Earnings Call Transcript - KURA Q1 2020

Operator, Operator

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. I would now like to turn the conference over to your host, Mr. Pete De Spain, Vice President of Investor Relations. Please go ahead.

Pete De Spain, Vice President of Investor Relations

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.

Troy Wilson, President and CEO

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 implications 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, healthcare 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 have 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 overexpress 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 underscores 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 towards 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 healthcare 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.

Marc Grasso, CFO

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 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.

Troy Wilson, President and CEO

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.

Operator, Operator

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

Tyler Van Buren, Analyst

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 de-risking for the class. But I noticed in your prepared remarks you mentioned that KO-539 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?

Troy Wilson, President and CEO

Sure, thanks for the three questions. We were really excited to see the reports of clinical activity in the MLL rearranged population from Syndax, and they deserve congratulations for their initial public report. We believe this could signify the next targeted therapy in AML after FLT3 and IDH, marking a significant step forward. Following that presentation, we now understand the structure of 5613, and we can confirm that our molecule, KO-539, is chemically distinct, possessing different drug-like properties. It is more highly protein-bound, has a larger volume of distribution, and features pharmacokinetics that allow for once-daily dosing. The clinical implications of this remain to be observed. It’s encouraging for AML patients to now have more options. Regarding your second question, most of the preclinical data published has focused on tool compounds, whether from us or others, with less publicly available information on the clinical candidates. Nevertheless, if we consider the tool compounds as a proxy for the clinical candidates, the preclinical efficacy data appears similar, displaying strong activity in MLL rearranged tumors, and significant activity in NPM1 mutant tumors seemingly independent of co-mutations. There haven't been substantial reports on the safety, tolerability, or drug-like properties of the clinical candidates, so we can't comment much on differentiation. Both companies are working quickly to establish a recommended Phase 2 dose. As for our progress, we are advancing through a traditional Phase 1 dose escalation with single patient cohorts, and we're making good headway. We aim to establish a recommended Phase 2 dose later this year, with the hope of having necessary safety data, pharmacokinetics, pharmacodynamics, and possibly evidence of antitumor activity by that time or earlier. We're reiterating our goal for the recommended Phase 2 dose and look forward to offering more updates throughout the year. I hope that answers your questions.

Tyler Van Buren, Analyst

That does. Thanks very much. Really appreciate it.

Troy Wilson, President and CEO

Sure. Thanks for the question.

Operator, Operator

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

Konstantinos Aprilakis, Analyst

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?

Troy Wilson, President and CEO

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 protein 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 1 dose 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.

Konstantinos Aprilakis, Analyst

Okay. Thanks for the color there. And then on Tipifarnib, 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?

Troy Wilson, President and CEO

Yes, I appreciate that question. The total enrollment in the study will increase somewhat; we don't believe it will be significant. However, since we're including some patients with lower variant alleles, we do expect the total enrollment to rise. Importantly, the primary efficacy objective remains unchanged. It is still focused on the elimination of a 15% null hypothesis in the high DAF population. The amendment we are implementing will introduce secondary objectives aimed at evaluating the clinical benefit in the overall population and possibly examining some survival endpoints. However, this will not affect the primary efficacy endpoint in any way.

Konstantinos Aprilakis, Analyst

Perfect. Thanks for the color.

Troy Wilson, President and CEO

Thanks, Konstantinos.

Operator, Operator

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

Jonathan Chang, Analyst

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?

Troy Wilson, President and CEO

Thank you for the question, Jonathan. Our current priority is fully focused on achieving a recommended Phase 2 dose as safely and efficiently as possible. We aim to enter the expansion cohorts with clear guidance and data for clinicians. While we understand the significant interest from the community, including investors and academics, we are not yet in a position to commit to any specific data presentation venue. We recognize the interest and, once we reach our goal of the recommended Phase 2 dose, we will seek an appropriate scientific setting to present the data. However, it's still early in May to make any commitments regarding a venue.

Jonathan Chang, Analyst

Got it. Thanks. Second question this is a clarification question. I think I heard you mention 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?

Troy Wilson, President and CEO

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 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 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.

Jonathan Chang, Analyst

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

Troy Wilson, President and CEO

Yes. Let me let Marc address that question, Jonathan.

Marc Grasso, CFO

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 compared to previously but we're maintaining our guidance attached into 2022.

Jonathan Chang, Analyst

Got it. Thank you.

Troy Wilson, President and CEO

Thanks, Jonathan for the question.

Operator, Operator

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

Chris Shibutani, Analyst

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?

Troy Wilson, President and CEO

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.

Chris Shibutani, Analyst

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?

Troy Wilson, President and CEO

Sure. If it's not available yet, it will be shortly. You will find a revised corporate presentation with a couple of slides that discuss this opportunity. In particular, you will notice that when you examine the databases, HRAS overexpression is significantly present in head and neck, lung squamous, and urothelial cancers. The corporate presentation is now live on our website for those following along. HRAS expression is notably higher in head and neck, lung squamous, and urothelial cancers, while it is considerably lower in lung adenocarcinoma and colorectal cancer, and possibly also in pancreatic cancer. Interestingly, the tumor types where HRAS is overexpressed align with the areas where we have seen clinical activity of Tipifarnib as a standalone treatment. We established our cutoff by identifying the highest levels of HRAS expression in other tumor types, and we consider anything above that to be HRAS overexpression. We estimate that this applies to about 20% of all head and neck squamous cases. You can review the data and references, and I'm happy to discuss that further if it's helpful. Regarding the second part of your question, there isn't any data from the historical clinical studies because those studies did not examine HRAS overexpression. Therefore, no dataset exists to reference. What’s intriguing in our preclinical findings is that HRAS overexpression—distinct from mutation—seems to contribute to a resistance mechanism that provides resistance to various therapeutic agents. The second slide will illustrate examples such as platinum-based therapies, PI3 kinase inhibitors, a TORC inhibitor, and cetuximab. Although those drugs do not show efficacy as monotherapies in PDX models, when we inhibit HRAS overexpression or the activity of the HRAS oncoprotein using Tipifarnib, we can achieve significant synergistic effects. Additional literature supports the idea that HRAS is a common driver of resistance to other therapies. Hence, we believe the best approach to address this issue is likely through combination therapy. We are currently evaluating which agents to prioritize and the specifics of the study design. If successful, this could benefit up to 20% of the overall head and neck cancer population, which represents a considerable opportunity. We will provide more updates on this throughout the year, as we view it as the next logical step beyond our current efforts in the relapsed and refractory HRAS mutant setting.

Chris Shibutani, Analyst

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

Troy Wilson, President and CEO

Thank you, Chris.

Operator, Operator

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

Ren Benjamin, Analyst

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?

Troy Wilson, President and CEO

Yes, it's a great question. As part of SEQ-HN, our non-interventional screening and outcomes cohort, we are screening patients for the presence of the HRAS mutation. If they have more than 20% VAF, they proceed to the next step. If not, we can follow them and consider re-biopsy if possible. The front end of the trial remains unchanged, and we are already identifying patients with an HRAS mutation who do not meet the 20% threshold. We expect that this change will add about 25% to 30% more participants beyond those with high VAF. Regarding data timing, we have suspended our guidance due to a consistent decline in the number of patients presenting at clinics, which affects the eligibility for the study. This decline may be related to COVID and social precautions, as well as patients choosing not to visit clinics. We lack clarity on how this will develop, which is why we have suspended our guidance on full enrollment until we observe how the situation evolves with the pandemic. At this stage, we cannot provide a timeline for the specific data you are asking about. We are actively monitoring and working to address these issues.

Ren Benjamin, Analyst

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 CYP3A4 interaction you may have or not have?

Troy Wilson, President and CEO

Yes, we can’t provide specific comments on that yet, though I appreciate your question. It’s not uncommon for patients with AML to be on strong CYP3A4 inhibitors; many are taking antifungals and, to some extent, antimicrobials. This raises important questions. However, we will need to wait to discuss the specifics of what we’re observing until we can share our data. What we want to convey is that the study is progressing well, the molecule is performing satisfactorily, and we are focused on achieving a recommended Phase 2 dose. While CYP3A4 interaction is something we can manage as long as we understand it, we aren’t at a point where we can draw clear distinctions yet. I would prefer to present our data first so that it can be evaluated on its own merits.

Ren Benjamin, Analyst

Got it. And just one final one for me.

Troy Wilson, President and CEO

Sure.

Ren Benjamin, Analyst

You have ended the development of the ERK inhibitor and delayed the start of certain clinical studies. It seems like a good opportunity to increase business development activities and explore potential partnerships to advance this forward. What are your thoughts on partnerships? Is that something you're considering, or do you prefer to retain most of these assets for yourselves?

Troy Wilson, President and CEO

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?

Marc Grasso, CFO

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 sales force. 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.

Ren Benjamin, Analyst

Good. Thanks for taking the questions.

Troy Wilson, President and CEO

Thank you, Ren.

Operator, Operator

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

Joe Pantginis, Analyst

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?

Troy Wilson, President and CEO

Thank you for the directness of your question. At this stage, there are possible options for 947, and I would refer to it as a shelf drug. As part of our strategic review, we are asking ourselves how we can best utilize shareholder funds to generate maximum value in the shortest time. While there are several avenues to create value, our efforts in treating head and neck squamous cancer with Tipifarnib and AML with 539 have proven to be the most promising. Therefore, that is where our focus will be. Based on what we observed in Phase 1 development, 947 does not seem to hold the same potential for delivering value to patients or shareholders in the near term. However, if there is a chance for someone else to explore it differently, we would be open to that.

Joe Pantginis, Analyst

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?

Troy Wilson, President and CEO

Yes, that's a great question. We definitely recognize the value in targeting the CXCL12 pathway to enhance antitumor activity. In the lymphoma study, our priority is to conduct the best possible study for both patients and shareholders in terms of value and efficiency. There's more work to do, but one positive aspect of the pandemic is the increased accessibility to investigators and leading experts, which is quite beneficial. Regarding pancreatic cancer, we see potential there as well, but when we consider the return on investment over the next 12 to 24 months, we believe it is wiser to concentrate our efforts on menin while maintaining a strong financial position for the company, which we take very seriously. Marc mentioned that we believe our guidance for 2022 remains intact. We hope people understand that we view it as our duty to make difficult decisions and to keep the company positioned strongly regarding development, financing opportunities, and business development. We believe these initiatives will help us achieve that. We look forward to coming back with more information and refined ideas concerning the CXCL12 opportunities in the future.

Joe Pantginis, Analyst

Got it. Appreciate it, Troy.

Troy Wilson, President and CEO

Sure. Thank you, Joe.

Operator, Operator

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

Jay Olson, Analyst

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 VAF? And then I had a couple of follow-ups.

Troy Wilson, President and CEO

Yes, thank you for the question. What’s interesting is that with our increased focus on operational execution and the emphasis on commercial opportunities since Kirsten joined us at the start of the year, we have really taken seriously our responsibility to communicate with physicians. They have confirmed for us the significant unmet need in second-line head and neck cancer. Several of them described it as a need similar to that seen in pancreatic cancer. In this context, we see a real opportunity to provide Tipifarnib and potentially clinical benefits to any HRAS mutant patient. This has been an ongoing consideration for us. Our primary mission as a company is to deliver clinical benefits and maximize those benefits for patients. Over the past three months, especially since the start of the year, we have been refining our approach and conducting a strategic review. We are quite excited about the expanded opportunity not just for HRAS mutants but also for HRAS overexpressed patients, where we believe Tipifarnib is uniquely positioned to address their needs. It effectively down-regulates HER2, allowing HRAS to detach from the membrane, and there is no other molecule that accomplishes this so effectively. We intend to build on our already strong clinical profile and the compelling data we have moving forward.

Jay Olson, Analyst

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?

Troy Wilson, President and CEO

Yes, that's a great question, Jay. You're definitely thinking ahead. It's a possibility, but there are challenges to consider. The standards of care for head and neck cancer and urothelial carcinoma are quite different. If we were to pursue a tumor-agnostic label for HRAS overexpression, we would need to take that into account. Looking at the bigger picture, there’s a significant opportunity to treat 20% of head and neck cancer patients, which is the sixth most common cancer globally. We have new slides in our corporate presentation that highlight this opportunity. If we can provide meaningful clinical benefits in that population, it addresses a major unmet need. I want to ensure we conduct the right studies methodically and move forward from a position of strength. Ultimately, if our approach proves effective, we could explore other tumor types as well, but I want to be cautious about taking on too much at once, especially since these upcoming studies will likely need to be conducted in combination.

Jay Olson, Analyst

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?

Troy Wilson, President and CEO

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.

Jay Olson, Analyst

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

Troy Wilson, President and CEO

Our pleasure, Jay. Thank you.

Operator, Operator

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

Peter Lawson, Analyst

Hi, Troy. Thanks for taking the questions. The over-expression of HRAS in tumors, does that correlate with any other markers PI 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?

Troy Wilson, President and CEO

Yes, that's a great question, Peter, and it merits a more in-depth discussion. In short, if you examine the population we're focusing on, we know that the current treatment standards yield response rates in the teens and progression-free survival measured in a few months. Therefore, we anticipate that there is significant unmet need. With combination therapies, we hope to achieve substantially better results. Currently, we don’t have sufficient human clinical data to address your question about the correlation with other biomarkers, but we are actively exploring this area. We have additional work planned for tissue profiling and similar initiatives, which are already underway. We aim to conduct the right studies with a strong rationale. There may be opportunities for more than one combination, and there are several reasons that support this direction. However, it remains a work in progress. We want everyone to realize that this will be a fundamental aspect of value creation for Kura in the future, and we see an opportunity to expand beyond the HRAS mutant relapsed/refractory context to a broader HRAS over-expressed setting, and we look forward to progressing in that area later this year.

Peter Lawson, Analyst

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.

Troy Wilson, President and CEO

Yes. We were excited that Syndax shared that data because it has generated significant interest and enthusiasm in this molecular target. Our approach to the Phase 1/2A trial remains unchanged. We are progressing as quickly as possible to determine a recommended Phase 2 dose. As mentioned in the prepared remarks, we are already considering how to expand into the pediatric population, explore combinations with targeted therapies and potentially chemotherapy, as well as moving to the front line. These are all aspirational goals, but the preclinical data we've published, along with Syndax's clinical data and our insights, lead us to believe that this is a key focus for value creation in the company over the next 12 to 24 months.

Peter Lawson, Analyst

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

Troy Wilson, President and CEO

My pleasure.

Operator, Operator

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

Troy Wilson, President and CEO

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.

Operator, Operator

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