Earnings Call: Q1 2019

May 7, 2019

Good day, ladies and gentlemen, and welcome to the Kura Oncology First Quarter 2019 Financial Results 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 introduce your host for today's conference, Mr. Pete De Spain, Kura's Vice President of Investor Relations. You may begin. Thank you, Skyler. Good afternoon, and welcome to Kura Oncology's Q1 2019 conference call. Joining me on the call from Kura are Doctor. Troy Wilson, our President and Chief Executive Officer Doctor. Antonio Galberto, our Chief Medical Officer and Head of Development and Doctor. Mark Grasso, our Chief Financial Officer and Chief Business Officer. Before I turn the call over to Doctor. 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 will now turn the call over to Doctor. Troy Wilson, President and CEO of Kura Oncology. Thank you, Pete, and thank you all for joining us this afternoon. We've made considerable progress over the past quarter as we continue to focus on the operational execution of our initial registration directed trial of Tipifarnib. The treatment cohort of this global open label non comparative trial is designed to enroll at least 59 evaluable patients with HRAS mutant head and neck squamous cell carcinoma, and I'm pleased to report that it's proceeding and on track. Meanwhile, we've enrolled additional HRAS mutant HNSCC patients in our ongoing Phase II trial, which we call RUN HN. We plan to provide an update from RUN HN in the second half of the year. We expect that this update will include additional follow-up on ongoing patients in the trial as well as preliminary data on newly enrolled patients in both the HNSCC as well as other squamous cell carcinoma cohorts. Our goal with our registration directed study is to generate a data package to support an application for marketing approval in HRAS mutant HNSCC as soon as possible, while we work to broaden Tipifarnib's potential use to include other diseases of high unmet need. We've also made significant progress toward the identification of farnesylated protein targets as well as the potential mechanistic linkage between farnesyltransferase inhibition and CXCL12 further supporting the development of tipifarnib in a number of CXCL12 driven hematologic and solid tumor indications. For more on this, I'll turn the call over to Antonio Roberto, our Head of Development and Chief Medical Officer. Thank you, Troy. Among the compelling features of the Tipifarnib program when we licensed it from Janssen were a signs of durable anti tumor activity observed across multiple hematologic indications as well as certain solid tumors. Despite this evidence of activity, the mechanism of action of farnesyltransferase inhibitors has remained elusive for decades. The data we had generated in SRAS mutant HNSCC provided a strong evidence of activity in tumors driven by this exclusively farnesylated oncogene. However, many of the other tumors in which evidence of activity have been reported such as lymphomas, myeloid leukemias, pancreatic cancer or breast cancer, do not typically carry SSAS mutations. In December 2018, at the American Society of Hematology Annual Meeting, we reported preliminary data from our Phase II trial of Tipifarnib in later stage peripheral T cell lymphoma. The data showed a significant association between CXCL12 expression and clinical benefit as well as clinical proof of concept in an immunoblastic T cell lymphoma, an aggressive form of PTCL often characterized by high levels of CXCL12 expression. At the same time, we reported results from an ancillary non clinical study, which indicated that high CXCL12 expression is in fact a negative prognostic factor for a standard of care PTCL therapy. We also showed that tipifarnib can down regulate CXCL12 secondretion in models of bone marrow stroma. The preliminary results reported at ASH validated our observation that the CXCL12 pathway is a therapeutic target of Tipifarnib and provided a potential path to expand the development of Tipifarnib well beyond SRAS mutant solid tumors by using CXCL12 related biomarker to enrich for patients most likely to benefit from tipifarnib treatment. Importantly, CXCL12 faC receptor are known to contribute to metastasis and elevated CXCL12 expression is known to be a poor prognostic factor in patients with certain tumors, including pancreatic cancer. We are increasingly encouraged by our growing body of CXCL12 related data. An outstanding question, however, still remains. What are the molecular mechanisms that relate the inhibition of the Farnesyltransferase enzyme with the observed antitumor activity of Tipifarnib in patients with high CXCL12 expiration? As previously stated, despite the fact that the number of large pharma companies and academic investigator have worked on farnesyltransferase inhibition for many years, no clear mechanism of such in the clinic have been defined. Last month, at the American Association For Cancer Research Annual Meeting, we reported new findings suggesting that the gene expression of the exclusively fun isolated protein, Rho E and PRECOL2 is strongly associated with CXCL12 expression in bone marrow stroma. We believe this funding may help us identify a molecular mechanism connecting Farneseyltransferase inhibition with the targeting of the CXCL12 pathway by Tipifarnib. In addition, an analysis of a subset of patients from a previously conducted Phase II trial in the large refractory lymphomas identified CXCL12 expression as a potential biomarker of clinical benefit from titifarnib in patients with diffuse LRB cell lymphoma as well as mycosis fungoides, the most common form of cutaneous T cell lymphoma. These findings provide further evidence supporting the inhibition of the CXCL12 pathway as a mechanism of action mediating the activity of Tipifarnib in the clinic. We believe that CXCL12 pathway biomarkers provide a common mechanistic basis to enrich for clinical benefit across multiple hematological and solid tumors indications. Now we look forward to providing additional data from the 2 cohorts in our ongoing Phase II trial of Tipifarnib in last stage lightest stage PTCL, including duration of response data from the AITL cohort and additional data from the CXCL12 positive PTCL cohort. I am pleased to report that these data have been accepted for oral presentation at both the European Hematological Association Annual Congress and the International Conference on Malignant Lymphoma, both in June. Meanwhile, we continue our efforts to further elucidate the biology of farnesyltransferase and the specific molecular mechanism for action of Tipifarnib, including the identification of genetic mutations potentially associated with elevated CXCL12 expression and we expect more to say on that at EHA and ICML next month as well. With that, I'll now turn the call back over to Troy. Thank you, Antonio. I continue to be very encouraged by the progress our team continues to make with the Tipifarnib development program. The discovery of CXCL12 related biomarkers offers the potential to significantly expand the therapeutic opportunity for Tipifarnib as a treatment for patients with cancer. Our development strategy for Tipifarnib in CXCL12 driven tumors follows a similar approach that has served us well in our development of tipifarnib for the treatment of patients with HRAS mutant HNSCC. Namely, as we consider potential CXCL12 driven indications, we would seek to prioritize those for which there is the potential for rapid clinical development and an opportunity to move into earlier lines of therapy. Other key elements of this strategy include optimizing dose and schedule, validation of biomarkers that enrich for clinical benefit, evidence of durable clinical benefit and securing patent protection and or regulatory exclusivity. Ultimately, we believe CXCL12 pathway biomarkers could enable registrational strategies for tipifarnib in multiple hematologic and solid tumor indications with high unmet need. In the meantime, we look forward to providing additional prospective data from our ongoing Phase 2 trial of tipifarnib in CXCL12 positive PTCL next month, followed by an update from our RUN HN trial in the second half. Now let's quickly turn our attention to our emerging pipeline programs, beginning with our ERK inhibitor KO-nine forty seven. KO-nine forty seven is a potent and selective small molecule inhibitor of ERK, which we're advancing as a potential treatment for patients with tumors that have dysregulated activity in the MAP kinase pathway. Our preclinical data suggests that KO-nine forty seven has antitumor activity in KRAS or BRAF mutant adenocarcinomas as well as certain subsets of squamous cell carcinomas. We continue to evaluate dosing regimens for KO-nine forty seven. Our goal is to reach a recommended Phase 2 dose or a maximum tolerated dose and we believe we remain on track to accomplish that goal later this year. We would anticipate providing data on the Phase 1 trial when available. Our 3rd product candidate is KO-five thirty nine, a potent and selective small molecule inhibitor of the menin mixed lineage leukemia or menin MLL protein protein interaction. We've generated preclinical data that support the potential anti tumor activity of KO-five thirty nine in genetically defined subsets of acute leukemia, including those with rearrangements or partial tandem duplications in the MLL gene as well as those with oncogenic driver mutations in genes such as NPM1. Our investigational new drug application for KO-five thirty nine has been cleared by FDA and we're preparing to initiate our Phase 1 clinical trial in relapsed or refractory AML shortly. With that, I'll now turn the call over to Mark Grasso for a discussion of our financial results for the Q1 of 2019. 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 Q1 of 2019 were $10,400,000 compared to $11,600,000 for the Q1 of 2018. The decrease in R and D expenses for the quarter was primarily due to a decrease in clinical development activities related to our Phase II trials of tipifarnib, offset by an increase in clinical development activities related to our registration directed trial for tipifarnib. General and administrative expenses for the Q1 of 2019 were $4,600,000 compared to $3,400,000 for the Q1 of 2018. The increase in G and A expenses was primarily due to increases in noncash, share based compensation and personnel costs. Net loss for the Q1 of 2019 was $13,900,000 or 0 point $3.7 per share compared to a net loss of $14,600,000 or $0.46 per share for the Q1 of 2018. As of March 31, 2019, we had cash, cash equivalents and short term investments of $165,500,000 compared with $179,000,000 as of December 31, 2018. We remain well funded through our upcoming milestones and expect that our current cash, cash equivalents and short term investments will be sufficient to fund current operations into 2021. With that, I will now turn the call back over to Troy. Thank you, Mark. This concludes our prepared remarks. But before we jump into Q and A, let me just quickly lay out our anticipated near term milestones. For tipifarnib, additional data from our Phase II trial in AITL and CXCL12 positive PTCL at EHA and ICML in June, additional data on biomarkers associated with elevated CXCL12 expression at EHA and ICML in June, additional data from our Phase 2 trial in HRAS mutant HNSCC and other HRAS mutant SCCs in the second half of twenty nineteen and additional data from our Phase 2 trial in chronic myelomonocytic leukemia in 2019. For KO-nine forty seven, data from our Phase 1 dose escalation trial in the second half of twenty nineteen and for KO-five thirty nine, initiation of our Phase I trial in mid-twenty 19. With that, operator, we're now ready for questions. Our first question comes from Jonathan Chang with SVB Leerink. Your line is now open. Hi, guys. Thanks for taking the questions and congrats on getting oral presentations at EHA and ICML. First question, as we look ahead to EHA, can you help set investor expectations on the upcoming PTCL data in terms of how many more patients, how much more follow-up, etcetera, will there be versus the data we got at ASH? And what do you see as the benchmarks in PTCL? And what would you consider a win in the upcoming data? Thanks, Jonathan. I'm going to ask Antonio to address your two questions. Yes. Thank you. So, thank you, Jonathan, for the call. So, the data that we presented at ASH indicated proof of concept in AITL. And if you recall at the time, we were still enrolling the CXCL12 positive cohort. So, without getting into the details, the intention is to provide data on both of the cohorts. And the only thing that I can tell you is that there's certainly excitement from the investigators and the data was sufficient to drive to oral presentations at the lymphoma meeting at Atiha. So, certainly, there was a strong interest from those in the field in the outcome of the data that was shown in the abstract. Got it. And I guess how much new data will there be in the abstract versus the ASH presentation? Or should we expect it to largely be a placeholder for the upcoming presentation? So that actually is a good question. So I can tell you that what you are expecting basically or what I will be expecting, maybe addressing your initial question, is to for the trial to have reach its objective. And if you recall, the intention was we saw some level of activity. We saw selection. And then, we were attempting to reach proof of concept with certain level of selection, either based on histology or based on the market. And again, based on that outcome, the data had driven to our presentations. But Jonathan, just to answer your question, given the timing of those abstracts, I mean, those I don't know that I'd say they're placeholders, but the data has continued to mature since then. So I would be expecting in June to see a more mature data set than perhaps what's described in the abstracts. Got it. And maybe just one more question. Can you talk about the current status of the KO-nine forty seven ERK inhibitor Phase 1 study? Where are you in the dose optimization process? And how close or far are we from seeing initial clinical data? So, Joe, this is a good question. As you know, it's quite a difficult target. There have been others that they have abandoned those programs. So, the one thing that I can tell you is that we have sufficient confidence to continue escalating. What we want to make sure is that we have the appropriate regimen either for the extension cohort or a Phase 2. So, there are no reasons for us. There are no stops in the escalations. We are just trying to see trying to optimize what is the best regimen. So, that may happen by the end of the year, but the intent is to get that recommended Phase 2 dose and then select the patients based on the markers that were suggested by our preclinical data. Got it. Thank you very much for taking the question. Sure. Our next question comes from Chris Shibutani with Cowen. Your line is now open. Yes. Thanks very much. I guess on the menin inhibitor, can you give us a sense for perhaps a little bit of preview of how you're framing the clinical development there? I believe there are there's another one that's also approaching the clinic. And so I think we will be keen to observe sort of what the different strategies and differentiation could be. Any additional insight would be helpful to kind of keep us engaged and tease us a little. That would be great. Yes. So, As you know, we appear to be ahead of others. We have an IND that was submitted, have been cleared by the FDA. We are on a start up basis. It's a question on how soon you open studies. But I can tell that that will happen shortly. We don't have major delays. This is just a question of IRB paperworks, contracts, etcetera. It is an standard dose escalation, has some digestion design, but it's not there are no major differences in what you will expect on a Phase 1 dose escalation is a refractory AML population. And our initial intent is not to select molecularly, although at some point, we will look for those AML rearrangements and NPM1 mutate population where you are expecting to get activity. Yes. No, that's helpful. I think as we think about how AML, the landscape has changed quite rapidly over the past few years with multiple new agents, many of the physicians and also folks in drug development are thinking about it in terms of potential for combinations. And I'm wondering if you could speak to the pathway and whether or not you believe that it makes sense to contemplate potential combinations even at a pretty early stage of your development? And if so, is there a logical potential set of other agents to combine with when you think about either kind of mechanistically or as you anticipate what the clinical paradigm could be and I realize that that's a long but insights there, particularly with regard to combinations, that would be helpful. Yes. It's a very good question. So, I would say that you don't need to turn your back on the monotherapy for the simple reason that there are not specific therapies against the adult NPM1 mutated population. Now, it's also true that NPM1 may be concurrent to other mutations. So, you may have find patients, for example, that have NPM1 mutations and FLT3 mutations. So, that gives you opportunities on combination. Although not that exciting, you should need to consider combination with the standard of care. So the way I will put it, you want to get your recommended Phase 2 dose immunotherapy And pending whether you get or not early responses, you can consider combination both with a standard of care or with targeted agents for those that may be targeting the co mutations that may appear with NPM1. Great. And then lastly for Troy, just on IP related to TIFI. I think in your current slide deck, you talk about some of the patent estate efforts that you've had, including where you outlined that you believe that you have for HRAS mutant out to 2,036 and CXCL12 expressing out to 2,037. From a pragmatic standpoint, are those the rough timelines that you're encouraging investor community to think about in terms of what the IP could go out to in terms of exclusivity? Thanks very much. Sure, Chris. So maybe just taking a step back before I answer your question, what we've brought to the table is an ability to connect the biomarkers, the disease and the dose and schedule. And if you look at the patents that have issued and the patent applications that are pending, that's the theme that runs throughout. That's the sort of inventive step, if you will. And we've been, I think, quite successful at getting patents issued not only in the U. S, but now they're beginning to issue outside the U. S. We are guiding, as we show in the corporate presentation, we are imagining patent protection under multiple overlapping patents out, as you say, to 2,030 7 or 2,038 in the US, potentially even longer in Europe. And I think there's reason for optimism. There really has never been a drug like this that, although it was in development, the exact molecular mechanisms were not known. And so, that's given us a lot of sort of fertile ground. And I think you'll continue to see interesting developments from our patent portfolio throughout this year and into next year. So, it's definitely something that is marching along very much hand in hand with the development strategy as that's playing out successfully. Great, thanks. We're certainly thirsty for data, so we'll look forward to those midsummer updates. Thank you, guys. Our next question comes from Joel Beatty with Citi. Your line is now open. Hi, guys. This is Sean Egan calling in for Joel. I think I got one for Troy and then one for Antonio. First, I have more of a clarification questions. For AMHN, the registrational study, if you hit the 15 confirmed responses or reject null, just kind of wondering how you'll roll that data out and then what will happen with that study kind of going forward? Will you continue to enroll patients to see if you reach your target objective response rate? And then for Antonio, I know a more comprehensive update on the pancreatic study is forthcoming, but I'm just kind of wondering how you'll be able to leverage your recent pain analysis as a means of enrichment. Is pain an objective enough to use as like an enrollment criteria? Or have you made any progress kind of tethering that to your KRAS hypothesis? Sean, thanks for the questions. Let me take your questions around AIM and then Antonio can address questions relating to the pancreatic data from ASCO GI. So, with respect to AIM HN, you're correct. The study is intended to enroll at least 59 evaluable patients. However, as we've said, if there are 15 confirmed objective responses, the study eliminates the null hypothesis and is a positive study. At that point, we would expect that the DSMB would notify the company that the trial had met its primary efficacy endpoint, we would, in turn, need to notify FDA. And we would likely also announce that publicly. It would be our expectation that the trial, if enrollment was not complete, the trial would continue to enroll patients, but that would give us an opportunity to begin a dialogue with the agency around next steps toward a submission, very much in the manner in which our Phase II trial in HRAS mutant head and neck achieved proof of concept prior to the completion of enrollment, and we were able to go and have an end of Phase II meeting with the agency. It's a very analogous situation. Thank you for the reference. The data that we presented at ASCO GI brought some excitement to the pancreatic investigators. So, you are referring to pain. So, pain actually, we use it as a connection with CXCL12 expression. And it's mostly potentially it will suggest a kind of like locally advanced population that is a good setting. But we have further some analysis. I don't know if you recall that there was a relationship between CXCL12 expression and the allele frequency of KRAS. And that can also be very helpful on the metastatic setting that could be potentially an earliest path for a registration. So, our intent is that to move potentially in a medical need setting. It could be potentially a second line and to select the patients based on molecular tools. So we can initiate selection patient, for example, in KRAS, lower than 5% allele frequency that gives you 30% of the population. It's a big chunk of patients and potentially then apply CXCL12 related markers to determine where you select a little bit better on how you can identify the patients that develop responses or better clinical benefits. So, we do have with those tools and a strategy and we are currently in discussion with several KOLs and our intent is to initiate a pancreatic study proof of concept this year. Great. Thank you so much for taking my questions. Sure. Our next question comes from Tyler Van Buren with Piper Jaffray. This is Alex on for Tyler. Two questions for you. First, given the significant opportunity for tipifarnib, how are you thinking about which indications to prioritize for internal development or for partnership? And secondly, on the 947 program, with the recent excitement in programs that target KRAS and bearing in mind, of course, we don't have any clinical data yet, How would you compare the potential for single agent activity between KRAS and ERK inhibition? Or in other words, would you expect one to be more powerful than the other? And secondly, would it make sense for the KRAS inhibitor programs to combine with your ERK inhibitor in combination therapy to improve clinical outcomes? Sure. Those are 2 pretty meaty questions. With respect to your first question on prioritization of indications, it's a great question. It's something that we're talking about a lot internally. I think we're quite encouraged by the way in which the hypothesis seems to be playing out. We've shown prospectively validated AITL retrospective looks at AML, pancreatic, potentially DLBCL. And now we're going to see, again, prospective data initially in PTCL and then later in the year in CMML. All of those indications have in common that the CXCL12 pathway seems to be driving the disease. One of the things that we've tried to focus on, and we alluded to this in the prepared remarks, is you want to get that initial anchoring indication that allows you to drive a smaller trial with a higher likelihood of success and gives you really a foothold to be able to become either part of the standard of care or displace the standard of care. I think we're increasingly encouraged that we see multiple opportunities for that. And we'll have more to say probably a little bit later in the year after we're able to share with you an update on our PTCL studies, as Antonio mentioned, at EHA and the Congress in Lugano. With respect to your second question, it's a good question. And they're 2 very, very different agents. And so, it's hard to draw comparisons, particularly in the absence of data. The promise of the KRAS inhibitors, the G12C inhibitors, is that you are inhibiting an oncoprotein directly. And as a consequence of that, you have the potential for a reasonable therapeutic window. You do have to worry about mutations and resistance. ERK, on the other hand, is a central actor. We're inhibiting the wild type protein that is really a choke point for dysregulations in that pathway. And we've talked about it in the past, but there are 2 different 2 sort of distinct ways forward. 1 is you identify with ERRC populations where you can drive meaningful single agent activity. The other is that you identify opportunities where you can drive clinical benefit in combination. As far as we can tell, we're still optimistic that both of those are possible. We would, of course, want to gravitate toward single agent smaller companies can just do that more tractively. Is there an opportunity to smaller companies can just do that more attractively. Is there an opportunity to combine a KRAS inhibitor and an ERK inhibitor? Certainly. But I think there's an opportunity to combine an ERK inhibitor with a number of different agents. But as Antonio mentioned, key to that is that you really have to understand what is your recommended Phase II dose and how best to use your agent, and then you can figure out how best to deploy it in a combination setting. So, we're very much keeping that question in the forefront of our mind as we work to finish out this Phase 1 setting and, hopefully, position 947 for the next step of development. So, I think the other thing I will add is that strategies are not necessarily mutually exclusive. So, you can work on Tipifarnib on a pancreatic indication that could be most likely a combination and will require randomized trials and may take several years, but it will give you a large commercial opportunity. And in parallel, you can pursue an AITL or diffuse L B cell lymphoma subset as monotherapy that translate to a registration. For a company like us, having one registration lineup after another half a tremendous value. So, you could do both strategies in parallel and pursue anchoring indications that you can expand then you can do label expansion. At the same time, you have this kind of like big commercial opportunity that is also developing on the background. Great. Thank you. Sure. My pleasure. Our next question comes from Jay Olson with Oppenheimer. Your line is now open. Hi, thanks for taking the questions. Maybe if I could ask you to look ahead into the future, assuming that Tipifarnib gets approved for an HRAS mutant population. Could you help us understand what percent of that population is going to be treatable and what we should expect for a peak penetration level since this is a very targeted indication, should we expect to see a high penetration level? I honestly will expect a high penetration for the simple reason that in a setting of a third line where you are expecting 5% response rate, if you are reaching 50% response rate on a setting in which those patients had no responses, you are immediately displacing the standard of care. And seeing that the standard of care could be immune therapies, they are not necessarily cheap. You are not displacing cisplatin. So, I can see that you can expand vertically, moving all the way to the frontline, trying to pursue a new adjuvant setting. And then, you can expand horizontally on those settings in which maybe the allele frequency is not the best for monotherapy, but you can add to the combination with immunotherapy, you can add to the combination with cetuzumab, and then you have been carried by those agents because the reality is that either the mutation is at very high frequency from the get go and is driving the tumor all appear later as a mechanism of resistance. So, that data that is published, half of those progressions on cetuzumab, they are RAS mediated. At least half of those, they are going to be SRAS. So, you can delay the resistance to the standard of care. So, that gives you another 5 at least 5%, 10% of the population. If you don't do selection, if you don't do directly combination, obviously, it's much larger potential. Okay, great. Thanks. That's very helpful. And then maybe as a follow-up, just thinking about the CXCL12 population, you had identified at AACR CXCL12 expression is a potential biomarker of clinical benefit in patients with DLBCL and the subset of CTCL. And apologies if I missed this, but are these indications on the horizon for development? And how will you prioritize them? So, first of all, I'm just going to reiterate that we are very excited, obviously, that the data coming at EHA and ICML. And this has been shared by a number of investigators on KOL. And that give us a big hit in lymphoma. So, seeing that we were only in T cell lymphomas, the anecdotal data mucosus fungoides give us the opportunity. So, sorry, just backing up, even within peripheral T cell lymphoma, we know that and this has been shown by Tom Wicksett that skin lesions were disappearing in the initial data that he presented in 2011. So, that together with now responses in CTCL, that show you that there's also activity in cutaneous T cell lymphoma. That actually doubled the population of T cell lymphoma. Diffuse large B cell lymphoma is and a very large population. So, we need to decide exactly do we do basket studies, do we do very targeted registration is something that we are still discussing internally with others. But we are going from a beachhead to a large opportunity. There will be companies that they will just develop in this area or lymphoma by itself. Yes. Jay, just to add to Antonio's comments, what we're trying to do is to demonstrate very clear Phase 2 proof of concept in these indications. So we started with HRAS mutant head and neck. You saw AITL at ASH last year. We're highlighting, obviously, the presentations in June and to the back half of the year, the CMML data, those are giving us beachheads into the CXCL12 positive indications. And then, as Antonio mentioned, we've said it a couple of times in a couple of different ways, this is I put this in our basket of high class problems. Can we pursue accelerated registrations as a monotherapy and, in the meantime, be laying the groundwork for these potentially much larger indications. Rest assured, we're doing both. And we're doing it in the context of tipifarnib being the only drug candidate we know of that has clinical proof of concept on the CXCL12 pathway. So, we're trying to be thoughtful and stake out a near term, an intermediate term, and a long term opportunity. And that's what's increasingly coming into focus. That's great. Thank you for the details. Super helpful. Thanks for taking my questions. Sure. Thank you. At this time, I'm showing no further questions. I'd like to turn the call back over to Troy for any closing remarks. So, thank you all once again for participating in the call today. We'll be at the Deutsche Bank Healthcare Conference in Boston tomorrow and the Bank of America Merrill Lynch Healthcare Conference in Las Vegas next week, and we look forward to seeing many of you there. In the meantime, if you have any additional questions, please feel free to contact Pete, Mark or myself. Thank you again, and have a good evening, everyone. Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.