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Edited Transcript of KURA earnings conference call or presentation 5-Nov-19 9:30pm GMT

Q3 2019 Kura Oncology Inc Earnings Call

LA JOLLA Nov 15, 2019 (Thomson StreetEvents) -- Edited Transcript of Kura Oncology Inc earnings conference call or presentation Tuesday, November 5, 2019 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 & Secretary

* 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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* Jay Olson

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

* Joel Lawrence Beatty

Citigroup Inc, Research Division - VP & Analyst

* John Christopher Barrett

SVB Leerink LLC, Research Division - Associate

* Pamela Ann Barendt

Cowen and Company, LLC, Research Division - Associate

* Pasquale Sansone

* Reni John Benjamin

JMP Securities LLC, Research Division - MD & Senior Research Analyst

* Tyler Martin Van Buren

Piper Jaffray Companies, 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 Third Quarter 2019 Kura Oncology Earnings Conference 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 today, Pete de Spain, Vice President, Investor Relations at Kura Oncology. 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, Sarah. Good afternoon, and welcome to

Kura Oncology's Third Quarter 2019 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.

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. I'd like to start by introducing the 2 newest members of our senior leadership team: Kathleen Ford, our Chief Operating Officer; and James Basta, our Chief Legal Officer. Kathy joined us in July at a time when strategic prioritization and operational execution became our highest priorities, and she's made an immediate impact. She most recently served at Merck Serono, where she led clinical and development operations towards successful drug registrations in both the U.S. and Europe.

Jim joined us just yesterday from Biogen, where he spent the past 13 years, most recently as Senior Vice President and Chief Corporation Counsel. He brings a healthy balance of strong business partnering and corporate guardianship, and we're excited to have them on board. Both are welcome additions to our team.

Now let me bring you up to speed on each of our programs, beginning with tipifarnib in HRAS mutant solid tumors. Last week, we reported updated data from our ongoing Phase II trial of tipifarnib in HRAS mutant head and neck squamous cell carcinomas at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics or the Triple Meeting in Boston. We were very pleased because the results demonstrated compelling level of clinical activity for tipifarnib in a difficult-to-treat patient population. They validate our strategy to enrich for clinical activity when the data strongly support the design of our ongoing AIM-HN registration-directed trial.

However, before I discuss the significance of these results in more detail, let me quickly recap the data themselves. As of the October 17, 2019 data cutoff date, a total of 21 HNSCC patients with high HRAS mutant variant allele frequency were enrolled in the ongoing RUN-HN trial, of whom 18 were evaluable for efficacy. 10 of the 18 efficacy-evaluable patients achieved a confirmed partial response for an objective response rate of 56%.

In addition, 8 patients experienced disease stabilization, including 2 who achieved an unconfirmed PR, one of whom was awaiting a confirmatory response assessment as of the data cutoff date. The median progression-free survival of the 18 evaluable patients treated with tipifarnib was 6.1 months compared to 2.8 months on their last prior therapy, including 8.3 months among patients who achieved a PR on tipifarnib and 4.5 for those patients with stable disease. Patients had a median of 2 prior lines of therapy, ranging from 0 to 6, with no responses observed on their last prior therapy.

As a reminder, the overall response rates for the 3 therapies currently approved for the treatment of HNSCC in the second line, pembrolizumab, nivolumab and cetuximab range from 13% to 16%, with progression-free survival of approximately 2 months. Recall that in our previous update from the RUN-HN trial presented at the European Society for Medical Oncology Conference or ESMO in October 2018, the data showed a significant association between tumor HRAS mutant allele frequency and clinical benefit from tipifarnib.

We also reported that although the trial was evaluating starting doses between 600 and 900 milligrams BID, our retrospective analysis of patients on study revealed that due to interruptions and discontinuations at the higher dose, the median dose for patients at the end of cycle 1 was approximately 600 milligrams BID. Based upon these observations, we introduced 2 changes into the RUN-HN study. First, we require a minimum HRAS mutant variant allele frequency as an entry criterion for enrollment; and second, we established 600 milligrams BID as the starting dose.

Notably, we implemented the same changes to the protocol for our AIM-HN registration-directed trial, which was initiated shortly thereafter in November 2018. Since the ESMO 2018 update a year ago, we prospectively enrolled 10 new patients with high HRAS mutant variant allele frequency in the RUN-HN trial. Of the 8 efficacy-evaluable patients, 3 achieved a confirmed PR, 5 had stable disease, including 2 patients who achieved an unconfirmed PR, one of whom is pending a confirmatory response assessment. Of the 2 nonevaluable patients, 1 discontinued prior to an initial tumor response assessment, the other was awaiting an initial response assessment as of the data cutoff date.

With regard to dose, a total of 5 efficacy-evaluable HNSCC patients started at the 600-milligram dose in the RUN-HN trial, all of whom achieved an objective clinical response. We believe there are 3 key takeaways from last week's RUN-HN update. Number one, the requirement of a minimum HRAS mutant variant allele frequency suggest an effective means to enrich for clinical activity in patients with HRAS mutant HNSCC. Number two, the 600-milligram BID starting dose appears to be better tolerated in this patient population and sufficient to drive durable antitumor activity. And number three, given that the RUN-HN trial is a multicenter study, including more than 30 clinical sites around the world, the data reflects valuable real-world experience with tipifarnib in this clinical setting.

Taken together, the results presented at the Triple Meeting, reinforce our view that tipifarnib can provide meaningful clinical benefit to HNSCC patients with HRAS mutations, and they further increase our confidence in the design, outcome and probability of success of AIM-HN, our registration-directed trial of tipifarnib in HRAS mutant HNSCC. AIM-HN was initiated exactly 1 year ago and is now open in more than 75 clinical sites in the U.S., Europe and Asia. The AIM-HN study is designed to enroll at least 59 evaluable HNSCC patients with high HRAS mutant variant allele frequency who have received prior platinum-based therapy.

We continue to believe that the AIM-HN study will take approximately 2 years for full enrollment. However, given the design of the study, there is the potential that the primary efficacy endpoint of AIM-HN could be met if and when 15 confirmed objective responses are observed. Also, it's worth noting that since the introduction of the minimum HRAS mutant allele frequency requirement, we continue to find that approximately 5% of the patients we screen, meet the HRAS variant allele frequency requirement for enrollment.

Our primary goal for the tipifarnib program is to generate a data package sufficient to support a first application for marketing approval in HRAS mutant HNSCC. However, with the compelling signals of activity demonstrated from the Triple Meeting data, we're also evaluating how we might pursue opportunities for combination with immune therapy, chemotherapy and cetuximab in the broader population, including the lower HRAS mutant variant allele frequency population. Given the role of HRAS mutations as a mechanism of resistance to standard therapies, we believe tipifarnib could potentially be expanded to 15% to 20% of the HNSCC population, a meaningful commercial opportunity and one in which today there are no direct competitors to tipifarnib.

Although we believe combinations in earlier lines of therapy in HNSCC represent immediate opportunities for future label expansion for tipifarnib, we're also laying the groundwork for expansion to other HRAS mutant solid tumor indications. For example, in September, we reported that an investigator-sponsored Phase II trial of tipifarnib in HRAS mutant urothelial carcinomas, met its primary efficacy endpoint prior to completion of enrollment. The trial is being conducted at the Samsung Medical Center in Seoul, South Korea. Further analysis of the trial is ongoing, and data are expected to be presented at a future medical meeting. In addition, an investigator-sponsored Phase II trial of tipifarnib in lung squamous cell carcinomas, continues to enroll patients. The trial is being conducted by a lung cancer consortium that consists of more than 150 public and private oncology centers in Spain.

Meanwhile, the discovery of CXCL12 pathway biomarkers offers the potential to expand the opportunity for tipifarnib well beyond HRAS mutant solid tumors. In June, we showed the first prospective validation of CXCL12 pathway biomarkers to enrich for clinical activity in our ongoing Phase II trial of tipifarnib in peripheral T-cell lymphoma, including a 50% complete response rate and a 100% clinical benefit rate in a subset of heavily pretreated patients with angioimmunoblastic T-cell lymphoma or AITL, an aggressive form of T-cell lymphoma often characterized by high levels of CXCL12 expression.

We believe the Phase II proof-of-concept data in PTCL AITL, presented at the European Hematology Association Congress and International Conference on Malignant Lymphoma earlier this year, support multiple registrational opportunities in relapsed/refractory lymphoma. And we continue to gather feedback from key opinion leaders and regulatory authorities around next steps for this program. Given the high level of clinical activity observed thus far in the AITL cohort, we continue to enroll patients in that cohort in order to acquire more experience regarding safety and tolerability in this patient population.

I'm pleased to report that additional data, including new patients from the AITL cohort have been accepted for an oral presentation by Dr. Thomas Witzig of the Mayo Clinic at the upcoming American Society of Hematology Annual Meeting in December. Based on our growing body of data, we believe CXCL12 pathway biomarkers may have the potential to unlock the therapeutic value of farnesyl transferase inhibition across multiple hematologic and solid tumor indications, including diffuse large B-cell lymphoma, acute myeloid leukemia, cutaneous T-cell lymphoma and pancreatic cancer.

Over time, we believe this could enable registrational strategies for tipifarnib in multiple hematologic and solid tumor indications. In further support of our development strategy for tipifarnib, I'm pleased to report that the U.S. Patent and Trademark Office recently issued a new patent, further extending our exclusivity to the use of any farnesyl transferase inhibitor for the treatment of CXCL12 expressing PTCL or AML. This adds to our growing portfolio of patents involving CXCL12 pathway biomarkers, and it follows the issuance of another patents this year directed to a method of treating patients with advanced metastatic relapsed or refractory HRAS mutant HNSCC using any farnesyl transferase inhibitor.

These new patents expire in 2037 and 2036, respectively, excluding any possible patent term extension. We believe these new patents strengthen our competitive advantage as we continue to advance the development of tipifarnib, and we intend to continue to aggressively pursue intellectual property protection, both in the U.S. and abroad.

Now let's spend a moment on each of the emerging pipeline programs, beginning with our ERK inhibitor KO-947. KO-947 is a potent and selective small molecule inhibitor of ERK, which we're advancing as a potential treatment for patients with tumors that have dysregulated activity of the MAPK pathway. Our preclinical data suggests that KO-947 has anti-tumor activity in KRAs or BRAF mutant adenocarcinomas as well as certain subsets of squamous cell carcinomas.

We continue to evaluate dosing regimens for KO-947, including a once-weekly dosing schedule and a more frequent intermittent schedule with the goal of reaching a recommended Phase II dose or maximum tolerated dose by the end of this year or early next year. We were encouraged to see data from an early stage ERK inhibitor presented at the Triple Meeting last week, including single agent responses using a similar weekly dosing schedule with intermittent therapy.

Although most of the patients enrolled in our study to date have been in more difficult-to-treat populations, such as pancreatic and colorectal cancer, the observation of single-agent responses from an ERK inhibitor support our confidence to move forward with KO-947. We continue to believe our Phase I strategy will provide a solid foundation to make data-driven decisions on the path forward for KO-947.

Our other emerging pipeline program is KO-539, a potent and selective small molecule inhibitor of the menin-mixed lineage leukemia or menin-MLL protein-protein interaction. Our preclinical data for KO-539 supports the potential for potent antitumor activity in multiple genetically defined subsets such as tumors with MLL fusions or rearrangements as well as NPM1 mutations.

In September, we dosed the first patient in our Phase I clinical trial of KO-539 in patients with relapsed or refractory acute myeloid leukemia, giving us our third wholly owned clinical stage oncology asset. The Phase I open-label dose escalation study is designed to determine the maximum tolerated dose of KO-539, which will be administered as a once-daily oral dose in 28 continuous day cycles. Upon completion of the dose escalation portion of the trial, expansion cohorts are planned to assess the safety and activity of KO-539 in specific genetic subgroups, such as NPM1 mutant.

We believe KO-539 represents a differentiated approach to the treatment of patients with AML, and we look forward to sharing further updates with you. With that, I'll now turn the call over to Marc for a discussion of our financial results for the third quarter of 2019.

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Marc Grasso, Kura Oncology, Inc. - CFO, Chief Business Officer & Secretary [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 of 2019 were $12.5 million compared to $11.7 million for the third quarter of 2018. The increase in R&D expenses for the quarter was primarily due to an increase in clinical development activities related to our registration-directed trial for tipifarnib.

General and administrative expenses for the third quarter of 2019 were $5.1 million compared to $4.3 million for the third quarter of 2018. The increase in G&A expenses was primarily due to increases in personnel costs and noncash share-based compensation. Net loss for the third quarter of 2019 was $16.4 million or $0.36 per share compared to $15 million or $0.40 per share for the third quarter of 2018. As of September 30, 2019, we had cash, cash equivalents and short-term investments of $250.1 million compared with $179 million as of December 31, 2018.

Based on our current plans, we continue to believe that our existing cash, cash equivalents and short-term investments will be sufficient to enable us to fund our operating expenses and capital expenditure requirements into the second half of 2021. 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 [5]

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Thank you, Marc. Before we jump into Q&A, I'd like to take this opportunity to welcome Diane Parks, the newest member of our Board of Directors. Diane has held senior commercial roles at leading companies, including Genentech, Pharmacyclics, Amgen and Kite, and she brings valuable experience to our board as we continue to execute on the initial registration-directed trial of tipifarnib, and we begin to focus on commercial readiness.

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 the line of Chris Shibutani with Cowen.

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Pamela Ann Barendt, Cowen and Company, LLC, Research Division - Associate [2]

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This is Pam Barendt on for Chris. I have a couple of questions. The first one is in regard to your biomarker strategy. So should we be expecting at ASH that you'll be breaking down those AITL responses by cursory mutations or other biomarkers?

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

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Pam, thanks for the question. Let me ask Antonio, who's here with us, if he can address your question.

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

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Yes. We're expecting to extend the data that was initially presented at EHA this year. We have continue in growing AITL patients. We want to further characterize the data with KIR3DL2. As you may recall, we saw up to 75% response rate, so that was quite exciting. And we are further investigating to determine whether we can sustain this high level of response in the subset of KIR3DL2 variants.

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Pamela Ann Barendt, Cowen and Company, LLC, Research Division - Associate [5]

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Got it. And then another logistical question. First, I guess, thanks for the Triple Meeting data, congratulations on that. What do you think the enrollment rate will look like compared with that trial in the AIM-HN trial.

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

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Sure, Pam. So if you look at RUN-HN and AIM-HN, RUN being the ongoing Phase II trial and AIM being the pivotal trial, they're completely different animals, right? RUN-HN is in 30 centers. It's been up and running here for a number of years. AIM is a global registrational-directed trial. We're pleased that we're at the point where we have more than 75 sites open. But much of the past year has been spent getting sites online, getting them activated, getting them screening. And we're really first-in-class here, so we're learning as we go.

I think we're very pleased with the data coming out of the Triple Meeting update. It showed that the amendments that we made to the protocol in terms of the variant allele frequency and the 600-milligram starting dose were the right changes. And now we're just sort of full on in operational execution of the pivotal. And we're still guiding to approximately 2 years to full enrollment. So hopefully, that addresses your question.

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Operator [7]

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Our next question comes from the line of Ren Benjamin with JMP Securities.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Senior Research Analyst [8]

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Congrats on the progress. Troy, maybe just starting off, just based on your discussions with the regulatory agency. I think you mentioned that once the first 15 responders are confirmed, you could potentially go ahead and file. Did I hear that correctly? Is there a minimum duration of response that's necessary for the agency?

And kind of can you talk to us a little bit, since we're getting close to this event, a little bit of the commercial strategy that you plan to unfold, about how many sales people do you think might come into the organization and how you plan on moving forward?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [9]

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Sure, Ren. Thanks for the questions. Let's start with -- let me ask Antonio if he can respond to your question about what happens if and when we reach 15 confirmed objective responses.

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [10]

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Yes. There's no particular requirement by the agency of a specific duration of response. As you can imagine, once you confirm the responses, you will be in cycle 4 or cycle 6 in some cases. So you already will have seen responses for 4 to 6 months. As a reminder, the medium progression-free survival in this setting is about 2 months. So that gives you an idea of the -- and we have also shown progression-free survival recently in our Triple Meeting update of 6 months.

So that give you an idea of the potential of tipifarnib in this setting compared with the standard of care. As you can imagine, this will be part of the review questions by the FDA. But this per se, there's not a particular duration or response requirement for filing in this setting.

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

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And Ren, with respect to the -- go ahead, I'm sorry. Go ahead.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Senior Research Analyst [12]

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No, no, I was just mentioning that the remaining of the question regarding the commercial strategy.

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

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Yes. So I think as I mentioned we're quite encouraged by the data that we presented at the Triple Meeting update. We are beginning the steps for commercial readiness and everything that, that entails. I think it's early to be giving you guidance on specifics around an organizational size or structure. But we're certainly working through a lot of those details in anticipation of what we hope will be a positive result for the AIM-HN trial here. And I would expect that as we get further into it, we'll provide you more guidance on the steps around commercialization. It's just a bit early at this stage, a bit premature.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Senior Research Analyst [14]

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Got it. And then just you mentioned the combination -- the potential for combinations and that the Triple Meeting data really led you to believe this. Can you maybe highlight what within the data is really leading you to this conclusion when these combinations' studies might, in fact, begin?

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

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Sure. Again, let me ask Antonio if he can speak to sort of the data and the rationale for the combinations.

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

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Yes. Thank you. So you can -- you have seen from the Triple Meeting update the patients carrying HRAS mutations, they were resistant to the standard of care. It is a matter -- if the standard of care, the prior line of therapy was chemotherapy, if it was immune therapy, if it was cetuximab alone or in combination. So in other words, the presence of the transmutation, dry-resistant to the standard of care.

Now when the tumor carries 20% variant allele frequency of HRAS or higher, you can see activity with tipifarnib as a single agent. The question then remains when the tumor, let's say, carries 5%, 7%, when it carries less than 20%. So in those setting the portion of the tumor with the transmutation may not be sufficient for tipifarnib to act as a single agent, but it could be an opportunity for tipifarnib to delay their resistant to the standard of care. So this is not so, say, just hypothetical. There's actually extensive data in the case of HRAS with cetuximab that have been published. They also have been published by Braig and coworkers that when a transmutation is there, normally, those patients progress to -- quickly in the first line.

So good opportunity for tipifarnib to combine with the standard of care, maybe an initial approach will be those patients with a low variant allele frequency of HRAS but obviously, tipifarnib will have an opportunity to combine with the standard of care eventually in the overall population.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Senior Research Analyst [17]

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And when do you think you might begin those kinds of exploratory studies?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [18]

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Well, obviously, there's a lot that we have done preclinically. And we need to make major decisions or what could be the potential combination partners, so this is currently that we have the discussion within the company and with others.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [19]

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Ren, well, I was just going to say on that point, I mean, I think now we see sort of 2 illustrations of our strategy, right? So we, as an initial foothold both with HRAS and now CXCL12 in the context of T-cell lymphoma, we're looking to prioritize those places where we can get accelerated development and, ideally, approval with a single-arm trial but looking with an eye toward moving to earlier lines of therapy moving in combination.

And it's important to note, I mean, to this point, we don't see any direct competition on either HRAS or CXCL12 from other farnesyl transferase inhibitors. So Antonio is right, we're at a point where we -- there's a lot of things we can do with farnesyl transferase inhibition, and we want to make sure we prioritize them and sequence them in the right order. And we'll have more we can share with that in the months to come.

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Operator [20]

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Our next question comes from the line of Jonathan Chang with SVB Leerink.

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John Christopher Barrett, SVB Leerink LLC, Research Division - Associate [21]

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This is John Barrett on for Jonathan. And congrats on having the AITL data being selected for an oral presentation at ASH. If you could, could you help us set investor expectations ahead of the AITL update in terms of how many more patients and how much more follow-up we might expect versus the data we saw at EHA?

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

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Sure. John, thanks for the question. Let me let Antonio answer your question.

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

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Yes. I will say that it's just incremental. So as you can imagine the primary endpoint of dose cohorts was reached. We have proof of concept, both in AITL and the PTCL NOS, we have continue -- obviously, we are driven now to the design of the pivotal study, the discussions with the agencies on this design. But we want to continue the engagement with investigators and the clinical sites. So the study remains open to add additional patients, something very similar to what we did with, say, KRAS. But I understand there will be at some point a switch from the Phase II testing to readiness for a pivotal study.

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John Christopher Barrett, SVB Leerink LLC, Research Division - Associate [24]

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Got you. And regarding those conversations, both internally and with regulators. How are you thinking about a development path forward for AITL and PTCL broadly, and what type of registrational trials you might run?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [25]

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So if you don't mind, Troy, I will address this. So the -- I think the fact that the treatment of tipifarnib with the AITL translated to a high rate of response rate, that opened the opportunity to a potential accelerated approval, typical condition accelerate depending on the agency, those normally have had designs of single arm, single agent and similarly towards our HRAS design and strategy.

In the case of the rates of peripheral T-cell lymphoma, we saw responses but we also saw a high rate of disease stabilization. That may need a different design, maybe a time to employing a progression-free survival, et cetera. So basically what I'm getting to is that it may be required for AITL and AITL-like histologies to follow a kind of like single-arm approach versus other designs may be required for other subsets of peripheral T-cell lymphoma.

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Operator [26]

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Our next question comes from the line of Tyler Van Buren with Piper Jaffray.

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Tyler Martin Van Buren, Piper Jaffray Companies, Research Division - Principal & Senior Biotech Analyst [27]

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With respect to the tipifarnib program, clearly, you're seeing great data and great response rates in head and neck and AITL on the hem side. But in solid, you've got to consider whether you move into earlier lines with combos in head and neck, you've got bladder, potentially lung, in hem you have CXCL12 positive PTCL NOS, DLBCL. You guys have a lot of potential indications to go after. So can you just take a step back and help us understand beyond these initial 2 indications which 1 or 2 might be most interesting to own and prioritize in terms of moving into late-stage development?

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

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Yes, Tyler, thanks for the question. And just to confess, it's still a work in progress. I think we're pleased really with 2 things: one is the level of activity that we're seeing in these biomarker-guided subsets -- maybe 3 things; the ability to move from the initial relapsed/refractory indications that we can access as a small company to potentially larger indications; and then third, as we said in the comments, the growing IP estate that's helping to potentially protect the use of not only tipifarnib, but to exclude others who might come along with farnesyl transferase inhibitors.

As Antonio mentioned, we see a clear and compelling opportunity in the head and neck squamous cell carcinoma space. The level of activity that we're seeing in terms of objective responses is compelling relative to the current standard of care, and there's good rationale to believe that you could move that to earlier lines of therapy and with thoughtful combinations that you could broaden the patient population. Those are studies that would likely need, initially, Phase I combinations and then probably a larger randomized studies. So those are things that we have to obviously think about carefully what we would want to take on and the timing, but that's clearly an area that we would prioritize.

T-cell lymphoma and AITL, in particular, is just, again, an example where tipi is the most active agent. It gives us a foothold in the hem space. And it gives us an opportunity, as I think you've just articulated, whether we do it alone or whether we do it with a partner, of being able to more meaningfully address some of these larger populations. And that question is very much on our mind and something that I think we're going to spend a considerable amount of time going forward, trying to get right.

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Tyler Martin Van Buren, Piper Jaffray Companies, Research Division - Principal & Senior Biotech Analyst [29]

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Do you guys expect to have increased clarity on this by, say, the first half or middle of next year? Is that possible kind of guidance to provide?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [30]

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Yes. I mean I don't know that -- I understand where you're coming from. We certainly want to be able to provide clarity on next steps. But to the point, some of these studies are -- some of these studies we can take on now. Some of them are probably better put off to a point where we have greater operational and financial resources, and that's something we'll have to factor in. But we expect to be able to give you increasing clarity on the next steps for tipifarnib and our farnesyl transferase inhibitor franchise as we keep going.

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Tyler Martin Van Buren, Piper Jaffray Companies, Research Division - Principal & Senior Biotech Analyst [31]

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Okay, got it. And then finally, on 539, the menin-MLL inhibitor. Can you just briefly describe the dose escalation scheme, and whether you would expect to -- whether you think there's the potential to see monotherapy activity, and if you guys plan to -- and particularly in the subgroups of patients, for example, the patients with fusions, et cetera?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [32]

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Yes. So great question, Tyler. Let me ask Antonio if he can answer that for you.

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [33]

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Yes. So the design path is a modified valuation design, but at a high level, it's not very different of 3 plus 3 design and maybe with an initial accelerated phase. We are not doing selection in the initial escalations without addressing to the NPM1 or the translocation, but we reserve our opportunity to select patients when we reach the higher doses. Regarding your initial question based on the critical data, yes, there is an expectation of the probability or responses as a single agent.

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Tyler Martin Van Buren, Piper Jaffray Companies, Research Division - Principal & Senior Biotech Analyst [34]

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Just a quick follow-up. For the patients, the genetic subgroups with MLL fusions or partial tandem duplications or NPM1 mutations, if you combine those, what percentage of the broader population would you say has these genetic classifications?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [35]

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So if we -- referring to the adult population, NPM1 will be the major target, is approximately 1/4 of the population. And regarding the other targets that you mentioned, the fact is that there's high level of commutation. So it's very difficult to determine what will be a pure population of, let's say, tandem FLT3 versus just NPM1. So most of these patients will have commutations. But if we refer to what will be our major target, NPM1, just based this on public data from TCGA and the like, is about potentially 1/4 of the population.

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Operator [36]

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Our next question comes from the line of Joel Beatty with Citi.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP & Analyst [37]

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The first one is maybe a follow-up to a couple other responses earlier in the Q&A. It seems like there's a lot that Kura is able to take on right now by itself regarding to your pipeline agents. But there's also been other opportunities that have been highlighted that may be better handled by a partner. So I'm just curious, just thoughts on how to think about the time line for partnering, is now a potential time line that could be looked at? Are there additional hurdles to get passed before that becomes a higher priority?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [38]

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Yes, Joel, thanks for the question, and Marc's here with me. Let me ask him if he can speak to that.

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Marc Grasso, Kura Oncology, Inc. - CFO, Chief Business Officer & Secretary [39]

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Sure. Joel, on partnering, from our standpoint, as we've articulated in the past, doing anything that encumbers rights on tipi, particularly in the U.S., the hurdle there is high for us. And we see a very attractive go-it-alone strategy, particularly in the initial markets we're talking about here, including relapsed/refractory head and neck and AITL. And I'd be cautious to set any timing or expectations around anything we might do on the strategic partnering front, whether it be on tipifarnib or any of the pipeline assets.

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Joel Lawrence Beatty, Citigroup Inc, Research Division - VP & Analyst [40]

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Got it. And maybe one other question on HRAS head and neck cancer data. You've demonstrated nicely that higher allele frequency correlates with a higher response rate. And my question is now that the data has been maturing with additional patients over time, have you looked at depth of response and duration of response just to see if there's any correlation on those measures with allele frequency?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [41]

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Sure, Joel. Let me let Antonio answer that one.

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [42]

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Yes, that's actually very nice question. So we are noticing some minor differences. So recall that we made some initial distinction last year between the 35% and then the 20%, if we are able to maintain the patient one study based on performance status, and we are using the albumin of 3.5%, and that's already the good performance status.

So if you look at the data from this year, you can see that out of 8 patients that they were in that 20 to 35 who responded versus 6 responders in the tender have higher than 35. Again, small differences, you probably will need more patients, but is still continuing the trend that higher allele frequency, you can see better response.

The duration response, obviously, we will need a little bit of more time to see any differences between the 2. Last time that I checked back personally I didn't see differences in progression-free survival between those 2 subsets. But in any case, there are good responses in the 20 to 35 and good responses and activity in higher than 35.

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Operator [43]

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Our next question comes from the line of Jay Olson with Oppenheimer.

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Jay Olson, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [44]

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And congratulations on the data at the Triple Meeting last week. According to our interviews, it seems like physicians were favorably impressed by the data you presented last week. I was wondering if you could please share with us some of the feedback you received from oncologists attending that meeting, and whether or not you think that data might potentially accelerate the enrollment rate in your AIM-HN study.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [45]

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Thanks, Jay, for the question. And let me let Antonio speak to your question.

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [46]

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Yes. So I have to say that we have received very positive feedback, not just from the physicians attending the meeting but also from the members of our trial sitting committee, and also we -- as you can imagine, many of the orthos were also European orthos. So there is actually much excitement for the confirmation of the strategy, the activity of the 600 milligram dose and the application of the variant allele frequencies.

So we agree with you that we expect this will -- potentially will increase -- we believe will increase the testing or further testing of patients with head and neck through next-generation sequencing, and that increase in the testing will translate to higher enrollment of eligible patients.

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Jay Olson, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [47]

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Okay, great. And then maybe if I could just ask one follow-up. As you contemplate moving tipifarnib into combination studies for head and neck squamous cell carcinoma, what is the HRAS mutant allele frequency cutoff that you would use in those combination studies? Would it be the same that you're using in monotherapy? Or would it be different?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [48]

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I'll address it also. So it's actually a very good question. And they are both kind of like clinical rationale, but also technical rationale. So currently, since they're higher than 20% allele frequency is optimal population for activity as a single agent, we'll continue pursuing tipifarnib monotherapy in that site percent of the population using current technologies, both of the NGS testing in tissue, but also we have available plasma cells that we can develop. We can identify perhaps another 20% of the patients.

But as you can imagine that limit is technological limits. So you can potentially expand the population going lower than 1%, perhaps 0.5%. So there is a possibility of expansion of the population based on the lower limit of detection of these assays. And we have a number of partners who are perfectly capable to identify that population.

Currently, we are giving that number of perhaps 20% of head and neck because we feel fairly confident of the assays that we have in hand. But the NGS technology improves every year. And there could be potentially, if anything, an increase of the potential target population.

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Operator [49]

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(Operator Instructions) Our next question comes from the line of Joseph Pantginis with H.C. Wainwright.

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Pasquale Sansone, [50]

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This is Pasquale Sansone from the line of Joe. Congrats on the update on RUN-HN trial. I've just a question on RUN-HN. So basically, by analyzing tipifarnib PFS curves, based on prior therapies, it looks like the tipifarnib shows a greater PFS in CKI failures, so after checkpoint inhibitors. So could this data suggest a potential rationale of combining a CKI to tipifarnib in order to increase durability of response? Can you please comment on this?

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [51]

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Sure. Thanks for the question. Let me let Antonio take that one.

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [52]

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Yes. So I mean just to be clear, we currently -- this may require more patients, but we currently do not see the differences based on the prior use of immune therapy versus prior use of cetuximab. The good news is that with the progression of the immunotherapy to the first line, if anything, further validate the use of tipifarnib in second line as monotherapy.

That said, I agree with your point that the presence of even low allele frequency FS mutation in the front line, that most likely will translate to the appearance of progressions on the use of immunotherapy along -- on combination with chemotherapy in the front line. So there could be an opportunity of potential regimens of chemotherapy, immune therapy plus tipifarnib. And we mentioned initially, maybe a high re-subset would be those patients that could, for example, be tested in plasma for the presence of circulating FS. So that could be a population that we are estimating of about 20% of the patients. But as I said previously that subset, some potential increase depending on the technological advantages of the use of NGS.

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Pasquale Sansone, [53]

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All right. And also a follow-up question. You said that you are starting different combination treatments in preclinical models. So are you seeing like more activity when you combine tipifarnib with immunotherapeutics or not?

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Antonio Gualberto, Kura Oncology, Inc. - Head of Development & Chief Medical Officer [54]

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Yes. I mean you can anticipate that we are going in that direction, but we currently have not released that data. But as you can imagine, yes, we are doing those experiments at the current time.

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Operator [55]

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This concludes today's question-and-answer session. I would now like to turn the call over to Troy Wilson for closing remarks.

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Troy Edward Wilson, Kura Oncology, Inc. - Chairman, CEO & President [56]

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Thank you, Sarah. Thank you all for the questions and for participating in our call today. Before we conclude, let me just quickly lay out our anticipated milestones over the next 12 months.

For tipifarnib, additional Phase II data in AITL at the ASH Meeting in December; regulatory feedback from our Phase II trial in AITL in the first half of 2020; additional Phase II data in chronic myelomonocytic leukemia or CMML in the first half of 2020; additional Phase II data in urothelial carcinoma in 2020; initiation of a proof-of-concept study in pancreatic cancer in 2020; and potential for full enrollment of AIM-HN by the end of 2020.

For KO-947, our ERK inhibitor completion of the dose escalation portion of the Phase I trial by the end of 2019 or early 2020 and initiation of 1 or more tumor-specific extension cohorts in 2020; and for KO-539, achievement of a recommended Phase II dose in 2020.

We're planning to be at the Stifel Healthcare Conference in New York in 2 weeks, and we look forward to seeing many of you there. In the meantime, if you have any additional questions, please feel free to contact Pete, Marc or myself.

Thank you again, and have a good evening, everyone.

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Operator [57]

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