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Edited Transcript of KURA earnings conference call or presentation 5-Nov-18 9:30pm GMT

Q3 2018 Kura Oncology Inc Earnings Call

LA JOLLA Dec 3, 2018 (Thomson StreetEvents) -- Edited Transcript of Kura Oncology Inc earnings conference call or presentation Monday, November 5, 2018 at 9:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Antonio Gualberto

Kura Oncology, Inc. - Head of Development & 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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* Joseph Pantginis

H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst

* Konstantinos Nikolaos Aprilakis

JMP Securities LLC, Research Division - Senior Analyst

* Pamela Ann Barendt

Cowen and Company, LLC, Research Division - Associate

* Shawn Michael Egan

Citigroup Inc, Research Division - Senior Associate

* Wei Ji Chang

Leerink Partners LLC, Research Division - Director of Biotechnology & Senior Research Analyst

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Presentation

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Operator [1]

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Good day, ladies and gentlemen, and welcome to the Q3 2018 Kura Oncology Earnings Conference Call. (Operator Instructions) As a reminder, this conference is being recorded.

I would now like to introduce your host for today's conference, Pete De Spain, Vice President of Investor Relations. You may begin.

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

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Thank you, operator. Good afternoon, and welcome to Kura Oncology's third quarter 2018 conference call.

Joining me on the call from Kura are Dr. Troy Wilson, our President and Chief Executive Officer; and Dr. Marc Grasso, our Chief Financial Officer and Chief Business Officer. Dr. Antonio Gualberto, our Chief Medical Officer and Head of Development, is also with us and available to answer questions during the Q&A session. Before I turn the call over to Dr. Wilson, I'd like 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. Earlier today, we were very pleased to announce our registration-directed study of tipifarnib in recurrent or metastatic patients with HRAS mutant head and neck cancer has been initiated and is now open for enrollment. As a reminder, the trial has 2 cohorts; SEQ-HN, a non-interventional screening and outcomes cohort; and AIM-HN, a treatment cohort. SEQ-HN is designed as a case-control study that should provide a better understanding of the natural history of patients with HRAS mutations, while helping to identify patients for potential enrollment into AIM-HN. AIM-HN is designed to treat at least 59 patients with HRAS-mutant HNSCC, who have received prior platinum-based therapy. The primary endpoint of AIM-HN is overall response rate. The study has approximately 80% power to detect the difference between a null hypothesis of 15%, which is the point estimate of second-line therapy, ORR, for recurrent and metastatic disease and 30% and ORR considerate of interest. We're targeting close to 100 clinical sites worldwide and expect the study to take approximately 2 years to fully enroll. However, it's important to remember that based upon the statistical assumptions, the trial could need as few as 15 confirmed responses in order to reject the null hypothesis and meet its primary efficacy endpoint.

Based on feedback from the U.S. Food and Drug Administration, we believe that the trial, if positive, could support an application for accelerated approval. We are excited that this global, multicenter trial is now underway. This milestone represents the culmination of nearly 4 years of rational drug development and this first registration-directed trial embodies the promise of our precision medicine approach. To our knowledge, tipifarnib is the first small molecule inhibitor of RAS oncogene in late-stage clinical development. Thanks in part to advancements in cancer genetics and new molecular diagnostic tools, coupled with evidence-based clinical strategy and execution, we now believe we can identify subsets of patients most likely to respond to treatment.

Last month, we reported an update on our positive Phase II study of tipifarnib in HRAS-mutant head and neck squamous cell carcinomas, or HNSCC, and preliminary results in other HRAS-mutant squamous cell carcinomas, or SCCs, at the ESMO 2018 Congress. As of the September 7, 2018, clinical data cutoff date, tumor size reductions were observed in 9 of 11 evaluable patients with 5 confirmed partial responses including 3 patients with durable responses lasting more than 17 months. A sixth patient achieved a confirmed PR after the date of cutoff. Four patients had stable disease, including 2 patients who experienced prolonged disease stabilization lasting more than 6 months.

Only 1 patient experienced progressive disease as best response. In addition, we're monitoring the progress of 1 additional HNSCC patient, dosed off protocol who has an unconfirmed PR. The patient experienced a 40% tumor size reduction at first assessment and is continuing to receive treatment. The ongoing Phase II trial also enrolled 6 patients in an additional cohort of other HRAS-mutant SCCs. One of the 2 evaluable patients in this cohort achieved a confirmed PR, and the other patient achieved prolonged disease stabilization lasting more than 8 months. Four patients were not evaluable as of the data cutoff date, including 2 patients, who were pending initial efficacy assessments.

As pioneers in the development of farnesyl transferase inhibitors as precision medicines, we are committed to advancing the science of how tipifarnib can best be used in patients. To that end, we were very encouraged by a novel observation that came from our updated ESMO. Our Phase II data showed a significant association between tumor HRAS-mutant allele frequency and clinical benefit. By way of definition, allele frequency in this case, is the measurement of mutated-HRAS DNA in a patient's tumor compared to non-mutated HRAS or wild-type DNA expressed as a percentage. As with most assay technologies, a limited detection and a clinical cutoff must be established. For example, in the case of HER-2 testing, a test detects the level of HER-2 protein in the cancer cells from 0 to 3 plus. Generally, only cancers with the highest levels respond to the medicines that target HER-2-positive breast cancers. Thus, although the assay can detect lower levels of a protein, the clinical cutoff for the assay is set at 3 plus.

In the same way, although current next-generation sequencing technologies can detect mutations lower than 1% allele frequency, an analysis of available tumor biopsy samples from patients enrolled in our ongoing Phase II study has shown that an allele frequency of at least 20% appears to be associated with clinical benefit in HNSCC or SCC patients with tipifarnib. Of the 13 HNSCC or SCC patients with a tumor HRAS-mutant allele frequency greater than 20%, 6 achieved PRs, 1 achieved an unconfirmed PR and is ongoing and 2 experienced disease stabilization greater than 6 months. In other words, meaningful clinical benefit was observed in 9 of 13 patients with an allele frequency greater than 20%.

In contrast, no meaningful clinical benefit was observed in the 7 patients with an allele frequency less than 20%. We believe, these findings give us insight into which patients are most likely to benefit from treatment with tipifarnib, namely those with HRAS-mutant allele frequencies greater than 20%, and we have incorporated allele frequency into AIM-HN as well as our ongoing Phase II studies.

The question we continue to address is how does establishing an allele frequency cutoff impact the way we think about the addressable population. The short answer is that the number of addressable patients depends on where we set the allele frequency cutoff. Specifically, our internal data indicate approximately 8% of HNSCC patients have an HRAS-mutant allele frequency greater than 1%. Data from a larger sample set in the Cancer Genome Atlas, or TCGA, indicate that approximately 5% of HNSCC patients have an HRAS-mutant allele frequency greater than 20%. We believe that HNSCC patients with allele frequencies greater than 20% are those patients who are most likely to experience clinical benefit from treatment with tipifarnib as a monotherapy. Meanwhile, we are investigating how tipifarnib may also address the unmet medical need of those patients with allele frequencies less than 20%.

A second takeaway from the data presented at ESMO is we now have a better understanding of the starting dose. Patients in the Phase II trial received oral doses ranging from 600 to 900 milligrams twice daily. Although our early clinical experience suggested that 900-milligram might be the optimal dose, after expanding into additional sites around the world, we've determined 600 milligrams twice daily to be the recommended dose.

As presented at ESMO, 4 of the responses and 2 disease stabilizations greater than 6 months were observed in patients while on treatment with the 600 milligrams twice daily dose, indicating that the dose is sufficient to drive clinical activity.

Furthermore, by selecting patients with tumors with high HRAS-mutant allele frequencies and increased sensitivity to tipifarnib, we believe we may achieve a higher therapeutic index in the clinic. As such, we've introduced a minimum tumor HRAS-mutant allele frequency of 20% in our registration-directed trial and are using 600 milligrams orally twice daily as the starting dose. We continue to be very encouraged by the growing body of data that support the potential of tipifarnib as a treatment for squamous cell carcinomas, characterized by HRAS mutations. With our registration-directed trial of tipifarnib, in HRAS-mutant HNSCC now underway, we remain focused on our goal of generating a data package to support an application for marketing approval in that indication, while we also work to broaden the potential of tipifarnib in both HRAS-mutant and non-mutant cancers.

In that regard, we are encouraged by preliminary signals of clinical activity observed in patients with HRAS-mutant SCCs, as we believe this may represent a near-term opportunity to expand the use of tipifarnib into a broader set of HRAS-mutant cancers.

In addition, we believe, tipifarnib may have utility to address the unmet medical need of those HNSCC patients with low tumor HRAS-mutant allele frequencies. Long term, our development strategy for tipifarnib is to advance toward earlier lines of therapy and ultimately, to treat patients with HRAS-mutant SCCs in the continuum of systemic treatment settings.

Now let's turn our attention to hematologic malignancies, which represent another significant opportunity for tipifarnib. As a reminder, previously conducted studies by Janssen demonstrated that tipifarnib can drive clinical activity in certain patients with hematologic malignancies. However, no molecular mechanism of action was identified that could explain its activity in those populations. Approximately 1 year ago, we presented new findings that identified activation of the CXCL12 pathway and bone marrow homing of myeloid cells as potential biomarkers of tipifarnib's activity in certain hematologic malignancies, including PTCL, MDS, CMML and AML. Based on these observations, we've been working to validate the CXCL12 pathway as a therapeutic target of tipifarnib and to prospectively validate potential biomarkers in our ongoing Phase II trials. PTCL was the first of the 3 trials to begin and has been actively enrolling patients into 2 expansion cohorts, 1 defined by histology, the other by genetics.

The first cohort includes patients with angioimmunoblastic T-cell lymphoma, or AITL, an aggressive form of T-cell lymphoma. Recall preliminary data from our Phase II trial of tipifarnib in an unselected population of patients with PTCL showed that patients having elevated levels of CXCL12 gene expression had a higher rate of clinical benefit in terms of objective response rate and progression-free survival. Of the 3 PRs, 2 occurred in the 2 patients on study with AITL. These findings are consistent with published data that show patients with AITL express high levels of CXCL12. The second cohort includes patients with PTCL, not otherwise specified, who have the absence of a single nucleotide variation in the 3’ untranslated region of the CXCL12 gene. We estimate that the combined addressable populations of patients with AITL and CXCL12-positive PTCL account for approximately 40% of PTCL cases.

Despite several approvals over the past decade, we believe, the treatment of relapsed and/or refractory PTCL remains a significant unmet medical need. Three of the more recent lunches, pralatrexate, romidepsin and belinostat were approved based on single-arm clinical trials of fewer than 130 patients, each with response rates in the range of 25% to 27%, and only 2 to 3 months of median progression-free survival in unselected populations. We believe, the CXCL12 pathway holds promise for identifying patients who will respond to tipifarnib, and we look forward to showing initial prospective data from the AITL and CXCL12 positive cohorts in our Phase II trial in PTCL at ASH in December. Our goal is to provide additional biomarker-enriched data from other hematologic indications in 2019.

Now a quick look at our 2 emerging pipeline programs, before we turn to the financials. Our Phase I dose-escalation trial of KO-947 in solid tumors continues, as we work to define a dosing schedule that will enable us to evaluate KO-947 in genetically selected patients whose tumors are sensitive to ERK inhibition. We anticipate having data from the dose-escalation portion of the trial available in 2019.

Meanwhile, we're currently conducting IND-enabling studies for our menin-MLL inhibitor, KO-539, and are targeting an IND submission in the first quarter of 2019. With that, I'll now turn the call over to Marc Grasso, for a discussion of our financial results for the third quarter of 2018.

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Marc Grasso, Kura Oncology, Inc. - CFO & Chief Business Officer [4]

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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-Q filed today for a more detailed discussion.

Research and development expenses for the third quarter 2018 were $11.7 million compared to $7.1 million for the third quarter of 2017. The increase in R&D expenses for the quarter was primarily due to an increase in clinical development activities related to our registration-directed study initiation, ongoing Phase II studies and companion-diagnostic activities for tipifarnib.

General and administrative expenses for the third quarter of 2018 were $4.3 million compared to $2.4 million for the third quarter of 2017. The increase in G&A expenses was primarily due to increases in noncash share-based compensation, professional fees and personnel costs.

Net loss for the third quarter of 2018 was $15 million or $0.40 per share compared to $9.3 million or $0.38 per share for the third quarter of 2017.

As of September 30, 2018, we had cash, cash equivalents and short-term investments of $187.4 million compared with $125.9 million as of June 30, 2018.

The increase in cash resulted primarily from the net proceeds of $74.5 million from our public offering of common stock that was completed on July 2, 2018, partially offset by cash used in operations. While we continue to believe our current cash puts us in a strong position to fund the registration-directed study for tipifarnib in HRAS HNSCC, we view the potential opportunity for tipifarnib as much broader in both HRAS and non-HRAS-driven tumor types, and we are looking to invest accordingly. We anticipate providing an update on expected cash burn on our year-end call in early 2019.

With that, I'll now 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, Marc. That concludes our prepared remarks. However, before we jump into Q&A, let me quickly lay out our anticipated near-term milestones.

Preliminary data from the AITL and CXCL12-positive cohorts and our ongoing Phase II trial of tipifarnib in PTCL at ASH in December, additional biomarker-enriched data from other hematologic indications in 2019, additional data from our Phase II trial of tipifarnib in HRAS-mutant SCCs in 2019, data from our Phase I dose-escalation trial of KO-947 in 2019 and submission of an IND application for KO-539 in the first quarter of 2019.

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) And our first question is from Jonathan Chang from Leerink Partners.

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Wei Ji Chang, Leerink Partners LLC, Research Division - Director of Biotechnology & Senior Research Analyst [2]

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First question, can you help set investor expectations with regards to the upcoming tipifarnib data in PTCL at ASH? What would you view as a win there?

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

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Sure, Jonathan. Let me ask Antonio if he can comment on that?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [4]

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Yes, Jonathan. So as you know, the patient population that we are currently treating in the study is a fairly advanced population. They have 3, 4 prior regimens. So that is a setting where is unlikely to see responses. Nevertheless, we put high burden for the AITL cohort because there's some data in the second line, for example, belinostat, with like with 20 patients that is around 40% -- is around 46%. So we put a threshold of around 30% response rate for the AITL, adding a 10% null hypothesis for that PTCL dose. Nevertheless, our intent is to select for the patients that are most likely to respond, they are most likely to receive clinical benefit. So personally, we will see response rate plus stabilization of about 40%, close to half of the patients that for me will be a good indication of success.

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Wei Ji Chang, Leerink Partners LLC, Research Division - Director of Biotechnology & Senior Research Analyst [5]

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Second question, how are you thinking about potential next steps for tipi in PTCL and maybe heme malignancies more broadly?

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

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Yes, so Jonathan, as Antonio mentioned, our focus in the lead up to ASH is really to get that data out there, to be able to demonstrate that CXCL12 offers us a means of enriching for clinical activity. Once that data is presented and we have a chance to discuss it, next steps would, obviously, involve -- is there a path forward, we need to get, regulatory input. I think -- our focus is directing people at the present time toward that ASH data. With respect to the other hematologic malignancies, as we indicated in the prepared remarks, the PTCL trial is advanced in that it was the first trial to start. We'd be looking to providing updates on those trials sometime in 2019 around a major medical conference.

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Wei Ji Chang, Leerink Partners LLC, Research Division - Director of Biotechnology & Senior Research Analyst [7]

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Great. And just one last...

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [8]

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Let me just add on my end. Obviously, we don't want to get ahead of the presentation. But in addition to the data, the activity of tipifarnib in every single patient that we have enrolled up to the time of presentation, we are also doing a number of retrospective looks to the PTCL populations, how they respond in the particular subset to the standard of care. So we will be able to compare the potential outcome of this standard of care in a particular subset versus the result of we see with tipifarnib. So that will provide you with the appropriate context to interpret it.

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Wei Ji Chang, Leerink Partners LLC, Research Division - Director of Biotechnology & Senior Research Analyst [9]

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Got it. Just last question from me. You've also guided to additional data from the Phase II tipi study in HRAS-mutant SCC in 2019. Can you talk about how much more data investors can expect given the announcement today of the initiation of the registration-directed study?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [10]

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Sure, Jonathan. So now that this -- the pivotal study, or the registration-directed study, has been initiated and is open for enrollment, our intent would be to try to enroll patients that qualify on that study. That being said, we will provide an update on the ongoing Phase II study in terms of the patients currently on study and any additional patients who are added. There is a bit of asynchrony between patients that are being identified and sites that are being opened in the pivotal. In addition, as we indicated, we were quite encouraged in connection with the ESMO presentation to see some early signs of clinical activity in other squamous cell carcinomas that are characterized by HRAS mutations. We're going to be implementing the same dose and allele frequency cutoff in that cohort. And we would -- in the same context and at the same time, we'd look to provide an update on that cohort as well. And of course, in both instances, in the context of a medical meeting or conference.

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Operator [11]

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Our next question is from Konstantinos Aprilakis from JMP Securities.

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Konstantinos Nikolaos Aprilakis, JMP Securities LLC, Research Division - Senior Analyst [12]

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Assuming AIM-HN enrolls steadily over approximately 2 years as you've guided, when do you expect to report initial data from the study? And what sort of cadence do you have in mind for subsequent readouts? And then 2 quick follow-ups.

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

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Sure. So Konstantine, this study is a little different than the ongoing Phase II study. The ongoing Phase II study is open label. We've been able to provide regular updates. We, the company, will be blinded to the outcome of the registration-directed study until we're appropriately notified by the data safety monitoring board. That being said, we did emphasize in the prepared remarks, our focus has not been as much on enrollment as it has been on how can we increase the rate of clinical benefit. And so in particular, the trial can achieve its primary efficacy endpoint with as few as 15 responses that are confirmed by an independent radiological review. We're currently just in the Phase II in about 25 sites, we continue to enroll about 2 patients per month. The pivotal trials intended to open in as many as 100 sites. We're able to give you a kind of total overall guidance, but I think, given that we're the pioneers in this space and there's no one else to our knowledge that's drug in HRAS, we don't really want to try at this point, guide to any sort of interim data update. We won't be in a position to provide an interim unless and until the study meets its primary efficacy endpoint.

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Konstantinos Nikolaos Aprilakis, JMP Securities LLC, Research Division - Senior Analyst [14]

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That's actually a perfect segue sort of into my next question. So after the update at ESMO, you are kind of tossing around maybe 20% cutoff for the HRAS-mutant allele frequency and maybe going as high as 35%, but it seems like you've now decided on 20%. So I guess, curious as to what the factors are that were considered? And what gives you the high degree of confidence that you seem to have in that 20% cutoff?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [15]

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Yes. Let me ask Antonio if he could answer that question for you, Konstantine.

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [16]

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So Konstantine, we are doing our best to improve the outcome of the patients. So you can -- and also you know I understand also the question about the enrollment, but we need to focus on the fact that the study will become positive once we see 15 confirmed responses. So what you may notice from the data that we presented from the Phase II is that while the rate of approval will be the one that is defined by they say, what we are reducing is the denominator. So the chances that by using the cut-off, we are going to see patients that have more likely to -- likelihood of response. So that doubles, let's say, higher possibility to see those 15 responses sooner than later. The cost also will be reduced because we don't have to extend the enrollment by focusing on the sensitive population.

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

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And Konstantine, just add to that. There was -- when we presented the ESMO data, there was 1 responder who wasn't included. We've now gotten the data from that patient. And that responder has an allele frequency of 27.5%. So that's entirely consistent with the 20% allele cutoff that we're using in the pivotal as well as that's being implemented in the ongoing Phase IIs.

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Konstantinos Nikolaos Aprilakis, JMP Securities LLC, Research Division - Senior Analyst [18]

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Okay, perfect. And then just one last one. The enrollment goal for SEQ-HN, how many patients are you looking to enroll in that trial? And do -- patients enrolled in AIM-HN, do they also count toward the enrollment total for SEQ-HN? Just a little clarity there would be helpful.

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [19]

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So the intent to SEQ-HN is to characterize the natural history of the patients with HRAS mutation. So you do have to do a match of patients with wild-type HRAS versus the patients with mutation. And normally to do a match to do in a proper way, the statistician that is blinded to the data, they need to have something like rate of maybe 3 or 4x the number of patients with HRAS mutation. So if you have 60 patients -- 59, 60 patients enrolled in AIM-HN, you want to have maybe threefold that amount, so the match could be done with sufficient number of background HRAS mutations -- sorry, HRAS wild-type patients. So that means that you need to enroll at least 200. You will screen maybe 1,500, but you need to enroll maybe 200, 250 patients in order to do a proper match. Does that answer your question?

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Konstantinos Nikolaos Aprilakis, JMP Securities LLC, Research Division - Senior Analyst [20]

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Yes, it does.

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Operator [21]

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Our next question is from Joe Pantginis from H.C. Wainwright.

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Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [22]

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Wondering if you can provide a little more color on the logistics around H -- AIM-HN, sorry, about that. Specifically, number 1, the geographical breakdown? And then further, can you discuss any particular bounds that are on the study? Are there restrictions as to the maximum patients a site or region can contribute to the study? And 3, where do you expect most of the patients to come from geographically?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [23]

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The study is planned as a global study. So it will be conducted in the U.S., Europe and a number of Asian countries. It is intended to generate data that will allow global registrations. I mean, the standard will be the U.S., the European, the EU, Japan, potentially, other Asian countries. The study will have competitive enrollment. Obviously, we are not expecting that, that will be a skew. So the intent is always to enroll a patient population that somehow represent the percentage of the characteristics of the U.S. population. So that will be acceptable by the FDA. With that I mean that you cannot put 50% per sample of Asian patients. Otherwise, as I said, it will be done by competitive enrollment to allow a registration for all potential territories.

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Operator [24]

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Our next question is from Chris Shibutani from Cowen.

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Pamela Ann Barendt, Cowen and Company, LLC, Research Division - Associate [25]

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This is Pam Barendt on for Chris. I'm trying to understand the differences or the key differences in inclusion and exclusion criteria between the previously ongoing and still ongoing Phase II and the pivotal. So can you comment on how many of the responders and nonresponders in RUN-HN would have qualified for AIM-HN?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [26]

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Sure, Pam, let me ask Antonio if he can address your question?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [27]

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There's nothing really esoteric. This is fairly a standard inclusion-exclusion criteria for recurrent head and neck cancer population. Obviously, the main change relates to the definition of the cutoff, what they say. This was treating as strong indicator because we have a very sensitive assay that can detect as low as 1% allele frequency. Obviously, at some point you have to define the appropriate clinical cutoff. So we were quite fortunate to be able to do that in Phase II. Otherwise, I mean, very quickly you will see the characteristics of the inclusion-exclusion criteria within clinical trial back off.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [28]

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And Pam, just to add to that. So as I indicated in the prepared remarks, if you look at the data that was presented at ESMO, for the patients -- HNSCC and the SCC patients, in the 13 patients whose tumors were profiled, 9 of them had meaningful clinical benefit in terms of either objective responses or disease -- prolonged disease stabilization. There was no meaningful clinical benefit in the 7 patients, who fell below the 20% cutoff. And then as I just indicated, the last responder, we got data and that patient is well, had an allele cutoff -- had an allele -- mutant-allele frequency of 27.5%. So it is -- as Antonio mentioned in his comments, the goal is enrichment of clinical benefit. Ideally, we will shrink the denominator and be able to drive clinical benefit and objective responses. I hope that helps to answer your question.

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Pamela Ann Barendt, Cowen and Company, LLC, Research Division - Associate [29]

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That does. For a follow-up, what proportion of the patients, for the pivotal, do you think or are you anticipating, will have received 1 versus 2 prior lines of therapy?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [30]

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That's actually related to the prior questions that I did not answer completely, regarding where the patients are coming from. So you will have an expectation that many of the patients come from Europe and that's fairly a standard in any pivotal study that is conducted across these regions. So that -- because of access to a number of regions, you will have the expectation that the predominant population could be a second-line population. But as you can imagine, there will be a mix there of second or third line. There could be even some patients that could be first-line patients. Remember, that the inclusion criteria is post-platinum with platinum having been received in any setting and may have been received in the primary of the -- in the neoadjuvant setting. So predominantly, I'll expect is second-line setting that will become third-line patients, maybe some few frontline patients.

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Operator [31]

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Our next question is from Joel Beatty from Citi.

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Shawn Michael Egan, Citigroup Inc, Research Division - Senior Associate [32]

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This is Shawn calling in for Joel. I have 2 on some of your early like frequency findings and then 1 on ASH. You talked about little bit with John's answer. But could you expand a little bit on opportunities to incorporate new findings in the new indications? And also are you planning on changing the non-small cell study to incorporate your allele frequency threshold?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [33]

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Sure, Shawn. So first, with respect to the first part of your question, we do see some encouraging preliminary clinical data in HRAS-mutants squamous cell carcinomas that are not head and neck. And that data was presented at ESMO. And as we indicated, we'll provide an update. Those are a variety of histologies you can see them on the slide in our corporate presentation or the presentation that Dr. Ho used. But it's penile, it's vulvar. They are -- what they have in common is that they are consistently that squamous cells carcinoma histology -- different organs, I should have said, I'm sorry, I misspoke. I think it's too early for us to really be able to characterize. We need to gather additional data to really understand the level of activity. But we are incorporating the same changes in terms of a 600-milligram starting dose and a 20% allele cutoff in that study. The -- to transition to the lung study that you asked about, as you know, that's not the study that's being conducted by the Spanish Lung Cancer Group. We can recommend changes and we will, we are. But that's ultimately their study and they can choose whether or not to implement those changes. But we do see it's an encouraging opportunity. And Antonio, if you want to add anything to Shawn's question?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [34]

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Yes. I will indicate that the ability for us to define -- actually -- let me -- it's actually a great question. And the fact that we can more clearly define the patient population, the patients that are most likely to see responses, now offer the possibility of tipifarnib to be firstly competitive with standard of care. So it means that now opportunity is open not in other -- not only in other squamous setting or other potential patient population, not other potential indications but also potential segments. So the obvious progression for us will be to go to earlier lines of therapy. Why -- if we can see response rates of the order of 50% response rate, why couldn't we be competitive, for example, in the neoadjuvant setting or adjuvant settings, so these give us a new opportunity to use tipifarnib in the continuum of treatment for head and neck patients and potentially other squamous patients.

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Shawn Michael Egan, Citigroup Inc, Research Division - Senior Associate [35]

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And just as a brief follow-up, how much variability is there in the allele frequency within the tumor? And what steps are you taking in the pivotal study to ensure that the allele frequency results are representative of the whole tumor?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [36]

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So we do have limited data at present. So as you know when the patients were initially enrolled in the study, they were enrolled based on allele frequency data that came from the sites. So some of the sites used their particular methods, for example, the Memorial Sloan Kettering used an impact, Next-Generation Sequencing that is quite effective, so -- and so on. So there are other very similar Next-Generation Sequencing panels that were used by other sites. So the data is limited. But at least, we can say when we independently, in a blinded manner, the data was then sequenced at the central laboratory at OncoDNA. We saw good concordance with the data that was generated from the sites. Certainly, we can concordance within over the cutoff and below the cutoff, that is what is really important. I know there have been a number of questions about the cutoff, but I believe the cutoff is appropriate based on the Phase II data. So you understand it will be necessary to when we offer the appropriate allele frequency cutoff for commercialization, that will require a larger number of tumors, again, assuming that we have approval. So it probably will require data from samples, from the current Phase II plus the tumors that will be enrolled in the pivotal study.

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Shawn Michael Egan, Citigroup Inc, Research Division - Senior Associate [37]

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Great. And then just quick one on your ASH. The skin reactions mentioned in your ASH after XN AITC target population, can you just comment on whether you think that's an on-target effect or more of a chance observation?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [38]

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I do believe that it is potentially related to the disease under study. So as you know, the peripheral T-cell lymphomas, there are novel disease but they are infiltrating. So they can infiltrate the bone marrow. They can infiltrate the skin. They could attack -- they are very similar to PTCL cutaneous T-cell lymphoma. But within PTCL, you have patients that they will also have cutaneous manifestation. So it could be a mix of whatever the effect of tipifarnib, plus disease under study while we have seen more rash in this particular indications versus in other studies.

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Operator [39]

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(Operator Instructions) At this time, I'm showing no further questions. I would like to turn the call back over to Troy Wilson for closing remarks.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [40]

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Thank you, operator, and thank you all once again for participating in our call today. We appreciate your attention this afternoon and look forward to providing additional updates in the months ahead. We'll be at the Stifel Healthcare Conference in New York next week and the Evercore ISI Conference in Boston later in the month. We're also planning to host an event at ASH here in San Diego, and hope to see many of you there. In the meantime, if you have any additional questions, please feel free to contact Pete, Marc or myself. Have a good evening, everyone.

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Operator [41]

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Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program. You may now disconnect.