Good afternoon, ladies and gentlemen and welcome to the First Quarter 2020 Kura Oncology Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session and instructions will follow at that time. [Operator Instructions] I would now like to turn the conference over to your host, Mr. Pete De Spain, Vice President of Investor Relations. Please go ahead.

Thank you, Bella. Good afternoon and welcome to Kura Oncology's first quarter 2020 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. Jim Basta our Chief Legal Officer; Kirsten Flowers, our Chief Commercial Officer; Kathy Ford, our Chief Operating Officer; and Dr. Bridget Martell, our acting Chief Medical Officer are 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.

Thank you, Pete and thank you all for joining us this afternoon. Our mission at Kura is to realize the promise of precision medicines to help patients with cancer live better, longer lives. I'd like to begin our calls with our mission statement because it's the driving force behind the priorities we've set and the decisions we make as an organization every day. Our commitment to patients and their families is why we do what we do and it serves as an important reminder in the current environment. As with other clinical stage drug development companies, we are beginning to see effects from the COVID-19 pandemic on the conduct and timing of our clinical trials. Specifically, our clinical sites are seeing fewer patients, who may be candidates for our trials, which is having an impact on both patient screening and enrollment. Furthermore, the ongoing pandemic and related social percussions are having an impact on our ability to open new sites and initiate new trials. In response to these challenges, we've implemented a number of mitigation steps. And although the situation is still very fluid, we expect the disruption and uncertainty to continue for the foreseeable future as the COVID-19 pandemic continues. In that context, we recently completed a strategic review, incorporating multiple stakeholder feedback with the goal of prioritizing those programs with the highest potential to create value for patients, health care providers and shareholders, while operating against the challenges of the COVID-19 pandemic and maintaining a strong financial position. Our strategic review resulted in three key outcomes. First, we intend to expand activities related to our Farnesyl Transferase inhibitors, Tipifarnib in HRAS dependent head and neck squamous cell carcinomas including HRAS mutant and HRAS overexpressed HNSCC. We have also prioritized development of our menin inhibitor KO-539 and KMT2A(MLL)-rearranged and NPM1-mutant acute leukemias. KO-539 and acute leukemias will now serve as one of our two major pillars alongside Tipifarnib and HRAS-mutant HNSCC. Second, we plan to pause activities related to Tipifarnib in CXCL12-driven tumors, including T-cell lymphoma and pancreatic cancer, while taking time to optimize these opportunities for future development. Third, we've decided to terminate development of our ERK inhibitor KO-947. While these were difficult decisions, we believe focusing our clinical development efforts enables us to enhance our focus on those development programs with the highest potential value and enables us to maintain a strong cash position through those potential value inflection points' namely clinical data from Tipifarnib and HNSCC and from KO-539 in adult AML. I'm very pleased to report that we have three abstracts that have been accepted for presentation at ASCO, including an oral presentation, featuring matured clinical outcome data from the ongoing Phase II study of Tipifarnib in HRAS-mutant HNSCC. In addition to a high response rate in patients with high HRAS-mutant variant allele frequency, we are encouraged to see a meaningful clinical benefit in the overall HRAS mutant population and we look forward to sharing those data at ASCO later this month. Based in part on the Phase II data set, we intend to amend our AIM-HN registration-directed trial to enroll all HRAS-mutant HNSCC patients, regardless of variant allele frequency, expanding the proportion of HRAS-mutant HNSCC patients who are being treated. Although, we will maintain the primary outcome measure of objective response rate in patients with high HRAS mutant variant allele frequency, our goal is to also assess the potential clinical benefit in the overall HRAS mutant HNSCC population. In addition to the more mature data sets from the Phase II trial, we are motivated to make this change in response to feedback we've received from physicians who've indicated the desire to treat all HRAS mutant HNSCC patients. We have heard from physicians that current treatment options are limited, with response rates in the low teens and moderate survival benefit. Based on the data we'll present at ASCO, we believe Tipifarnib has the potential to provide a meaningful benefit to these patients. We intend to implement this amendment as quickly as possible at our existing clinical sites and we'll continue to enroll patients throughout the process. We expect to communicate more specifics on the amendment to the AIM-HN trial following the data presentation at ASCO. Our AIM-HN trial of Tipifarnib in HRAS mutant HNSCC, a disease of high unmet need, remains a primary focus. However, given the proposed amendment and the ongoing impact of COVID-19 on screening and enrollment for the trial, we are suspending our guidance on full enrollment until we have more clarity on timing. In addition to pursuing the first registrational opportunity in recurrent or metastatic HRAS mutant HNSCC, we're also planning for how we can expand the use of Tipifarnib into larger patient populations and earlier lines of therapy. In particular, we are increasingly interested in HNSCC patients whose tumors overexpressed the HRAS gene. These patients may represent a significant subset of HRAS dependent tumors, with distinct biology that may be targeted by Tipifarnib. It's estimated that up to 20% of HNSCC patients have tumors that overexpress HRAS, which can drive resistance to other therapies. Based upon the unmet need and our encouraging preclinical data, we intend to pursue the clinical development of Tipifarnib in combination with other therapies as a strategy to treat HRAS overexpressing HNSCC patient. Now, let's quickly turn our attention to Tipifarnib in CXCL12-driven tumors. We continue to believe that CXCL12 pathway biomarkers have the potential to unlock the therapeutic value of Farnesyl Transferase inhibitors across a range of hematologic and solid tumor indications. Just last month, Tipifarnib received orphan drug designation from the FDA for the treatment of T-cell lymphoma, recognizing its potential to address a high unmet need for patients. However, for reasons I outlined earlier in the call, we believe the initiation of new studies are especially challenging during a global pandemic. So we are pausing the initiation of our proposed registration-directed trial of Tipifarnib in T-cell lymphoma, as well as our proof-of-concept study in second-line treatment of pancreatic cancer. We intend to use this time to conduct additional advisory board meetings, refine our market insights and further optimize these opportunities for future development. That brings us to our second major area of focus KO-539. KO-539 is a potent and selective small molecule inhibitor of the menin KMT2A(MLL) protein-protein interaction. Preclinical data support the potential for potent antitumor activity in genetically defined subsets such as KMT2A(MLL) fusions and rearrangements as well as NPM1 mutation. KO-539 has also received orphan drug designation from the FDA for the treatment of acute myeloid leukemia, recognizing its potential to address this population of patients with high unmet need. We were pleased to see the presentation from Dr. Gerard McGeehan at AACR last week, which represented the first public report that menin inhibitor can drive meaningful antitumor activity in KMT2A(MLL)-rearranged AML patients. This encouraging data only underscore our excitement around KO-539, which is a chemically distinct molecule with different physical chemical and drug-like properties. We dosed the first patient in our Phase 1/2a clinical trial of KO-539 in relapsed/refractory AML late last year. And the trial which we have named KOMET-001 continues in dose escalation. Although, it's still early, we're encouraged by the progress we're making in the clinic. We remain focused on our goal of reaching a dose at which we can safely drive antitumor activity after which we intend to open expansion cohorts in NPM1 mutant and KMT2A(MLL) rearranged AML. Selected patient populations where we believe KO-539 has the potential to demonstrate increased clinical benefit. We recently amended the protocol to enable us to move aggressively into the expansion cohorts following achievement of a recommended Phase 2 dose. In addition, we are exploring options to further expand the label, potentially broadening the opportunity in the treatment of acute leukemias in both children and adults, as well as the combination of KO-539 with chemotherapy and targeted therapies. We believe that KO-539 represents a differentiated approach to the treatment of patients with AML, with the potential to target approximately 35% of all AML patients. We're enthusiastic about its potential. And as such, have prioritized its development as one of our two major pillars, alongside Tipifarnib and HRAS-mutant HNSCC. Our remaining drug candidate is KO-947, a selective small molecule inhibitor of ERK. Earlier this year our Phase I trial of KO-947 was placed on a partial clinical hold, due to a dose-limiting, adverse drug reaction, in a single patient on study. Although the partial clinical hold has been lifted, and our interest in 11q13 amplified solid tumors remains, we've opted to terminate further development of KO-947. I'd like to take this opportunity to thank all of the investigators and especially the patients and their families for their participation in the study. After a thorough strategic review of our portfolio, we've decided instead to focus our resources toward advancing Tipifarnib in HNSCC and KO-539 in AML, two programs that we believe have a higher potential to benefit patients and create value. This decision demonstrates our commitment to prioritizing the interest of patients who critically need new therapies, our health care providers who treat these patients and our shareholders. With that, I'll now turn the call over to Marc Grasso for a discussion of our financial results, for the first quarter 2020.

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 file today for a more detailed discussion. Research and development expenses for the first quarter of 2020 were $12.6 million, compared to $10.4 million for the first quarter of 2019. The increase in R&D expenses was primarily due to an increase in clinical development activities related to our KOMET-001 trial and personnel costs and other expenses. General and administrative expenses for the first quarter of 2020 were $7.6 million, compared to $4.6 million for the first quarter of 2019. The increase in G&A expenses was primarily due to increases in personnel costs and non-cash share-based compensation. Net loss for the first quarter of 2020 was $19.2 million or $0.42 per share, compared to a net loss of $13.9 million or $0.37 per share for the first quarter of 2019. As of March 31st 2020 we had cash, cash equivalents and short-term investments of $216.9 million, compared with $236.9 million as of December 31st 2019. We remain in a strong cash position as we advance towards potential value inflection points. Cash remains a critical asset for us, as we position ourselves amid the COVID-19 crisis. And together with the portfolio prioritization discussed, we intend to manage the company accordingly. With that, I will now turn the call back over to Troy.

Thank you, Marc. Despite the continuing challenges arising from the pandemic, we believe we are well equipped to evolve, adapt and overcome those challenges. By concentrating our clinical development efforts, we believe we've enhanced our efforts on our programs, with the highest potential to provide meaningful benefit to patients of high unmet need, while creating greater operational leverage and helping to ensure, we are in a strong cash position, as we approach important catalysts. Now more than ever, we're poised to realize the promise of precision medicines to help patients live better, longer lives. With that operator, we're now ready for questions. Question-and:

[Operator Instructions] We have our first question from the line of Tyler Van Buren with Piper Sandler. Your line is now open.

Hey guys. Good afternoon. Thanks for taking my questions. I had three on, KO-539 menin-MLL inhibitor. So, clearly the recent index data was derisking for the class. But I noticed in your prepared remarks you just -- you mentioned that KO-539 is chemically distinct -- is a chemically distinct molecule with different physical and drug-like properties. So I was hoping you could elaborate on that point? And then second, fairly is there any preclinical data that could suggest a differentiation between the two? And then thirdly, in the press release you mentioned, encouraging progress in the clinic. So could you speak towards the progress that has been observed at all? And what gave you confidence behind moving forward with the program?

Sure. Thanks Tyler for the three questions and we can take them in turn. So, we were very excited, I think as many were to see the reports of clinical activity in the MLL rearranged population from Syndax. And there to be congratulated I think for the first public report. This really offers we think the potential for the next targeted therapy in AML after FLT3 and IDH. And it's a big step in the right direction. From the standpoint of your question, we now -- after that presentation, we now know the structure of 5613. And what we can say is our molecule KO-539 is chemically distinct. It has different drug-like properties. It has -- it's much more highly protein bound, it has a much larger volume of distribution, and it has pharmacokinetics that permit once-daily dosing. Will that manifest? How will that manifest itself in the clinic? I think that remains to be seen. I think it's great for AML patients to have a couple of options now. And with respect to your second question, the preclinical data that has been published, most of it has actually been on tool compounds either ours or others. There's less data that has been publicly presented on the clinical candidates. But if you assume that the tool compounds are a good proxy for the clinical candidates, the efficacy data -- the preclinical efficacy data looks very similar. You see strong activity in MLL rearranged tumors, you see strong activity in NPM1 mutant tumors that seems to be independent of co-mutations in the case of NPM1. And I don't think there's really been any reports of safety, tolerability or drug-like properties for the clinical candidates. So we're not really in a position to comment on differentiation. I think both companies are moving as quickly as they can to establish a recommended Phase 2 dose. As far as our comment that we're encouraged by the progress in the clinic, we are as we've indicated advancing through at this point a fairly traditional Phase 1 dose escalation, single patient escalation cohorts. We're making good progress in that regard. We've reiterated our goal to achieve a recommended Phase 2 dose later this year. And the hope is that either at that point or along the way, we will have the requisite safety data, pharmacokinetics, pharmacodynamics and potentially evidence of antitumor activity. So we're here reiterating that goal of a recommended Phase 2 dose and look forward to providing further updates throughout the year. I hope that addresses your three-part question?

That does. Thanks very much. Really appreciate it.

Sure. Thanks for the question.

Your next question comes from the line of Konstantinos Aprilakis with DB. Your line is now open.

Thanks for taking my question guys. I have a follow-up to the last one on KO-539 and then another question on Tipifarnib. So there were a few instances of low-grade QT prolongation attributed to SNDX-5613 and this activity on HER. I was wondering if you could share with us if KO-539 inhibits HER2 to any significant degree. And should we expect to see results from patients with NPM1 mutant AML once we get a first look at the KO-539?

Yes. Konstantine thanks for the questions. So we're not going to comment specifically on what we're seeing in the clinic in terms of safety or tolerability for obvious reasons. We'll wait until a presentation of the clinical data. Something that we have highlighted is the extent, to which 539 is protein bound. It's much more highly brain bound in excess of 95%. That may or may not be relevant. I think we just need more clinical data from both molecules. But as I mentioned to Tyler's question previously, we've continued along with a fairly standard Phase 1doses escalation. With respect to your second question about NPM1 mutant AML, so our trial is structured in such a way that we don't require either an MLL rearranged or an NPM1 mutation genetic lesion for a patient to go on study. That being said, the investigators are aware of the rationale and the scientific data. And if they can recruit patients that are more likely to receive clinical benefit, I think they endeavor to do so. But with that being said, I don't think we can speak at this point to exactly what the composition of the patients will be at the time we reach the recommended Phase 2 dose. It is thought that about 30% of adult AML patients have mutations in NPM1 with varying degrees of co-mutation. So if you cast a wide net, you have a reasonable probability of getting an NPM1 mutant patient. But given that these are Phase 1s with small N, small numbers of patients, I don't think there's a guarantee there. But we'd certainly like to be in a position where we can explore the genetic backgrounds where we expect the highest degree of clinical benefit. That's certainly something that we're looking forward to being able to do.

Okay. Thanks for the color there. And then on tipi, I was wondering what the guided expansion to AIM-HN? What does that do to the success thresholds that have been previously established for the study in particular having to the minimum of 15 confirmed responses?

Yes. So I appreciate that question. It will expand the total enrollment in the study somewhat not, we don't think significantly, but given that we're going to be bringing some lower variant allele patients and we do expect the total enrollment to go up. Importantly, and I think this is the thrust of your question, the primary efficacy objective hasn't changed. It remains elimination of a 15% now hypothesis in the high DAF population. The amendment that we're putting in place will be the introduction of some secondary objectives meant really to assess the clinical benefit in the overall population as well as looking at potentially some survival end points. And so -- but that shouldn't change the primary efficacy end point in any way.

Perfect. Thanks for the color.

Thanks, Konstantinos.

Your next question comes from the line of Jonathan Chang with SVB Leerink. Your line is now open.

Hi, guys. Thanks for taking my questions. First question, when could we see clinical data from KO-539? And what are the factors you're considering in terms of whether or not to present 539 data this year?

Yes. Thanks, Jonathan for the question. So our sequence here. I'm laughing because it's a completely reasonable question. Our focus is 100% on achievement of a recommended Phase 2 dose. And to get there as safely and as efficiently as we possibly can such that when we go into the expansion cohorts, we're going in with very clear guidance and data for the clinicians on what to expect. Our hope is that we achieve that recommended Phase 2 dose. And we understand the high degree of interest in the community, the investor community, the academic and the industrial communities in that data, but we're not at a point yet where we can commit to having a data presentation in a given venue. But we're well aware of the interest. And I think if we can stay focused on our goal of reaching a recommended Phase 2 dose then we'll look for an appropriate scientific venue to be able to present the data. We're just not -- given that it's still May, it's a little bit early to be committing to a venue at a time.

Got it. Thanks. Second question this is a clarification question. I think I heard you mentioned a KO-539 protocol amendment to facilitate moving quickly after reaching or in Phase 2 dose. Did I hear this correctly? And if so could you expand on this?

Yes. So you did hear it correctly, that amendment has actually already been implemented. So when we initially started the study, the study provided for a Phase 1 dose escalation and the -- and really didn't speak to expansion cohorts. We have subsequently amended the protocol and are now in a position where we can implement two separate expansion cohorts, one in patients that have the MLL rearrangements or fusions the second in patients that have NPM1 mutations. And that's predicated on reaching a recommended Phase 2 dose and the data monitoring committee determining that we're -- that the study is ready to proceed to the expansion phase. Said more simply, we've put in place all the steps that we need from a clinical perspective to be able to move into the expansion cohort. Now it's a matter of continuing to work our way through dose escalation.

Got it. Thanks. Just one last question. With the strategic changes announced today, can you talk about your cash runway?

Yes. Let me let Marc address that question Jonathan.

Hi, Jonathan. To your question, we continue as you'll see in the 10-Q filed to reiterate our current cash guidance of cash into 2022. So it's unchanged from the last update in the 10-K. What we would say is that, the cash runway is obviously very important to us. Cash is an important strategic asset. In light of the COVID-19 crisis, we have undertaken the strategic review to prioritize our efforts. And while there will be some offset from the standpoint of reduction in spend on the T-cell lymphoma study, pancreatic study and ERK that offset isn't that significant because a fair bit of that spend was in later years. And we may see some reduction in spend relating to the COVID-19 crisis. But so far we're really not seeing that right now. And the company does continue to expand its efforts in menin and HRS at a neck. So those spends will be increasing. So we think there will be some additional runway into 2022 as compared to previously but we're maintaining our guidance attached into 2022.

Got it. Thank you.

Thanks, Jonathan for the question.

Your next question comes from the line of Chris Shibutani with Cowen. Your line is now open.

Great. Thanks very much for the opportunity for the questions. I guess with Tipi upcoming at ASCO, just noticing the wording about the oral presentation you're referring to that has matured data from the Phase II. Can you provide a little bit of color on that? And also whether, we should expect to see anything in particular at the mid-May abstract posting?

Yes. Chris, thanks for the question. So this trial has been ongoing now for several years. And so we have really a better look. And we want to be respectful, obviously of the ASCO embargo, which is why I'm going to couch my answer carefully. But we have a better look now into the mature clinical data and in particular, some of the survival data that I think we'll be able to speak to. The abstract, the focus will continue to be head and neck. Because we see that as, obviously the opportunity with AIM-HN and we're putting a stake in the ground on the HRAS overexpressed population, which is quite a bit larger than the HRAS mutant. That being said, there has been some data in salivary and urothelial. And so you'll see that in reference to the abstract. That won't be as much the focus as the updated head and neck data. We're not expecting there's going to be new patients but it will be further in time. So more of a longitudinal look at the existing data set.

Got it. And then you also described in your release about looking into HRAS overexpressed and HNSCC. Can you maybe elaborate a little bit more in terms of how that should be defined to get to your 20% patient population? Also if any, historical clinical data from the troves of Tipifarnib historically have revealed anything to move you in that direction as well?

Sure. So you will -- if it's not up it will be shortly you will find some a revised corporate presentation with a couple of slides that speak to this opportunity. And one of them in particular you'll see that if you go into the databases and you look at the extent of HRAS overexpression across different histologies, what's interesting is that you see the HRAS overexpression is elevated in head and neck in lung squamous and in urothelial. And I'm hearing from Pete that the corporate presentation is now live on our website for those of you who are following along. So you'll see that the HRAS expression is elevated in head and neck in lung squamous and in urothelial. It's quite a bit lower in lung adeno in colorectal and there's one other, I believe, it may be pancreatic. That -- it may be coincidence but it's interesting that the areas where it's elevated or the areas where we've seen clinical activity of Tipifarnib as a monotherapy. The way that we've set the cutoff is we've taken the highest level of HRAS expression in the other tumor types and said okay, anything above that is HRAS overexpression. And that depending on how you look at it, we're trying to be conservative in saying that's approximately 20% of all head and neck squamous. So that's the population. You can look at the data and look through the references and happy to walk you through that if it's helpful. To the second part of the question, there isn't any data from the historical clinical studies that were conducted primarily because no one was looking at HRAS overexpression. So there's just no data set to look at. What is interesting when we look at our preclinical data is HRAS over expression not mutation, but just excess protein seems to control a resistance program that provides resistance to a number of other therapeutics. And you'll see in the second slide for examples Platinum two targeted therapies PI3 kinase and a torque inhibitor and then also cetuximab. And what's interesting is that, although, you don't see activity of those other drugs as monotherapies in the PDX models when you suppress HRAS overexpression or the activity of HRAS the oncoprotein with Tipifarnib you can then drive very profound synergistic activity. And there's a lot -- there's additional literature suggesting that HRAS is driving this common resistance mechanism to other therapies. So our thought is the way to tackle this problem is probably to go in combination. We would have -- we are right now considering what agents to prioritize and exactly what that study design looks like, but that -- if that's successful that would provide a therapeutic benefit to potentially up to 20% of the total head and neck population, which is a fairly significant opportunity. We'll have more to say on this throughout the year. It's really as we see it the next logical step beyond what we are currently doing in the relapsed and refractory HRAS mutant setting.

Great. We’ll look forward to more updates. Thank you.

Thank you, Chris.

Your next question comes from the line of Ren Benjamin with JMP Securities. Your line is now open.

Hi. Good afternoon. Thanks for taking the questions. To Troy maybe just starting off with AIM-HN. I guess, I'm trying to get a sense as to the timing of the data. So you're suspending guidance for full enrollment. But the way I kind of look at it is, if suddenly you start bringing in more lower allele frequency patients the potential of reporting the data from the higher frequency primary endpoint may get pushed out. So can you give us a sense? Are you still prioritizing these higher frequency allele patients so that the timing of the data might stay the same? Or how should we be thinking about this?

Yes. Ren, it's a great question. And without getting into the -- how the sausage is made the -- we are -- as part of SEQ-HN, which is our non-interventional screening and outcomes cohort, we are screening patients for the presence or absence of the HRAS mutation. And then if they have higher than 20% VAF, they're currently -- they go to the next step. If they don't then we're able to follow them and potentially they can be re-biopsied if they're available. Nothing about the front end of the trial changes. And we're already finding patients that meet that criteria of having an HRAS mutation, but not reaching the 20% threshold. We do anticipate when we make this change that it's going to be -- it's going to add about another 25% to 30% to the total population beyond the high VAF population. In terms of the timing to data which is I think the thrust of your question, that's partly why we've suspended our guidance, and what we've tried to communicate is we have seen a pretty consistent step down in terms of numbers of patients who are presenting at these clinics. And by extension the number of patients who would be eligible to come on to the study. And we think that's in part because the sites are engaged with COVID or otherwise having to take these social precautions. And the second part and probably equally important is the patients are just determining not to go to clinic. And so that we don't have as much clarity on which is why we've suspended our guidance on full enrollment to this point until we continue to see how this plays out as it's working -- as the pandemic is working its way around the world. I don't know at this point whether we'll be able to come back to you and in what time frame, but it's something that we're monitoring and working to mitigate quite actively. And we're not really in a position to speak to the question you're asking of the specific timing of data. That's not something I feel comfortable that we can really project for you yet.

Got it. And then switching gears to KO-539, we noticed in the Syntax presentation a strong CYP3A4 interaction. And you had mentioned in your prepared remarks that you have different drug-like properties and a different structure. Can you talk or provide any color regarding any sort of CIP three or four interaction you may have or not have?

Yes. It's -- we can't really comment Ren yet, although, I appreciate the spirit of the question. It's not -- it's -- I would say it's not uncommon that patients with AML are on strong CYP3A4 inhibitors, many of them are on antifungals and to some extent on antimicrobials. So, it is a population where that's a question one has to ask. We'll have to hold that question on the specifics of the -- precisely what we're seeing until we're in a position to show you the data. What we are trying to communicate is that from our perspective, the study is going well. The molecule is behaving well and we are very focused on achievement of a recommended Phase 2 dose. CYP3A4 interaction is certainly something that one can work with so long as you understand it but we're not yet at a point to really be able to draw points of differentiation. I would rather let us present our data and then the data can speak for itself.

Got it. And just one final one for me.

Sure.

You have the termination of development of the ERK inhibitor. You've postponed the starting of certain clinical studies. It seems to me like this will be a great time to maybe be increasing BD activities and trying to see if there are partners out there who could be moving this forward. What -- kind of what are your thoughts regarding partnerships? And is that in the works or do you want to still keep the majority of these assets for yourselves?

Yes. It's a great question Ren. Why don't I let Marc comment on sort of how we're viewing the business development potential?

Hi Ren, thanks for the question. So, in terms of business development, we continue to have discussions from a partnering perspective across the pipeline. We wouldn't see any immediate need to do anything on the partnering front certainly that encumbers any major commercial rights to Tipifarnib or menin, particularly in the U.S. those are very core to us. These are concentrated markets with profiles that would make sense for a company of our size and stature to potentially commercialize ourselves from the standpoint of very concentrated prescribers in a targeted salesforce. That said from the standpoint of potential partnerships outside of key areas like the U.S., it's something that we have ongoing discussions. Although again no real urgency to do that from a cash-on-cash runway perspective.

Good. Thanks for taking the questions.

Thank you, Ren.

Your next question comes from the line of Joe Pantginis, your line -- with H.C. Wainwright. Your line is now open.

Hi guys. Good afternoon. Thanks for taking the question. I hope you're all doing well. The first question is just black and white. I just want to confirm the characterization of 947 being terminated. Is this a shelf drug or is this a dead drug?

So, Joe I appreciate the bluntness of the question the black and white as you called it. At this point, there are potential paths forward with 947. And so I would characterize it as a shelf drug. That being said, as part of our strategic review, when we ask the question internally how can we take these very precious shareholder dollars and create the most value in the shortest period of time? Although there are multiple ways to creating value, the efforts in head and neck squamous with Tipifarnib and in AML with 539 came out on top. So, that's where we're going to focus. 947 just given, what we saw in Phase 1 development, and what would be required moving forward didn't -- from our standpoint didn't have the same potential to create value for patients or for shareholders in that time period. But, if there's an opportunity, if someone else can take it in a different direction, we would welcome that.

Perfect. I appreciate the clarity. And then just switching quickly to Tipifarnib, but specifically, the CXCL12 axis, I appreciate the color you gave earlier on the call looking to potentially have added advisory board meetings, I believe you said, further market analysis. I guess, what would be part of your wish list or some of your view of a great outcome, I guess with regard to improved clinical trial designs? How you look at the studies? Or what are you really looking for beyond the factors you talked about?

Yes. That's a great question. So, we definitely see value in inhibiting the CXCL12 pathway in terms of driving antitumor activity. And with the lymphoma study, I think we really want to make sure that, we are running the absolute best study for patients and the best study for creating value for patients and shareholders per unit dollar and per unit time. And more work to do there, we're getting great -- one of the advantages of the pandemic, if there are any, is that it's easier to get access to sort of investigators and leading KOLs. So that's very helpful. In pancreatic, I think there we see an opportunity. But again, when we look at that relative to dollar for dollar, what we think we can do with menin in the next 12 months to 24 months, we think it's better to focus our resources on menin and also to keep the company in a strong financial position. And we take that responsibility very seriously. Marc commented, where we think our guidance remains into 2022. But hopefully, people take away from this we're -- we view it as our responsibility to make hard decisions and to really keep the company on a strong front foot as far as development and financing opportunities, as well as business development. And so we think these initiatives do that. We will happily come back with more inflation and we think sharpened ideas to those CXCL12 opportunities in the future.

Got it. Appreciate it, Troy.

Sure. Thank you, Joe.

Your next question comes from the line of Jay Olson with Oppenheimer. Your line is now open.

Oh, hey. Thanks for taking the question. Can you elaborate on the feedback that you received from physicians that enabled you to expand the enrollment of AIM-HN to all patients with HRAS mutant HNSCC regardless of VAS? And then I had a couple of follow-ups.

Yes. Jay, thank you for the question. What's interesting is we've -- with the increased operational -- we focus on operational execution and with the sort of heightened focus on commercial opportunities after Kirsten joined us around the beginning of the year, we've really taken very seriously the obligation and the opportunity to talk to physicians. And they have reiterated for us the very, very high unmet need in second-line head and neck cancer. A number of them characterized, it as an unmet need that is equivalent to what one season pancreatic. In that context, we really see an opportunity to be able to provide Tipifarnib and potentially clinical benefit to any HRAS mutant patient. It's something that, we've been considering internally all along. We -- that's really why we exist as a company is to not only provide clinical benefit, but maximize the clinical benefit to patients. And over the last three months or so we -- since -- really since the beginning of the year we've really been sharpening our pencil, sharpening our focus and going through this strategic exercise. And I think we're quite excited at the expanded opportunity not only in the HRAS mutant, but then also looking forward to potentially the HRAS overexpressed where by our way of thinking there's no other way to address that patient population. Tipifarnib and the ability to down-regulate HER2 to essentially cause HRAS to disassociate from the membrane there's no other molecule that does that effectively. So we'd like to double down on already a very strong clinical profile and some strong data moving forward.

Great. Thanks for that additional color. And I am curious about that HRAS overexpress patient population. Can you share any thoughts about the possibility of pursuing a tumor-agnostic indication for all patients with HRAS overexpression?

Yes. That's a really good question, Jay. You're several steps ahead. It's a possibility. I would say the challenge is the following. The standards of care now between head and neck and urothelial are quite different. And so, if one we're going to pursue a tumor-agnostic label around HRAS overexpression you'd have to take that into account. If we just take a step back, the opportunity to treat 20% of head and neck cancer -- head and neck cancer is the sixth most common cancer in the world. And again, we've got some new slides in the corporate presentation that we think speak to the opportunity. If we can just deliver meaningful clinical benefit in that population that's a very, very significant unmet need, I want to make sure we do the right stepwise studies and we go from position of strength to position of strength. But ultimately, if it works one could think about other tumor types as well. I just wouldn't want to take on too much at the same time, particularly given that as we've communicated it's likely these next studies will need to be doing -- done in combination.

Okay. Great. And that actually brings me to my last question. You were talking about the potential synergistic combinations for Tipifarnib. And I was wondering if you have any preclinical data to help guide you in your decision about the combos that you want to start with?

We do. We do. So we've shown just a very quick snapshot of preclinical data in the new corporate presentation. And it's a slide with the spider in the web. We use the metaphor of the spider, where the HRAS is sitting in the middle of the web. And no matter what else you come at it with, come at head and neck whether it's pancreatic kinase or platinum you're going to see resistance and that resistance is mediated by HRAS. We do have much more preclinical data behind what we're showing. And we continue to do two things: to gather preclinical data. One of the things we're not showing is preclinical data with immune therapy. Those studies are in progress. We're also continuing to gather feedback from advisory boards investigators and other experts on how best to think about the next steps in head and neck cancer. And I'm optimistic that we'll have more to say about that a little bit later in the year.

Sounds great. Look forward to that. Thank you again for taking the question.

Our pleasure, Jay. Thank you.

Your next question comes from the line of Peter Lawson with Barclays. Your line is now open.

Hi, Troy. Thanks for taking the questions. The over-expression of HRAS in tumors, does that correlate with any other markers P1 or anything on the IO side of things? And how is that potentially guiding how you're thinking about combinations and what lines of therapy?

Yes. It's a great question, Peter. And I probably stock for a longer more in depth discussion. The short answer is, if you just look at where -- if you look at the second line population, we know that the existing standards of care give you response rates in the teens and PFS measured by a couple of months. So, we would expect that that's the unmet need. In combination, you would hopefully be able to do significantly better than that. I don't think we have enough human clinical data to be able to answer the question that you're asking about the relationship to other biomarkers, but it's something we're looking very intensively at we have more work to do in terms of tissue profiling and so forth. And some of those efforts are underway. So, we really want to make sure that we're doing the right study that there's a strong rationale. There maybe opportunities to do more than one combination, and there are potentially good reasons for that. But I think, it's still a work in progress. What we want people to understand is, this will be a central pillar of value creation for Kura going forward, and we see an opportunity to move beyond the HRAS mutant relapsed/refractory setting to a larger HRAs over-expressed and look forward to being in a position to do that later this year.

Great. Thank you. And then just on the AML inhibitor. How is Syndax's data in any way kind of change the way you're thinking about the development program, which combination agents you're thinking through? And is there anything in your own data that says you could get deeper responses or not? Any kind would be appreciated.

Yes. I think there's nothing -- I mean other than we were thrilled that Syndax shared that data, because it's really -- it's injected a lot of interests and a lot of enthusiasm throughout from all corners in this molecular target. It hasn't changed at all the way that we are going about prosecuting our Phase 1/2A. We -- we're moving as quickly as we can to reach a recommended Phase 2 dose. As I alluded to in the prepared remarks, we're already thinking about how does one move into the pediatric population? How do you move in combination with targeted therapies, potentially with chemo? How do you move to the front line? These are all aspirational. But the preclinical data that we've published, the Syndax clinical data and then the insights we have on our own program, all come together to make us believe that it's the right thing to do to make this one of the two major pillars of value creation in the company again over the next sort of 12 to 24 months.

Great, thank you so much. Thanks for taking the questions.

My pleasure.

And I'm showing no further questions at this time. I would now like to turn the conference back to Troy Wilson.

Great. Thank you, operator. And I want to thank all of you for participating on our call today. If you have any additional questions, please feel free to contact Pete Marc or myself. We appreciate your participation and we hope everyone has a good evening. Thanks, again. Bye.

Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and have a wonderful day. You may all disconnect.