Good afternoon, ladies and gentlemen, and welcome to the Q2 2023 Kura Oncology, Inc. Earnings Conference Call. At this time, all lines are in listen-only mode. And following the presentation, we will conduct a question-and-answer session. This call is being recorded on Thursday, August 3, 2023. I would now like to turn the conference call over to Mr. Pete De Spain, the Head of Investor Relations. Please go ahead.

Thank you, Kelsey. Good afternoon, and welcome to Kura Oncology's second quarter 2023 conference call. Joining me on the call are Dr. Troy Wilson, our President and Chief Executive Officer; and Tom Doyle, our Senior Vice President of Finance and Accounting. Before I turn the call over to Dr. Wilson, I'd 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 Troy.

Thank you, Pete, and thank you all for joining us this afternoon. Let's jump right in. In June, we reported updated data from the KOMET-001 trial of our menin inhibitor ziftomenib, including durable activity in patients with heavily pretreated and co-mutated relapsed/refractory NPM1-mutant acute myeloid leukemia. These data were featured during a late-breaking oral session at the European Hematology Association Annual Congress in Frankfurt. As of the April 12 data cutoff, seven of the 20 patients with NPM1-mutant AML who were treated at the recommended Phase 2 dose of 600 milligrams achieved complete remission with full count recovery for a CR rate of 35% and an overall response rate of 45%. This represents one of the highest response rates reported for a targeted therapy in the setting of relapsed/refractory leukemia. An eighth patient who had a CR with partial count recovery after treatment with ziftomenib subsequently evolved to a CR with full count recovery after transplant and remained on study as of the date of the EHA presentation. In addition, a patient with NPM1-mutant AML treated at 200 milligrams remained on ziftomenib for 36 cycles as of the cutoff date. The median duration of response for all NPM1-mutant patients was 8.2 months, with a median follow-up of 8.8 months. Continuous once-daily dosing of ziftomenib was well tolerated in the Phase 1 study and the reported adverse event profile remained consistent with features of underlying disease. As a reminder, NPM1-mutant AML accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists. Once the disease becomes relapsed or refractory, the prognosis for NPM1-mutant AML patients is especially poor. NPM1-mutant AML is further compounded with co-mutations such as IDH and FLT3. Notably, in our Phase 1 study, 33% of patients with FLT3 co-mutations, 15% of patients with IDH co-mutations, and 50% of patients with both FLT3 and IDH co-mutations achieved a CR on ziftomenib— all of whom had failed prior treatment with IDH and/or FLT3 inhibitors. We remain impressed with the ability of ziftomenib to drive durable remissions as a monotherapy in this difficult-to-treat population, and we believe these data further demonstrate its potential best-in-class product profile. Building on momentum generated by our EHA data, enrollment in our Phase 2 registration-directed trial of ziftomenib in patients with relapsed refractory NPM1-mutant AML continues to outperform projections, which speaks to both the size of the population and its significant unmet need. Our study is expected to enroll a total of 85 patients in the United States and Europe. In parallel with our efforts to advance ziftomenib as monotherapy, we're conducting a series of studies in combination with current standards of care in earlier lines of therapy and across multiple patient populations, including NPM1-mutant AML and KMT2A-rearranged AML. Our approach to combinations is to establish ziftomenib as a foundational therapy that can be combined safely with various commonly used regimens. And then prioritize those combinations that represent the greatest unmet medical need and the greatest potential commercial value, namely venetoclax and FLT3 inhibitor containing regimens. Combination approaches also offer the potential to mitigate differentiation syndrome, particularly in the KMT2A rearranged population as has been previously demonstrated in the development of IDH inhibitors in combination with azacitidine. In that regard, I'm pleased to report we're now dosing patients in the first of our combination studies, which we call COMET-007 in both the newly diagnosed and relapsed/refractory settings. COMET-007 is a Phase 1 study designed to assess safety, tolerability and preliminary activity of ziftomenib in combination with either venetoclax and azacitidine or standard induction cytarabine, daunorubicin chemotherapy, commonly known as 7+3. The study is expected to enroll patients with NPM1-mutant or KMT2A-rearranged AML across sites in the U.S. and Europe. We anticipate having preliminary data from the COMET-007 study in the fourth quarter of 2023 or the first quarter of 2024. We're also working to initiate our COMET-008 study of ziftomenib in combination with additional standards of care, including the FLT3 inhibitor, gilteritinib later this year. In addition, we expect to begin our post-transplant maintenance program for ziftomenib in the first quarter of 2024. We are very excited about the potential for these studies to further demonstrate the value of our menin program and establish ziftomenib as a backbone of therapy across the continuum of care for AML patients. Now let's turn our attention to our farnesyl transferase inhibitor programs, beginning with tipifarnib. We continue to work to unlock the substantial therapeutic and commercial value of farnesyl transferase inhibition, and we believe this novel mechanism is uniquely positioned to deliver clinical benefit in multiple large solid tumor indications. The first such opportunity is in head and neck squamous cell carcinoma through the combination of tipifarnib and the PI3 kinase alpha selective inhibitor, alpelisib. Head and neck cancer is the seventh most common cancer worldwide, and it remains a significant unmet medical need with no approved small molecule targeted therapies. The objective response rate for the three FDA-approved therapies for the treatment of HNSCC in the second line ranges from 13% to 16%, with a median progression-free survival of two to three months and a median overall survival of just five to eight months. Recall, we previously reported the first demonstration of a durable clinical response with the combination of tipifarnib and alpelisib in a patient with PIK3CA mutated squamous cell carcinoma of the tonsil. Since that time, our dose escalation study has continued with no dose-limiting toxicities observed for the combination. We are encouraged both by the safety profile as well as the clinical activity we're seeing in the trial, which we call current HN, with continued evidence of activity at multiple doses and enhanced activity relative to our expectations for either drug alone in this population. We are now evaluating patients in the study's highest planned dose cohort to help inform selection of the optimal biologically active dose for the combination. Once we determine the OBAD, we intend to initiate a small dose expansion of patients with PIK3CA mutant HNSCC to validate the safety profile and activity of the combination at the recommended Phase 2 dose. Meanwhile, we've generated a growing body of preclinical data that supports the combination of farnesyl transferase inhibitors with multiple classes of targeted therapies to either prevent or delay the emergence of drug resistance in large solid tumor indications. In April, we presented encouraging preclinical data at the American Association for Cancer Research Annual Meeting supporting the potential use of FTIs in combination with two additional distinct classes of targeted therapies. The first of two posters revealed robust synergy between tipifarnib and the standard of care anti-angiogenic tyrosine kinase inhibitor, or TKI, axitinib in cell and patient-derived xenograft models of clear cell renal cell carcinoma. The second poster reported regression of multiple models of KRAS inhibitor resistant non-small cell lung cancer by the addition of tipifarnib to either adagrasib or sotorasib therapy. These promising preclinical data illustrate the potential for FTIs to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance to targeted therapies. In addition, we believe these data strongly support our rationale to combine our next-generation farnesyl transferase inhibitor, which we call KO2806 with TKIs in clear cell renal cell carcinoma and with KRAS G12C specific mutant specific inhibitors in non-small cell lung cancer. Earlier this year, we received FDA clearance of the investigational new drug application for KO-2806 for treatment of advanced solid tumors. We intend to evaluate the safety, tolerability and preliminary anti-tumor activity of KO-2806 in a Phase 1 dose escalation study, which we're calling FIT-001. We've begun site activation in FIT-001 and look forward to dosing the first patients in the study later this year. Concurrent with the dose escalation as a monotherapy, we plan to evaluate KO-2806 in dose escalation combination cohorts in advanced solid tumors beginning with clear cell renal cell carcinoma. With that, I'll now turn the call over to Tom for a discussion of our financial results.

Thank you, Troy, and good afternoon, everyone. I'm happy to provide a brief overview of our financial results for the second quarter of 2023. Research and development expenses for the second quarter of 2023 were $28.2 million compared to $24.3 million for the second quarter of 2022. The increase in R&D expenses was primarily due to the increases in clinical trial costs related to our ziftomenib and KO-2806 programs. General and administrative expenses for the second quarter of 2023 were $11.8 million compared to $11.1 million for the second quarter of 2022. Net loss for the second quarter of 2023 was $37.2 million compared to a net loss of $34.8 million for the second quarter of 2022. This includes non-cash share-based compensation expense of $7 million compared to $6.5 million for the same period in 2022. As of June 30th, we had cash, cash equivalents and short-term investments of $477 million compared to $438 million as of December 31, 2022. This includes net proceeds of approximately $94 million from our public offering completed in June of 2023. We believe that our cash, cash equivalents and short-term investments will be sufficient to fund our current operating plan to mid-2026. With that, I'll now turn the call back over to Troy.

Thank you, Tom. Before we jump into the question-and-answer session, let me lay out our anticipated milestones for the remainder of this year and next year. For ziftomenib, we hope to dose the first patients in the COMET-008 combination trial in the second half of 2023, preliminary data from the COMET-007 combination trial in the fourth quarter of 2023 or the first quarter of 2024 and dose the first patients in the post-transplant maintenance program in the first quarter of 2024. For tipifarnib, we aim to initiate dose expansion in the current HN trial in mid-2024. And for KO-2806, we expect to dose the first patients in the FIT-001 dose escalation trial as a monotherapy in the second half of 2023 and dose the first patients in the FIT-001 dose escalation trial in combination with the targeted therapy in clear cell renal cell carcinoma in the second half of 2024. With that, Kelsey, we're now ready for questions.

Thank you. Ladies and gentlemen, we'll now begin the question-and-answer session. And your first question comes from Jonathan Chang from Leerink Partners. Please go ahead.

Hi guys. Thanks for taking my questions. First question, can you give us any more color around enrollment progress and the registration-directed study of ziftomenib and NPM1 mutant AML? And what do you mean by outperforming projections?

Thank you for the question, Jonathan. We expect to fully enroll the 85 patients in the study around the middle of next year. To provide some context, we chose a trial size of 85 patients because we believe that a potentially best-in-class therapy would need approximately 100 patients' safety data at the recommended Phase 2 dose. It’s still early, but we are ahead of our expectations for site activation and patient enrollment in the study. While we have projected enrollment curves under various scenarios, we have not yet adjusted our timing guidance for overall enrollment. We prefer to see how the rest of the summer and into fall progresses, as there could be a slowdown in late summer. Nonetheless, we want to emphasize that there is strong interest from both physicians and patients, which is reflected in our enrollment numbers. Additionally, there seems to be a greater number of patients than we anticipated, despite what some competitors have experienced in the NPM1 space. Anecdotal comments suggested enrollment might be difficult; however, our experience has been quite the opposite. After the EHA, we are observing significant interest that translates into enrollment. This interest appears to be driven, in part, by our data showcasing activity in patients who have failed FLT3 and IDH therapies with various co-mutations. We are not seeing patients drawn toward those other trials; instead, there is strong enthusiasm for the ziftomenib monotherapy study, and we expect that to carry over into the combination studies as well, for which it's still early, but we feel quite encouraged.

Got it. Thank you. And second question, can you discuss the post-transplant maintenance opportunity for ziftomenib?

Sure. Let me clarify that we are planning to conduct both post-transplant maintenance and maintenance without requiring a transplant. These are different approaches. For those not needing a transplant, our protocols allow patients to continue in the study. For instance, patients enrolled in the 7+3 plus zifto regimen can remain on zifto in a maintenance setting. We have incorporated this flexibility wherever possible, which is crucial and has the potential to create value. Our team is strategically thinking about the post-transplant scenario, aiming to include patients regardless of how they reached transplant, whether they have previously used a menin inhibitor or not, as long as they meet the entry criteria and are post-transplant, they will qualify for the study. Given our favorable safety profile—no QT prolongation and no signs of drug-induced myelosuppression—we believe we have a chance to become the preferred agent in maintenance. Feedback from knowledgeable parties indicates that this is a compelling commercial opportunity, as retaining patients for a year or two could significantly benefit both the patients and the overall value of our enterprise. Lastly, I want to highlight that all the studies we've initiated are specific and sponsored by Kura to maintain control over timing. We are also focusing on valuable outcomes. For the maintenance study, we will start with a Phase 1 investigator-sponsored study to gather sufficient data before transitioning it to a Kura-sponsored study if it moves to Phase 2/3. We are doing our best to retain control of the studies to manage timelines and execution effectively, and so far, this strategy is working well.

Understood. Thanks for taking the questions.

Our pleasure. Thank you.

Thank you. And your next question comes from Roger Song from Jefferies. Please go ahead.

Congratulations on all the progress and thank you for taking my question. I understand you have already begun the first combination trial, which is very encouraging. Troy, could you provide some insight into the enrollment progress so far? Additionally, how should we anticipate the initial data to look later this year or early next year in terms of numbers and the activity you are tracking? Lastly, when do you expect to determine the recommended Phase 2 dose? Thank you, and I apologize for the multiple questions.

I'll address each of your questions, Roger. First, regarding the design of the trials, these are dose escalation trials where each genotype is treated separately according to the standard of care. For instance, we have a KMT2A cohort and an NPM1 cohort, typically with six patient escalation cohorts starting at a dose of 200 milligrams. In terms of the venetoclax regimen, during Phase 1, we observed no dose dependence between 200 and 600 milligrams related to differentiation syndrome. This is crucial as we consider data and the recommended Phase 2 dose (RP2D). Our primary focus in any study is on safety and tolerability, particularly concerning differentiation syndrome. We believe we can safely combine this treatment with current standards and that these standards may help reduce differentiation syndrome, especially in the KMT2A population. Your question about activity is valid. The backbone therapy in use has a significant level of clinical activity, which complicates any discussions at this point about outcomes. However, once we identify the optimum biologically active dose, we can move to an expansion cohort to better assess clinical activity compared to the backbone alone. By the end of this year or early next, we anticipate seeing some clinical activity, but we want to ensure we prioritize safety, tolerability, and progress in dose escalation first. Currently, we expect to have around 40 U.S. sites involved in Phase 1a, with a few already open and starting patient enrollment. We anticipate that number will grow in the coming weeks and months, and there has been strong interest so far. Our philosophy with this trial, and the accompanying 008 trial, is focused on ensuring no patient is overlooked. If a patient needs a venetoclax containing regimen, they can be treated with ven plus zifto. If they are better suited for 7+3, they can receive that instead. There's significant interest in combining with gilteritinib for the 008 study, especially after seeing the recent data linking quizartinib to FDA approval, where half of the patients treated had NPM1 co-mutations. We are committed to advancing the 008 trial as quickly as possible. I hope this clarifies your questions, Roger, and let me know if you need any further details.

No, that's great. That's great. Okay. So that's very clear now. Maybe just shift gears to the tipi. So understanding you're figuring out the RP2D for them. In the past, you seem to kind of guide towards the data release around the mid-year for the RP2D. And now you're kind of guiding towards the expansion cohort second half next year. So maybe just let us know what's the current thinking around the tipi? Thank you.

Yes, that's a great question. In short, the combination is better tolerated and more active than we anticipated. Prior to dosing any patient, when asked about the greatest risk, I highlighted the challenges associated with combining tipifarnib and alpelisib, as our industry has struggled with the combination of MAP kinase pathway inhibitors and PI3-kinase pathway inhibitors. However, we have been pleasantly surprised by the safety and tolerability of this combination. We have observed hyperglycemia but it hasn't been dose limiting or hindered our ability to escalate either tipifarnib or alpelisib. To clarify, the final escalation cohort includes a full dose of tipifarnib at 600 milligrams twice daily and a full dose of alpelisib at 300 milligrams daily. I was pleasantly surprised by the results. Additionally, we are observing evidence of clinical activity, particularly in the second-line head and neck population where response rates typically range from 13% to 16% and progression-free survival and overall survival averages only two to three months. We are seeing responses, and while I won't go into specifics, we're noting good safety and tolerability at different dose levels. We need to identify the optimum biologically active dose, which is the lowest dose that maintains full activity with acceptable safety. The key questions driving our guidance for next year are determining that dose and evaluating the level of activity at that dose to shape the Phase 2/3 trial. To recap, HRAS mutations occur in 4% to 6% of the population, while PIK3CA mutations are observed in 15% to 20%. This is reflected in our enrollment data, and we might have the opportunity to treat up to one-fourth of head and neck cancer cases. However, we want to ensure accuracy in our approach. We've already demonstrated this with a patient who had a significant tumor reduction after one cycle of treatment. The next crucial step is determining the proper dose and evaluating safety, tolerability, and activity to position for a registrational trial in a space lacking approved small molecule targeted therapies. Our team is working diligently on this, and we anticipate reasonable guidance for the expansion cohort around mid-next year.

Excellent. Thanks, Troy, for all the comments. That's it for now. Thank you.

Your next question comes from Peter Lawson from Barclays. Please go ahead.

Thanks so much for taking the questions. Just kind of firstly, a follow-up around the maintenance setting, whether resistance mutations could preclude zifto from being used in that maintenance setting? And then other question just around moving zifto beyond AML and ALL into other hem indications, solid tumors or other diseases? Thank you.

Thank you for the question, Peter. We don't believe that resistance mutations pose a significant threat to the use of zifto in the maintenance setting. Among the approximately 29 patients we've tested, only one developed a resistance mutation while on zifto. Some may wonder if our assay wasn't sensitive enough, but we see no evidence that resistance mutations are leading to progression or resistance to zifto. While patients do develop resistance and experience progression, it does not seem to be linked to these mutations. Currently, we've observed a resistance mutation rate of about 3% to 4% in our sampled data. Importantly, ziftomenib remains fully effective against two of the three mutants and retains substantial activity against the third, the 327 mutant, which differentiates it from several other inhibitors in the class. As we noted during our discussions at EHA, we have seen clinical activity in patients who have participated in our study after failing another menin inhibitor. Overall, we believe that zifto is very well positioned for the maintenance setting. Furthermore, it's user-friendly and has not shown any toxicities that would necessitate extra monitoring or vigilance in this context. We are excited about the potential of zifto in maintenance treatment. Regarding the second part of your question about additional indications, I appreciate your inquiry.

The second half of the question was expanding outside hem indications or other hem indications into solid tumors and other diseases, just your thoughts there and where you are?

I believe it's essential to be data-driven when considering opportunities beyond acute leukemia for menin inhibitors. We need to be aware of the potential effects of the Inflation Reduction Act. In summary, our best analysis, based on discussions with experts including CMS, indicates that we can operate within AML while remaining exempt from the Inflation Reduction Act due to our orphan designation for AML. However, if we expand to other indications, such as ALL or others, we risk inclusion under the IRA. To mitigate this risk, we have developed a next-generation menin inhibitor program that improves upon zifto. The team has identified a promising compound that we would likely pursue for additional indications, including possibly solid or liquid tumors and even diabetes. We see several opportunities for additional menin inhibitors, but given the current legal, regulatory, and pricing environment, it's crucial to proceed carefully. We believe we can create significant value solely within the AML space, focusing on frontline relapsed/refractory maintenance, and we are committed to enhancing the standard of care and transforming the market with zifto in that context. While we may explore additional opportunities, we would likely leverage a second-generation compound to maximize the full commercial potential of our franchise.

Great. Thank you so much. Really appreciate it.

Pleasure.

Thank you. And your next question comes from Li Watsek from Cantor. Please go ahead.

Hey, congrats on the quarter. And thank you for taking our questions. I guess first one is on the Phase 2 pivotal study of zifto. Troy, can you maybe just clarify if you have seen greater traction in terms of patient enrollment after your EHA update in June, I mean, especially for some of the EU sites that you have? And also for the potential combo data later this year or early next year, can you give us a sense of the variables here? Is it just a matter of enrollment speed? Or do you want to reach a certain number of patients or a certain period of follow-up before you disclose the data?

Yes, Li, thanks for your question. Regarding the first part, in any trial, feasibility studies are conducted, and there's an enrollment curve influenced by site feedback on how many patients they see and can enroll. Our clinical operations team has performed exceptionally well with the 001 study, surpassing our projections. There are several reasons for this success, including physician enthusiasm, strong data, and a greater number of patients available than we anticipated, with minimal loss to other studies. It's challenging to pinpoint a single factor, but we believe there's no significant delay in time to market, especially based on the data we have, particularly in the NPM1 setting. If our combination trials perform well with good safety and tolerability, we expect this momentum to continue. It's widely accepted that AML treatment is about combination therapy, and whoever finds the best combinations with optimal safety and activity will be the market leader. We believe zifto is well-positioned in this context, and we anticipate that the excitement will carry through to the combination studies. As for the second part of your question regarding data release, we recognize that analysts and investors are eager to know if we can manage differentiation syndrome through the co-administration of standard care regimens, potentially enhancing the effectiveness of ziftomenib, particularly in the KMT2A rearranged population. While everyone we've spoken to suggests this is likely the way forward, it requires thorough work. That's why our initial focus is on safety, tolerability, and mitigating differentiation syndrome. This syndrome typically occurs between the first and third cycles, and once leukemia is eliminated, the risk decreases. If leukemia isn't eliminated, the patient will likely progress and exit the study anyway, so we'll know fairly quickly if we've managed differentiation syndrome. We haven't decided to gradually release data on a patient-by-patient basis. Instead, we want to have a sufficient number of patients enrolled so we can present comprehensive data and draw meaningful conclusions. These are six patient dose escalation cohorts, which means that we can gather meaningful numbers quickly, even in the early stages of dose escalation. We still lack clarity on how various genotypes and combinations will enroll, but we are encouraged that, like with the 001 study, physicians are successfully screening and enrolling patients. As we approach our next earnings call in November and look towards the ASH meeting at the end of the year, we expect to be able to provide a substantial update on why we believe zifto has a best-in-class profile. I hope that provides some clarity.

Thank you. I have a second question. Regarding the patients you're enrolling in the pivotal study with co-mutations, do you have any information on the breakdown for FLT3 versus IDH co-mutations?

No. At least I don't think so. You're talking Li about the breakdown of co-mutations in patients enrolled on the study. Is that what you're asking?

Yes, yes.

We are in the early stages and observing very high levels of co-mutation. That's why I mentioned that if you look at the quizartinib label, 50% of the FLT3 cases are NPM1 co-mutant. This means you need to combine it with the FLT3 inhibitor or you'll miss out on 15% of the population. We're seeing this with FLT3, IDH, and DNMT3A, which are all key players. It's very similar to what we observed in the Ib. I don't think we have specific breakdowns yet regarding the co-mutational content in the population.

Okay. Thank you.

Sure.

Thank you. And your next question comes from Bradley Canino from Stifel. Please go ahead.

Hi, this is Bijan on for Brad Canino. Congrats on the progress. So first question is on tipifarnib. I'm glad to see responses in some limited safety issues. How should we be thinking about the contribution of parts for tipi and PIK3 in the next data? And then will we be getting data in both the HRAS overexpressed population and PIK3CA?

Earlier this year, we decided not to continue enrolling in the HRAS overexpressing cohort and instead focus our efforts on the PIK3CA mutant. This decision stems from the fact that, like any company, we have limited resources and more investment opportunities than available funds. From our experience, the best chance to identify the OBAD is in patients with driver mutations in the target oncogene, whether it's HRAS mutant in the context of our RUN and AIM studies or PIK3CA mutants in our current research. Targeting driver mutations typically leads to higher activity levels. However, once we establish the OBAD, we may revisit investigating HRAS overexpressed or PIK3CA amplified cases, but we want to approach this in stages, managing our capital wisely and being strategic in our drug development efforts. Regarding your question about the contributions of each treatment: tipifarnib is unlikely to drive responses in a PIK3CA mutant population when used alone. Alpelisib has shown limited response rates, with only a few instances of durability. Our preclinical research has provided strong mechanistic rationale for why the combination of these drugs is effective, highlighting how this approach could enhance activity against PIK3CA. We are seeing clinical activity that is better than either drug alone, and we are in the process of gathering more data. Additionally, as we consider our future developments, particularly with 2806, we are excited because we can safely combine tipifarnib and alpelisib, achieving at least additive, if not synergistic, results. This is promising as we prepare 2806 for clinical advancement. In the second-line renal cell carcinoma setting, the response rates with current TKIs are low, and while KRAS inhibitors exhibit impressive activity, resistance often develops quickly. The field is looking for effective combination partners, and we believe that FTI holds significant potential in these contexts. The outcomes from the tipifarnib and alpelisib data could pave the way for opportunities in head and neck cancers as well, but we will need to start patient dosing in the upcoming study to validate these expectations.

Yes, great. Thanks for the comments there.

Sure. Appreciate the question.

Thank you. And our last question comes from Justin Zelin from BTIG.

This is Julian on for Justin. Thanks for taking our question. I was just looking to get your take on your view on menin for diabetes based on recent competitor data at ADA? And I had a follow-up question.

We're closely monitoring the data about menin inhibition and its connection to beta cell regeneration. There are still many questions we have regarding this relationship. We plan to keep an eye on the data set and are currently evaluating ziftomenib along with other menin inhibitors in appropriate diabetes models, both alone and in combination. I remain hopeful that by later this year we will have data that allows us to assess potential opportunities. If an opportunity for menin inhibitors in diabetes arises, we will ensure to maximize that value for our shareholders through partnerships or licensing. While we probably won't become a diabetes-focused company, we will find ways to leverage that value. Importantly, we believe it’s best to pursue this with another menin inhibitor, partly to maintain separate safety databases for our diabetes and oncology compounds. Furthermore, due to the Inflation Reduction Act implications, we need to be strategic. We’re developing a next-generation menin inhibitor that may be promising if the data supports it. We’ll rely on insights from our translational research and clinical teams to determine how we can create value with menin inhibitors in diabetes. If the potential is there, I am confident we can develop a best-in-class compound. Our focus will be on conducting disciplined experiments, generating robust data, and assessing the results.

Makes sense. And just as a follow-up, I was hoping you can maybe just clarify the number of patients being treated for the head and neck expansion cohort for tipifarnib. And secondly, what other indications outside of head and neck and RCC numbers are promising for FTIs in your view?

Yes, that's a great question. For the head and neck expansion cohort, we are considering having around six to twelve patients. This is similar to what we did with ziftomenib in the Phase 1b study, where we aimed to collect enough clinical data to guide future development. Regarding other indications, we have solid and evolving clinical data for both tipifarnib as a standalone treatment and in combination with alpelisib. Although we had to stop enrollment in our AIM study due to operational challenges, the compound is indeed effective. Nonetheless, with limited resources, tough decisions must be made. We aim to include both the HRAS mutant and PIK3CA-mutant populations, which represent about one-fourth of head and neck cases, using tipifarnib and alpelisib. We also need to consider introducing a second and possibly a third FTI, focusing on renal cell carcinoma and finding ways to address the KRAS challenge. At this stage, our goal is to generate data while ensuring we have various options available. There have been queries about tipifarnib, especially since the composition of matter patent has expired, but our intellectual property team has successfully built a strong patent portfolio around FTIs and head and neck cancer that we can utilize. If we can successfully bring tipifarnib and alpelisib to market for patients, it would be a significant achievement, especially since there are currently no targeted small molecule therapies approved for this indication. If another FTI can be developed to outperform these, that would be excellent, but let’s focus on advancing tipifarnib and alpelisib first. You will see us allocate more resources to 2806, but for now, we are not making any definitive decisions. We want to continue generating data in both renal cell carcinoma and KRAS, while also exploring more FTIs in the chemical space. These are three important solid tumor indications, and I believe the data is aligning well for us. It’s quite interesting that the most promising use for FTIs is returning to KRAS, where it initially began, but now as a combination therapy. That would feel like coming full circle, and I hope that’s the direction we ultimately take.

Makes sense. Thank you so much.

Sure.

Thank you. And our last question comes from Reni Benjamin from JMP Securities. Please go ahead.

Hey guys, thanks for taking the questions. Troy, can you talk to us a little bit about maybe the strategic rationale for starting off with RCC and what's the unmet need there versus starting off with KRAS and KRAS mutant in NSCLC? And then a question for all your combination programs. Are you in any sort of discussions with the companies that are marketing the approved drugs that you're combining either zifto or tipi with — in order to set up an MTA or try to get some free drug? I mean how important is that for cost mitigation and maybe enrolling patients quickly and getting the clinical trials off the ground?

Sure, that's a great question, Reni. Let me break it down. Starting with RCC, we are fundamentally improving as an organization compared to a few years ago and have a strong cross-functional effort from preclinical research to life cycle management. We have conducted research on renal cell carcinoma, consulted key opinion leaders, and analyzed the market landscape. We plan to share more about our specific partner in RCC later this year. This area is relatively mature, and while it's still evolving, the feedback from doctors indicates that enabling the use of TKIs in second-line treatment would be significant. The preclinical data from Francis' group shows strong synergy between tipifarnib and TKIs, especially axitinib. The doctors are enthusiastic about this development, and I believe we should move quickly. Switching to KRAS, this is an emerging field that is gaining a lot of attention and is rapidly evolving. We recognize that resistance will be a challenge for everyone. One of our targets is rapamycin, which seems crucial in driving resistance to TRS inhibitors, regardless of their specificity or type. If you target KRAS, it engages the tumor, which then looks for ways to create resistance. Therefore, we are proceeding thoughtfully to ensure we make the right decisions. Regarding your last question about building clinical collaborations or supply agreements, the answer is yes. Ideally, we want either reimbursement for the drug or to work with sponsors to establish drug-sharing agreements or clinical collaborations. We have done this successfully with Novartis for the tipifarnib and alpelisib trial, and we plan to adopt a similar approach when exploring opportunities for 2806.

Perfect. Thanks for taking the questions.

Sure.

Thank you. There are no further questions at this time. Mr. Troy Wilson, you may proceed with closing remarks.

Thank you. And thank you all for joining our call today. We'll be participating in the Cantor Healthcare Conference next month and hope to see a number of you there. In the meantime, if you have any additional questions, please contact Pete, Tom, or me. Thank you again for attending our call, and have a good evening, everyone.

Ladies and gentlemen, this concludes your conference call for today. We thank you very much for participating and ask that you please disconnect your lines. Have a great day.