Q4 2023 Kura Oncology Inc Earnings Call
Participants
Pete De Spain; Executive Vice President of Investor Relations & Corporate Communications; Kura Oncology Inc
Troy Wilson; President, CEO, Board Member; Kura Oncology Inc
Tom Doyle; Senior Vice President of Finance & Accounting; Kura Oncology Inc
Jonathan Chang; Analyst; Leerink Partners LLC
Jason Zemansky; Analyst; BofA Securities
Li Watsek; Analyst; Cantor Fitzgerald & Co.
Peter Lawson; Analyst; Barclays Bank PLC
Justin Zelin; Analyst; BTIG LLC
Reni Benjamin; Analyst; JMP Securities
Brad Canino; Analyst; Stifel, Nicolaus & Company
Eva Privitera; Analyst; TD Cowen
Presentation
Operator
Good afternoon, ladies and gentlemen, and welcome to the Q4 2023 Kura Oncology Incorporated financial results conference call. (Operator Instructions) This call is being recorded on Tuesday, February 27th, 2024. I would now like to turn the conference over to Pete De Spain, Head of Investor Relations. Please go ahead.
Pete De Spain
Great. Thank you, Eric. Good afternoon, and welcome to Kura Oncology's Fourth Quarter and Full Year 2023 conference call. Joining me on the call are Dr. Troy Wilson, our President and CEO, and Tom Doyle, our Senior Vice President of Finance and Accounting before I turn the call over to Dr. Wilson, I'd like to remind you that today's call will include forward-looking statements based on current expectations.
Such statements represent management's judgment as of today, and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to Chorus' 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.
Troy Wilson
Thank you, Pete, and thank you all for joining us. Let's jump right. In last month, we reported preliminary clinical data from the first 20 patients in KOMET-007, a Phase 1 dose escalation trial of our menin inhibitor demented in combination with standard of care in patients with NPM1 mutant and KMT2A rearranged acute myeloid leukemia. The first 20 patients were enrolled and fewer than four months from July to November of last year, including five newly diagnosed patients with adverse risk AML and 15 patients with relapsed refractory AML.
The estimated demonstrated a highly encouraging safety and tolerability profile in combination with cytarabine plus donor represents or seven plus three as well as with venetoclax plus a decided in enabling continuous administration has implemented while effectively mitigating the risk of differentiation syndrome.
In fact, no differentiation syndrome events of any grade were reported among the first 20 patients. Furthermore, no dose-limiting toxicities, QTc prolongation, drug-drug interactions or additive myelosuppression were observed as of the data cutoff on January 11th, all five newly diagnosed patients with adverse risk NPM1 mutant or KMT2A rearranged AML treated with symptomatic seven plus three achieved a complete remission with full count recovery for a CR rate of 100%.
The overall response rate among the 15 relapsed refractory patients treated with symptomatic and ven aza was 53%, including the 40% ORR among the 10 patients who had received prior venetoclax setting with very limited effective treatment options. Notably the CR CRh rate among the nine relapsed refractory patients who were menin inhibitor naive was 56%.
As of the data cutoff, 16 of the first 20 patients remained on trial, including all 11 NPM1 mutant patients, continuous daily dosing of zip demented at 200 milligrams QD was well tolerated and the safety profile was consistent with features of underlying disease and backbone therapies. As we reported on January 30th, the 200 milligram doses implemented has been cleared in both relapsed refractory ven aza cohorts and enrollment at the 400 milligram dose continues.
In the meantime, I'm pleased to report we've also escalated to the 400 milligram doses if demanded in the frontline adverse risk, NPM1 mutant seven plus three cohort. And we anticipate clearing the 200 milligram dose in the frontline KMT2A rearranged seven plus three cohort shortly. At this rate, we expect to determine the recommended Phase two dose for Swift amended in combination with ven aza and in combination with seven plus three by the middle of this year.
After determination of the recommended Phase two dose, we plan to initiate a Phase 2 dose validation expansion, which Domenic been ven aza in newly diagnosed with patients with NPM1 mutant and KMT2A rearranged AML. In the meantime, we're now dosing patients in our comment zero zero eight study of zip demented in combination with additional standards of care, including the flit three inhibitor, gilteritinib flag, Geita or LD, all for the treatment of relapsed refractory NPM1 mutant or KMT2A rearranged AML, roughly half of patients with relapsed or refractory NPM1 mutant AML have co-occurring slipped three mutations, and the prognosis for these patients is particularly poor.
Preclinical data for Zevtera, many of in combination with plus three inhibitors demonstrates strong synergistic effects compared to either a single agent alone. We believe a best-in-class safety and activity profile and optimum pharmaceutical properties will enable system added to become a cornerstone of therapy for patients with acute leukemias.
This belief is supported by growing investigator enthusiasm as evidenced by rapid enrollment across all of our ongoing Zip demented studies. We continue to be encouraged by the rate of enrollment in common zero zero one, our Phase two registration directed trial of system ended in patients with relapse refractory NPM1 mutant AML, and we remain on pace to complete enrollment of all 85 patients in the trial by the middle of this year.
Our mission is to develop this momentum across the continuum of care for all patients with acute leukemias whose disease is driven by the menin pathway, including pediatrics, where poor outcomes unfortunately remain. In December, we announced that amended was selected for the Leukemia and Lymphoma Society's pediatric acute leukemia master clinical trial, commonly known as PedAL as part of the studies of demand and will be evaluated in combination with chemotherapy in pediatric patients with relapsed refractory KMT2A rearranged 98 rearranged or NPM1 mutant acute leukemia.
In addition, we recently began dosing patients with KMT2A rearranged acute lymphoblastic leukemia, a relatively small group of patients, but with a very large unmet medical need as well as a cohort of patients who have neither NPM1 mutant nor KMT2A rearranged AML. We also have a growing body of preclinical data that supports attractive opportunities for menin inhibitors beyond acute leukemias.
We're now preparing to initiate a proof-of-concept study in an undisclosed solid tumor indication later this year. Meanwhile, we continue to make progress toward a next-generation menin inhibitor, which we intend to direct to an additional soon to be disclosed indications. And with our recent financing, we remain in a strong financial position, which enables us to invest aggressively in research development and pre-commercial activities to maximize the value of this momentum and support our other pipeline assets.
Now let's turn our attention to our farnesyl transferase inhibitor programs. Beginning with KO-2806. Despite success of targeted cancer drugs such as tyrosine kinase inhibitors and KRAS inhibitors, a considerable need remains it drive enhanced antitumor activity while addressing mechanisms of innate and adaptive resistance.
We are developing our next-generation farnesyl transferase inhibitor, KO-2806 to address this need 2806 was designed to improve upon the potency, pharmacokinetic and physiochemical properties of earlier FTI. drug candidates. Last year, we presented compelling preclinical data supporting the rationale for combining KO-2806 with distinct classes of targeted therapies, including tyrosine kinase inhibitors and KRAS inhibitors.
In October, we began dosing patients with KO-2806 as a monotherapy in a Phase one dose escalation trial that we call FIT-001. FIT-001 uses an innovative design that enables us to begin dose escalation of KO. 2806 in combination cohorts very early on in the study while continuing to dose escalate concurrently as a monotherapy, we're now preparing to dose the first patients with KO-2806 in combination with cabozantinib in clear cell renal cell carcinoma and in combination with aggressive in KRASG12C mutated non-small cell lung cancer by the middle of this year. Recall in November, we announced a clinical collaboration and supply agreement with Mirati Therapeutics now Bristol-Myers Squibb to support that latter study.
We're encouraged that the strong operational execution seen in the domestic trials has carried over to the FIT-001 study and look forward to realizing the promise of the combination. If successful, we believe KO-2806 could become an ideal combination partner for multiple targeted therapies in large, solid tumor indications. Meanwhile, we continue to evaluate our first-generation FTI. tipifarnib in combination with the targeted therapy alpelisib building on impressive clinical benefit we observed with tipifarnib alone in head-and-neck cancer.
We continue to evaluate patients in the dose escalation study of tipifarnib and alpelisib, which we call current HN. Given encouraging clinical activity observed at multiple dose levels. We're adding additional patients to help inform selection of the optimal biologically active dose for the combination.
Once we determine the oh bad later this year, will determine the next steps for the program. Importantly, we are encouraged that tipifarnib continues to demonstrate a favorable safety and tolerability profile at its full dose. In combination with alpelisib, we believe this significantly derisks development of our next generation FTI, KO-2806 as we begin to evaluate it in combination with other targeted therapies.
With that, I'll now turn the call over to Tom Doyle for a discussion of our financial results. Tom?
Tom Doyle
Thank you, Troy, and good afternoon, everyone. I'm happy to provide a brief overview of our financial results for the fourth quarter and full year 2023. Research and development expenses for the fourth quarter of 2023 were $32.5 million compared to $22.7 million for the fourth quarter of 2022. R&D expenses for the full year 2023 for $115.2 million compared to $92.8 million for the prior year. The increase in R&D expenses was primarily due to increases in clinical trial costs related to our existing amended and KO-2806 programs.
General and administrative expenses for the fourth quarter of 2023 were $14.2 million compared to $12.5 million for the fourth quarter of 2022. G&A expenses for the full year of 2023 were $50.6 million compared to $47.1 million for the prior year.
Net loss for the fourth quarter of 2023 was $42.8 million compared to a net loss of $33.1 million for the fourth quarter of 2022. Net loss for the full year of 2023 was $152.6 million compared to a net loss of $135.8 million for the prior year. Net loss for the fourth quarter and full year of 2023 included non-cash share-based compensation expense of $7.2 million and $28.1 million, respectively.
This compares to $6.8 million and 26.3 million for the same periods in 2022. As of December 31, 2023, we had cash, cash equivalents and short-term investments of $424 million compared to $438 million as of December 31, 2022. Subsequently, on January 26, 2024, we completed an oversubscribed private placement with a select group of institutional and accredited health care specialists investors as adjusted for the approximately $146 million in net proceeds resulting from this private placement Kura had on a pro forma basis, $570 million in cash, cash equivalents and short-term investments. We believe that our cash, cash equivalents and short-term investments will be sufficient to fund our current operating plan into 2027.
With that, I'd now turn the call back over to Troy.
Troy Wilson
Thank you, Tom. Before we jump into the question and answer session, let me lay out our anticipated upcoming milestones for Swift amended initiate the post-transplant maintenance program in the first quarter of 2024, complete enrollment of 85 patients in the common zero zero one registration directed trial in NPM1 mutant AML by mid 2024, determine the recommended Phase 2 dose in combination with ven/aza and initiate dose validation expansion in frontline AML by mid 2024 and determine the recommended Phase two dose in combination with seven plus three by mid 2024 for KO-2806 of six dose.
The first patients in combination with cabozantinib in clear cell renal cell carcinoma by mid 2024 and dosed the first patients in combination with adagrasib in KRASG12C mutated non-small cell lung cancer by mid 2024 and for tipifarnib, complete enrollment of two expansion cohorts to support determination of the optimal biologically active dose in combination with alpelisib by the end of 2024 with that, Eric, we're now ready for questions.
Question and Answer Session
Operator
Thank you. Ladies and gentlemen, we will now begin the question-and-answer sessions. (Operator Instructions)
Jonathan Chang, Leerink Partners.
Jonathan Chang
So hi, guys. Thanks for taking my questions. First question on the momentum. Can you discuss your thoughts on the combinability with ven/aza and your thoughts on whether you need to adjust the dose and then due to drug-drug interactions and potential SiP 3A4?
Troy Wilson
Yes, sure, Jonathan. Thanks for the question. So I'll actually direct folks and there is a revised slide in the corporate deck. If you want to take a look at it, I mean, has the on the exposure curve by dose on the right side and on the left side, some of the key points, Jonathan, from zero zero one study. Most importantly, from the clinical data, we've now generated the human clinical data.
We can say is if demand is not a clinically meaningful SiP 3A4 substrate, we don't have to adjust its dose at all in the presence of Azores, for example, and it is not also not a clinically meaningful SiP 3A4 inhibitor. In other words, to your specific question, we don't have to adjust the dose of venetoclax, which is the SiP 3A4 substrate in the presence of 15 minutes.
Now I want to be clear, the protocol does allow for the adjustment of venetoclax dosing. If a patient, for example, is on a nasal that as per the label of venetoclax, but there's no dose adjustment needed when venetoclax is combined with estimated. So just to just to underscore, it's neither a substrate nor an inhibitor of SIP 3A4 Got it.
Jonathan Chang
Thanks for clarifying. And then just second question with the comment zero zero eight study started. And can you discuss the opportunity for Zevtera minute in combination with the three inhibitor? And what are your reasons for confidence in the combinability of these drugs?
Troy Wilson
Thank you. Sure. So the rationale is on or maybe just taking a half a step back when you look at the various combinations of the zero zero seven zero zero eight protocols, what our team Mollie Leoni, Stephen Dale and others on the team have endeavored to do is to provide a foundation where physicians can for in principle combined have demanded with any available standard of care, giving them maximal flexibility as they're dealing with patients in various lines of therapy.
More specifically to your question about Flip three. So Flip three mutants are represent roughly half of the NPM1 population. And you can see that, for example, in the gilteritinib and quizartinib studies of the extent of overlap between NPM1 mutant simply three mutants is roughly 50%. That's number one. Number two is if we could provide those patients with an all oral targeted therapy regimen that was effective and well-tolerated. We think that would be be broadly embraced up InnoRx in our discussions with physicians. Gilteritinib is very popular and the preclinical data that we've generated.
Admittedly, it's preclinical, but the preclinical data combining flit three inhibitors with domain at the results of our newly curative. I mean, I'll say that curative, I use that word carefully, but the potential Jonathan, to have an all oral regimen that could drive such a profound clinical benefit in patients we think would be very attractive. So it's a huge slice of the population, the possibility for an all-oral regimen and something approaching a cure with the way with excellent tolerability in terms of managing the safety.
The thing that really that we've just want to make sure we pay attention to is the potential for differentiation syndrome. It was observed with the flit three inhibitors. However, we think that by sequencing and sort of careful monitoring and mitigation will be able to deal with that. We, along with the field and the investigators understand differentiation syndrome much better now. And so I think we're feeling we're feeling optimistic that we'll be able to find a dose and schedule that gets those two agents working well together with them.
Jonathan Chang
And we'll look forward to sharing our progress later this year. Understood. Thanks for taking the questions.
Troy Wilson
My pleasure.
Operator
Jason Mansky, Bank of America.
Jason Zemansky
Perfect, and good afternoon and thank you for taking our questions. I I'm curious about oh seven as the patients continue to hopefully be well on therapy and potentially approach hematological recovery with longer duration of therapy what are your expectations in terms of moving them off of therapy? Is the idea maybe to keep them on Xarelto and maybe pull back on S. as which usually happens or why would you necessarily discontinue the menin inhibitor at some point? And then a follow-up, if I may.
Troy Wilson
Yes, Jason, thanks for the question. So importantly, when you've heard it in the prepared remarks, we don't see any additive myelosuppression. And as a result, we don't have to hold the dosing of this deal at all to allow counts to recover on at one time, it was thought that there might be a class effect.
We certainly don't see that was implemented to your to your question, which I think is the well formulated our experience has been that physicians use. I mean, obviously, they used seven plus three for seven days or three days that has indicated for ven/aza that they're using it to really drive the clinical activity and then they're pulling back their keeping patients on zifto.
I think our our intent and sort of what we're seeing is that these patients are staying on this, though if they go to transplant, they might take a break while they're conditioning for transplant, but then they're coming back on to zip demented monotherapy arm post transplant in a in a in a maintenance setting sort of using the air quotes. That's how we would expect this to be used.
Jason is literally from day eight and then really only within interruption, perhaps for transplant patients would stay on demented until disease progression or and or the alternative. And we haven't had patients on long enough to say do they no longer need to be on as if they'll have we cured them of the disease. That's a that's a dream. But so that's that's for someday in the future.
Jason Zemansky
Got it. And then looking at your time lines and thinking about the bigger commercial dynamics here, you're potentially looking at a scenario where you may be a next to market menin inhibitor in the NPM1 space with potentially better efficacy. How are you thinking about launching into this space? I guess what I'm really driving at here is at this stage, do you get the sense that the community, the prescribing community is the two different menin inhibitors is more distinct versus similar. I mean, what what's the feedback been like here?
Troy Wilson
Yes. So you know, look, we've done a small amount of sort of precommercial work with them with physicians. And what we found is when we profile the system in a target product profile as informed by data and we put it up against the competition. We hear sort of an overwhelming preference to use this momentum, primarily driven by by the safety and tolerability.
No, no SiP 3A4 liability, no dose-limiting toxicity. And I think that's only going to continue and get amplified, Jason, as we as we move into combinations.
So and on, I would also say I'm not I think we're not really willing to concede yet that we're going to be second to market in the NPM1 setting. To my knowledge, neither study has yet completed enrollment. I know maybe there are some updates today from the competition, but our enrollment continues to be robust. And if we've got a well-powered study and we intend to move very aggressively, I think we'll be well positioned.
And if anything, again, I keep going back to our enrollment because all other data points, you know, they can be shaded in various ways. Enrollment is objective and rapid enrollment is difficult to argue with and we've already mentioned we continue to make progress. We're looking forward, I think, to being able to move into the 600 milligram cohort cohort here before too long. That enrollment speaks for itself, and we expect to see that pull through into the commercial marketplace. (multiple speakers)
Jason Zemansky
But but that was a follow up. Thank you so much for that for the insights and color.
Troy Wilson
Our pleasure. Thank you for the questions.
Operator
Li Watsek, Cantor Fitzgerald.
Li Watsek
Hey, good afternoon. Congrats on the progress and maybe just a couple follow up questions from me. I'm just wondering if you can clarify the plan for data disclosure for zero seven stay around next year and other than RP2D dose selection, would you be sharing data at higher doses and also, can you comment on if you have started to dose patients at 600?
Troy Wilson
Yes. So thanks, Lee, for the questions, but let me take them in reverse order. So as of today? No, we haven't started yet dosing patients at 600. I think you can you can hear from us. We're encouraged thus far by what we're seeing. And as you know from the monotherapy, there's nothing that we've seen that really gives us cause for concern.
But one still has to run the experiment in terms of what data one might expect and so obviously, going back to the January update, which feels like a lifetime ago, but was just about a month ago on that point, we had 20 patients that we for which we shared data and we were focused on safety, tolerability, combinability and then some early signs of activity on the next logical update. Ideally, you said it in your question.
I think it's right, is around the RP2D, are we able to dose escalate? What does that look like from again, safety, tolerability, combinability? Is there any difference or are we simply giving more Cisco. When we give an update, we'll give an update on all the patients on study. And you can tell everyone probably remembers each of these four cohorts are at least six patients per dose.
And I want to be careful with that. There may be additional patients simply because if we get them in screening and but we're not yet ready to escalate. We might tack on a couple of more patients at a given dose. So expect six plus patients per cohort per dose. And you can hear us moving moving pretty pretty aggressively through these dose cohorts.
Finally, as to timing, yes, there, I think we're keeping all the options open. I obviously we're going to have a presence at each half. It's one of the most important team meetings.
In terms of the update on this study, there might be something there that could be something in a corporate update. I think we know what people are looking for and we want to make sure we have that data rather than sort of being necessarily constrained by the precise timing of the medical meeting. We still have lots of time until that happens, and we're making good progress and we'll certainly look forward to giving a more fulsome data update on oh seven a bit later this year.
Li Watsek
Okay. And then maybe a follow-up question. And George, you mentioned about your enrollment speed here and given the very strong data from those seven study last month, I guess what is your expectation for the enrollment rate for the digital age? And also in terms of from clinical sites? What's the degree of overlap between these two studies?
Troy Wilson
Yeah. Good question. So again, I appreciate it's a two-part question. Let me take the second part first, because it's a little easier at this point. There's sort of minimal overlap between oh seven and oh eight. We're trying not to create situations where where sites are our competing, although the trial that they go on to is largely driven by the line of therapy.
So the frontline patients obviously have frontline options for oh seven once we reach the RP2D, for example, for ven/aza, we'll do the expansion validation in the frontline, right, so that that will be self limiting the job. I think it's early only we've we've just really, you know, gotten gotten going. We're sort of taking the first tentative steps on oh eight. We'll have a better sense of how that's going as as the weeks and months continue.
Oh seven is going very robustly and job as is oh one. I think we have every expectation oh eight will as well. We particularly expect to see interest in gilteritinib. We have the investigators fondly refer to to this study as the Flip three study on. I think they're excited to see this combination, and we're excited to get going on this study and begin to get some experience. So look forward to an enrollment update on oh eight. Again, the next time we have the microphone or a little later in the year.
Li Watsek
Thank you very much.
Troy Wilson
Sure.
Operator
Peter Lawson, Barclays.
Peter Lawson
Great. Thank you so much. Thanks for the update. Had a quick question on comm at zero zero seven combo. And just why is if those starts on day eight, there's any worries about drug-drug interaction or just the rationale?
Troy Wilson
Yeah. So actually the opposite, Peter. So I don't know if you heard the answer to the question that Jonathan asked, but there is a new slide in our corporate presentation that I would direct everybody to that says, as clearly as we can say at Cisco is neither a SiP 3A4 substrate nor a SiP 3A4 inhibitor. There is no to date, no observed drug-drug interaction, full stop right in anything that we've seen either monotherapy or combo.
The rationale for the day eight start is actually pretty simple number. It gives you it gives you three things, three advantages. Number one, you debulk the patients less disease means you have a lower propensity for differentiation syndrome. You're just physically debulking the tumor. Number two, you get a baseline safety view so you can differentiate. What's what are effects due to the backbone versus effects due to Z still plus the backbone.
And number three, it gives you time to ensure that you're enrolling the right patients, particularly NPM1 sometimes the turnaround time takes several days. And so you want to make sure that you're not you're not losing slots on patients who aren't who ultimately are not are not eligible.
Those are the three reasons. And we've been I'm extremely pleased by the results, I will say, as folks know, we have Bristol-Myers Squibb as an equity investor back to at ASH 2022, they made a $25 million equity investment and we have a continued good relationship with them. They were actually encouraged us to do that staggered dosing and all of our combos for exactly the reasons that I enunciated to you and these are folks who do research development commercialization in the market. I think that was very good advice that has served the program well.
Peter Lawson
Perfect. Thank you so much. Thanks for clarifying that. And then just on the expansion cohort, that's really interesting. So patients without NPM1, KMT2A or they've got particular mutations you're targeting, or is that kind of an all-comers approach. Just curious on how you're kind of focused.
Troy Wilson
Yes. So thanks for the question. So to clarify for everyone in the prepared remarks, we announced that we've dosed the first patient in in in a in addition to zero zero one. It's not part of the registrational study, but it's part of the oh one protocol that is looking to dose system ended at its RP2D at 600 milligrams in patients who are neither KMT2A nor NPM1 mutant at.
Why are we doing that? Well, if you go back to the results from the Phase Ia Ib, you'll recall we saw a number of patients, multiple patients who had evidence of clinical benefit, blast count reduction, disease stabilization. We even went so far as a patient with [SST to run x one double] mutant who had a CR at the 100 milligram dose at that time. I don't think we understood and how to use this dose as well as we do today.
And B, really what to look for and investigators confused in some cases, differentiation and to progression, they're no longer making that mistake. So no, it's a great time to go back into that population. It could be as much as 10% to 15% of AML and ask the question, what do we see as a monotherapy if we see evidence of clinical benefit, we might pursue it as a monotherapy, we might pursue it in combination. It might help broaden the scope of the combinations.
Peter, to your specific question. The way those patients are selected is via an algorithm that picks among selected mutants that we have evidence it confers a sensitivity to menin inhibition. So it's not an all comers population. It is enriched and it's enriched via an algorithm.
Peter Lawson
Perfect. Perfect. Thanks so much. Really appreciate it.
Troy Wilson
Pleasure.
Operator
Justin Zelin, BTIG.
Justin Zelin
Thank you for taking the questions and congrats on the progress so far you mentioned on interrogating men in other indications outside of acute leukemia. As you mentioned, some solid tumor and non-oncology indications so that the with this though or next-gen molecule and do you have an idea of when we might see some early translational data from this programs?
Troy Wilson
Yes, just in a really good question. So so let's tease those two. Those two parts. Apart on, we really view this domain as having an ideal, some ideal properties for oncology applications and I'll confess to you and it was partly by design and partly by good fortune. As you know, Xenical accumulates it has very high tissue penetrants it. You know, essentially you are saturating the tissues with high concentrations of menin inhibitor, and there's never a time when the target isn't covered.
As a consequence, that's really attractive for oncology indications where you kind of need and always on for non-oncology applications, you may actually want to have somewhat of a different profile. I will tell you we've made a significant investment in next-generation compounds. We have ones for both oncology and non-oncology, and we're waiting to share the translational data until we're further along toward execution of the clinical experiment because like let's be honest, this is a competitive field.
We view ourselves as scientific innovators on it that we know we're going to attract competition. So we're holding those cards a little closer to the vest. And but we're quite excited. We're doing the work to prepare for that study and to share with you some of those data a bit later in the year we'll do the oncology, the solid tumor experiment just and we think with this, though, on the other applications, I think we're leaving that open and we'll use the best menin inhibitor for the job, and I think we're going to have multiple options there.
Justin Zelin
Great. Looking forward to and thanks for taking the questions.
Troy Wilson
Sure. Thank you.
Operator
Reni Benjamin, JMP Securities.
Reni Benjamin
Hey, thanks for taking the questions, guys, and congratulations on the progress. And maybe just two questions from me. Troy, one in the prior data that you guys had already reported from oh seven, you talked about 10 patients already received prior venetoclax, and you are still seeing a 40% ORR. And I don't know if this was asked before and I suggest when could potentially be taken out of that regimen and a less toxic call it Zip, though is a combination could or should be evaluated on? Or does it suggest maybe something else that maybe menin inhibition is really sensitizing patients to be seen? And that's one question.
The other is more from a commercial and it seems you're evaluating that throughout the continuum of AML treatment and it might actually resolve if I'm thinking about this right in the cannibalization of Zyflo in later lines of treatment. And so how does this work in the real world as you're kind of evaluating this? Or is this are all these combination studies really more to maximize BD discussions and ultimately confirmatory studies will be run in hands?
Troy Wilson
Right. Okay. So several questions on several questions. Packed in there around maybe taking your second question, second set of questions. First. So the yes, you will by design cannibalize those them cannibalize those later lines. If you're successful our goal, I think the goal of everyone in this field is to prevent the need for use in the relapsed refractory setting by treating patients in the upfront setting. And our goal is to treat patients early in lines of therapy where the benefit the clinical benefit is potentially much greater. Will that come at the expense of the relapsed refractory?
It will. But ultimately that's that's better for patients, offers them a better clinical benefit and it is arguably a more compelling commercial case on the the combinations that we're doing, we really are wanting to make wanting to generate safety data to give physicians freedom of choice for example, there are fewer drugs approved in Europe than in the US. The all that combination might be very attractive in Europe.
On Dr. Mollie Leoni, yes, you know, who's the clinical lead and you know, and our EVP of clinical development for four for Curragh has said it doesn't really matter how you get patients to a response. If you can get them there with a quote-unquote softer response that's better. You don't have to use a hard chemo. Your goal is to get them to respond to an LTE. It might be an attractive way to do that.
You heard me answer the question on Flip three. That's another option, not so much driven by BD considerations, although I will say to you, we recognize to fully maximize the value of menin inhibition in these various indications.
As I think we've said this before, at some point, we would likely need to engage a partner in some sort of strategic relationship because that's just what it's going to take to generate, you know, a multi-billion dollar sales numbers in a in a in a multi-player market with respect to your specific questions on the oh seven study in ven aza, I guess a couple of clarifications.
So the significance of seeing responses in patients who are venetoclax failures is you're in these these are single-arm dose escalation studies. I mean, you're really kind of sprinting at times to say what's clinical activity, but it's pretty well established for patients who failed, then they don't respond to ven retreatment that I think most physicians will agree with that. That is a disease of high unmet need.
How is that happening? Is it that we're blocking a driver mutation like an NPM1 or KMT-2806A-r, we blocking MCL1 are we interacting with BCL-2 to resensitize the tumor. We're still figuring that out what does appear to be clear is that a menin inhibitors plus then are better than ven alone? That seems clear to your question. I don't think you would go man in Asia.
I think you might go up venetoclax menin inhibitor and do the doublet. You may not need the Asia. And as we've talked about in the past, we will do that experiment when the time is right, we'll actually ask the question. Do we need the triplet of ven is amended or can the doublet will the doublet suffice and that's something you just have to figure out empirically, but we're going back to oh seven. And again, I'll acknowledge our colleagues at Syndax. We've both seen activity in venetoclax failures, and I think that's highly encouraging of the clinical benefits that these menin inhibitors can provide.
Reni Benjamin
Great. Thanks for taking the question.
Troy Wilson
Sure.
Operator
Brad Canino, Stifel.
Brad Canino
good afternoon, Troy, how important does response durability become at your next combo data updates?
Troy Wilson
I mean, it's important, Brad, it's always important, but I would say I cautioned people at the time with the 200 milligram dose, we're looking at an immature data cut in a dose escalation study. So I'd be careful not to over-interpret up ideally you should be seeing a direction of travel that is better than the monotherapy, right? It will the data be mature enough and hard to say we're still. I mean, obviously, we haven't dosed a patient yet at 600 milligrams.
So if we were to disclose in the next several months, we'll be limited in terms of what we can say about durability I do think it's important. We have every reason to believe as we go into combinations as we go earlier, durability will improve. There isn't anything that's suggesting it. There's nothing we're seeing there's nothing we're seeing from others that would suggest that that wouldn't be the case. And I wouldn't have an undue reliance on that one data point.
What I would be looking for Brad is can we combine effectively at 600 milligrams with those standards of care? Because if you go back to the monotherapy, that's the optimal dose from a monotherapy perspective, it maximizes exposure after that it plateaus, it should be no different. And the combos, that's the critical data point to look for the durability will come in time. And I'm on. I think we're cautiously optimistic. it will inform in the right direction.
Brad Canino
Okay. And then another question. We talked a lot about potential best-in-class drug properties on this call. And in others. But as we move towards more substantial than a triplet data from both you and and other MET inhibitors that are being developed, how do you expect potential differentiation might emerge in those clinical data reported in the Phase 1, 2 studies?
Troy Wilson
Yeah. So it's it's going to take the form in a couple of different ways. So there's a I would say does one need to hold the menin inhibitor to allow counts to recover. That's question number one. And when you get out into the real world in a broader population, if you have to hold the menin inhibitor that potentially gives the disease a chance to escape.
The second is one of our competitors presented data in a post-transplant maintenance study and you can look at the rate of dose reduction or interruption or discontinuation due to AEs. And with several minute inhibitors, we're seeing a high rate of thrombocytopenia that is not that is not on mechanism. That's something else. We don't see that couple of the other compounds don't see that, but that is a characteristic of some menin inhibitors.
So I think Brad is going to go kind of both directions. Number one, can you keep constant pressure and constant exposure? Number two, can you really saturate all the sites in the body on a sustained basis. I would argue to you that if you can base a patient in a menin inhibitor, essentially indefinitely with no tox, that's probably the best thing you can do to delay recurrence. I think that's a good setup resistance because of its physical chemical properties because of its tolerability, how that's going to manifest itself, that's going to take time. You're going to see it emerge in the form of resistance and then that's going to play out in survival.
But that will take some time. Something I've said pretty consistently is if you show me a race between two drugs and their equivalent on activity, the safest, most well-tolerated, most combinable drug always wins full stop, and I think Zip does well positioned there. But yes, there's not for people who were looking for some kind of knockout blow. That's not coming right? This is going to be a multiplayer, hopefully, multi-billion dollar market. That's really good for patients will be competing out there. The more data we generate with Zifto, the more excited we become.
Brad Canino
Very helpful. Thank you.
Troy Wilson
Sure, thanks.
Operator
Eva Privitera, TD Cowen.
Eva Privitera
Hi, good afternoon and thank you for taking your questions. So with escalation going really well and 007 and the RP2D expected midyear, when could shift or potentially move into pivotal development to-date with either chemo or ven/aza combos? And what could be a potential design? Do you think MRD negativity could be a registrational endpoint.
Troy Wilson
Yes, a bit of thanks on saving the best questions for last. So on in terms of timing for development, it's a little bit early. We recognize again, it's a competitive landscape. I think realistically you probably wouldn't dose a patient in a pivotal until early next year. But you can imagine we're already putting the designs together on the basis of the data we've generated thus far, right, based on what we're seeing in the oh seven study.
I think we're highly encouraged. It's a matter of dropping the data into supporting a big part of that is the lead time to actually engage with global health authorities. And you could potentially have the study up and running by the end of the year, but you would it would be very aggressive to dose the patient. I dare say it would be impossible to dose patients just because these things take time right and we do need to do the expansion to make sure that we validate the dose.
As for your question about MRD, probably not an end point at this point I think you know, there are a number of parties that are working as part of a consortium to help the field move in that direction. It's not likely to be an endpoint, but it is likely to be supportive of. We do think that there's likely to be an integrated design where you'd go with an accelerated endpoint probably based on response and then a full endpoint based on survival and the agency that it's been pretty clear. That's what they're looking for project Front Runner. They want to see that as a first approval but the themes of project Front Runner carry through to designs, how can we do a seamless design? That's very much what we'll be looking at here in the various combinations.
Eva Privitera
Thank you, that's helpful. And a quick follow up on an earlier question about additional genetic subtypes and Dirk, where you're pursuing other activity, does this patient selection algorithm enrich for the hockey nice transcriptional pathway.
Troy Wilson
It's so there is an association of EVA. I think we remain unconvinced that if you use hops nice expression and as your selection algorithm that that's going to work. What we're doing instead is mutations, which are a proxy for that. What's clear is, you know, this is a central no rights. This biology is fundamental to leukemia. It's wired into MCL1 to BCL-2 to Flip3 to IDH.
I don't think we fully understand all the wiring. And so we're going to do our best and see if we can enrich for a signal. And I think we're particularly optimistic of what might be possible when you then go and layer that on top of say example, venetoclax or Flip3 or something that might give you an extra arm on back in the 1a 1b days, people kind of shrug.
Everybody wants to see a CR, right, but actually blast count reductions, you know, sustained disease stabilization in this setting is really clinically meaningful. And it's telling you like spend more time here. Look here, it's giving you a little neon sign. So that's what we're doing and we'll see where it goes. But but it's associated with hogs.
Nice, but it's not it's just an association. It's not going to be a direct correlation. I hope that helps.
Eva Privitera
That helps a lot. Thank you.
Troy Wilson
Sure.
Operator
I would now like to turn the call back over to Troy Wilson for closing remarks. Please go ahead.
Troy Wilson
Thank you, Eric, and thank you all once again for joining our call today. We'll be participating in several investor conferences over the next couple of weeks, and we look forward to seeing many of you there in the meantime, if you have any additional questions, please feel free to reach out to Pete to Tom or to me. Thank you again, and have a good evening, everyone.
Operator
Ladies and gentlemen, this concludes the conference call for today, and thank you for participating. You please disconnect your lines.
