Q4 2024 Kura Oncology Inc Earnings Call
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Speaker Change: Good day everyone and welcome to today's Q4 2024 Cura Oncology, Inc. Financial Results Conference call.
Speaker Change: At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question and answer session.
Speaker Change: You may register to ask a question at any time by pressing star 1 on your telephone keypad. Please note this call is being recorded. I will be standing by if you should need any assistance. It is now my pleasure to turn the conference over to Patty Bank, Investor Relations. Please go ahead.
Patty Bank: Thank you, Angela. Good afternoon and welcome to Cura Oncology's fourth quarter and full year 2024 conference call.
Patty Bank: Joining me on the call are Dr. Troy Wilson, President and Chief Executive Officer, Dr. Molly Leone, Chief Medical Officer, Brian Powell, Chief Commercial Officer, and Tom Doyle, Senior Vice President of Finance and Accounting.
Patty Bank: 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.
Speaker Change: 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.
Speaker Change: please refer to CURS filings with the SEC, which are available from the SEC or on the Cura Oncology website for information concerning risk factors that could affect the company. With that, I'll turn the call over to Troy.
Thank you, Patty, and thank you all for joining us.
Troy Wilson: We're continuing the momentum generated in 2024 as we continue to make meaningful advancements across our pipeline.
Troy Wilson: We're poised to submit our first NDA for Zyfta-Menib. We're preparing to commercialize Zyfta-Menib as a potentially best-in-class Menin inhibitor for patients with relapsed endorrefractory NPM1 mutant AML, which serves as a first step to providing clinical benefit to patients across the treatment continuum.
Troy Wilson: and we've delivered unprecedented development and regulatory pathways for Zyfta-Medivine frontline AML.
Troy Wilson: Specifically, we've reached alignment with FDA on potential pathways for accelerated approval in the U.S. in both the intensive and non-intensive frontline settings by allowing the trials to use MRD negative CR and CR as primary endpoints respectively.
Troy Wilson: We can now report we've also gained alignment with the European Medicines Agency, or EMA, on the Comid-O-17 protocol.
Troy Wilson: We believe these advancements could meaningfully accelerate the development and commercialization of Zyftominobid frontline AML with top-line results from the MRD-CR accelerated endpoint in the intensive chemotherapy setting anticipated in 2028.
Troy Wilson: As we look beyond Zyptomedib and AML, we're advancing a strong product candidate pipeline with clinical data updates expected throughout this year, and we're well-financed and resourced to create significant value for patients and our stakeholders.
So with that, let's turn to specific updates.
Troy Wilson: Starting with our most recent news, earlier this month we announced positive top-line results from Comet-001, the Phase 2 registration-directed trial of Ziftaminib in patients with relapsed refractory NPM1 mutant AML.
Troy Wilson: The trial achieved its primary endpoint, consistent with a targeted 20-30% CR-CRH rate. The data have been submitted for presentation at ASCO. The benefit-risk profile for Ziftomenib is highly encouraging and the safety profile was consistent with prior reports.
Troy Wilson: As a reminder, Zifta-Menib is the first and only investigational drug candidate to be granted breakthrough therapy designation, or BTD, for treatment of relapsed refractory NPM1 mutant AML.
Troy Wilson: Facilitated by the BTD status of Zyptometib, we completed our pre-NDA meeting with FDA and anticipate submitting an NDA next quarter.
Troy Wilson: We believe the combination of safety, tolerability, and clinical activity in a once-daily oral medication support a competitive profile in the relapsed refractory market as well as advanced clinical development in those critical frontline indications.
Troy Wilson: And speaking of the frontline AML indications, I'm going to turn it over to Molly to review the unmet need in this patient population as well as feedback we've received from regulatory agencies.
Troy Wilson: We're excited to share these updates because we believe the frontline usage of menin inhibitors could be a transformative clinical and commercial opportunity with the U.S. market for menin inhibitors in frontline AML reaching over $7 billion annually. Molly, over to you.
All right, thank you, Troy.
Troy Wilson: Our intent with Zyfta-Amenib has always been to treat AML patients throughout the continuum of care. And despite advances over the last 20 years, there remains a significant unmet need, even in the frontline setting.
Troy Wilson: Specifically, even with approved therapies, up to 70% of patients who achieve a first remission will see their AML return within three years. The five-year survival rate for AML is only 31.9%, and is as low as 11.2% for patients older than 65.
Troy Wilson: Given the unmet need, we are addressing the frontline AML population through two independent randomized placebo-controlled Phase III trials contained within a single trial protocol we call COMET-017.
Troy Wilson: On our investor call a few weeks ago, we announced reaching alignment with the FDA on the COMODO-17 trial protocol. We were particularly pleased by FDA's willingness to allow the trial to use MRD-CR and CR respectively as primary endpoints for accelerated approval in the IC and non-IC populations.
Troy Wilson: We also stated that we would continue to work with other global health authorities and we're now pleased to report that we have also gained alignment with EMA on key aspects of the Comet 017 protocol, with both FDA and EMA aligned on the survival-based endpoints, including EFS and the intensive chemotherapy combination to support potential full approval.
Troy Wilson: By combining two trials under a single protocol, we intend to facilitate study, start-up, and execution. And we believe the protocol is more attractive to clinical sites because it provides treatment options to the broadest patient pool.
Troy Wilson: Comidose-17-NIC or non-intensive chemotherapy is a trial that will evaluate ziftimenib with phenetoclax and azacitidine in newly diagnosed NPM1 mutant patients unfit to receive intensive chemotherapy.
Troy Wilson: The trial will assess complete response and overall survival as dual primary endpoints to support potential U.S. accelerated and full approvals.
Troy Wilson: COMET-017-IC, or intensive chemotherapy, is a trial that will evaluate Zift-Amenib with intensive chemotherapy, or 7 plus 3, in newly diagnosed NPM1 mutant and KMT2A rearranged AML patients.
Troy Wilson: The trial will assess MRD negative complete response and event-free survival as dual primary endpoints to support potential U.S. accelerated and full approvals.
Troy Wilson: We believe the best opportunity to achieve long lasting remission and extend survival for these patients is to achieve MRD negativity with the first attempt at treatment. By utilizing this endpoint in Comet 017 IC, we are paving the way in the field to establish this new surrogate endpoint.
Troy Wilson: Based upon our current assumptions around the Comet 017 IC trial, we believe we may have top-line MRD-CR results for the Intensive Frontline Trial in 2028.
Troy Wilson: This is notably faster than we expected and well within the time window funded under our collaboration with Kiyo Akiran for the development and commercialization of Zeptymineb in AML.
Troy Wilson: We look forward to collaborating with our colleagues at Keowa Cure and to expedite study startup timelines and expect to initiate COMET-017 trials in the second half of 2025.
Troy Wilson: Not only are we now working to develop Zift Amended across the continuum of care and AML, but we are also looking ahead to multiple clinical updates later this year across both our Meningen inhibitor and FTI programs.
Troy Wilson: with the goal of developing innovative therapies for patients in areas of unmet medical need. And with that, I'll turn it back over to Troy.
Thanks, Molly.
Troy Wilson: Turning now to other opportunities for Ziftaminib, we remain on track to initiate the COMET-015 trial in the first half of 2025, which will evaluate the combination of Ziftaminib and imatinib in patients with advanced gastrointestinal stromal tumors, or GIST.
Troy Wilson: This will be the first expansion of a menin inhibitor into solid tumors for us and it's supported by extensive preclinical data
Troy Wilson: The combination of zyptomenib and imatinib shows robust and durable antitumor activity in both imatinib-sensitive and imatinib-resistant GIST preclinical models representing the full GIST treatment continuum.
Troy Wilson: Until now, all therapeutic approaches to treating GIST have been through targeted kit inhibition via tyrosine kinase inhibitors or TKIs.
Troy Wilson: Menin inhibitors offer the potential to shift the treatment paradigm, and zyptomenib may delay the onset of resistance to the frontline standard of care imatinib, or overcome such resistance in patients pre-treated with imatinib, a drug to which 60% of patients develop resistance within two years.
Troy Wilson: Because of the unique mechanism of action and the demonstrated synergy between ziftiminib and imatinib, this preclinical data has been described by our clinical collaborators as potentially transformative.
Troy Wilson: Given the unmet need and the continued significant interest in novel therapeutic approaches to GIST,
Troy Wilson: We're working hard to initiate the Comet 015 study, which we believe will begin in the first half of 2025. And we believe Zift Omenib's market potential in GIFs may represent an additional $1 billion peak sales opportunity.
Troy Wilson: Now, while much of the focus externally is rightfully on our ZIF-dominant program in AML, our team has also been hard at work on our Farnesal Transfer Ace Inhibitor programs.
Troy Wilson: Despite multiple advances, innate and adaptive resistance remains a challenge for many classes of targeted therapies in cancer.
Troy Wilson: We've learned a lot from our growing body of clinical and preclinical data demonstrating the potential of tipifarnav and KO-2806 as companion therapeutic agents to augment the anti-tumor activities of various targeted therapies and to overcome resistance in combination.
Troy Wilson: We're making good progress in our FIT-001 trial, evaluating our next generation farnesyl transferase inhibitor, KO-2806, and the dose escalation portion of our current HN trial is now complete.
Troy Wilson: We look forward to presenting the first clinical data for KO2806 as a monotherapy and in combination, as well as clinical data from the current HN trial.
Troy Wilson: If successful, we believe KO-2806 and other forensic transferase inhibitor drug candidates could drive enhanced anti-tumor activity and become combination partners to multiple targeted therapies in large solid tumor indications.
Troy Wilson: All of this work is made possible through the support of our shareholders, as well as the global strategic collaboration we announced in November with our partner Kyocuren, to develop and commercialize Zip2Minute, funding the expansive AML development program through frontline U.S. commercialization.
Troy Wilson: Our financial health was strengthened by our team reaching alignment with FDA on potential paths to accelerated approval in the large frontline AML indications.
Troy Wilson: Under our partnership with Kila Kiran, we're now well capitalized and resourced to prepare for NDA submission of ZIF-Demented, to continue our preparation for commercialization, and to expand and accelerate our ZIF-Demented development program.
Troy Wilson: With that, I'll turn the call over to Tom Doyle for a discussion of our financial results. Tom? Thank you, Troy. And good afternoon, everyone. I'm happy to provide a brief overview of our financial results for the fourth quarter of 2024.
Tom Doyle: Collaboration revenue from our KEOA-Carin partnership for the fourth quarter of 2024 was $53.9 million compared to none for the fourth quarter of 2023.
Tom Doyle: Research and development expenses for the fourth quarter of 2024 were $52.3 million compared to $32.5 million for the fourth quarter of 2023.
Tom Doyle: General and administrative expenses for the fourth quarter of 2024 were $24.1 million compared to $14.2 million for the fourth quarter of 2023.
Tom Doyle: Net loss for the fourth quarter of 2024 was $19.2 million compared to a net loss of $42.8 million for the fourth quarter of 2023.
Tom Doyle: This includes non-cash, share-based compensation expenses of $8.6 million compared to $7.2 million for the same period in 2023.
Tom Doyle: As of December 31st, 2024, Cura had cash, cash equivalents, and short-term investments of $727.4 million, including the upfront payment of $330 million from Keogh O'Curran.
compared to 424 million as of December 31st, 2023.
Tom Doyle: We believe that our cash, cash equivalents, and short-term investments as of December 31st, 2024 will be sufficient to fund our current operating plan into 2027.
Tom Doyle: and combined with payments anticipated to be received under our collaboration agreement with Kiowa Caron should support our zip-dominated AML program through commercialization in the frontline combination setting.
Troy Wilson: With that, I now turn the call back over to Troy.
Thank you, Tom.
Speaker Change: Before we jump into the question and answer session, let me just quickly lay out our anticipated upcoming milestones.
Troy Wilson: We expect 2025 to be a robust year of research, development, and pre-commercial activity for the company with several expected data readouts across multiple programs. Notably, we look forward to potentially providing updates across our pipeline at every major medical meeting this year.
Troy Wilson: For ZIF-demented, we expect to submit an NDA in relapsed refractory NPM1 mutant AML in Q2.
Troy Wilson: Present top-line data for Comet 001 for presentation in Q2. Present preliminary clinical data from the Comet 007 Phase 1b Expansion Cohort, evaluating ZIFT-Amenib with intensive chemotherapy at a medical meeting in Q2.
Troy Wilson: Initiate the COMET-015 trial evaluating in patients with advanced gist in the first half. Initiate two independent phase 3 registration enabling trials in frontline intensive and non-intensive AML in the second half.
Troy Wilson: Present preliminary clinical data from the Comet 007 Phase 1b expansion cohort evaluating Ziftaminib with venetoclaxonazacitidine at a medical meeting in the second half and nominate a next-generation menin inhibitor development candidate for use in diabetes in mid-2025.
Troy Wilson: For our Furnace Transparency Inhibitor Programs, we expect the following milestones.
Troy Wilson: Initiate one or more expansion cohorts of KO-2806 and cabozantinib in patients with advanced renal cell carcinoma in the first half.
Troy Wilson: Present data from the Phase I monotherapy dose escalation of KO-2806 in patients with RAS mutations in the second half.
Troy Wilson: Present data from the Phase 1 trial evaluating KO2806 and cabozantinib in patients with renal cell carcinoma in the second half.
Troy Wilson: and finally present data from the dose escalation portion of the current HN trial evaluating Tipifarnov and Alpelisiv in PIK3CA dependent head and neck squamous cell carcinoma in the second half. And with that Angela we're now ready for questions.
Troy Wilson: At this time, if you would like to ask a question, please press star 1 on your telephone keypad.
Troy Wilson: You may remove yourself from the queue at any time by pressing star 2.
Once again, that is star one to ask a question.
Unnamed Moderator: We'll go first to Leigh Watson with Cantor Fitzgerald. Please go ahead.
Hey everyone, thank you very much for taking my questions.
Speaker Change: Troy, you guided to the phase 3 top-line, in-front-line, you know, intensive AML setting in 2028.
Speaker Change: You know, just curious what assumptions went into that guidance and anything you can share on the trial size, that plan, or enrollment timeline.
Speaker Change: Yeah, Lee, thanks for the question. We thought it was important because we've been getting questions from, you know, both analysts and investors
to give people some idea of the timeline, particularly
Speaker Change: now that we've gained alignment with both FDA and EMA, but specifically with FDA on pathways to accelerated approval in the U.S.
Speaker Change: And we feel comfortable, you know, we think we're being conservative, but we feel comfortable saying that we think we can have top-line results.
for that accelerated approval endpoint in 2028.
Speaker Change: We'll give you more detail on the trial size, the powering, et cetera, as we get a little bit closer to the trials actually going live and being posted on clintrials.gov, and that's being driven both by we're just doing some further refinement and we're in the process of study startup.
But, you know, that's...
Speaker Change: That is meaningfully faster than what we were projecting for prior to our engagement with the health authorities.
Speaker Change: And, obviously, it positions us well in the context of the funding received under the Kila Kiran collaboration. I would say look forward a little later this year for more updates, Lee, not only on the intensive trial that you're asking about, but the non-intensive trial as well, the sizes, the powering, and then, you know, how do we get to both the potential for accelerated and then the survival-based endpoints.
I hope I hope that's helpful
Lee: Yeah, understood. And I'm just wondering what are the remaining items that you may need to work through before the NDA submission? Any notable feedback from the pre-NDA meeting?
No, I mean, that's...
Lee: Thank you for the question. I don't know if at the time we made that announcement a few weeks ago, if that, you know, if people sort of read over that.
Lee: We were deliberate, actually, in not saying anything until after we'd had the pre-NDA meeting. And the team, Molly and the team, did a phenomenal job of, again, gaining alignment with the agency on all the aspects of the submission. Clearly, the clinical data is always the long pole in the tent, and that's what is driving the timing of the submission at this point, but given that we have BTD and given that we've had, you know, pretty constructive engagement, not only on the monotherapy,
Lee: in the combination setting with FDA, we feel like we're in good shape. And again, we're guiding to a second quarter submission. The team is doing everything in its power to accelerate those timelines. But so far, I think we have everything we need and we've gotten very, it's been a very constructive series of interactions with the agency.
Unnamed Moderator: Angela, should we go on to the next question? We'll go next to Jonathan Chang with Leering Partners. Please go ahead.
Speaker Change: Hi, this is Yander Li for Jonathan Chang. Thanks for taking my question.
Yander Li: So, the first question I have is that when we look at the commercial opportunities for Zyptomanib, I guess the most important variable is the treatment duration. Could you share the reason behind your confidence that a first-line AML patient would be able to stay on the treatment for more than a year? Thank you.
Speaker Change: Yeah, let me actually, Yanzer, thank you for the question. I'm actually going to do this in two parts. Maybe Molly can speak to...
Yander Li: how we've informed the duration of treatment from our experience with Comid-07. And then I'll ask, after she answers, I'll ask Brian to comment on how does that translate into our assumptions around the commercial potential in the frontline. Molly, if you would.
Sure.
Yander Li: As Troy alluded to, the 007 trial has been highly informative to how we handle designing and our expectations for the 017 trial and for use in the front line in general.
Yander Li: I think initially we thought that, especially with the intensive chemo setting, the use would be, you know, some induction, some consolidation, then the patient would go off to transplant.
Yander Li: and potentially some proportion would come back after transplant post-consolidation maintenance. What we're seeing is incredibly different, especially for the NPM1 patients that make up such a large majority of the patient population. These patients are coming on doing induction, consolidation and post-continuation consolidation immediately with few trips to transplant.
Yander Li: except for the KMT2As who get transplant whenever possible and then almost universally either have returned or intend to return to post-consolidation, post-transplant maintenance.
Yander Li: But with that, Brian, I'll turn it over to you to how you see that translating.
Sure, thank you Molly and
Yander Li: You know, based on the assumptions that we're observing, or what we've observed in the trial, like Molly said, we do think there's tremendous potential that menin inhibitors could transform.
the treatment of AML with patients being able to get
Yander Li: to get on therapy, stay on therapy for a for a long period of time. When you think about our opportunities with, as we've stated, that we think this could be, as Troy said, it could be a seven billion dollar potential market. If you're able to get patients to receive a meta-inhibitor for 18 to 24 months, and you know there could be potential for longer than that, but if you think...
Yander Li: between that 18-24 months in the fit intensive chemo population and then 18 months plus within the non-intensive that gives you a significant duration that we think really could
Yander Li: you know reflect that transformative potential and really kind of align with what we've seen in some other markets like multiple myeloma where long duration of treatments with with IMITs have really transformed the market and also the outcomes for patients.
Speaker Change: Got it. Thanks for the comprehensive answer. And I have also a follow-up question related to that.
So, for the COMET-017 intensive combination study,
Speaker Change: If I recall correctly, the patient will include both transplant and non-transplant chemo as consolidation options, and is there a concern about the imbalance of consolidation treatment receiving each arm, and do you have any, like, protocol to mitigate such concern? Thank you.
Speaker Change: Yeah, Yander, let me let Molly speak to that. Molly, do you want to take a shot at Yander's question?
Molly Leone: Sure. Well starting with the KMT2A patients, we really don't think there'll be an imbalance. The intent is always to get them to transplant, so it's likely that all that can will get to transplant. With regards to the NPM1 mutants, it may be that some of the patients do better, hopefully they do better, in the active arm and so are less
Molly Leone: requiring the transplant. So we've built in multitudes of sensitivity analyses to be able to account for that.
Molly Leone: But, ultimately, we built the trial, sized the trial, powered the trial, taking that into account and weighing in the effects that the KMT2A patient population would have.
Molly Leone: on the overall population and being able to assess the effects of transplant or no transplant in the active versus placebo arms, if that's helpful.
Yeah, that's helpful. Thank you so much.
Molly Leone: We'll go next to Jason Zemanski with Bank of America. Please go ahead.
Jason Zemanski: Good afternoon. Thank you so much for taking our question and congrats on the progress.
Jason Zemanski: I was curious, as you look to the additional dose expansion data from the 007 study, what in your view would be encouraging from the 7 plus 3 combo as you start to expand into the non-adverse risk?
Jason Zemanski: group, specifically in terms of MRD negativity, what would give you confidence that addition of Zyfto would ultimately give you survival benefit?
Tom Doyle: Yeah, Jason, thanks for the question. I'm going to ask Molly to speak to it, but Molly, maybe you can take a minute and help folks understand, you know, how we think about the MRD negativity and sort of what the what the standard is as you as you answer Jason's question.
Molly Leone: Absolutely. So what we understand, obviously we're part of a consortium of a large amount of pharmaceutical companies that are really looking into this MRD negativity for this patient population and we have access therefore to both published and unpublished data from those other
Molly Leone: pharmaceutical companies as well as from some of the key opinion leaders that are really advancing the MRD as an endpoint in AML.
that are performing patients, so your NPM1s, for instance.
Molly Leone: So, we would expect that any, you know, incremental increase in that
Molly Leone: would be encouraging for translation into the overall survival as well. So that's the way we're thinking about our data as we continue to look at these patients enrolling. Obviously, you've seen the patients do very well from a response perspective, so I wouldn't expect to see much
Molly Leone: different than that you know they're going to continue to do well but it's it's as you're pointing to the MRD that is is what we're looking at to make sure we're headed in the right direction.
Speaker Change: Got it, makes sense. Thanks for the color Molly. And maybe just a quick follow-up here. I noticed the other mutations bucket about 10 to 15 percent of the population. Curious, you know, what does it take to get there to that group of individuals and what gives you confidence, I guess, that a METID will be active in these subtypes?
Jason Zemanski: Yeah, I'll take that Jason and then Molly can add her comments.
Speaker Change: You know, we have seen what we call off-target activity, not only with the CETD2-RNX1 patient, but we've seen other patients as well who appear to be receiving clinical benefit from from Ziftaminib in, you know, in the monotherapy studies. One of the obvious areas there, of course, is split three.
Speaker Change: And, of course, there's an approved standard of care in the intensive setting. There's actually a couple of them, less so in the non-intensive setting. But if one were to look at KMT2A, NPM1, and then FLIP3, that gives you approximately half of the eligible AML patients.
Speaker Change: We have a study ongoing with Giltirritinib in the relapsed refractory setting that is...
Speaker Change: supporting the notion that one can combine a menin inhibitor and a FLT3 inhibitor with appropriate safety and tolerability.
Speaker Change: Clearly, if you want to go into the frontline, you need to go with an approved agent. There are a couple, Midostorin and Quisartanib. We've guided that, you know, we anticipate starting a, hopefully, I should say potentially, a frontline combination study of Ziftomenib plus Quisartanib. And again, we're optimistic that we can go straight into the frontline because now we have adequate safety of Ziftomenib.
is GOING CRAZY.
Speaker Change: But as I think we mentioned when we, you know, talked more about the deal with Kyowa Kirin, the collaboration is structured and we are actually funded to run multiple global phase 3 trials, and one could potentially be an upcoming flip 3 trial. So, you know, it...
Speaker Change: There are a lot of priorities at the moment. Clearly the NDA submission, the pre-commercial activities, Commodore 17, but Flip 3 is very much on the team's mind and something that I think you'll see us move toward here in the second half.
Got it. Appreciate the feedback. Thanks.
Sure.
Peter Lawson: We'll go next to Peter Lawson with Barclays. Please go ahead.
Peter Lawson: Hey, thanks Troy. I wonder if you could just kind of talk a few minutes just around where you stand for diabetes in the nomination of the candidate and kind of where that fits in into your priorities and you know how you're thinking whether it's type 1, type 2 or particular stages of disease. Thank you so much.
Yeah, yeah Peter.
I appreciate the question. That wasn't expected, but is welcome.
So, a couple of comments. Going for everybody's benefit,
Peter Lawson: We put out data at the American Diabetes Association meeting last summer. That data shows four things, four hallmarks.
Peter Lawson: glucose lowering, stimulation of insulin production, insulin sensitization, and selective expansion of pancreatic beta islet cells.
Peter Lawson: you know, all the, to our knowledge, all of the existing antidiabetics do, you know, do various of three of those four. We haven't yet had an agent that selectively expands pancreatic beta islet cells. And that's really kind of the, the, the, you know, the Holy Grail.
Peter Lawson: The work that we did preclinically is with zyptomenib. We wouldn't take zyptomenib forward into diabetes.
Peter Lawson: for safety reasons, pricing reasons, IRA reasons. That's why we've been very clear from the get-go, if you're going to go into diabetes, you go with a different molecule. And Peter, we have been carpet bombing the chemical space in Mennon for now going on three years.
Peter Lawson: So we have molecules that have different PK profiles, different tissue distributions. We really feel like, you know, one can actually ask that question you know, in the right way with chemical, you know, with drug candidates.
To your specific question,
Peter Lawson: In our internal work, our work with investigators and KOLs and our work with
certain
shall we say strategic partners that know diabetes well.
Peter Lawson: There really is an interest in exploring both type 1 and type 2.
Peter Lawson: We wouldn't put restrictions on those populations today based on what we know. It appears that if one has some reservoir of pancreatic beta islet cells, there's probably good applicability. What we want to be clear about is, you know, there is potentially a lot of value here to be created for patients first and foremost.
Peter Lawson: but also for Cura shareholders, but we have to do that in the right way.
Speaker Change: We are a specialty oncology company. We know what we know. If you see us...
Speaker Change: work in diabetes, we could do some initial, you know, we can do the preclinical work, maybe some initial clinical work.
Speaker Change: But we recognize you pretty quickly need to get that into the hands of a company that is going to be invested from the get-go at running, you know, the large global phase three that would be required to test those hypotheses.
Speaker Change: So there are a lot of creative ways one can do that. The good news is we have the chemical matter I think we have a as good due to Francis Burroughs who's not on the call with us today our CSO We have as good an understanding as anyone about menin inhibitors and diabetes at the moment The nearest term milestone is nomination of a development candidate we're going to take our time because the Demands on the therapeutic index are quite different than oncology and you want to have the right molecule
Speaker Change: the right drug-like properties and the right therapeutic window and we want to have a molecule, Peter, that has the potential to go the distance.
Speaker Change: Does that answer your question? Yeah, that's great. Thank you. I guess there was a breadcrumb in there for me. What's the right route forward so you kind of capture the potential upside of something like diabetes, yet not dilute yourself?
Speaker Change: What's the right, say that again Peter, what's the right, the right what? What's the right strategy there? Is it like a JV, partnership? How should we think to kind of capture upside yet you don't lose your focus around oncology?
Yeah, so yeah, understood. I mean, a few things there.
Speaker Change: I think you want a flexible structure that allows you to cleanly separate
Speaker Change: the biology and, importantly, the IP, the oncology from the non-oncology. Ideally, you want to make certain that the value is captured for Cura shareholders.
Speaker Change: you know this could be a this this could be the first
Speaker Change: you know, novel mechanism of action in diabetes since GLP-1, but I don't think we're under illusions that current shareholders are looking for royalties, you know, a decade out from now. So we want to be thoughtful about how we do it.
You would ideally, Peter, look for...
Speaker Change: You know, look to a structure that really allows you to go very fast.
Speaker Change: may allow you to take more than one molecule forward and ideally, you know, allows you to monetize that IP.
Speaker Change: in a way that you could, again, either extend runway or do other creative things, you know, stock buybacks, et cetera. So, you know, fortunately, this, you know, we're not inventing the wheel here. There's lots of wheels that have been demonstrated to work. But you'll see, those are sort of the themes that we're looking at.
Speaker Change: The good news is, you know, this is essentially a call option on the story. I think it's...
Speaker Change: scientifically and clinically really interesting. It is not as high a priority as what we need to do in AML in this year and everyone at CURA knows that.
Speaker Change: But we wouldn't be doing our best for patients if we didn't find a way to get this into the hands of the clinicians and let them really test the hypothesis.
Speaker Change: Great. Thank you so much. Thanks for letting me deviate the conversation away from AML. Thanks, Troy. Sure.
Speaker Change: We'll go next to Phil Nadeau with T.D. Cowan. Please go ahead.
Speaker Change: Hi, this is Enrique Rodriguez for Health Central taking our questions. I will start with, I have two questions. The first one is on the competitive landscape. Now that we have, that you have at hand, the results from COMET-001 and we had updated
Speaker Change: data from several other mini-inhibitors that were presented at ASH. How do you think, or would you expect SIFTA to be differentiated from the others, or how do you see the competitive landscape ultimately playing out?
Speaker Change: yeah thanks for the question I mean that's a that's a big question but we'll try to be maybe brief and hit the high points if we go back to so
Speaker Change: So there's an opportunity to do the very best you can for relapse and refractory patients with it with you know NPM1 mutant leukemia. That's what we're targeting with ZIFTO and we think we're going to be very competitive in that space.
As you heard Molly say, and I think Brian echoed,
Speaker Change: When you talk to the physicians who treat these patients day in and day out, they will say to you, you need to treat early and you need to treat in combination.
Speaker Change: And ideally, you keep these patients in remission for as long as you can.
What ZIFTO is allowing the physicians to do
is
to keep these patients on therapy.
Speaker Change: Regardless of whether the backbone is intact or the backbone has fallen away, these patients are staying on Ziftomenib for prolonged periods of time in our 007 study, as Molly said, in both the intensive with, you know, 7 plus 3 and the non-intensive with Veneza. The Veneza may fall away, but they're remaining on Ziftomenib.
Speaker Change: And in the case of NPM1, many of them are not going to transplant.
Speaker Change: Why is that? It's because, of course, you know, the compound has meaningful clinical activity, but it also has a safety, tolerability, and convenience factor that allows for once-a-day daily dosing with very good tolerability.
Speaker Change: We've been touting this, you know, from the get-go and continue to believe that as you look toward those large front-line indications...
combinability is going to be key.
Speaker Change: That is what is going to give patients the best chance to stay on therapy for prolonged periods of time. We have, you know, no QT prolongation, no myelosuppression, once-daily dosing, no clinically meaningful drug-drug interactions. It's a very easy drug to use.
Speaker Change: For folks who may be listening, I would refer you to when we did our investor event after the ASH presentations, the commentary that Dr. Zaidan gave around his experience with intensive chemotherapy patients.
Speaker Change: That's really how we see Zip2Menub being differentiated from the competition.
Got it. Thank you. That's very helpful.
Speaker Change: The 015 on GIST, you have mentioned the potential to delay the onset of resistance in that population. So as we look forward to the clinical data in the future, do we...
Speaker Change: Is it more relevant for us to be looking at the duration of the response, aside from ORR, or how should we be looking at the data once?
wanted for it to come.
Speaker Change: Yeah, that's a good question, and Molly, let me ask you if you can speak to that, and I'll just, you know, summarize the question. What are we looking for in terms of a clinical, you know, clinical evidence of activity in the O15 study combining zyftymenib with imatinib? What are we looking to do clinically?
Speaker Change: Yeah, so I think there's several different things we could see and each would be very positive and very Confirming of what we think the combination could do
Speaker Change: For those patients that are on imatinib and starting to fail, hopefully we're able to save that response and get that patient back into a response.
Speaker Change: patients that are on imatinib, and this is something we will be exploring at certain points, but after we finish most of the dose escalation, seeing if you can deepen the response to imatinib. Most of the patients that
Speaker Change: respond to a MATINAB, do so only partially. You rarely see a complete response. So getting patients into a complete response would also be obviously of great importance.
Speaker Change: And then finally, as you referred to, the durability. So having a good duration of that response, a good progression-free survival, prolonging, you know, the usual two years till resistance that these patients...
are able to stay on drugs with their imatinib backbone.
Speaker Change: And those are the three areas that I'm looking to, deepening of the responses, saving responses once they've been lost with a matnib, and then maintaining the responses to a matnib for prolonged periods of time.
Awesome, thank you and thanks for taking our questions.
It's a pleasure.
Speaker Change: We'll go next to Brad Canino with Stiefel. Please go ahead.
Speaker Change: Hi, this is Dara Zahrahan for BRAD. Thanks for taking our questions.
Speaker Change: First, on the frontline development, do you expect EMA to have an entirely different opinion than the FDA on MRD negativity as a regulatory endpoint? Maybe tell us more on how you expect to conduct
017 trial to support a global approval
I do have a different question.
after this.
Thanks for watching!
Speaker Change: okay yeah those are those are two good questions Molly would you like like to take those
Molly Leone: Sure, so I do think that there's the potential for EMA and FDA to be at slightly different points and where they would be accepting of MRD negativity, although both regions recognize
The MRD negativity is clearly a very significant piece.
Molly Leone: of getting these patients into a successful remission. I think what you're kind of drawing attention to is, are we going to do things differently between the regions? And the answer is yes.
Molly Leone: The accelerated approval endpoints were always intended to be for the United States, whereas we intended the survival-based endpoints to support the approvals in the EU. Does that help?
Yeah, helpful commentary.
Speaker Change: Switching over to relapse and refractory, will the data cut and patient denominators match between your upcoming medical meeting presentation, I suppose first would be ASCO abstract and the NDA submission?
Thank you, Marlee, Marlee do you want to take that?
Speaker Change: We'll go next to Charles Hsu with LifeSci Capital. Please go ahead.
Charles Hsu: Hey guys, good evening, and thank you for taking the questions
Charles Hsu: maybe one outside of AML. So, you know, maybe one program where frankly lots of folks have been paying very little attention to. The far-nestle trans races, KO 2806, I mean like
Speaker Change: I don't know, what would you say you need to deliver here in second half of 2025 in order to gain more conviction on this asset, also to gain more conviction?
Speaker Change: You know, from the investment community on these, you know, especially not only in context with the assets themselves, but also in context of some of the emerging competitive landscapes in areas like RAS or renal cell cars.
Thank you.
Speaker Change: Yeah, Charles, thank you. Thanks for the question. I mean, very simply.
Speaker Change: You're looking to do something that people have been trying to do for a long time I think largely without success and that is
you know, how do you develop a companion target to...
Speaker Change: some of these big oncogenes. People have looked at SHIP-2, they've looked at SOS-1, in the case of KRAS.
Speaker Change: People have tried to combine inhibitors of the MAP kinase pathway and the PI3 kinase pathway largely without success.
Speaker Change: But we know, and you see it in every single study, you get responses in, if you're lucky, half the patients, the other half don't respond, and many of the responders actually eventually relapse due, in many cases, to mechanism-based resistance.
Speaker Change: So to your question, what are we looking to do? You're looking to show that you can combine a farnesyl transferase inhibitor with these other targeted therapies with acceptable safety and tolerability. You can't skip over that because that's what kills most combinations.
Speaker Change: You know, you can have the best preclinical data in mice, and if the patients can't tolerate it, it, you know, you're not going anywhere. So that's first and foremost. The second is you're looking for evidence of activity.
Speaker Change: initially, and these are, you know, these are phase one studies, right, dose escalation studies, you're looking for evidence of clinical activity that is unanticipated, unexpected.
Speaker Change: So I mentioned to you in the case of both Tippi Farnab and Del Pellicib
Speaker Change: In PI3KH mutant head and neck, alpellisive delivers at best stable disease. Tipifarinib is inactive.
Speaker Change: So, what are you seeing when you combine those two in that population?
in the case of RCC, the one that you mentioned.
Speaker Change: Are you seeing activity either after the appropriate standards of care and in particular in combination with gabozantinib?
Speaker Change: you know, what are you looking for? If you see clinical activity in patients who have failed the existing therapy, and then you, and this is what Molly was alluding to with JIST.
Speaker Change: patients who, you know, you give them the drug, they begin to progress, then you give them your novel agent and the drug again, and you restore the response, and you have good tolerability, that's telling you, keep going, right? You've got an encouraging signal. I think the thing that has us...
encouraged continuing to move forward is...
We're evaluating
Speaker Change: 2806 and and and Tippi Farnab really as a sort of a test case
in TKIs.
Speaker Change: If we're able to deliver this, I think that could really be a significant contribution to patients.
Speaker Change: We have the ability to take our time. 2806, we're confident, is a very good drug, and we look forward to sharing data with you and, you know, the community in the second half of the year, hopefully at a major medical meeting.
Great, thank you.
Sure.
Speaker Change: We'll go next to David Dye with UBS. Please go ahead.
David Dye: Hey, thanks for taking my questions. Two from me, actually. One is just on the Redux Refractory Pivotal Data readout at ASCO.
Speaker Change: You mentioned that it will be a later data cut, so could you maybe just help us understand how this later data cut
Speaker Change: could change the CR-CRH rate. And then on that, can you just tell them more about the baseline characteristics of the patients that we'll potentially see? Would you expect the patients to have similar or prior venusoclax treatment?
Speaker Change: Yeah, David, let me just correct you on something you said because we may have misstated it or you may have misheard it. It's not a later data cut. What we said was it's the same, it's effectively the same data cut the agency is seeing.
Speaker Change: We're not trying to slice and dice it, and as Molly said, we're not going to be looking to add patients, you know, to the denominator or the numerator. So it'll be the same data cut that is going in as part of the NDA submission.
Speaker Change: On the baseline characteristics, Molly, could you answer David's question to the extent that we can?
Speaker Change: Yeah, sure. Expect to see similar patient characteristics to what we saw in the Phase I.
Speaker Change: Again, patients are heavily pre-treated. Most have seen venetoclax. Many have had prior transplants. It's really largely a very similar patient population to the one for whose data we've already presented.
Speaker Change: on the clinical trial, and do you think they could potentially have them help out with some of the clinical trial developments, expedite the clinical trial development?
Molly, do you want to speak to that?
Speaker Change: Yeah, I mean, that's absolutely the hope. They're very good partners to have. They have, you know, a good presence in areas we don't, like the EU, like Japan. So they would be very good partners on the ground, helping to get sites up and running. Of course, they are also good standing boards for our particular strategies, especially in some of the regions they're most familiar with. So we expect them to be, well, to continue to be a very big help on both.
design and study startup.
All right, thank you so much.
Thanks, David.
Speaker Change: We'll go next to Justin Zelen with BTIG. Please go ahead.
Justin Zelen: Thanks for taking our question. Maybe to follow up on Charles's earlier question, I also find the FDI is quite interesting and also important given that you have wholly owned economics on the programs and are
Speaker Change: You know, the only company that's developing the programs. Troy, you mentioned the combination approach with K-RAS, which I find quite compelling.
Justin Zelen: Can you talk to whether you have preclinical data with a pan-KRAS inhibitor and just how you kind of view that landscape on the combination potential with the pan-KRAS inhibitors or the KRAS variants?
You do see potentially synergistic activity with both.
It depends, interestingly, on the cellular and the organ context.
So...
Justin Zelen: That's not terribly surprising, even though we think of both of them as being RAS-driven, it does appear that colorectal is probably more multigenic.
Speaker Change: And one of the things we're looking to do, Justin, I mean, when we started this combination, we went with Adagrassiv because, frankly, it was one of only two commercially available KRAS inhibitors with a well-understood safety and tolerability profile. We are eager for the KRAS field to catch up to us.
There are opportunities to combine with G12-D, G12-V, Pan-RAS.
Speaker Change: and we are, you know, that's an opportunity, it's also a challenge.
of How Do You Think About...
Speaker Change: you know, doing what's best for patients while at the same time threading, you know, threading the needle to get to the market and ideally take the largest segment of the market.
Speaker Change: So, you know, we are in discussions with a number of different folks.
Speaker Change: I would say we've been encouraged thus far by the combinability of farnesyl transferase inhibitors with these other agents. Back in the day, before we started dosing with Tipifarnib and Alpelesiv, people had said, what are you most worried about? And I would say to them, it's the tolerability.
You don't, you know...
Speaker Change: That is what most of the time does these combinations in.
Speaker Change: 2008-06 has shown itself to be very well tolerated in combination. Now it really comes down to, you know, what kind of clinical activity are we seeing and how do we think about that forward development strategy. And what you're seeing, what you will see us do, Justin, is likely move multiple FTIs forward to give ourselves optionality in light of, you know, competitive dynamics, pricing,
Speaker Change: because as I said, each of those tumor types could be an entire program unto itself.
Speaker Change: and we want to think carefully about how we do that, we've made a very, you know...
Speaker Change: Sustained investment in farnesyl transferase. I think we're you know, we're ahead of everyone else It starts to get interesting here in the second half as we start to show clinical data I would encourage anybody who's interested. We've got a ton of preclinical data available on our website
Speaker Change: As I said, we will look to do some sort of event.
Speaker Change: probably ahead of the clinical data with the analyst and the investor community to help educate folks on how do you think about FTIs, what's the scientific rationale, what's the current landscape, how should you think about the clinical data. Look for us to do that in the second half. We want to get on the other side of the COMET-001 data, on the other side of the 007 data, but that's, you know, it's something to look forward to in the second half.
Speaker Change: Thanks, Troy. And maybe just quickly, how do we think about business development activities from Cura, either in licensing or out licensing, you know, throughout the rest of the remainder of this year and into next?
Speaker Change: In licensing, I mean, we get pinged probably several times a week. We have yet to pull the trigger on anything. We have a very high bar to bringing anything in, given everything we have going on. You know, our...
Speaker Change: Our goal would be to deliver a blockbuster in AML, a blockbuster in GIST, and a blockbuster in one of those FTI indications. I think if we could do that, we don't need to add anything else.
Speaker Change: To be quite frank, and we're funded to do that, but there are a couple of interesting opportunities in terms of outlicensing.
At the moment, our focus is really clinical collaboration.
Speaker Change: How can we generate clinical data that will help inform the development path?
You'll see that we've prioritized
Speaker Change: drugs that are either, you know, that are ideally standard of care and generic or generic in the foreseeable future, because it gives you and, you know, anyone in the future maximum optionality. But when we start to think about KRAS, PI3 kinase,
Speaker Change: Those are going to be novel agents and you need to find people that have a shared vision of what you might do together.
Speaker Change: So, I don't know about BD as much as clinical collaborations. Justin, with one footnote, and that would be back to Peter's question around diabetes. I think we have to think carefully about what we do there, and I would say stay tuned.
Speaker Change: Got it. Some more partnerships rather than D. Okay, got it. Thanks so much, Troy. Thanks for taking our questions.
Our pleasure. Thank you.
Speaker Change: We'll go next to George Farmer with Scotiabank. Please go ahead.
George Farmer: Hi, good afternoon. Thanks for taking my questions, a couple from me.
Troy, you and Molly indicated on your last call that...
We would be seeing a slightly later data cut.
George Farmer: at the medical meeting versus what you would be submitting to the agency and now you're saying it's going to be the same cut. I was, you know, perhaps you could elaborate on why that shift. And then also, in your conversations with the agency, agreeing to this MRD end point, that seems to be very different than how the agency has approached it.
George Farmer: other hematologic indications like multiple myeloma where they call the committee to talk about this. Can you talk about your interactions with the agency and do you think this is something that we could see with other programs beyond CURES? Thanks.
yeah
Maybe on the first question, I mean, there's a...
George Farmer: We're talking about a ton of data here, right? So, there's what's in the abstract, there's what's hopefully at ASCO, potentially at ASCO, and then there's what's going to the FDA. Those are slightly different, but they're all contemporaneous. And to Molly's point, I don't think they're going to move the numbers around significantly.
George Farmer: which is what people are really getting to. The numbers that you see in the abstract and ultimately the poster or the oral presentation should be consistent with what we see, with what we will be submitting to FDA for review.
George Farmer: So, to the extent that we, you know, no intention to create any confusion there, it's just, you know, you're talking about ever larger sort of, you know,
data packages, if you will.
Molly Leone: On the engagement with the agency around MRD negativity and how that might differ from myeloma, I think, again, our work with the IMPACT Consortium is instructive, but I'll let Molly speak to that because she's really been spearheading that, George. Molly, do you want to take George's question?
Speaker Change: the relationship between MRD-CR and overall survival. Ultimately, as we've said before, we don't need any more data right now to get our trial started. But obviously, to confirm the endpoint and to analyze the data, we'll have to be submitting a larger data package.
Speaker Change: It's hard to know in three years or less, more than likely, when we start submitting these data packages that the FDA will be looking at in advance of our data to
to start to establish MRD-CR.
Speaker Change: as a surrogate endpoint if they'll be calling a committee or not. They seem to be very accepting of the fact that their own internal expertise suggests that it is
Speaker Change: in fact, a good surrogate endpoint once we get their data packages together. And so we will see how that plays out over the coming years.
Speaker Change: We expect them to do a lot more work in the area. We're going to help support them doing the work. And all of this work is just expected to be submitted at the time we submit our own data supporting the accelerated endpoint.
Okay, great.
Speaker Change: I was going to just add to that, you know, this is
Speaker Change: Not unprecedented. Kronos, a couple of years ago, reported that it had alignment with the FDA.
Speaker Change: developing its sick inhibitor in NPM1 mutant, you know, frontline AML as well.
So, um, as Molly indicated...
You know, our interactions have been, there's a willingness to...
to create a pathway for accelerated approval.
Speaker Change: Obviously, we have to run the trial and show up with the data, but there's a willingness to consider that, and that builds on, as you indicated, myeloma and some of the other areas where we've seen that endpoint become widely accepted. Just wanted to add that point.
Speaker Change: Yeah, that's very helpful. And when do you think you would capture the EFS endpoint from the study?
We haven't
Yeah, we haven't got it. So we've been careful.
Speaker Change: We're still working through putting those dates down. You know, we want to make certain that when we put dates out, we can stand behind them. All of these endpoints are driven by number one, enrollment assumptions, and then other assumptions...
Speaker Change: around time on therapy and survival and whatnot. Give us a bit more time. We'll come back again with more details on the trial design, more details on the timing of the endpoints later this year as we get closer to study startup.
Okay, great. Thanks very much, Troy. Our pleasure. Thanks, George.
Speaker Change: Our last question comes from Salim Syed with Mizzouho. Please go ahead.
Speaker Change: Hi, this is Eric on for Saleem. Thanks for taking our question.
Speaker Change: Just another divergence from AML real quick, if you don't mind, what with the whirlwind of changes at FDA, staffing cuts, just wondering if you...
Speaker Change: come across anything in your engagement with FDA recently that has given you any cause to update your expectations on how quickly they're able to come back to you, you know, their share of timelines, you know, whether
Speaker Change: You know, things might be picking up or slowing down due to anything that's going on in from the FDA side at this point. Thanks.
Speaker Change: Ben, just incredibly professional, timely, cooperative. We're not getting any indication. They are, you know, they are such good partners. We're, we, you know, we're lucky as an industry to have.
Speaker Change: such a good regulator, you are going to see us be conservative on our timing and our guidance. I don't think we'll be guiding to things coming in ahead of schedule because you just never know in this environment, right?
Speaker Change: and then, you know, hope for the best. I don't think people should necessarily be guiding to more aggressive timelines, but we're not getting any indication yet that there have been major disruptions at the FDA. And I think that's, you know, let's hope that that continues.
All right, very helpful. Thank you.
Sure.
Speaker Change: This does conclude today's question and answer period. I will now turn the call back over to Dr. Wilson for closing comments.
Troy Wilson: Thank you, Angela. Thank you all once again for joining our call today. We'll be participating in the Cowan, the Lyrinc, and the Barclays Investor Conferences in Boston and Miami over the next couple of weeks, and we look forward to seeing many of you there.
Speaker Change: In the meantime, if you have any additional questions, you know how to reach us, please reach out. And thank you once again and have a good evening, everyone.
Speaker Change: This does conclude today's program. Thank you for your participation. You may disconnect at any time.
Speaker Change: Do it otherwise I'll make you do it Instead I would like you to do it I'd better tell you if you considered or like to completely blow your way into this I mean come on Well you do think I państ is fine