Kura Oncology, Inc. (KURA) Q1 2022 Earnings Report, Transcript and Summary

Good day and welcome to the Kura Oncology First-Quarter 2022 Earnings Conference Call. All participants will be in listen-only mode. [Operator Instructions]. After today's presentation there will be an opportunity to ask questions. [Operator Instructions]. Please note this event is being recorded. I would now like to turn the conference over to Mr. Pete De Spain, Senior Vice President of Investor Relations. Please go ahead.

Great, thank you Ren. Good afternoon and welcome to Kura Oncology’s first-quarter 2022 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. Dr. Stephen Dale, our Chief Medical Officer, is also with us and available to answer questions. Before I turn the call over to Dr. Wilson, I would like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Kura's filings with the SEC, which are available from the sec or on the Kura Oncology website for information concerning risk factors that could affect the company. With that, I'll now turn the call over to Troy.

Thank you, Pete. And thank you all for joining us this afternoon. Despite what continues to be a challenging, broader market environment, we continue to operate from a position of strength here at Kura, armed with 3 independent drug development programs, a strong experienced team, a well-designed clinical development strategy, and a cash runway through 2024. Now, as we approach a series of important catalysts driven by completion of enrollment in the Phase 1b study of our Menin Inhibitor, Ziftomenib. And culminating in top-line data next quarter and a full data presentation in the fourth quarter. As mentioned, I'm pleased to report, we recently completed enrollment of the patients in the Phase 1b portion of KOMET -001, required to identify a recommended Phase 2 dose for Ziftomenib. Recall the study was designed to enroll 2 expansion Cohorts, 200 milligrams and 600 milligrams, with each Cohort comprised of patients with NPM1 mutant, or KMT2A rearranged, relapsed, and/or refractory acute myeloid leukemia. The goal of the Phase 1b is dose optimization, consistent with FDA's guidance around project optimist. And the 2 doses were selected based on the encouraging clinical activity, safety profile, and tolerability demonstrated in the Phase 1a portion of the study. We're now assessing the patients in each expansion cohort for safety and tolerability, Pharmacokinetics and exposure, as well as efficacy. We remain on track to identify the recommended Phase 2 dose for Ziftomenib, and to report top-line data from the Phase 1B study in the third quarter with a more complete dataset from common 001 reserved for presentation at a medical meeting in the fourth quarter. As a reminder, the study protocol gives us flexibility to enroll additional patients in the Phase 1B, enabling us to maintain momentum while we transition into a subsequent Phase 2 registration directed portion of comments 001. We believe data from all patients treated at the recommended Phase 2 dose will have potential to contribute to the registration on patient population. Meanwhile, we remain enthusiastic about the encouraging safety profile, tolerability, and clinical activity we're observing in the Phase 1B study. As we continue to add sites in the U.S. and Europe in anticipation of the subsequent Phase 2 portion of common 001. We also intend to conduct a comprehensive development strategy that builds upon the potential to register Ziftomenib as a monotherapy while giving us flexibility to access larger opportunities through combinations and in earlier lines, we look forward to sharing much more regarding our global development strategy for Ziftomenib later this year. Following identification of the recommended Phase 2 dose. Now let's turn our attention to our Farnesyl Transferase Inhibitor programs. We continue to view Farnesyl Transferase Inhibition as a potentially valuable therapeutic and commercial franchise, one with potential to deliver multiple opportunities in oncology. One of the first examples of the use of FTI s as a targeted therapy was demonstration of the potential for Tipifarnib to drive durable responses in recurrent and metastatic HRAS mutant HNSCC and our ongoing NHN registration directed trial continued in that indication. More recently, we've begun efforts to debuild upon the initial monotherapy activity of Tipifarnib with two goals: 1. To drive deeper and more durable responses, and 2. To expand the potential patient population. Toward this end, we're pursuing the current HN trial to evaluate the combination of Tipifarnib, and Alpelisib, an inhibitor of PI3 kinase alpha in selected HNSCC patient cohorts. By combining Tipifarnib and Alpelisib, we believe we can achieve both goals. Our preclinical data suggests the combination has potential to provide meaningfully better antitumor activity relative to inhibiting either target alone and by targeting both PIK3CA and HRAS dysregulated HNSCC. The combination has potential to increase the total addressable population for Tipifarnib to as much as 50% of patients with HNSCC. In December, we dose the first patient in our Phase 1-2 current HN trial of Tipifarnib in combination with Alpelisib in HNSCC. The initial cohort includes patients who have PIK3CA dependent HNSCC. Screening has commenced in an Hrs over-expression cohort, and we expect to dose the first patient in this cohort by the third quarter. Our goal with the current HN trial is to identify a recommended Phase II dose and schedule for the combination, and look for early signs of clinical activity. Our team is making excellent progress and we look forward to providing an update. Beyond HNSCC, we're beginning to understand FTI's may represent an ideal combination partner for certain classes of targeted therapy in large solid tumor indications. The first of these emerging combination opportunities was highlighted last month in a late-breaking presentation at the American Association for Cancer Research Annual Meeting in New Orleans. The new findings were generated through a collaboration with INSERM, the French National Institute of Health and medical research. The presentation featured pre -clinical data supporting the potential for Tipifarnib to prevent emergence of resistance to Osimertinib in EGFR mutant non-small cell lung cancer. Several farnesylated targets were identified that appear to control the ability of lung cancer tumor cells to enter and exit, a state that makes them tolerant to Osimertinib using preclinical and Vivo models of EGFR mutated lung tumors, core treatment with tipifarnib durably prevented relapsed to osimertinib for up to 6 months with no evidence of toxicity. Collectively, these data strongly support the potential use of an FTI to prevent or delay the adaptive response to osimertinib. We're preparing to initiate a Phase 1 study of tipifarnib in combination with osimertinib in treatment naive, locally advanced, and or metastatic EGFR mutated non-small cell lung cancer. And we expect to dose the first patient in that study, which we call the current lung trial in the third quarter. We intend to perform initial clinical evaluation with tipifarnib or osimertinib while in parallel advancing KO-2806, the lead development candidate in our next-generation FTI program through IND enabling studies. We remain on track to submit an IND application for KO-2806 in the fourth quarter. 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 first quarter 2022. I invite you to review our 10-Q file today for a more detailed discussion Research and development expenses for the first quarter 2022 were $20.9 million compared to $20.3 million for the first quarter of 2021. The increase in R&D expenses was primarily due to the increase in Ziftomenib clinical trial and personnel cost. General and administrative expenses for the first quarter of 2022 were $11.9 million compared to $10.6 million for the first quarter of 2021. The increase in G&A expenses was primarily due to the increase in professional fees and non-cash share-based compensation. Net loss for the first quarter of 2022 was $32.5 million compared to a net loss of $30.7 million for the first quarter of 2021. This included non-cash share-based compensation expense of $6.7 million compared to $5.1 million for the same periods in 2021. As of March 31, 2022, we had cash, cash equivalent and short-term investments of $480.1 million compared to $518 million as of December 31, 2021. Based on our current plans, we believe that our cash, cash equivalents and short-term investments will fund current operations through 2024. With that, I now turn the call back over to Troy.

Thank you, Tom. Before we jump into the question-and-answer session, let me just lay out our anticipated milestones for 2022. For our Menin Inhibitor program, identified the recommended Phase II dose of Ziftomenib, and report top-line data from the Phase 1b study in the third quarter, present updated data from comment 001 at a medical meeting in the fourth quarter. And for our FTI programs, dose the first patient in the HRAS over-expression cohort of current HN in the third quarter, dose the first patient in the current lung trial in the third quarter, and submit a IND application for KO-2806 in the fourth quarter. With that Operator, we're now ready for questions.

We now begin the question-and-answer session. [Operator instructions] At this time, we'll pause momentarily to assemble our roster. First question comes from Jonathan Chang, from SVB Leerink. Please go ahead.

Hi, guys. Thanks for taking my questions. Jonathan Chang, as you know, SVB Securities. First question on Ziftomenib. Can you please refresh our memory as to what investors can expect in the top line third quarter data versus the medical meeting presentation in the fourth quarter?

Sure Jonathan, thanks for the question. So the focus of the topline data will really be around the safety tolerability and clinical activity at the recommended Phase 2 dose, Jonathan. With particular focus on the CR -- CRH rates in the patients that were enrolled in the dose that we've identified as the recommended Phase 2 dose. That's what you should look for in the topline in the data for that'll be reserved for a little bit later in the year at a medical meeting, there you should look for a much more fulsome presentation of the data from the comment 001 study. And that's where we'll get into the breakdown between the specific genetic subtypes. More detail around both the safety and tolerability as well as the efficacy, potentially specific anecdotes around patients that are interesting. And just a much more comprehensive data set. The topline is really intended, as we've guided consistently, just to communicate that we've identified the recommended Phase 2 dose and to help inform investors that we continue along the path toward what we believe will be the start and ultimately the execution of a successful Phase 2.

Got it, thank you. And second question, within enrollment, completion and the Phase 1b expansion cohorts, can you provide any color on how many patients in the cohorts has NPM1 mutation versus KMP2A rearrangement?

Yes, it's a good question, Jonathan and thank you for it. Without getting specific, what I can tell you is we actually see a pretty good balance between the 2 populations. I'm going to hold off on the specific numbers until we get to the data of presentation in the fourth quarter. But suffice it to say, we didn't see a disproportionate enrollment to one genetic subtype or the other. We see good balance and that gives us confidence that as we've said all along, from our perspective, we think there's going to be one recommended Phase 2 dose to treat both patient populations. And we're seeing what we want to see in both populations. Hopefully that helps give you a little bit more color on your question.

Great. Thank you. Thanks for taking the questions.

Sure. Thank you.

Our next question comes from Peter Lawson of Barclays. Please go ahead. Mr. Lawson your line is now live.

Thanks so much Troy. First question is just around safety. Just how much safety data we'd see in the 3Q update, and if you've seen any further cases of differentiation syndrome, and how's the management strategy going with that?

Thank you, Peter, for the questions. So given that it's going to be a top line cut of the data. We’ll probably give some color around the safety and tolerability. I can tell you what we've seen thus far. Ziftomenib appears to be -- have a very encouraging safety and tolerability profile. To the second part of your question, really the one thing of note is, we have continued to see differentiation syndrome. But as we discussed on prior calls, we now have what we believe to be a very robust and enhanced mitigation strategy. And it seems to have given the investigators the toolkit that they need to manage it. And to that end, neither we nor the investigators run away from differentiation syndrome. To the contrary, if you see it, it's usually an indication of clinical activity. The key is, is can you manage it effectively? And can you keep the patients safe? And at this point, I can tell you, the enhanced mitigation strategy appears to be doing exactly what it was designed to do. We'll probably have some very high-level color around it in the top line release with much more data to follow. But it should be very consistent with what we've said all along.

I may have missed this. I apologize, but the current head-neck trial, when did we see the first carrier readouts of that?

Yes, you didn't miss it, Peter. We were a little bit vague, but let me answer your question. So this trial is intended to determine the recommended Phase 2 dose and schedule for the combination. It's a Bayesian design that allows us to adjust the levels of both drugs Tipifarnib end Alpelisib. The primary focus is safety and tolerability, but we are looking for clinical activity. I think at this point, Peter, we in the prepared remarks, I commented that the trial's going well and we are encouraged. There may be an opportunity I hope there will be an opportunity in the not-too-distant future to share some more data with you but we haven't put a specific guidance around what that data would be or the venue. Once we have it, will be sure to share it with you and others on the call.

Great. Thanks so much.

Sure.

Thank you, Peter.

Our next question comes from Tiago Fauth of Crédit Suisse. Please go ahead.

Hi, guys. Jonathan Ofertiago, thanks for taking our question. So we already know a lot about the differentiation between Ziftomenib and [Indiscernible] you are frequently compared to, but they're not several other Menin Inhibitor trials running. So with that in mind, it looks like you're likely ahead of those. But from what you've seen from those trials so far, is there anything you could say about the relative differentiation between those programs or anything preclinically or even from the standpoint of trial design? Thanks.

Yeah, Jonathan Ofertiago. Thanks for the question. I'm going to defer on addressing our competitors. I'll let them speak to their data and their designs. And I'll maybe highlight something I think that a year ago was perhaps viewed as a negative and now I view very much as a positive and that is the Phase 1B design for which we've just completed enrollment. At the time, the concern was you've lost time, why is the FDA making you do this. This was very early in the dawn of project optimist. What it's provided us is significant amount of experience at two different doses, one of which will be our recommended Phase 2 dose. So as we now look to transition from Phase 1B to Phase 2, I think we have a very solid understanding of the safety, the tolerability, the pK exposure, and the efficacy at ultimately what will be the recommended Phase 2 dose. That -- that perhaps wasn't fully appreciated by everyone at the time, but what it means is you're going to get a very full picture at the RP2D in Q3. And it should give everyone much more confidence that those parameters are going to follow through, not only through the medical meeting presentation in Q4, but on into the Phase 2. That's probably the most significant difference Jonathan that we've seen between what we're doing and others and I think it positions Ziftomenib very competitively relative to the other drugs in the landscape.

Helpful. Thank you.

Sure.

Our next question comes from Roger Song of Jefferies. Please go ahead.

Great question. Maybe Troy, can just comment on so far the regulatory interaction. So have you discussed with the FDA about your RP2D plan and when you will discuss the pivotal, once you will that be after the topline data in 3Q versus the four data in 4Q are maybe later?

Yes, Roger. So I want to be careful here on specifics. We interact with the agency regularly across all of our programs. We're very much work in partnership with the agency and we found them to be very productive partners. I don't want to speak to the specifics just given the timing and some of the sensitivities, suffice it to say, today it's significant and that we've completed enrollment of the 24 patients needed to support the Phase 1b. We are in the process of collecting and analyzing that data ultimately to identify the recommended Phase two dose. And then that's going to require a package that needs to be submitted to the FDA that hasn't happened yet but the team is, the team knows exactly what it needs to do and it's very much focused on that. I don't want to be a lot more specific as to the timing. Just out of respective for the agency and for their process. But I will tell you, I think the team is not only doing everything they need to do, but I hope is clear, is executing with the diligence and the urgency that's needed for this program to really be competitive.

Got it. Yes, I think last time we removed and clinical [Indiscernible]. It seems that big promptly as well. Okay. Got it. Maybe just another question from us. Is the -- so for the Tipi, this combo trial, can you just remind us, where are you at the monotherapy, the period of study, and also if the combo data looks good and how you're going to stretch at, this combo versus monotherapy moving forward. Thank you.

Right. Yeah, Roger. Thanks for the question. And Roger, let me just pick up on something that you said because I can't resist. If you don't mind. It wasn't that long ago that the clinical hold was lifted and at the time shortly thereafter, we said, we were seeing high interest and high engagement among the investigators in the AML community for Ziftomenib. I hope now that we've come back exactly on schedule with the cohorts enrolled, and enrollment ongoing, that that underscores what we said back then. There is a very high level of interest and engagement in this compound and in this class, in the AML community. Just wanted to round out the answer to that. On your FTI question. Yeah. We find ourselves at an interesting point. So enrollment in AIM, which is the Monotherapy registration directed study for Tipifarnib in Hrs mutant head and neck, enrollment is continuing. We know the drug is active. We know you've seen the data from the Phase II run HN. We continue to see monotherapy activity. The challenges that we face, is that the patients coming to that study have typically coursed through both platinum and IO. And as a result, a large majority of them are just not sufficiently fit to go on to a study. It sort of is what it is that the team is working very hard to execute against that, but that's the reality of that patient population. Current really addresses that in three different ways. The first is by combining Alpelisib and Tipi, you open up the potential population from 4-8% which is the HRAS monotherapy to as much as 50% when you look at HRAS disregulated and PIK3CA disregulated populations. Nearly a tenfold difference in the potential patient population. The second of course, is by providing additional biomarkers, you're giving positions more reasons to due screening. You heard us say in the prepared remarks, the HRAS overexpression cohort is open and in screening. We of course have patients who are being screened for both PIK3CA mutations and amplifications that helps just open the funnel up if you will. And then the final point is the pre -clinical data suggests that there's really a strong potential for drug-drug synergy with this combination in these genetically selected populations and had a neck. We see synergistic activity that's greater than either drug -- what you could do with either drug as a monotherapy. Obviously, if you can offer patients better efficacy with acceptable safety and tolerability, that's a win. It's a very good question, how do you -- how do you integrate those two development streams aim on the one hand, current on the other. And -- Stephen and the development and regulatory teams at Kura are very much engaged in that right now. I don't have a lot more to tell you, but it is it is very much top-of-mind and we'll share additional updates as we have them. We're -- you can tell we're quite encouraged by the progress that the team is making on current and will share more progress as we have it.

Great. Thanks for the comprehensive comments Alex, thank you.

Thank you.

Our next question comes from Reni Benjamin of JMP Securities. Go ahead.

Hey, good afternoon, guys, thanks for taking the questions. Maybe just starting off with Ziftomenib. I think, in the past we've talked about the potential combination studies, [Indiscernible] was one of the potential partners. There were some others. I'm just curious, as you continue to progress through both preclinical and clinical development, have there been any changes to your thoughts, or are you still looking -- what are the top 2 combination studies that you'd like to get started? And when do you think that might get started?

Yes. Ren, thanks for the question. There's a lot sort of packed in there. Let me see if I can unpack it. Combinations are of high interest to us. Ultimately, that's probably going to be the highest best use for Menin Inhibitor s if you want to serve the most patients and provide the greatest unmet need. I think there's a very -- continuing to believe there's a very strong case to be made for the monotherapy registration, but AML will be a disease -- the treatment paradigm will be one of combinations. The predicate to any of those combinations, of course, is identification of a recommended Phase 2 dose so that you know where to start with the combo. We are moving toward that goal with all due speed we've just -- we've now completed enrollment and we're looking forward to giving the topline data next quarter. There are a lot of activities, Ren going on in the background on to support the combination studies, both in the frontline and in earlier lines of therapy. We haven't said a lot yet about timing because again, we want to be respectful of interactions with the agency. But I can assure you that those activities are going on very actively in the background and we'll say more when it's appropriate and the studies are underway. In terms of prioritizing them, I mean, you put your finger on at least a couple of them, Venetoclax continues to be a very attractive combination partner. There's strong evidence for potential synergy between Venetoclax and Ziftomenib. There's some suggestions clinically that that synergy may carry over into patients. Obviously, we have that's not a substitute for running a study, but I think there's a very strong rationale to do that. The other of course is flit three. Foot threes is a very large patient population. When we unveil our development strategy, I think you'll find it's a continuation of what we've done. Well, it's efficient. It's meant to be comprehensive, it's meant to target both patients in the to genetic sub types, as well as looking for expansion opportunities outside of those genetic sub types and we're looking forward to sharing it with you. Probably a little later in the year as we get closer to the medical meeting. So hopefully that gives you some color and much more to share, I think here in the second half as which we're very quickly approaching.

Got it. That's just perfect. Maybe just switching gears too from Tipi. The first with the current had a next study in combination. You're going to be starting enrollment of the HRAS overexpression cohort. And so outside of it being a target for Tipi, is there any other rationale? Is that a bypass mechanism for patients who get exposed to PI3K alpha? Or are they patients as it a patient population that has a much worse prognostic factors. How should we be viewing this overexpression cohort?

Yeah. So it's a really good -- it's a great question, Ren, and you have to questions in there, and I'm just going to tease them apart and answer each of them. So there are at least 2 populations in that current trial that relate to farnesylated targets. And I'll just draw everybody's attention, we updated our corporate presentation this afternoon in connection with this call, and there's a very nice graphic that shows both the relevance of Tipifarnib to HRAS over expression. Where HRAS is the farnesylated target. And then, a second major mechanism, which is rev farnesylation. So Ren, in your question, you mentioned a bypass resistance. That's exactly what you see with PI3 kinase inhibitors. Once you inhibit the anchor protein, often times you'll see up regulation at TOR, which is the next node down. Personally, I worked on this 12 or 13 years ago in the context of TOR kinase inhibitors and PI3 kinase alpha. But that is one of the principal resistance mechanisms. And Tipifarnib silences that. It deletes the Darnesyl group off of rev, and potentially blocks that bypass resistance. That's why we think there's a strong rationale in the HRAS overexpressers where you're just removing RAS, which is a bad actor for a lot of reasons, even if it's not mutated. And then in the PIK3CA populations, you're directly addressing tore through rep. And again, I would direct everyone if you're interested to the graphics in our corporate presentation. But for those reasons, Ren, we think -- we think it's a very strong rationale for combination. The team's doing a terrific job and we look forward to sharing results with you in the future.

My final question is just the current lung trial, I really like the preclinical work that was highlighted at ACR. Can you talk a little bit as to the mechanism of action? How might have actually prevent resistant mutations? Kind of the goals of the study and what might be kind of go no-go, decision metrics that you might be looking at it. Would it be progression free survival mainly, or would you be looking at things like overall response rate primarily?

Right. Yeah. Great question, Ren. And again, it sound like a broken record here, but I would direct everyone to our revised corporate presentation that's available on our website. There are three or four slides now in there that speak to current long, and that really distill it down to its essence. So Ren, let's just quickly jog through your questions. The mechanism of action is it is now well-understood that there are a subpopulation of cells that are drug tolerant cells when you treat lung tumors, EGFR mutant lug tumors with Osimertinib. A small fraction of those tumors are so called drug-tolerant cells. The reason those cells are drug tolerant as they actually rewire their cellular architecture. They actually de -differentiate and they become DTC cells, drug-tolerant cells. The process by which they enter that drug-tolerant state depends on a farnesylated protein. The process by which they exit that state depends on a farnesylated protein. If you block the entry and exit, essentially you bar the door. Now you don't allow those cells to enter their DCTTC state and they then become susceptible, they eventually die off under pressure from Osimertinib. It is those DTC cells, Ren to your next question that are believed to seed the molecular origins of adaptive resistance. In that drug tolerant state, they can sit there essentially and cook and find a way around those Osimertinib. So you don't allow the sales to ever get there. And the consequence of that, and again, I'll point you to the cartoon and then the data on the next slide in the corporate presentation. In the case of osimertinib alone, eventually you see the tumor relapse. You get little seeds of resistance, they grow out and boom, the tumor comes back. In the case when you're double -- where you're adding Tipifarnib to the osimertinib, you see an extended delay on that resistance. In some cases, a prevention, nearly a complete prevention, these are pre -clinical data. To -- the third-party your question, Ren, what are you looking for? What are we looking for in current lung? You're looking, of course at safety and tolerability, you need to establish a recommended Phase two dose for the combination. And then PFS is the primary endpoint, but we're going to be looking at a number of endpoints along the way. Given the high activity of osimertinib as a monotherapy you'd have to have a pretty significant trial to for difference in response rate. But if the clinical data recapitulate what we see pre -clinically, you'll see it and PFS and the, the trial is designed to look for just that. And if we see that, obviously, that's a big deal because you could keep patients on Osimertinib then that much longer and really provide them with a high-quality of life and this is just the final comment I'll make Ren. This is what you'll see Alpelisib and Tipi is the first example. OCTP is the second. I hope you'll see a third and then a fourth, we're using this concept of precision medicine now to go after much larger patient populations, but using all of the -- this real strength of precision medicine. And I think it's going to be an exciting several years coming up as we see the -- whether this -- the clinical data recapitulates the very strong preclinical data. We're cautiously optimistic and look forward to sharing updates with you in the future. I hope -- I hope I've answered all the various parts of your question.

You definitely have. Thank you very much for backing it so nicely. Have good one.

Sure. Thanks, Ren.

[Operator instructions] At this time our next question will come from Eva Privitera of Cowen. Please go ahead.

Thanks for taking our questions and congrats on completing the enrollment. So you mentioned earlier that you've seen additional cases of DF (ph). Just wanted to follow up on that with a few details. What was the severity and at what dose?

Yes. Thanks Eva for the question. Starting with dose, there doesn't -- at least in our experience, between the two Phases 1b cohorts, there doesn't appear to be a dose dependent. The differentiation syndrome is a pure -- just to take a step back. One expects to see differentiation with this mechanism. The extent and the severity of differentiation syndrome appears to be more patient-specific, maybe related to tumor burden, maybe more comment among KMT2A. We have such a small number. It's hard to draw really any definitive conclusions. But our experience has been with the enhanced mitigation strategy that physicians have the toolkit that they need to be able to manage the differentiation syndrome. And ultimately our experience either has been, again, if you're seeing differentiation and differentiation syndrome, that's usually a marker of clinical activity. And so what we've found with the investigators now is that they're leaning into that. They're making sure that they can get the patients through it and they have the -- we've talked about in the past than I can. I'm happy to summarize it again, if it's helpful, but we have a very thorough and expert enhanced mitigation strategy to give them the tools that they need. So it's something to watch out for with this mechanism of action. But it isn't really, we think, going to be any part of the determination of whether 200 milligrams or 600 milligrams is the recommended Phase 2 dose.

Thank you, that's helpful and just one other point to confirm that the top line data and nomination of the RP2D will that be disclosed together at the same time?

Yes. Yes.

Okay. And can we expect --

Yes

Any new PKPD or any additional data along with RP2D disclosure to support the rationale?

I don't know that we'll get into PKPD either because we want to make sure we protect the sanctity of the data set for the eventual presentation at a medical meeting. Suffice it to say all of the data will line up in support of the ultimate recommended Phase 2 dose. I think the thing that will matter is, again is, does the safety and tolerability continue and I can tell you now it does. And are you seeing a level of clinical efficacy that gives you confidence in a successful Phase 2. And what are the elements of that. This is going to be top-line data. They're probably going to be questions. I think it'll be a very fulsome presentation at the medical meeting in Q4 where will be able to get into things more like exposure and the kinds of questions that you are getting too.

Got it. Thank you so much.

Thank you.

That concludes our question-and-answer session. At this time up. Now, let's turn the conference back over to Mr. Troy Wilson for any closing remarks.

Thank you, Operator. And thank you all once again for joining our call today. We'll be participating in the Cowen Oncology Innovation Summit. The Jefferies Healthcare Conference in the JMP life sciences conference next month 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, Tom, or me.Thank you again, and have a good evening, everyone.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.