been approved in PTCL and what would be expected for a level of activity in a second-line setting. We mentioned that each of the 2 independent objectives has a 9% null hypothesis. So that's a reasonably low bar. We would obviously want to see a higher level of activity, both in terms of objective response and durability, if we want to displace the existing therapies.

And we're encouraged because in a patient population that has experienced a median of 3 priors. So a fourth-line setting, we're seeing a 40% to 50% response rate with the ability to drive that to 70% in the KIR mutant subset and a 40% CR rate.

So there is the potential, we think, to drive a higher level of activity and displace the other agents. But specific to your question, those 2 arms each have a 9% null. And the guidance that we got was that success, eliminating the null hypothesis on either arm -- or either endpoint, I should say, I misspoke, would be sufficient to eliminate the null hypothesis and potentially support an application for accelerated approval. Does that help you?

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Jay Olson, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [23]

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Yes. That's perfect. And then maybe as a follow-up, as you get closer to commercialization of tipifarnib, can you talk about how you envision the timing of all the various indications you're pursuing? And how you want to sequence those potential approvals and manage the life cycle of tipifarnib.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [24]

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So Jay, that's a great question. And probably one that I'm going to give you an unsatisfactory answer to. But let me just say we are following the science, we are following what we see in the clinic, and we are informed by the commercial opportunities. So we chose HRAS mutant head and neck, and now nodal T-cell lymphomas of the T follicular helper phenotype as initial indications because they offer a fast-to-market strategy and you could -- the potential for accelerated approval.

We see an opportunity to expand, expand into T-cell lymphomas and potentially other hem malignancies, potentially the opportunity to move into second line pancreatic cancer, that will obviously take time. But if you look back of -- and several of you on the phone have been following the story almost from the beginning, it wasn't more than a couple of years ago that we did -- we couldn't conclusively tell you that tipifarnib was CXCL12 pathway inhibitor. Now I think we can tell you that. We can tell you that we see knockdown of both message and protein in pancreatic stellate cells and an encouraging preclinical data and clinical data. So that encourages us.

We are talking and working internally on a strong stand-alone plan to take Kura forward as well as considering optionality by combinations and other things. And we'll give more light to that over time. At this point, I think we're going to continue to do what has served us well, which is follow the science and focus very much on execution.

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Operator [25]

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(Operator Instructions) Our next question comes from Joseph Pantginis with H.C. Wainright.

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Pasquale Sansone, H.C. Wainwright & Co, LLC, Research Division - Research Analyst [26]

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This is Pasquale from the line of Joe. A few questions for me. So my first question. So, for the tipifarnib trial in metastatic urothelial carcinoma, what kind of updates should we expect in terms of additional treated patients? And also, what frequency of HRAS mutation are you looking at?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [27]

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Yes. Pasquale, thank you for the question. So that study -- that urothelial HRAS -- that HRAS mutant urothelial carcinoma study, is an investigator-sponsored study being conducted at the Samsung Medical Center. It's not under our control. It's actually fully was designed and was directed by Dr. Park at Samsung. So Dr. Park is the one who will make the determination of how many patients. We guided in the prepared remarks that we would expect a more complete data set to be presented and/or published later this year. Again, it's Dr. Park's study, it's not ours. So we can guide to that, but we can't control it. But I think we're optimistic if things go well to see that data presented a bit later this year.

In terms of your question about the HRAS mutant frequency, estimates vary anywhere from 5% to 15%, depending on the literature reference that you look at. So it's a meaningful percentage of urothelial carcinoma. And I think we'll have more to say once the kind of the full data set has been presented from Dr. Park.

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Pasquale Sansone, H.C. Wainwright & Co, LLC, Research Division - Research Analyst [28]

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That's very helpful. So another question for me. I mean I saw your IP slide on your corporate presentation, it's very nice. So I was wondering if you can provide color on the ongoing novel farnesyl transferase inhibitors program? And specifically, what kind -- what is the status of the preclinical work? Any success in identifying potential novel farnesyl transferase inhibitors? And have you have ever filed for novel compositions of matters' IPs?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [29]

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Yes. So you have a few things packed into that question, Pasquale. Let me see if I can unpack them and answer your question. So if we take a step back, before we get to the novel FTI. One of the things that I think we've done -- we've absolutely delivered on is the ability to unlock the biological insights of farnesyl transferase inhibition. So when we brought this program in from Janssen, it was clear that tipifarnib was active. It was -- it had a reasonable tolerability profile, but there was not a good molecular-level understanding of what was driving the clinical activity.

We now have 2 sort of major mechanisms: one, HRAS mutant solid tumors; the other, CXCL12 hematologic and solid tumors. And we're going to continue to flesh that story out throughout this year. I don't want to say too much, but we really view ourselves as the leader in farnesyl transferase inhibition. And that is understanding the molecular mechanisms; understanding opportunities as a monotherapy, understanding rational combinations. And we've been very successful both in the U.S. and now increasingly ex U.S. at getting patent offices to issue fairly broad patents covering not only tipifarnib but any farnesyl transferase inhibitor in certain settings.

And that's because we did what no company working previously was able to do, and that was to assign the molecular targets. With that, that was -- that took, as you can imagine, kind of an alignment of planets to get that right. But here we are. Now we're at a point where we understand the opportunity. We understand the farnesylated targets and there are things we think we can improve upon, even with a drug that is as well positioned as tipifarnib. So we've started a second-generation compound. I've made this reference before, one of the analogies I make is to formally Celgene that worked with initially thalidomide and then Revlimid and then pomalidomide and simultaneously worked out the IMiD biology and developed a very robust franchise. We'd like to be in a position to do something similar in farnesyl transferase inhibition.

I can't really speak to where the program is at. But this is -- we obviously have crystal structures. We have a number of highly potent compounds both ours and others. And I think it's a good opportunity for a very efficient drug discovery effort, and I hope that we'll have something more to say either later this year or early next year.

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Pasquale Sansone, H.C. Wainwright & Co, LLC, Research Division - Research Analyst [30]

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That's very helpful. Last question on my end. So what kind of updates should we expect for the tipifarnib trial in chronic myelomonocytic leukemia?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [31]

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Sure. Yes, that's a good question. So if we take a step back, we initially reported data in CMML that, one -- we had an initial Phase II study where we were looking to exclude KRAS and NRAS mutant patients from those patients with CMML. Because it had been established that KRAS and NRAS we're not driver oncogenes that could be addressed with tipifarnib or farnesyl transferase inhibitor as a monotherapy. That study was successful.

We then -- once we identify the molecular insight of the CXCL12-CXCR4 interaction, we took a look at T-cell lymphoma, at additional lymphomas as well as into leukemias and thought, should we be enriching on the basis of the CXCL12 pathway and continue to run the study but not looking at NRAS -- KRAS and NRAS but at CXCL12 and CXCR4. So we'll provide an update on that study. Our expectation is some time we hope kind of midyear to second half of the year.

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Pasquale Sansone, H.C. Wainwright & Co, LLC, Research Division - Research Analyst [32]

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Congrats on the progress.

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Operator [33]

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And I'm not showing any further questions. I'd like to turn the call back to Troy Wilson for any further remarks.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [34]

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Okay. Thank you, operator, and thank you all once again for participating in our call today. We're going to be at a number of upcoming investor conferences, beginning with SVB Leerink, tomorrow in New York. We'll look forward to seeing many of you there. And in the meantime, if you have any questions, please feel free to contact Pete, Marc or myself. Thank you, and have a good evening, everyone.

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Operator [35]

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Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, you may now disconnect.