Q3 2023 Kura Oncology Inc Earnings Call
Good afternoon, ladies and gentlemen, and welcome to the third quarter 2023.
Water Oncology, Inc earnings Conference call.
At this time all lines are in listen only mode. 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 November two 2023.
I would now like to turn over the call to Pete de Spain head of Investor Relations. Please go ahead.
Thank you Lisa good afternoon, and welcome to Kura oncology third 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 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 <unk> filings with the SEC, which are available.
But from the SEC or on the current 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 let's jump right in.
We believe our lead drug candidate system and it is well positioned for market leadership with multibillion dollar global revenue potential in acute leukemias and beyond.
Conviction is supported by a growing body of clinical data as a monotherapy and more recently in combination with standards of care, our rapid pace of enrollment in our ongoing studies driven by strong clinical data and robust enthusiasm among investigators and patients and the best in class safety and Tolerability.
The profile that we believe will enable <unk> to become a backbone of therapy across the continuum of care for AML patients.
So if demand him as a once daily oral drug candidate that targets. The menin <unk> protein protein interaction and has potential to address all patients for whom the men in Kmt to a pathway, it's a disease driver representing up to 50% of patients with AML.
In our phase one trials, if two men have demonstrated an impressive 35% CR rate and 45% overall response rate in 20 patients with N. P. M. One mutant AML treated at the recommended phase two dose of 600 milligrams importantly, zipped them and have demonstrated a favorable safety profile and was well tolerated.
With no evidence of drug induced qt prolongation or mono suppression, no patterns of toxicity and adverse events consistent with underlying disease building upon the strength of the data from our phase one trial, we initiated a phase two trial of <unk> in patients with M. P. M. One mutant relapsed or refractory AML.
This year the registration directed trials expected to enroll a total of 85 patients in the United States in Europe, we continue to be encouraged by the pace of enrollment in the trial, which in our view speaks to the size of the NPM, one mutant patient population in the relapsed and refractory setting.
As well as <unk> potentially meaningful advantages in safety profile and clinical activity relative to available therapies, we expect to complete enrollment of all 85 patients in the phase two registration directed trial no later than mid 2024.
Increasingly our clinical investigators refer to zipped a minute that's a potentially transformational therapy. We believe their enthusiasm reflects not only their experience with it as a monotherapy, but the tremendous potential benefit to patients there could be realized by advanced exhibitor minute to earlier lines of therapy and combining it with standards of care.
Indeed, our vision for ZIP Joanna design can provide benefits to leukemia patients throughout the continuum of care, enabling deeper and more durable remissions in frontline and relapsed refractory populations in combination and is a potent mono therapy in the maintenance settings.
ZIP to a minimum can do that it has potential to transform the treatment of AML and ultimately to transform the commercial market for anti leukemic therapy.
As these transformations in the standards of care that have enabled meaningful advances for patients in areas, such as CML lymphoma, and multiple myeloma with corresponding increases in market opportunity.
AML has lagged behind these other areas due to the complexity heterogeneity and aggressive nature of the disease. We believes if demand. It may represent an inflection point for treatment of leukemia and potentially other diseases as first steps toward realizing this vision, we're evaluating zipped no men had been combination studies both in newly.
Diagnosed and relapsed refractory acute leukemia, including N P M. One Newton and Kmt <unk> rearranged AML our approach to combinations is to establish <unk> as a foundational therapy that can be combined safely with various commonly used regimens and then to prioritize those combinations that represents the large.
Just unmet medical need and the greatest potential commercial value.
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 I D. H inhibitors in combination with a decidedly.
We began dosing patients in the first of our combination studies, which we call a comment 007 in the middle of this year comment 007 is a phase one dose escalation study designed to assess safety tolerability and preliminary activity of <unk> in combination with either venetic class and he decided he in patients with <unk>.
Lapsed refractory MTM, one mutants and Kmt <unk> rearranged AML or standard induction cytarabine, Donna Rubinsohn chemotherapy, commonly known as seven plus three in N. P. M. One mutant then Kmt <unk> rearranged patients in the frontline setting.
We're very pleased with the pace of enrollment in the comment 007 study, which currently includes patients with newly diagnosed and relapsed refractory N. P. M. One mutant then Kmt <unk> rearranged AML across the United States at this rate, we anticipate being in position to share preliminary data with sufficient follow up from.
20 patients in comment Zero-zero seven in early Q1 2024, we expect the data set to include safety and Tolerability from M. P. M. One mutant and Kmt to a rearranged patients treated with ziff demand had been both settings.
We're also working to initiate our comment 008 study of <unk> in combination with additional standards of care, including the flip three inhibitor gilts retina as well as our post transplant maintenance program preserved a minute both of which are expected to begin in the first quarter of 2024.
Meanwhile, we continue to make progress toward a next generation Menin inhibitor, which we intend to direct to additional as yet undisclosed indications of high clinical commercial and strategic interests. As we continue to build the clinical datasets that we believe will support FDA registration and commercialization of lift a minute we recently enhanced.
Our own commercial expertise with the addition of Brian Pal to our senior leadership team as our Chief commercial officer.
Brian joined us over the summer with more than 20 years of experience in building commercial brands and hematology and oncology with expertise in patient focused strategies across sales marketing and market access for global biotech and pharmaceutical products. He is already making an impact in the organization as we continue to realize this.
Significant significant potential zipped, a minute as well as our rapidly emerging farnesol transfer ace inhibitor programs.
We continue to unlock the substantial therapeutic and commercial value of Farnesol transpiration inhibition and believe this novel mechanism is uniquely positioned to augment clinical benefit in multiple large solid tumor indications.
Last month, we presented positive results from our aim HN registration directed trial of <unk> in patients with <unk> mutant head and neck squamous cell carcinoma. The results were featured during a late breaking many oral session at the European Society for medical Oncology Congress in Madrid, or aim HN data demonstrate that.
That if one understands the proper biological context in which to use an F. T. I. It has the potential to drive meaningful clinical benefit for patients. We believe these data validate the therapeutic value of Farnesol transfer Ace inhibition as we look to advance beyond our initial strategy to target <unk> mutant tumors.
With our aim HN data in hand, we continue to evaluate whether the combination of <unk> and El <unk> has potential to extend the clinical benefit observed in the aim HN trial to a broader set of H N. S. C. C patients in our ongoing current H M study.
We continue to evaluate patients in the dose escalation study to inform selection of the optimal biologically active dose for the combination once we determine the aubade will continue to evaluate whether the activity supports development and commercialization of the combination in H N F C C.
One of the most important takeaways thus far from current age yet is that to be foreign and demonstrates a favorable safety and tolerability profile at its full dose in combination without palisade. We believe this significantly de risks development of our next generation Farnesol transfer Ace inhibitor K O 28, six as we look forward to.
<unk> in combination with other targeted therapies.
With the success of targeted therapies, such as K Ras inhibitors tyrosine kinase inhibitors in Egfr inhibitors. There is now considerable focus on the development of companion therapeutics that have potential to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance last month, we presented exciting preclinical.
Data at the Triple meeting supporting our rationale to combine K O tornado sex with allografts and K Ras G 12, C mutated non small cell lung cancer and with Cabozantinib in clear cell renal cell carcinoma. A week later, we announced the first patient was dosed in the fit of one phase one dose escalation trial of <unk> 28 a M.
Six concurrent with the dose escalation as a monotherapy in the fit or one trial. We also plan to evaluate <unk> in dose escalation combination cohorts without a graphic and cabozantinib.
Earlier today, we announced a clinical collaboration and supply agreement with Marathi therapeutics to evaluate the combination of <unk> 28, or six and data grasp them in patients with <unk> mutated non small cell lung cancer under the terms of the agreement Kerr will sponsor the phase one study in Marathi will supply us without a graph that for the study.
This collaboration highlights the potential to address the urgent need for more durable and effective treatment options for patients with cancers, driven by the K Ras each we'll see mutant oncogene, we look forward to collaborating with Marathi an established leader in targeted oncology.
We expect to begin dosing <unk> hundred $28 six in combination with out of grass had been K recipe club <unk> mutated non small cell lung cancer and in combination with cabozantinib in clear cell renal cell carcinoma by the middle of 2024, if successful we believe K O 20, 806 could become an ideal companion.
Asian partner for multiple targeted therapies enlarge solid tumor indications, we look forward to sharing our continued progress in the months ahead 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 third quarter.
Of 2023.
Research and development expenses for the third quarter of 2023 or $29 $3 million compared to $25 million for the third quarter of 2022.
The increase in R&D expenses was primarily due to the increase in clinical trial cost related tours at Dominion and K O 20 806 programs.
General and administrative expenses for the third quarter of 2023 were $13 $1 million compared to $11 $6 million for the third quarter of 2022.
Net loss for the third quarter of 2023 was $38 $6 million compared to a net loss of $35 5 million for the third quarter of 2022.
This includes noncash share based compensation expense of $7 $1 million compared to $6 4 million for the same period of 2022.
As of September 30th 2023, we had cash cash equivalents and short term investments of $452 $6 million compared to $438 million as of December 31, 2012.
We believe that our cash cash equivalents and short term investments will be sufficient to fund our current operating plan to the mid 2026.
Today, we are filing a shelf registration statement and a corresponding prospectus supplement for an at the market facility for our common stock we are refreshing our shelf, which was set to expire next month, along with an ATM in order to maintain good corporate housekeeping.
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 preserved a minute report preliminary clinical data from 20 patients in the comment 007 trial in combination with Ven Asia or seven plus three early in the first quarter of 2000.
24.
Dose the first patients in the comment zeros, there a trial in combination with additional standards of care, including the slipped three inhibitor gilts Red nipped in the first quarter of 2024.
Initiate the post transplant maintenance program in the first quarter of 2024 and complete enrollment of 85 patients in comment Zero-zero, one registration directed trial in N. P. M. One mutant AML by mid 2024.
Particularly farnham determine the optimum biologically active dose in combination without Palestine and determine next steps for the program by mid 2024, and <unk> 28, a six dose the first patients in the fit zero-zero, one dose escalation trial in combination with out of grasses NK rescue <unk> mutated non small cell lung.
Cancer and with Cabozantinib in clear cell renal cell carcinoma by mid 2024th with that Lester We're now ready for questions.
Thank you ladies and gentlemen, we will now begin the question and answer session.
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Your first question comes from.
Jason Symanski from Bank of America. Your line is now open.
Good afternoon, everyone. Thank you so much for taking our question and congrats on the quarter.
Regarding the upcoming Com.
Comet Zero-zero seven update what do you think investors should be looking for from the data are what's necessary before the community can start to feel confident about the potential for combinations and we know what are we looking for in safety and efficacy and then a follow up if I may.
Sure Yeah do you want to ask a follow up now Jason do you want to wait let me answer this one.
Why don't we go ahead.
Okay.
So in terms of what investors should expect so 007 is a phase one dose escalation study as I indicated.
We are evaluating <unk> in combination with then Asia in the relapsed setting and with seven plus three in the frontline setting importantly, we're evaluating Kmt two E and M. P. M. One mutant patient separately in separate cohorts. So there are six patients per cohort so think of it.
For cohort six patients each that's 24 patients at a 200 milligram dose and then as we dose escalate 24 patients at 424 patients at 600.
In terms of what to look for whether it's our data or anyone else's data I think you start with safety and Tolerability.
<unk> ability to combine.
Drug drug interactions do you have to discontinue doses do you have to dose reduce and then ultimately of course, there is there will be activity, although it of course in combination.
Thank Jason we feel confident based on the monotherapy data that we've shared thus far from the O L. One study if you'll recall we had a.
Among 20 patients with NPM, one mutant AML, we had a 35% CR rate with full count recovery. Thus, we have no Qt prolongation, we have no drug induced mile suppression. We have we have no predicted adverse drug drug interactions.
Once daily we're not as sensitive Sip III for substrate all of those considerations will become important as you look to combine with the standards of care. This will be a preliminary look we wanted to get it out there so that investors could assess safety tolerability ability to combine and importantly ability to mitigate.
Yes that was a question that we were getting a lot as to why do you see a difference between Kmt Joanne M. P. M. One and we feel confident Jason that in early Q1, when we shared the data with you. Among those 20 patients will be able to answer investors' questions. We will of course, hopefully continue dose escalation and look to reach a recommended phase.
Two dose in each of those two settings to then help inform the design of ultimate registration, enabling phase II III studies, but one step at a time.
Got it and then in terms of the opportunities here, how do you prioritize seven plus three versus <unk>.
That line versus.
Maintenance and I guess.
Among those two is one.
Better able to kind of give you a glimpse into how our combination with with a foot three wood wood look.
Yeah. So so two good questions. There let me, let me take them kind of in order.
If you look simply at the commercial opportunity.
Venetic class combinations and maintenance probably stand the tallest.
And again, given given some baseline assumptions.
Probably more detailed than we have time for right here, but ultimately what we'd like to do.
And I think it'll be important we look toward doing this eventually with someone right went through some sort of partnership with us with a strategic partner you really want to be able to two positions if demand in every combination settings why do I say that you you you referenced specifically flit three led.
Three is half the NPM one mutant combination you now have <unk> approved in the frontline use gilts written are approved in the relapsed refractory setting.
That's half of N P. M. One it's 15% of AML in the preclinical models that we and <unk> have both.
Enabled through publications that combination is curative in a preclinical setting. So if you add an all oral regimen that could drive that kind of clinical activity that would be pretty impressive I think Jason what we'd like to do and you see us doing it where we are laying the foundation for what I think is the broadest in potentially most value.
Creating zip menin inhibitor.
Franchise in AML and that is going to be frontline, that's going to be relapsed that's going to be maintenance. Then you also heard us reference.
Additional undisclosed indications that we're that we're thinking about directing our nextgen menin inhibitor too will speak more to that we pick our spots carefully.
But there again our goal is to have not just a best in class Menin inhibitor, but truly a best in class franchise throughout the continuum of care.
Perfect. Thank you for the color.
Our pleasure thank you.
Your next question comes from Peter Lawson from Barclays Youre not your line is now open.
Great. Thank you so much thanks for taking my questions.
Just follow up on the comment.
Kevin.
Kind of field safety and differentiation or lack of differentiation benefits what are the kind of the response rate baas or durability Baas, you kind of want to hit there as well.
Yeah, Peter it's a good question, let's let me let me give you let me give you a caveat and then I'll kind of give you the numbers to think so.
The caveat is the numbers I'm about to sites you are come from either retrospective analysis of our phase III studies, right and Theres always kind of an emotional desire to compare those numbers to a phase one dose escalation study, we all do that at our peril I just want to give that important caveat.
I think I think one of the things. We do is very very credible drug development and let's just put that out there that being said the bar for those standards of care that kind of what you would expect in the frontline and seven plus three youre looking at depending on the literature reference of 70% to 90% CR Cri rate.
And then Eva in the relapsed setting you are looking at roughly a 40% to 60% CR Cri rate. So that's kind of the way to think about it.
Our goal is of course, our safety tolerability drug or their drug drug interactions that require changes in dose or interruptions.
Of course, combinability ability to mitigate D. S. And then and then of course efficacy will be looking at that as well I'll just highlight for you and this is why I took pains to explain to Jason's question. It's 24 patients at 200 milligrams. So we're going to share 20 patients' worth of data, but the goal of course should.
Let's get a let's get a robust dataset of up to 72 patients across the cohorts to help inform our recommended phase two dose for each of those two regimens, but I hope that gives you the numbers and be it gives you the appropriate context in which to think about them.
Great. Thank you and then just on 28, who sits in that.
Cabozantinib combination just kind of where you're thinking about driving that would that be a partnership as well like you did for the K Ras so would that potentially be an ice tea.
Yeah. So.
No.
So just to be clear because you have a couple of things in your question. So let's start with the clinical collaboration between Marathi and and and and corrupt Mirage.
Marathi is supplying.
At aggressive to us they've of course had input on the protocol they have all of the appropriate.
Safety reviews, and whatnot, we're not yet formally co developing that combination together right. This is this is early days, it's an exploratory study they're supplying it under our supply agreements.
With Cabozantinib, our expectation is that given that we'll be in the labeled indication.
<unk> and Cabozantinib is fairly widely used will be going into a second line setting, but that will largely be covered by insurance thus not at <unk>.
Mediate need for a clinical collaboration and supply agreement or even any other agreements.
Well understood.
And if you again look at the preclinical data that was published at the Triple meeting.
Very very impressive activity in a second line setting and in particular, even after patients have progressed on one teekay <unk>. The combination of a second Teekay I plus 20, 806 really drives meaningful benefit and that's again a lot of the things that we've learned about ftes over the years they have anti angiogenic.
Properties. They have other other reasons that make that combination really pretty slick and so we'll look forward to attitude getting into that combination again approximately middle of next year.
Perfect. Thanks, so much.
Our pleasure thank you Peter.
Your next question comes from Roger song from Jefferies.
Your line is now open.
Great.
I'm glad for the progress and thanks for taking the question.
A couple from us maybe still focusing on the combo given that won't be that the most upcoming data Readouts you will have.
Maybe just to drill down on some of the details.
Or if you can for those 20 patients how balanced the we shall see.
For the first time versus the relapse refractory and M.
<unk> came to chewy understanding you have two co hall by that dosing that how.
Balanced within the dose.
We will be able to look at it.
And also just confirm that 20 patient hall will be from that 200 milligram, but not that 600 milligram.
That's my first question. Thank you.
Sure Yeah, Roger So let me take your second question first so we're starting we're starting the dosing at 200 milligrams, obviously I don't want to.
There is an intention to escalate all four cohorts I don't want to speak to exactly sort of what youll see yet, but what I can tell you with respect to your first question is we have Kmt two eh and NPM. One is six patient each separate cohorts for each of the two regimens I can tell you this they're all enrolled.
Well, there's strong activity for all four for each of the four of those cohorts.
We anticipate that the dataset when you see it in early Q1 next year will be well balanced in terms of N. P. M, one and Kmt <unk>, both frontline and relapse. So.
Again.
Early data set but we think an important data set in terms of addressing this question of can we mitigate differentiation syndrome, and it's just a credit to our team and we talk a lot about being highly encouraged we started dosing. This study in July where we're already at a point, where if we can guide to giving you data in early Q1 24.
Sure.
Our team is just crushing it on the operational execution and and and will of course continue to dose escalate as appropriate that's why I want to be careful how we answer the question on exactly what dose level, let's just when we shared the data we think it will address these questions around safety Tolerability combinability.
Ability to mitigate D. S et cetera will of course look then to providing a subsequent updates that'll continue to flush out that picture.
Sure Yeah I agree.
Pretty rapid enrollment.
And then so don't want to lose side of your pivotal monotherapy data the study for <unk>.
So that I think that's the first time you Guy you will close the year old man Bye.
Hi.
Mid year.
Just curious.
Any statistical plan, you have disclosed to us.
In terms of maybe any interim analysis or that the null hypothesis.
What is that made him a follow up to you to have the final readout and since you are guiding that.
Enrollment completion any guidance around the timing of the readout. Thank you.
Sure Roger So Theres again, a few questions in there.
So this is the first time, we've really put it on our milestone slide.
Drawing a line.
As far as completion of enrollment of an 85 patient study no later than the middle of next year.
Jim.
I'll note that one of our principal competitors is expecting to enroll it's N. P. M. One cohort now sometime between Q1 and Q2 of next year Ah 64 patient study. So we're clearly I think neck and neck and closing ground. The reason we picked 85 patients was driven by safety and Tolerability.
That always has to be Paramount. That's why we are doing our seven the way we're doing it that's really what the FDA wants to see even in these devastating diseases. So 85 patients plus the experience we have in MTM one from the phase. One study, we think gives us approximately 100 patients.
That should meet the agency's expectation as far as safety and Tolerability, we have not disclosed our statistical plan or the.
The null hypothesis I can tell you we are being very conservative we are I think quite encouraged by the 35% CR rate with full count recovery in the in the phase <unk> that we saw but we're giving the the trial every opportunity to be successful and we're taking advantage of every.
We can to pull the timelines forward.
I think it's important to put that out there as far as disclosure of data that was the last of your questions.
Let's let's get to that maybe a little a little farther along we want to make sure. We've got really clear visibility into the end of enrollment.
And as you'll as you know you need enrollment you need follow up you need data cleaning and ideally your data released coincides with a scientific or medical meeting we want all those stars to align.
Well, we're working on it we will give you an update when it's appropriate.
Think I've answered all your questions Roger but tell me if I missed anything.
No that's great. Thanks same choice.
As always and congrats again, that's all from us.
I appreciate the questions.
Okay.
Your next question comes from Lee what sick from Cantor Fitzgerald.
Your line is now open.
Okay, great. Thanks for taking our question.
Just wondering if you can just comment on the combo data from your competitor released from Ash abstract. This morning, and then since you had some initial experience with your own combo I understand it's not really apples to apples that just from the safety perspective.
How do you see a trend.
Relative to your competition.
Yeah really good question two good questions. So I.
I think the.
Let's just a lot of drug development is sort of pattern recognition and learning from the past and if we if we go to other areas where people are developing targeted therapies safety tolerability drug drug interactions ability to combine or what stymie everybody right. We've seen this in the K Ras.
<unk> ability or not to combine with checkpoint inhibitors, we've seen it in in combining with inhibitors.
Inhibitors of the Ras pathway in the <unk> kinase pathway. It's why we're so excited about 20% <unk> here is no different I think lead some of the critical questions are going to be what are the drug related aes that you see both as a monotherapy and in combination are you seeing high rates of neutropenia.
Thrombocytopenia Febrile neutropenia, that's what we're seeing you would of course expect activity. The standard of care gives you activity right, but what you're really looking for is are there going to be challenges that are going to be posed in being able to either administer the standard of care or really optimize.
I'll just go back to what are you already know about ziff down.
We've given you a very robust dataset at the 600 milligram dose that I believe despite the data from our from the handful of competitors here at Ash really.
You know really shows that we have a best in class.
Our menin inhibitor from the perspective of safety and Tolerability, that's going to have two important considerations. Later, one is the challenges that limit the duration of exposure in combo. That's one of the things you want to focus on and the other of course is the maintenance setting right you want to have the most benign compound there so.
What we as sort of players in the field are looking at as we as we look forward to the ash presentations and I would say, we're looking forward to sharing our early clinical data with you.
Early but we're encouraged by enrollment and looking forward to sharing it in Q1.
Okay that makes sense and then maybe just a follow up on your own combo data in Q1.
Just curious I'm curious is there any reason shrink back to a different responses seen in one person can <unk>.
So.
So again, let's go back to the to the standards of care.
You would expect in general to Kmt <unk> patients to not respond as well, but depending on what regimen you look at what line of therapy, it's pretty close.
It's been as I believe for NPM. One is in the is in the mid <unk> is kind of in the low <unk>.
Theres not theres not you can't drive a truck between them.
But.
In general the Kmt two eh patients probably do a little worse as you look across different regimens.
Well.
I do want to be careful Lee again.
It is it is though as tempting as it is.
Wanted to just be careful whether we're looking at our data or at our competitors' data.
Want to make sure you have enough patient experience before you try and draw any kind of conclusions on activity because youre looking at also at duration at Mardi and Theres a whole lot of factors here. Our goal is to keep patients on therapy months or even years, and that's going to be driven by safety and tolerability.
It is going to be maintaining clinical activity, but safety and tolerability is really going to be paramount and it'll be an interesting next next two or three months here.
Great. Thank you.
Sure. Thank you.
Your next question comes from Justin Southern from BTG.
Your line is now open.
Yes, hi, thanks for taking our questions. This is jeet Mukherjee on for Justin So on the topic of the combination study with <unk> Ziff Doe you've elaborated on the efficacy bar that one would want to look for it but could you just give a bit more color on the safety bar that one would be looking for at least in the.
Text of the various cytopenia is knowing that myelosis oppression has very much characteristic of agents in the frontline and relapsed refractory setting.
Thanks, and I have a follow up question.
Sure so.
Yeah.
What you worry about of course, and I think you've correctly called it out cytopenia as are not uncommon in the frontline setting.
You do see is not insignificant Milo suppression with Ven Asia. So to the extent that you have an AE profile of drug related AE profile that runs the risk of compounding that once you run the risk of is are you going to need to dose reduce or you're going to need to discontinue or are you going to require continuous monitoring.
Whether it's Q T R. Various cytopenia, if that's what you're looking for.
The biggest risk and the thing that gets the combinations of any flavor in trouble is when that the toxicity profiles are overlapping in a phase one study just to put it simply you're looking to show a combo safety profile, that's at least no worse than the standard of care right now.
Yeah, it's rare that you do better because youre not in mitigating the toxicities, but youre not looking for a lot of additive toxicity, that's that's where.
And that's where you can you can create issues.
So the other thing is youre potentially looking to improve upon the backbone as you have additional experience with your agent and other agents in terms of how to combine right can you take certain things away can you do dose optimization, but that's you know that's later on down the line for these early combo studies.
<unk>.
It's really about what's the safety of the backbone and then what's the safety of your company of your agent plus the background I do want to <unk>. Since you asked the question I wanted to just call something out and its credit I think to our team the way. Our studies designed we begin patients on standard of care on day one.
One we dose them for seven days and then we start Ziff Dow on day eight the reason, there's really three reasons for doing that number one you get a safety baseline on the standard of care. So that helps you de convolute any talks that you see in the in the combination secondly of course. It allows you time to genotype and then third it helps to debug.
Look the patients further mitigating the risk of differentiation syndrome, I don't want to speak to what others are doing but we've found that approach to be very successful and it's something that we're implementing kind of across the board starting with these two combinations and as you hear in OE, we're going to roll out to some additional combinations, most notably delta written it.
Got it that makes perfect sense and just a second question I had turning to the FDI programs could you just share your thinking and strategy a bit more broadly around this program what would you be looking for from a safety and efficacy perspective to justify moving forward as a monotherapy or.
I will tell us that combo.
Yeah, so so sorry.
GE you asked you're asking specifically about <unk> or about 28 six.
I just want to make sure I understood. The question you asked you asked about <unk> in head and neck.
Oh, Yeah perspective on both programs would be helpful.
Okay. So so with head and neck I mean, and this is one of the takeaways from that from the aim data that was presented by Dr. Ho and the many oral session at ESMO.
At best in the second line standard of care at 20% response rate. The third line is 5%.
Tippy as a mono therapy is driving sort of meaningful activity with very.
It has a favorable safety and tolerability profile.
What we know is <unk> is not active as a monotherapy in the <unk> setting our palisade is reported to drive only stable disease.
Clearly if you can drive responses with with reasonable durability and you have an acceptable safety.
Safety and Tolerability profile, then you start to look at it the bigger question and let me come to 28 six is as Youre hearing. This is a busy quarter I think subsequent quarters may be equally busy we have a number of investments in ziff do you've heard relapsed setting frontline settings, we're going to start into maintenance Youre here.
Seeing us now push forward with 28 six in both non small cell lung and <unk>.
Renal cell carcinoma.
I'm I'm interested if theres, an opportunity with 20% <unk> in pancreatic cancer, Ras driven pancreatic I think that's a huge unmet need and a huge opportunity in a rapidly evolving space. The other thing we've got to do is be good fiduciaries and say how can we be as disciplined on the on the investment side as we are on the <unk>.
<unk> and clinical side and that's the calculus, we go through on a pretty regular basis. So we're going to get everything we can out of head and neck and then we're going to continue we're going to fold that into.
Where do we where do we make these investments where are we going to drive the greatest amount of value for patients for employees and for our shareholders and Thats, how we will do it.
Okay.
Thank you.
Sure.
Okay.
Your next question comes from Phil Nadeau from Cowen.
Your line is now open.
Okay.
Two questions.
Hello.
Hey, Phil Eva for you.
Yes.
Hey, guys, sorry about that.
Thanks for.
Thanks for taking our question.
Quick question from Us.
On the on the updated enrollment timelines when do you think youll have clarity.
So when the enrollment in the pivotal trial is going to kind of complete do you think thats likely early next year or.
Or will we know that completes well once it's completed.
I think Phil so today, we put down in our milestone slides for the first time its no later than mid 2024.
Based on what we're hearing from the competition guiding that they'll complete enrollment Q1, Q2, I think even that lets hit that we're super competitive right, where we're maybe a few weeks apart maybe a couple of months at the most we're going to do everything we can to to drive enrollment we've resisted the urge even.
Though we continue to say, we're highly encouraged we've resisted the urge to pull those milestones and until it's really a fait accompli. So I would I would say to you don't anticipate us to move any milestones on enrollment of our of our MTM. One pivotal I think we're very much to do as well as that.
If not better and I would say just stay tuned.
Fair enough. Thanks for taking my question.
Our pleasure thank you Phil.
Okay.
Your next question comes from Brad Canino from Stifel. Your line is now open.
Okay.
Thank you.
I just want to pull back and ask a question about the men in class in General I think the street view is that <unk> is the more sensitive population to men. In addition, which might just because the name of the alteration is more similar but nevertheless, some struggled with investing in this class because the best efficacy is unexpected in this.
Smaller patient population, but as I was reflecting on all of the men and datasets. This afternoon from J&J from syntax and of course your own the common trend, it's actually see more responses in NPM, one and I want to know where do you stand with your synthesis of the data across the class should we on the street actually recalibrate and expect the best efficacy to be.
Affirmed in a larger NPM one population.
Yeah, Brian It's a good question and thank you it's actually not a question I've heard before and I think it is worthwhile to set expectation. So so we have to be careful what we're talking about here right.
The registrational endpoints for the relapsed refractory setting our CR CRH for the frontline setting they will be CR for the maintenance setting they will be survival.
Other companies and we got a raft of abstracts out our reporting or ours.
In one case, even including stable disease.
Mmm MLS at Cri those are all measures of clinical activity and those are important but I think the registrational endpoints or at least at this stage are what's important can you drive a CR CRH and in frontline can you drive the CR the reseller frame it that way is.
That can be a little confounded by are you getting full count recovery are patients going onto transplant.
So thats why CRC is also worth looking at I, probably we probably wouldn't go beyond CRC and at this point I think is although again emotionally intuitively it makes sense that <unk> should be more sensitive in reality, we're seeing activity pretty robust activity in both populations across.
Loss, the class and I think that's only going to improve in combination what we're really hoping in combination to do is can we drive deeper responses can we eliminate extra medullary disease and minimal residual disease can we drive lengthened the time to recurrence and drive better survival that and I'll go back to something I said.
A couple of as an answer to a couple of calls ago, that's going to come down to who has the ability to keep men and pressure on in the presence of combo and then ultimately in the maintenance setting as a monotherapy without having to jump through a lot of hoops. That's what we've seen with every targeted therapy. There is no reason to believe men as any.
Different I think Ziff Doe has to stand pretty tall, when you look at it that way.
I appreciate it thanks Rick.
Our pleasure thank you.
Okay.
Ladies and gentlemen, as a reminder, should you have any questions. Please press star followed by the number one on your keypad.
There are no further questions at this time Docker Troy. Please proceed with your closing remarks.
Thank you Lester and thank you all once again for joining our call today, we will be participating in the Stifel Healthcare conference and the Jefferies London Healthcare conference in a couple of weeks, we look forward to seeing many of you. There in the meantime, if you have any additional questions. Please feel free to contact Pete Tom or me. Thank you and have a good evening everyone.
Yes.
Ladies and gentlemen. This concludes today's conference. Thank you for participating you may now disconnect.