Kura Oncology, Inc. (KURA) Earnings Call Transcript & Summary

Hello. This webcast presentation is for Bank of America clients only. If you are a member or representative of the press or media, please disconnect now. And now I would like to turn the call over to the moderator. Thank you.

Thank you, and good day, everybody. And hi, my name's Jason Gerberry, and I cover SMID cap biotech at Bank of America. I am pleased to be introducing our next company presenter, Kura Oncology; and Troy Wilson, President and CEO. For those of you unfamiliar, Kura is a clinical stage oncology company focused on precision medicines, and Troy is going to walk you through the corporate presentation and talk about some of the interesting clinical programs in development. So Troy, I'll turn it over to you.

Great. Thank you, Jason. I appreciate the introduction and appreciate the invitation from Bank of America Securities today. Good afternoon, everyone. My name is Troy Wilson. I am President and Chief Executive Officer at Kura. And I'm going to -- it's my pleasure to have the opportunity to tell you a little bit more about the company and the exciting programs that we have underway. I'm going to be referencing slide numbers of our corporate presentation that is available on our website. And I'll start by turning to Slide #2, which is our forward-looking statements. I will be making forward-looking statements during the presentation today, and I would refer you either to our website or to the SEC's website for more information about Kura Oncology and some of the risks and uncertainties associated with investment in the company. If we turn to the next slide, Slide 3, titled Investment Highlights. As Jason mentioned in his introduction, we are a development clinical stage oncology company. We are utilizing a precision medicine approach with our programs. There are a number of advantages and this is an area that has been marked by some pretty notable successes of late. We have 2 programs in our pipeline. The first is tipifarnib, which is our farnesyl transferase inhibitor. That - tipifarnib is in a first registration-directed trial in HRAS-mutant head and neck squamous cell carcinomas. There is an opportunity to expand from that setting, which is the relapsed/refractory setting in HRAS mutant to potentially up to 20% of all head and neck squamous cell carcinomas by targeting HRAS dependency, and I'll have more to say about that in a few slides. Beyond the opportunity in HRAS mutant solid tumors, we have shown that tipifarnib can drive clinical benefit in T cell lymphomas, in leukemia, potentially in other solid tumors. There are multiple -- we've achieved multiple clinical proofs of concept that would support life cycle expansion opportunities, and I'll allude to that briefly in the slides to come. The other major pillar of our proprietary pipeline and our development activities is a compound called KO-539. This is our inhibitor of the menin-MLL interaction, also known as the KMT2A protein-protein interaction. And this molecule is under development for the treatment of acute leukemias. It has a strong preclinical data and the potential to target up to 35% of adult patients with acute myeloid leukemia. We currently have a Phase I/II dose escalation trial underway that we call KOMET-001, and I'll have a chance to walk you through the preclinical data and the clinical trial design a little bit later in the presentation. We were just successful at raising additional capital late last week and have now put the company in a very strong cash position. We had $351.9 million in cash and cash equivalents pro forma as of the end of the first quarter of this year, and I'll have a bit more to say about that at the end and what that will do. Turning to Slide #4. I'm fortunate to have a very strong leadership team and a terrific Board of Directors, and you can see their names here. I won't go through them just given the time. But the people that we've recruited, both to the leadership team and the Board have experience with oncology research, drug development and commercialization across a number of different modalities and I'm hopeful that a number of these names are familiar to you. Very, very good team, working well together. Turning to Slide #5. This is the -- just a conceptual overview of the 2 pillars of value creation that we have currently at Kura Oncology. So on the left-hand side. This is a summary of tipifarnib. As I indicated, we're going to focus almost exclusively today on the opportunity in HRAS mutant solid tumors. We have received fast track designation for the treatment of head and neck squamous cell carcinoma from the FDA. We are pursuing the initial opportunity to address patients with very high unmet need in the relapsed and/or refractory HRAS mutant head and neck squamous population. But we see opportunities to expand beyond this initial registrational study to target both further opportunities within head and neck cancer, HRAS -- other HRAS mutant solid tumors as well as potentially CXCL12-driven tumors. On the right-hand side of Slide #5 is a summary of KO-539. The other of the 2 pillars of our company. KO-539, as I mentioned, is an inhibitor of the menin KMT2A or MLL interaction that is responsible for a significant fraction of acute leukemia. Here we've received orphan drug designation from the FDA. There's an opportunity to address a significant fraction of patients with relapsed/refractory AML. And consistent with other targeted therapies that have been developed in this space, there's the opportunity to move to earlier lines of therapy and potentially into combination and treat potentially even more patients. We'll walk through each of these programs in turn. So turn -- we're going to turn now to tipifarnib and HRAS mutant solid tumors, and we can jump to Slide #7. Tipifarnib, by inhibition of farnesyl transferase, it represents, to our knowledge, a unique mechanism of action currently in the industry. We are targeting an enzyme, farnesyl transferase, that is an essential enzyme for the activity of HRAS mutant tumors and HRAS-dependent tumors. That -- I'll show you both preclinical and clinical data, but the proof here is in the pudding. We currently have Phase II data in relapsed/refractory head and neck patients with HRAS mutations, where we show approximately a 50% objective response rate and approximately 6 months progression-free survival in a setting where the standard of care provides response rates in the teens and a PFS of approximately 2 months, so really a significant advantage. Tipifarnib has a favorable safety and tolerability profile that we think will allow us to expand to other indications and potentially in combination with other agents. As I mentioned, we have fast track designation from the agency. And as you'll see, there's a very strong rationale and preclinical data supporting the ability to combine with potentially checkpoint inhibitors and other immune therapy, targeted therapies as well as chemotherapy. And then we've been successful at building a strong patent estate that we believe will provide exclusivity to 2036 and potentially beyond in the major markets. Turning to Slide #8. This is a cartoon of the mechanism of action of tipifarnib. So in blue, we can see the enzyme, farnesyl transferase. That enzyme transfers lipid groups, farnesylate -- farnesyl groups onto intracellular proteins and allows those intracellular proteins to remain associated with the inner leaf of the cell membrane. By blocking the activity of farnesyl transferase, one blocks the farnesylation of intracellular proteins that can include HRAS, both the wild-type shown in purple, and the oncoprotein shown in orange with the yellow explosion, marking the mutation. By blocking farnesylation, we're able to reverse a number of the hallmarks of tumorigenesis and drive, as you'll see, meaningful anti-tumor activity in both preclinical models and in patients. So if we turn now to the next slide, Slide #9. We have characterized tipifarnib, a lot of the biology of the compound. And here, we can see, it acts to disrupt the association of the HRAS oncoprotein with cell membrane. By focusing on HRAS mutant tumors, we can drive meaningful antitumor activity, as shown in the upper right-hand corner. And consistent with the mechanism of action, we see reversal of a number of the hallmarks of tumorigenesis, including -- by arresting the cell cycle, by reducing angiogenesis, by potentially dedifferentiating the tumors. So all positive things from the standpoint of driving antitumor activity. As we transition now from Slide 9 to Slide 10, we move from a preclinical environment to a clinical environment. Slide 10 has a swimmer plot of tipifarnib in our Phase II trial in HRAS mutant head and neck squamous cell carcinoma. This is a study that has been ongoing now for several years. I should just note there in the banner at the top of the slide in green, we will be providing an update to this trial in the form of primarily survival data at the ASCO 2020 Virtual Scientific Program later this month. But the key takeaways from this slide, which were summarized in one of the preceding slides is one sees a high level of clinical activity in the form of both patients with partial responses shown in dark blue, stable disease shown in light blue. Again, the standard of care would typically be response rates in the mid-teens and a progression-free survival of approximately 6 months. Here, you can see we have a number of patients who are out on therapy well beyond 1 year. So really the potential for a meaningful advance in the HRAS mutant HNSCC population. Turning now to the next slide, Slide 11. Building on that Phase II data set, we have 2 studies underway at the top of Slide 11. We have AIM-HN. This is our registration-directed trial of tipifarnib in the same setting that is HRAS mutant HNSCC. In this trial, we are recruiting recurrent or metastatic patients who have failed at least 1 line of platinum therapy. The study is open on a global basis at 90 clinical sites in the U.S., Europe and Asia. We recently amended the study to try to enroll patients of any HRAS mutant variant allele frequency. And based on our feedback from the FDA at our end of Phase II meeting, we believe that this trial, if it meets its primary efficacy endpoint, which is elimination of a null hypothesis of 15% ORR, we believe that the data package would be sufficient to file an NDA seeking accelerated approval. In parallel or I should say, in advance of AIM-HN, we are also conducting SEQ-HN. SEQ-HN is a prospective observational cohort of HRAS mutant HNSCC patients. Here, the intent is to characterize the natural history of HRAS mutant HNSCC patients and also to use it as a funnel to be able to route patients for enrollment into AIM-HN. Given that we can't speak to the specific clinical progress of HRAS mutant patients on standard of care, it's our hope that the SEQ-HN study will provide more insight on the natural history of these patients, which we think could be helpful for labeling discussions, post-approval commitments and, of course, commercial considerations. Turning to the last slide, Slide #12, of this section before we move on to the expansion opportunities. This really speaks to both the unmet need and the potential for tipifarnib to be the first small molecule targeted therapy for this disease. So head and neck squamous cell carcinoma is the sixth leading cancer worldwide with nearly 800 -- more than 850,000 patients per year developing the tumor and nearly 0.5 million deaths every year. Has a very grim prognosis, only 1/3 of patients with advanced head and neck survive 5 years. And you can see that the current standard of care, although they provide an advantage relative to what was before, they still leave a very large unmet need. So in both the -- in the second line, which is where tipifarnib is currently being evaluated in the AIM-HN study, you can see the second line agents provide an OS of 5 to 8 months, PFS of 2 to 3 months and response rates ranging from 13% to 16%. Contrast that to what you saw on Slide #10, where we saw approximately a 50% response rate and approximately a 6-month PFS in the Phase II study with tipifarnib. If we turn now to Slide #14, I just want to highlight potential expansion opportunity, something that we're quite excited about. So HRAS mutant -- mutant HRAS represents a druggable oncogene, but even HRAS overexpression can drive the hallmarks of cancer. And as it turns out, in head and neck squamous, lung squamous, in urothelial, one -- if you look at the genome databases, you will see that -- you see levels of HRAS overexpression that are 5 to 10x higher than other tumor types. And as you'll see on the next slide, we think this is driving resistance to other therapy and potentially a number of the hallmarks of tumorigenesis. So we think there's an opportunity to move beyond the HRAS mutant recurrent and metastatic setting and potentially address up to 20% of HNSCC patients. Slide #15 shows the preclinical data that helps to support the rationale of moving into this expanded indication. Here, what we see is that tipifarnib displays either additive or synergistic activity when we combine it with a number of other drugs, again, in PDX models of HNSCC. So going clockwise, cetuximab, platinum, a TOR kinase inhibitor and a CDK4/6 inhibitor with palbo. As a monotherapy, one does see tumor growth inhibition, but one can drive regressions and really sort of meaningful antitumor activity preclinically with combinations that come in lower than the dose required as a monotherapy. We do have preclinical models underway for immune therapy. And the way we think about this is that HRAS overexpression is driving a resistance program that is providing resistance to these other agents as monotherapy. By combining, again, either with immune therapy or chemo or potentially targeted therapies, we think we can drive meaningful clinical benefit in up to 20% of the head and neck squamous cell carcinoma population. Turning to Slide 16. I alluded to this on the slide with the HRAS overexpression, but one does see HRAS mutations in other solid tumors. At ASCO, we will see the first presentation of an investigator-sponsored study conducted by Dr. Park at the Samsung Medical Center, where he evaluated tipifarnib in HRAS mutant recurrent and metastatic urothelial carcinoma patients. One can see good evidence of antitumor activity, shrinkage of tumor and reasonable durability. And we'll -- this is -- although this is not currently an active area of development, it is something that we are considering in the larger context of what we're doing in HRAS mutant solid tumors. Turning to Slide 17. This is really just a single slide advertisement for the opportunity in a completely different subset of tumors. Those are the CXCL12 dependent tumors. So remember that tipifarnib inhibits farnesyl transferase. Farnesyl transferase mediates the farnesylation of intracellular proteins. If those proteins are involved in disease processes, then tipifarnib can act as a monotherapy -- that CXCL12 is a very important chemokine, driving a number of hallmarks of cancer. And this is a slide that is excerpted from data that was most recently presented at ASH last year, where we show that tipifarnib as a monotherapy can drive approximately a 50% response rate in relapsed/refractory patients with T cell lymphoma. There is, we think, a pretty significant opportunity to move into what we call the CXCL12 dependent indications. For now, we are focusing our effort in HRAS mutant and HRAS overexpressed, but these represent opportunities for label expansion in the future. Slide 18 is a comment on the patent exclusivity. So the headline is that we have built a patent estate that is evolving in the major markets. We believe we have exclusivity up to 2036. The exclusivity relates to our inventions and insights into biomarkers and methods of use. We are also pursuing patents on combinations, and I've alluded to some of those in the earlier slides. We are also pursuing a next-generation farnesyl transferase inhibitor program. And I hope to have more to say about that either later this year or early next year. Slide #19 is the last slide before we leave tipifarnib and turn to our menin program. And this is just to highlight for you, we have 3 presentations coming up at the virtual -- the ASCO 2020 Virtual Scientific Program. The top one will be an oral presentation presented by Dr. Alan Ho from Memorial Sloan Kettering. Dr. Ho has been a principal investigator on the RUN-HN study since inception, and he's going to provide an overview of tipifarnib in tumors of head and neck, salivary gland and urothelial track with HRAS mutations. And my hope is you'll see a consistent level of antitumor activity across those different tumor types. We will be providing a presentation -- poster presentation on the design of the registrational study. And then Dr. Park has a presentation more in-depth on the opportunity for tipifarnib as a treatment for metastatic urothelial carcinomas, harboring HRAS mutations. So with that, we can now turn the page and turn to Slide 20, which is KO-539, our menin inhibitor for treatment of acute leukemias. As I mentioned, this is the second major pillar. Now turning to Slide 21. So we're moving away from farnesyl transferase and head and neck and now into epigenetic regulation. Our menin inhibitor is a potent selective oral inhibitor of a protein-protein interaction between the protein menin and KMT2A, or also known as MLL, which is an essential complex that's driving this program of stem-like phenotype in leukemic blasts. This is a novel mechanism of action. By inhibiting the menin MLL interaction, one can remove a break on differentiation and have the potential to treat up to 35% of patients with acute myeloid leukemia. We currently have our KOMET-001 study underway. That's a Phase I/II dose escalation. And at the time we reached a recommended Phase II dose, we are already cleared with the FDA to move into 2 expansion cohorts: one in the KMT2A rearranged population, the second in the NPM1 mutant population. Together, those represent about potentially 35% of patients with AML. There are opportunities that we are already investigating preclinically to combine with other targeted therapies as well as with induction chemotherapy. And similar to tipifarnib, this has a strong IP estate we think will provide protection out to 2036 and beyond. Turning to Slide 22. Menin -- by disrupting the interaction between menin and the MLL domain, one can drive -- remove a block on differentiation and, therefore, drive antileukemic activity, either in the KMT2A rearranged population at the top of the slide or in the NPM1 mutant population at the bottom half of the slide. And what we're doing is we are downregulating gene expression, as you can see here, of the HOXA and MEIS1 gene, which are 2 of the principal drivers driving this gene expression program that's leading to the maintenance of leukemic blasts. And you can see the effects of blocking that interaction on the next slide, Slide 23. So just to orient you, the color code, black is the vehicle control. Blue is a FLT3 inhibitor, quizartinib, and is an active control. And then red is our development candidate, KO-539. And this is in an aggressive AM750 -- AM7577 model, you can see in addition to NPM1 mutation, it has mutations in the genes, DNMT3A, IDH2 and FLT3. This is a very, very aggressive model. What's interesting, if one looks at the survival is with the FLT3 inhibitor, one can drive really a doubling of survival, which is meaningful. And actually when it translated clinically, not with quizartinib, but with other FLT3 inhibitors, has led to approval of that -- of several drugs in that class. But by contrast, with the menin inhibitor, one can drive survival out essentially indefinitely. We see no loss of animals, 10 out of 10 becoming long-term survivors. Moving from the top left to the top right, we see that in -- when one looks at the CD45 positive human AML blasts in the models, so in contrast to what one sees with either the vehicle control or the active comparator, FLT3, where you see the tumors relapse and growing out, we see these very persistent regressions, responses, I should say, in with KO-539 in this model, and the model is well tolerated in the preclinical studies. So very, very strong activity, differentiated from the other active drugs that have come before in that we can drive robust, persistent responses that are qualitatively different than what has been done previously with targeted therapy. Slide 24 now translates from those preclinical studies to our current clinical study. As I mentioned, this is called KOMET, the KOMET trial 001, and this is a first-in-human study of KO-539 in patients with relapsed and/or refractory AML. We are currently in the Phase I dose escalation. We're pursuing an accelerated design using a modified TPI strategy, and our goal is to reach a recommended Phase II dose and/or a maximum tolerated dose. We're characterizing, of course, safety and tolerability. That's the primary focus of this phase of the study. We're also looking at pharmacokinetics, potentially pharmacodynamics and any early evidence that we might observe of antitumor activity. At the time that we reach a recommended Phase II dose, we would then look to expand into 2 predefined expansion cohorts, one in the NPM1 mutant AML population. The second in the MLL, or as it's now referred to, KMT2A rearranged population. And as I indicated, we've already received approval from the agency. At the time we reach a recommended Phase II dose, to be able to move forward into that expansion cohort, where we'll look again further at safety and tolerability and at antitumor activity. Turning to Slide 25 now. We could see the unmet need and the potential opportunity in these populations. Despite the approval of multiple therapies for the treatment of AML, it remains a very, very challenging disease, 50% of patients relapsing within 1 to 5 years and only 1 in 10 surviving beyond 5 years. There's really a very significant unmet need. The larger of the 2 opportunities is in the NPM1 mutant AML. As you can see in the lower left corner, approximately 6,000 new cases per year in the U.S., which represents about 30% of the incident population. The KMT2A rearranged population is smaller with about 1,000 patients per year, approximately 5% of the incident population. Together, this gives us the opportunity, as a monotherapy, to treat up to 40% of patients with acute leukemia. So we're very excited. We are targeting achievement of a recommended Phase II dose later this year and hope to be in a position where we can share data. Coming back to the last slide, Slide 26, the investment highlights. So as I've told you, Kura is a precision medicine company with 2 significant programs. The first, our farnesyl transferase inhibitor, where we have a registrational study ongoing in head and neck squamous cell carcinomas with HRAS mutations. We see an opportunity to expand that now to the HRAS dependent head and neck squamous population. That's up to 20% of the population, and then opportunities potentially to move into other HRAS mutant solid tumors as well as CXCL12-dependent tumors. We would look to do the expansion potentially early next year into the HRAS overexpressed. The menin inhibitor that's our potent selective inhibitor of the menin KMT2A protein-protein interaction. Here, we're targeting up to 35% of AML. We have our KOMET study ongoing, and our goal is to reach a recommended Phase II dose later this year. With the added support from investors late last week, we have $351.9 million in cash pro forma as of the end of the first quarter. That puts us in a very strong position as we approach these significant value inflection points for the company. So with that, I'll conclude -- turn to Slide 27, and would welcome the opportunity to talk with anyone who's interested in more detail about what we have underway at Kura. But thank you for your time, and thank you, again, to Bank of America for the opportunity to present.

Great. Well, it doesn't look like we have any questions from the field. So Troy, I want to thank you for participating in the conference and the presentation. And with that, I think we can wrap up the call. Thanks so much.