Q2 2023 Kura Oncology Inc Earnings Call
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Good afternoon, ladies and gentlemen, and welcome to the Q2 2023 care Oncology, Inc earnings Conference call.
At this time all lines are in listen only mode and following the presentation, we will conduct a question and answer session.
At any time during this call you require immediate assistance. Please press star zero for the operator.
This call is being recorded on Thursday August three 2023.
I would now like to turn the conference call.
Over to you Mr. Pete de Spain, the head of Investor Relations. Please go ahead.
Thank you Kevin Good afternoon, everyone and welcome to current oncology second quarter 2023 conference call joining.
Joining me on the call are Dr. Troy Wilson, our President and Chief Executive Officer, and Tom Doyle, Our senior Vice President of Finance and accounting before I turn the call over to Dr. Wilson I would like to remind you today's call will include forward looking statements based on current expectations.
Such statements represent managements judgment as of today and May involve risks and uncertainties that could cause actual results to differ materially from expected results.
Please refer to <unk> filings with the SEC, which are available from the FCC or on the curl oncology website for information concerning risk factors that could affect the company with that I'll now turn the call over to Troy.
Thank you Pete and thank you all for joining US this afternoon, let's jump right in.
In June we reported updated data from the comment 001 trial of our met inhibitors at the minute, including durable activity in patients with heavily pretreated and co mutated relapsed refractory N. P. M. One mutiny acute myeloid leukemia. These.
These data were featured during the late breaking oral session at the European Hematology Association annual Congress in Frankfurt.
As of the April 12 data cut off seven of the 20 patients with N. P. M. <unk> mutant AML, who were treated at the recommended phase two dose of 600 milligrams achieved complete remission with full count recovery for a CR rate of 35% and an overall response rate of 45%. This represents one of the highest response rates rips.
And for a targeted therapy in the setting of relapsed refractory leukemia.
Any patient who had a CR with partial count recovery. After treatment was just a minutes subsequently evolved to a CR with full count recovery after transplant and remained on study as of the date of the Ehow presentation. In addition to patient with N. P. M. <unk> mutant AML treated at 200 milligrams remained on Ziff demand for 36 cycles as of the cutoff date.
The median duration of response for all <unk> mutant patients was $8 two months with a median follow up of eight eight months continue.
Continuous once daily dosing of just a minute was well tolerated in the phase one study and the reported adverse event profile remains consistent with features of underlying disease.
As a reminder, M. P M <unk> mutant AML accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists once the disease becomes relapsed or refractory the prognosis for N. P. M. <unk> mutant AML patients is especially poor.
N P. M. One mutant AML is further compounded with co mutations such as <unk> and flip three notably in our phase one study, 33% of patients with <unk> mutations, 50% of patients with <unk> mutations and 50% of patients with both slipped three and <unk>.
<unk> achieved a CR <unk> ziff demand.
All of whom had failed prior treatment with IV H <unk> three inhibitors.
We remain impressed with the ability of <unk> to drive durable remissions as a monotherapy in this difficult to treat population and we believe these data early further demonstrate its potential best in class product profile building.
Building on momentum generated by our <unk> data enrolment in our phase II registration directed trial of <unk> in patients with relapsed refractory <unk> mutant AML continues to outperform projections.
Which speaks to both the size of the population.
And it's significant unmet need.
Our study is expected to enroll a total of 85 patients in the United States and Europe .
In parallel with our efforts to advance <unk> as a monotherapy we're conducting a series of studies in combination with current standards of care in earlier lines of therapy and across multiple patient populations, including <unk> mutant AML and <unk> rearranged AML.
Our approach to combinations is to establish <unk> as a foundational therapy that can be combined safely with various commonly used regiments and then prioritize those combinations that represent the greatest unmet medical need and the greatest potential commercial value, namely Venetic class and flip three and.
Herbert are containing regimens.
Combination approaches also offer the potential to mitigate differentiation syndrome, particularly in the Kmt <unk> rearranged population as has been previously demonstrated in the development of <unk> inhibitors in combination with a society in that regard I am pleased to report we're now dosing patients in the first of our combination studies.
Which we call comment 007 in both the newly diagnosed and relapsed refractory settings.
<unk> 007 is a phase one study designed to assess safety tolerability and preliminary activity of <unk> in.
In combination with either <unk> or standard induction cytarabine, Donna Rubinsohn chemotherapy, commonly known as seven plus III. This study is expected to enroll patients with MTN, one mutant or Kmt <unk> rearranged AML across sites.
In the U S and Europe .
We anticipate having preliminary data from the comment 007 study in the fourth quarter of 2023 or the first quarter of 2024.
We're also working to initiate our comments 008 study of <unk> in combination with additional standards of care, including the flip three inhibitor Delta written Nib. Later this year. In addition, we expect to begin our post transplant maintenance program for <unk> in the first quarter of 2024, we are very excited about the potential.
For these studies to further demonstrate the value of our Menin program and establish <unk> as a backbone of therapy across the continuum of care for AML patients.
Now, let's turn our attention to our Farnesol transfer Ace inhibitor programs, beginning with <unk>, we continue to work to unlock the substantial therapeutic and commercial value of Farnesol transfer Ace inhibition and we believe this novel mechanism is uniquely positioned to deliver clinical benefit in multiple large solid tumor indications.
The first such opportunity is in head and neck squamous cell carcinoma through the combination of <unk> and the Pi three kinase alpha selective inhibitor <unk>.
And neck cancer is the seven most common cancer worldwide and it remains a significant unmet medical need with no approved small molecule targeted therapies.
The objective response rate for the three FDA approved therapies for treatment of <unk> SCC in the second line range from 13% to 16% with median progression free survival of two to three months and a median overall survival of just five to eight months recall, we previously reported the first demonstration of a durable.
<unk> response, with the combination of <unk> and <unk> in a patient with <unk> mutated squamous cell carcinoma of the tonsil since that time, our dose escalation study has continued with no dose limiting toxicities to date observed for the combination.
We are encouraged both by the safety profile as well as the clinical activity, we're seeing in the trial, which we call current HN with continued evidence of activity at multiple doses and enhanced activity relative to our expectations for either drug alone in this population.
We are now evaluating patients in the studies highest planned dose cohort to help inform selection of the optimal biologically active dose for the combination.
Once we determine the aubade, we intend to initiate a small dose expansion of patients with <unk> mutant <unk> FCC to validate the safety profile and activity of the combination at the recommended phase II dose.
Meanwhile, we've generated a growing body of preclinical data that supports the combination of Farnesol transfer ace inhibitors with multiple classes of targeted therapies to either prevent or delay emergence of drug resistance and large solid tumor indications.
In April we presented encouraging preclinical data at the American Association for cancer Research annual meeting supporting the potential use of <unk> in combination with two additional distinct classes of targeted therapies. The first of two posters revealed robust synergy between <unk> and <unk>.
Standard of care anti Angiogenic tyrosine kinase inhibitor or TK I exit nib in sell in patient derived xenograft models of clear cell renal cell carcinoma.
Second poster reported regression of multiple models.
<unk> K Ras inhibitor resistant non small cell lung cancer by the addition of <unk> to either at <unk> or <unk> therapy.
These promising preclinical data illustrate the potential for <unk> to drive enhanced anti tumor activity and address mechanisms of innate and adaptive resistance to targeted therapies. In addition, we believe these data strongly support our rationale to combine our next generation Farnesol transfer Ace inhibitor, which we call <unk> 28, a six.
With TK is in clear cell renal cell carcinoma, and with <unk> specific mutant specific inhibitors in non small cell lung cancer.
Earlier this year, we received FDA clearance of the investigational new drug application for <unk> 26 for treatment of advanced solid tumors.
We intend to evaluate the safety tolerability and preliminary antitumor activity of <unk> in a phase one dose escalation study, which we're calling fit 001.
We've begun site activation and Fitzgerald zero, one and look forward to dosing the first patients in the study later this year concurrent with the dose escalation as a monotherapy we plan to evaluate <unk> six in dose escalation combination cohorts in advanced solid tumors, beginning with clear cell renal cell carcinoma with that.
I'll now turn the call over to Tom for a discussion of our financial results.
Thank you Troy and good afternoon, everyone I'm happy to provide a brief overview of our financial results for the second quarter 2023.
Research and development expenses for the second quarter of 2023 were $28 2 million compared to $24 3 million for the second quarter of 2022.
The increase in R&D expenses was primarily due to the increases in clinical trial costs related to our system and it until 'twenty six 'twenty six programs.
General and administrative expenses for the second quarter of 2023 were $11 8 million.
Compared to $11 1 million for the second quarter of 2022.
Net loss for the second quarter of 2023 was $37 $2 million compared to a net loss of $34 8 million for the second quarter of 2022.
This includes noncash share based compensation expense of $7 million.
Compared to $6 5 million for the same period in 2022.
As of June 30, we had cash cash equivalents and short term investments of $477 million compared to $438 million as of December 31, 2022.
This includes net proceeds of approximately $94 million from our public offering completed in June of 2023.
We believe that our cash cash equivalents and short term investments will be sufficient to fund our current operating plan to mid 2026.
With that I'll now turn the call back over to Troy.
Thank you Tom before we jump into the question and answer session. Let me lay out our anticipated milestones for the remainder of this year and next year for <unk> dosed. The first patients in the comment zero-zero eight combination trial in the second half of 2023.
Preliminary data from the comment 007 combination trial in the fourth quarter of 2023 for the first quarter of 2024 and dose the first patients in the post transplant maintenance program in the first quarter of 2024.
<unk> initiate dose expansion in the current HN trial in mid 2024.
And for <unk> 20, 806 dose the first patients in the Fitzgerald zero, one dose escalation trial as a monotherapy in the second half of 2023 and dose the first patients in the fit 001 dose escalation trial in combination with a targeted therapy in clear cell renal cell carcinoma in the second half of 2024 with that.
<unk>, we're now ready for questions.
Thank you.
Ladies and gentlemen, we will now begin the question answer session. So do you have a question. Please press the star followed by the one and you touched on funding.
You will then hear three tuned prompt acknowledging your request and your questions will be pulled in the order that they are received.
Should you wish to decline from the polling process. Please press the star followed by the Q can.
And if you are using a speaker phone please lift the handset before pressing any keys one moment. Please for your first question.
And your first question comes from Jonathan Chang from Leerink Partners. Please go ahead.
Hi, guys. Thanks for taking my questions.
First question can you give us any more color around enrollment progress and the registration directed study of Cisco minutes, and NPM, one ml and what do you mean by outperforming projections.
Sure. Thanks, Jonathan for the question so.
We have guided or I should say, we anticipate a full.
Full enrollment of the 85 patients in the study.
Approximately the middle of next year, and just to take a half a step back just to remind everyone. We size. The trial at 85 patients because it was our view that for a potentially best in class therapy. The agency would likely want to see approximately 100 patients worth of safety data at the recommended phase two dose.
It's it's still early days, Jonathan but in terms of both site activation and now enrollment of patients on the study.
We are.
Ah.
Ahead of quite a bit ahead of where we expected to be.
And we obviously have enrollment curves under different scenarios.
We haven't yet made any adjustments to our guidance in terms of timing of overall enrollment.
Want to see how the rest of the summer goes in a little bit into the fall, sometimes you see a slowdown in the late summer.
Want to just be mindful of that but what we want to communicate is there's very strong interest.
Among both physicians and patients and that seems to be translating directly into enrollment. There also jonathan appear to be more patients. Then I think we had anticipated both from potential competitors and other folks who've tried to enroll trials and the NPM one space.
There was some sort of anecdotal comments out there that it might be challenging to enroll that hasn't been our experience at all in fact quite the opposite.
Since <unk> now on the other side of Ehealth, we're seeing very very very strong interest, which is translating into enrollment and I think thats driven Jonathan in part because of the data that I just very summarily walked through the fact that we are seeing activity in patients who failed flip three patients who.
Failed ADH patients with various co mutations I don't think were seeing a siphoning off of patients to those other trials instead there.
We're seeing very strong interest in putting them on the <unk> monotherapy study and we have every expectation that's going to translate into the combos.
Which is which is its even earlier days, there, but but I think we're quite encouraged.
Okay.
Got it. Thank you and second question can you discuss the post transplant maintenance opportunity Francisco minutes.
Sure Yeah, let me just clarify there.
We're actually going to do both the post transplant maintenance as well as just the maintenance.
Without requiring transplant and let's talk about how those are different. So so first of all without needing to get to transplant. Our protocols have made allowances for patients to be able to stay on study. So for example patients who are enrolled in <unk>.
Seven plus three plus Ziff Dell can stay on Ziff Dell.
Maintenance type of.
Setting.
But and that's and we've built that in.
Everywhere, we can so that's obviously important and I think has.
<unk> has the potential to drive value.
Our team I think is thinking very cleverly of the post transplant setting Jonathan.
What we're shooting for is to be able to capture patients no matter, how they get to transplant, whether they've had a prior <unk> inhibitor.
We're not no matter no matter, where they have gotten if they meet the entry criteria and they are on the other side of transplant there'll be eligible to go into that study. It's our view Jonathan that given we have such a favorable safety profile. We have no Qt prolongation, we have no evidence of drug induced <unk>.
And we just have a very very attractive safety profile.
We really have the opportunity to be a preferred agent in the maintenance setting and we've heard from sophisticated parties. That's a very attractive commercial opportunity. If you can keep patients on there for a year or two.
That has the potential to drive really significant value both for the patients as well as for the value of the overall enterprise. So and then the final thing Jonathan I'll comment on is we are trying.
If people have been paying attention to the way we've laid these studies out thus far all the studies we've undertaken our current specific studies Corresponsive studies. So that we can drive the timing and they are all sort of very much value, creating with the maintenance study. We will do an initial phase one study as an investigator sponsored.
<unk> to gather enough data and then we'll flip it over into a <unk> sponsored study if it makes the transition into a phase II three so we're trying as much as we can to retain control of the studies to be able to drive timelines and execution and thus far that's that's working quite well.
Understood. Thanks for taking my questions.
Our pleasure thank you.
Thank you Andy.
Your next question comes from Roger song from Jefferies. Please go ahead.
Alright.
Congrats for the progress and thanks.
Thanks for taking the question.
I think you mentioned you already start to dose the first combo combo trial, which is a very encouraging maybe.
Troy you can give us some color on the enrollment progress so far and how should we think about the expectation for the initial data later this year early next year in terms of the number maybe the activity you are looking for and also when you will potentially decide <unk>. Thank you.
Multiple parts sorry.
Yes, that's okay I'll take each of them are Roger and if I if I Miss one. Please please remind me or correct me. So first of all just just a comment on the design of the trials. So these are dose escalation trials.
Each of the genotype is being treated separately with standard of care. So in the context of seven plus three we have the <unk> cohort we have in NPM. One cohort. These are typically six patient escalation cohorts.
And we're starting it in N minus two dose the 200 milligram dose similarly for the <unk> containing regimen.
I'll remind you that in the phase one there really was no dose dependence within that between 200 600 milligrams as it pertained to differentiation syndrome.
And that's important because you talked about kind of how do we think about data and RPT. So so as with any study first.
First and foremost what we're going to focus on I think and we're guiding to fourth quarter this year or or at the latest first quarter next year is safety and Tolerability, specifically with respect to differentiation syndrome. So can we safely combine with current standards of care, we believe we can and.
<unk> do those standards of care help mitigate the differentiation syndrome that was seen in the <unk> population.
And the question of activity Roger is a good one however, as youll appreciate the backbone therapy has a meaningful level of clinical activity. So that really isn't going to be anything I think we can speak to.
That's really when you get further on and you take once you're at a at a dose that is the optimum biologically active dose or the <unk>, you'll take it potentially into an expansion cohort and then we can get a better sense of clinical activity relative to the backlog backbone alone the update as it pertains.
Two.
The end of this year or early next although although we fully expect there will be clinical activity I think we want to make sure we step through it safety and Tolerability can we mitigate differentiation syndrome and then.
How are we making progress in the dose escalation and.
Yeah.
We expect Roger ultimately to have 40 U S sites in the phase <unk>, we have a handful of them that are open now and enrolling patients that number will increase in the weeks and months ahead, but thus far again interest has been very robust and we have a philosophy Roger with this trial and the.
Accompanying OA trial of what we sort of called no patient left behind right, a patient who presented a physician's office, if he or she needs of <unk> containing regimen. They can go on ven, plus if doe if they need if there are more elledge or they are better suited for seven plus three they can go on seven plus three plus <unk>.
When we get to <unk> eight there is a lot of interest in combining with <unk>. Those of you who saw the the data from <unk> nib that supported the recent FDA approval you saw that half of those split three patients in the <unk> trial, where NPM one co mutants fully 50%. So there's a lot of interest in.
Combining <unk> inhibitors with <unk> inhibitors, and our team is is moving as aggressively as possible to get <unk> opened.
I'll open as soon as we can so I hope that gives you some color Roger and I think I addressed all the components of your question, but let me know if I need to follow up on anything.
No that's great that's great.
Okay. So that's very clear now.
You just shift gears to the tip fee.
So understanding you're figuring out the opportunity for them and but in the past they used to.
Kind of guide towards that data release around mid year with <unk> and.
And now you're kind of guiding.
Guiding towards.
Cohort second half next year, so maybe just to let us know what's the current thinking around the <unk>. Thank you.
Yeah, It's a good question.
It's I think it's a reasonable question in the REIT question. So in short Roger the combination is both better better tolerated and more active than we expected.
That's the short answer.
We had so if we take a step back before we ever dose to patients.
When when investors and analysts asked me, what's the greatest risk I was.
I said from my perspective, the greatest risk is the challenges with combining <unk> and <unk>.
Particularly we as an industry have not had good success in combining inhibitors of the map kinase pathway.
Yes.
And inhibitors of the <unk> kinase pathway, we have been I think very pleasantly surprised at the safety and Tolerability that we've seen with this combination we have seen evidence of hyperglycemia, but it hasnt been dose limited it hasn't inhibited in any way our ability to escalate both tip.
<unk> and El <unk>, and just to put up to put a point on that now this final escalation cohort as a full dose of Tippy 600 milligrams twice a day and a full dose of <unk> 300 milligrams daily.
Honestly I was I was surprised I wouldn't say shocked but pleasantly surprised.
The other thing Roger is we're seeing evidence of clinical activity now in this population.
Why I cited to you second line head and neck, you're typically seeing response rates in the teens, 13% to 16% and really.
Challenging PFS and OS PFS of two to three months you can assume we are seeing responses I don't want to get into the granularity of the data, but we're seeing activity at <unk>.
First of all good safety and Tolerability, we're seeing activity at different dose levels.
We do need to make sure that we select the optimum biologically active dose and that's the lowest dose at which we have full activity and acceptable safety.
No.
We're sorting that out I think the critical questions and the reason we're guiding to next year is what doses that and then importantly, what level of activity are you seeing at that dose to help inform what a phase two three trial might look like.
Just to remind everyone.
HRS mutant is 4% to 6% of the population pick <unk> mutant is 15% to 20% of the population we've seen that reflected in the enrollment curves in the end.
Enrolment on this study.
We could potentially be treating up to a quarter of head and neck cancer, Roger but we want to make sure we get it right and we've already shown we showed the example of the patient with the <unk>.
The tonsil, the metastatic head and neck cancer from the Tunstall.
And 85% tumor reduction after one cycle and a durable response. So the next critical question is what's the dose and then how do you think about the safety tolerability and activity to frame the opportunity for a registrational trial in a disease, where there's been no approved small molecule targeted therapy. That's the work we have.
To do and the teams cranking as fast as they can we think reasonable guidance on on that expansion cohort is sort of middle of next year.
Excellent Thanks Troy.
That's it thank you.
Thank you. Your next question comes from Peter Lawson from Barclays. Please go ahead.
Thanks, so much for taking the questions just kind of firstly, a follow up around the maintenance setting where the resistance mutations could.
<unk>.
Thanks, Terry from being in using that maintenance setting.
Then.
Another question just around moving beyond AML and <unk>.
Oh, the heme indications solid tumors.
Thank you.
Sure Yeah. Thanks, Peter for the question so.
We don't think resistance mutations are going to be a big threat to using <unk> in the maintenance setting.
We've only ever seen one patient of the ones, we've tested the 29% or so we've tested who had a who developed a resistance mutation <unk> ziff dough and people might ask the question well.
Or is your assay sensitive enough and my answer would be.
We don't see any evidence of resistance mutations driving.
Progression or or or resistance to ziff dose patients do develop resistance. They do they do progress but.
It doesn't appear to be due to these resistance mutations that's part number one we've got about a three.
Three 3% to 4%.
Right of resistance mutations in the data that we have sampled thus far Peter but the other important point is <unk>.
<unk>, it's fully active on two of the three mutants and it retains.
Meaningful activity on the third the 327 mute.
So and that's in contrast to a number of the other inhibitors in the class.
And we've actually seen that as we as we spoke to around <unk>, we've seen that when we treated patients who have come to our study having failed. Another menin inhibitor. We do have a measure of clinical activity long story short Peter I don't think it's we don't think it's going to make a difference we think ziff does very well positioned for the maintenance.
Setting and importantly, Peter even probably more importantly.
It's very easy to use it doesn't have any other toxicities that thus far that have revealed themselves that we require sort of extra extra detection or extra vigilance.
And in that setting.
So I think we are.
We're looking forward to using <unk> in the maintenance setting and forgive me Peter the second part of your question is.
Additional indications out of the question was expanded outside Haim indications.
Yes Rahim indications.
Solid tumors and other diseases, just your thoughts there.
Sure So I think there.
There Peter.
You want to be data driven there are other opportunities that we see beyond acute leukemia for <unk> inhibitors, I think one needs to be very mindful of the potential impact of the inflation reduction Act.
And and.
Long story short.
The best analysis, we have and we.
We've talked to all the experts, including CMS is that we can do anything within AML.
And we stay out of the inflation reduction act by virtue of having an orphan designation that covers AML.
Once you go to another indication be it a L. L. B at any of the others, you're potentially put your program at risk of being included in the IRA.
And I think we think Peter the appropriate weighted to mitigate that risk is we have a next generation Menin inhibitor program. We've taken everything about <unk> that we think can be improved and the team as is.
As a very attractive compound.
That would be the one we would probably take into additional indications be those other solid or liquid tumors be that potentially diabetes.
Got multiple opportunities for additional Menin inhibitors, and just given the evolving sort of.
Legal and regulatory and pricing landscape I think one wants to be thoughtful there. We think we can drive significant value just in AML alone and you hear US right, we're talking about frontline relapsed refractory maintenance.
We really think you can transform the standard of care and transform the market and we're going to do everything we can with <unk> in that setting if theres additional opportunities I think we might do some early exploration, but wed likely pick those up with a second generation compound and that way you can really drive the full commercial value for.
The franchise.
Great. Thank you so much really appreciate it.
Pleasure.
Thank you and your next question comes from Lee.
I think from Cantor. Please go ahead.
Hey, congrats on the quarter and thank you for taking our questions.
I guess first one is on the phase two study.
So Troy can you maybe just clarify if you have seen greater traction in terms of patient enrollment after <unk> update.
Update in June .
Initially for the EU sites.
<unk>.
And also for the potential Commvault data later this year or early next year can you give us a sense of that the variable here is it just a matter of enrolment speed or you want to.
Reach a certain number of patients werent certain peer and a follow up before you disclose that data.
Yes. Thanks, Thanks for the question so on the first question.
It's.
When you do this with any trial you do you do feasibility studies and you have a.
And enrollment curve and that enrollment curve is driven by the feedback that you get from the sites how many patients do they see how many do they think they can put on et cetera, and our clinical operations group.
Is done that very well.
With the <unk> one study.
We are ahead of our projections Les and I think.
There are a lot of reasons for that.
It's physician excitement I think it's the data itself I think there's more patients than perhaps we expected and we're not losing them to other studies.
It's hard to say kind of it's hard to isolate one variable what we're communicating is for people who think.
There's going to be a big gap in terms of time to market.
Think we have a different view, that's perhaps informed by data.
Particularly in that NPM, one setting and you fully expect.
If the combination trials go well and we have good safety and Tolerability.
You would expect that traction to continue because everyone acknowledges that.
As these molecules eventually go in front of the FDA and potentially come to market we're still.
AML is a disease of combination therapy. So.
The party that can get to the combinations with the highest the best safety Best Tolerability Combinability and activity is ultimately going to be the market leader and we think that sets up very nicely for <unk>.
I expect that that excitement and enthusiasm will pull through into the combo studies.
With respect to the.
The second part of your question Lee.
In terms of how we think about data release, so we understand that one of the questions in the minds of all of the analysts and the investors is can we mitigate differentiation syndrome through co administration of the standard of care regimens and does that unlock the activity of <unk>.
More fully particularly in the <unk> rearranged population.
Every indication everyone. We talk to tells us that that's likely the appropriate path forward, but you have to do the work you have to actually do it that's why that's why I'm focusing initially safety tolerability mitigation of DFS Ds's typically something you see.
And between cycle one in cycle three once the leukemia is eliminated there is no risk of DFS and if the pay if youre not eliminating the leukemia patients likely going to progress.
Leave the study anyway, so youll.
Relatively early on if you've mitigated DFS.
Think we're going to share data, we're not going to dribble the data out with an eyedropper on a patient by patient basis, we want to get a sufficient number of patients on study that we can come to you and say here's the data and we can draw some meaningful conclusions and I've indicated to you. These are these are six patient dose escalation cohorts.
So the numbers get to be meaningful pretty quickly even when were in the first dose escalation or two we don't know yet will each of the.
What are the are the genotype and the various combination is going to enroll at different rates, we don't have enough clarity into that yet what we've been encouraged by is that.
Just as with L. O. One physicians are finding patients screening patients are coming on study.
The machine is working and I think as we look toward our next earnings call in November as we look towards ash and the end of the year I think we'll be in a position to possibly give a meaningful update on the <unk>.
Why we think <unk> has a best in class profile.
Hope that helps.
Okay. Thank you.
I have a second question so in terms of the patients that.
Youre enrolling into the pivotal study with the commutation.
Do you have a sense in terms of the breakdown between for instance, <unk> commutation.
We.
No at least I don't think so.
Youre talking about the breakdown of co mutation patients enrolled on the study is that what youre asking.
We are seeing so so.
I think it's early days we're.
We're seeing very high levels of co mutation, that's why I highlighted for you.
If you go pull the <unk> label, 50% of the flit, three or NPM, one coat mutated right. So you need to be able at some point to combined with a <unk> inhibitor or you've given up 15% of the population.
We're seeing that as well Lee both flit three H DMT three a all the central actors.
It's exactly it's very similar to what we've seen in the <unk> I don't have I don't think we have specific breakdowns yet in terms of the co mutational content in the population.
Okay. Thank you.
Sure.
Thank you and your next question comes from Matt Bradley can Nino from Stifel. Please go ahead.
Hi, This is <unk> on for Brad Congrats on the progress.
So first question on to perform that glad you're seeing responses in some limited safety issues.
Should we be thinking about the contribution of parts for <unk> and the <unk>.
Next data and then will we be getting data in both HRS over express population pick <unk>.
Yes, Sean so thank you.
So if I if I may let's take those in opposite order so.
Earlier this year, we announced that we were not going to continue enrolling in the HRS over expressing cohort, we're going to focus our effort in the <unk> mutant.
And that was really for a couple of reasons number one.
We will as with every company, we have finite resources and we have more things we can invest in than we than we have.
Funds with which to invest so, particularly as you hear us articulate everything we're doing with <unk>.
If one wants to identify the aubade the best place in our experience to go is in those patients who have driver mutations in the targeted oncogene, whether they be a kras mutant in the case of the the run and the aim studies or pick <unk> mutants in the case of the current studies.
If youre going to define the aubade go there because thats, where youre going to have the potential of the greatest level of activity because the closer you get to a driver mutation in <unk>.
I'd say a gain of function mutation and a driver oncogene typically that's where you see the highest activity that doesn't bejon preclude that once we get the old bad we would come back and investigate either HRS over expressed or <unk> amplified. We just want to do it in stages and we want to be good stewards of capital.
Good fiduciaries and be smart about doing drug development. So we are the pictures coming into focus in the <unk> mutant your question around contribution of parts.
There.
So <unk> you would expect it has no. It has no ability to drive responses in the <unk> mutant population as a monotherapy that that I can say with great confidence.
Our palisade in the experience of Novartis has had a very limited ability to drive responses and those responses typically.
Aware of only one or two.
Typically not durable.
What youre seeing here.
We have some very nice preclinical work that our translational research team published showing that.
The mechanistic rationale for why this combination is so effective in this disease.
How how tour and particularly Rab.
Allows you potentially to drive more activity on pick <unk> up it is clear to us that the combos doing better clinical activity than either drug as a monotherapy.
At this point now we're just continuing to gather data and gather confidence I will say something I didn't I didn't get a chance to address address it with the with Roger's question, but the other thing that gives us great confidence in is as we look to 28, six and we've already given you a heads up look.
At Teekay is in renal cell look at mutant selective inhibitors in <unk>. The fact that we can safely combined chip P&L palisade and get data that get activity that is at a minimum additive, possibly better than additive maybe maybe synergistic I think bodes very well for as we are.
Are now preparing to advanced 26 into the clinic because if you look at at second line RCC again, Youre talking about a response rate with Teekay is it's in the teens and the activity and K Ras inhibitors is impressive, but the resistance happens pretty rapidly and I think.
That entire field is looking for the preferred combination partner is it shipped to its source.
What do you do.
I'm going to tell you. We think we think FTR stands a very strong chance of being a preferred partner in both of those settings and the tippy, our palisade data potentially gives us an opportunity to head and neck and it also then I think again bodes well for 2008, a six but let's let's start dosing patients on that study and see if that's correct.
Yeah.
Got it okay, great. Thanks for the comments there.
Sure.
I appreciate the question.
Thank you and your next question comes from Alan <unk> from <unk>.
<unk>.
You May go ahead, yes, hi, Yes, hi, this is jeet on for Justin Thanks for taking our question was just looking to get your take on the on your view on <unk> for diabetes based on recent competitor data and I had a follow up question.
Sure.
So we're following as many are we're following that data with interest.
There is certainly a relationship between Menin inhibition and beta cell.
Regeneration.
I think in our minds theres still a lot of gaps and questions as to why.
What exactly is going on there.
We've decided to do is to we'll continue to watch fully weight that dataset, we're actually evaluating ziff dohmen, Ed as well as a number of other menin inhibitors in the appropriate models of diabetes, both as monotherapy and in combination and I'm home.
That will have some data later this year to make an assessment as to do we see an opportunity and if so how do we how do we make sure we take advantage of it if there is an opportunity for menin inhibitors in diabetes.
I will tell you today, we will find a way to to maximize that value for shareholders.
Either through a partnership or an out licensing I doubt will will will become Curragh current diabetes.
But we will find a way to get the value in it but importantly, and this is.
An answer I gave previously our view is you probably want to do that with us with another menin inhibitor. Both because you don't necessarily want your diabetes compound in your oncology compounds to have the same safety database and number two from the standpoint of the inflation reduction Act you have kind of shot yourself in the foot.
So we have.
We have as I said, our next generation Menin inhibitor that we've been bringing along that may if if the data supports it and we're going to we're going to look for the recommendation from our translational research and clinical colleagues Thats, how youll see us.
Generate value with Menin inhibitors in diabetes is through our next generation compounds and I'll tell you. This if if it's there I have no doubt we can generate a best in class compound. It's just a matter of let's let's be disciplined let's do the right experiments.
And let's generate generate the data and see.
Okay.
Makes sense and just as a follow up was hoping you could maybe just clarify the number of patients being treated for the head and neck expansion cohort for <unk> and secondly, what other indications outside of head and neck and RCC are most promising for MTS.
Yeah, great Great question, so so within head and neck.
You probably want an expansion cohort of sort of and I'm, just I'm spit balling here sort of six to 12 patients.
Similar to what we did with <unk> in the phase <unk> you wouldn't have enough enough clinical data there that <unk> got a strong steer on how to think about future development.
So thats.
That in terms of other other indications.
We've got I think very good and evolving clinical data, both with <unk> as a monotherapy and increasingly tippy foreign <unk>.
Although we terminated enrollment in our aimed study we terminated it for operational feasibility.
The compounds active its actually quite active but again in a world of limited resources, you have to make some difficult choices.
We would do our best to try to capture both the <unk> mutant and the <unk> mutant population, which is about a quarter of head and neck.
That I would think about <unk> and El <unk>.
You would then want to come with a second and possibly third FTE I and think about RCC and.
And how you crack the K Ras Riddle.
At this point you want to generate data you want to make sure you have optionality, but chip.
There've been questions about <unk> the composition of matter patent has expired, but once you bundled it up with our palisade. Our IP colleagues have done a great job of building a a.
Strong patent estate around.
<unk> in head and neck cancer that we can leverage and if we could beat it if we could get TP in El <unk> to market for patients like that would be an amazing accomplishment theres no targeted no small molecule targeted therapy approved if you then wanted to come along with another FTA and try to beat it great, but but I always.
Joke.
Walk then run and then run the four minute mile. So, let's keep <unk> moving along Youll see us put increasing resources on 26 and at this point, we don't have to make a decision we want to generate data in both RCC and K Ras.
And continue to mine the chemical space for more Ftes and see where we go.
Those are three very significant solid tumor indications and I think the datasets coming together nicely.
It's turning out to be who knew that the killer application of <unk> was going to be back to K, Ras where it all started but just as a combination therapy that would be sort of coming home. If you will I hope, that's where we end up.
Okay.
Makes sense. Thank you so much.
Sure.
Thank you and our last question comes from Ren Benjamin from JMP Securities. Please go ahead.
Hey, guys. Thanks for taking the questions.
Troy can you talk to us a little bit about maybe the strategic rationale for starting off with RCC and what's the unmet need there versus starting off with K Ras.
And then S CLC and then.
A question for kind of all your combination programs are you in.
And any sort of discussions with the companies that are marketing the approved drugs that youre combining.
Ziff Doe or tippy with in order to set up an.
The MTA or try to get some free drug I mean, how important is that for kind of cost mitigation and maybe.
Enrolling patients quickly and getting the clinical trials off the ground.
Sure. It's a great question, Randy let me take it in parts.
So with respect to RCC going first.
We are.
We are improving as an organization.
<unk>.
Fundamentally different than where we were just a few years ago and really have.
Great Cross functional effort as we think about going from sort of preclinical R&D all the way through to lifecycle management and so we've done the work on on renal cell carcinoma.
Talk to the Kols, we've done market research, we understand the landscape.
And we will speak more to our specific partner in RCC, probably a little later this year, but thats ran a relatively more mature space. We know what it's still evolving but it's relatively more mature. So for example, the docs were very clear if they could if we could enable them to use teekay.
And the second line.
That would be phenomenal and if you look at the preclinical data that France is this group has generated theres really potent synergy between <unk> and <unk>.
Teekay <unk>, most notably exit nib in that setting.
It's a great setup the docs love it.
In my view, we can't get there fast enough now.
Now take K Ras K Ras is.
<unk> is an emerging area.
I know, it's got a lot of heat a lot of light.
It is a rapidly evolving area. It's clear that resistance is is is going to be something that everybody is going to have to contend with and tour targeted profit myosin, which is what we one of the targets that we that we deal with with with Tippy and 28, 6%.
That seems to be a central actor in driving resistance to <unk> inhibitors across the board, whether theyre mutant selective whether they're rason, whether theyre <unk> C or G 12 D.
If you hit K Ras core tour gets engaged and tries to develop resistance. The tumor tries to find to work around so it's taking we're just being ran very deliberate and making sure that we're making the right decisions.
With respect to your last question are we trying to.
Build.
Clinical collaboration or supply agreements the answer is yes.
You either want the drug to be reimbursed.
Or you want to work with the sponsor to try to get.
A.
Comp drug sharing agreement or a clinical collaboration we did that of course with Novartis initially with the tippy foreign about palisade trial and you can assume we are taking a similar strategy as we think about the opportunities for <unk>.
Perfect. Thanks for taking my questions.
Sure.
Thank you.
There are no further questions at this time Mr. Trey Wilson you May proceed with closing remarks.
Thank you and thank you all for joining our call today, we will be participating in the Cantor Healthcare conference next month and hope to see a number of you there in the meantime, if you have any additional questions. Please contact Pete Tom or me.
Thank you again for attending our call and have a good evening everyone.
Okay.
Ladies and gentlemen, this concludes your conference call for today, we thank you very much for participating and ask you. Please disconnect your lines and have a great day.