Kura Oncology at ASCO: Strategic Moves in AML Treatment

On Monday, 02 June 2025, Kura Oncology (NASDAQ:KURA) presented at the American Society of Clinical Oncology ASCO Annual Meeting 2025, unveiling promising data for its drug Ziftamenib. The company highlighted strategic advances, including FDA acceptance of its New Drug Application with priority review. While the results were largely positive, challenges remain in differentiating Ziftamenib from competitors.

Key Takeaways

• FDA accepted the NDA for Ziftamenib with a priority review and a PDUFA target date of November 30, 2025.
• The COMET-one trial showed significant improvement in remission rates for AML patients.
• Kura plans to initiate COMMOD 17 Phase three trials in the second half of this year.
• The company has over $700 million in reserves, with potential to earn an additional $375 million in near-term milestones.
• Strategic discussions included predictors of response and commercial launch preparations.

Financial Results

Kura Oncology reported a robust financial position with over $700 million on the balance sheet as of the end of the first quarter. The company anticipates earning up to $375 million in near-term milestones, which will support ongoing research, development, and commercialization efforts.

Operational Updates

The COMET-one trial results were a focal point, demonstrating statistically significant improvements in complete remission rates compared to historical controls. The median overall survival for responding patients reached 16.4 months, and the drug was well-tolerated with low rates of myelosuppression.

Future Outlook

Kura Oncology plans to present preliminary clinical data from the COMET-seven phase 1b trial at the upcoming EHA meeting in Milan. Furthermore, the initiation of the COMMOD 17 Phase three trials is expected in the second half of the year, targeting both intensive and non-intensive AML treatments.

Q&A Highlights

During the Q&A session, key topics included strategies to mitigate pseudo-progression and the potential differentiation of Ziftamenib from other menin inhibitors like Revumenib. The company also discussed its commercial launch preparations and predictors of response to Ziftamenib.

For more detailed insights, please refer to the full transcript below.

Full transcript - American Society of Clinical Oncology ASCO Annual Meeting 2025:

Operator: Hello, everyone, and welcome to the CURA Oncology ASCO Virtual Investor Event. At this time, all participants are in a listen only mode. After the speakers’ presentation, there will be a question and answer session. To participate, you will need to press 11 on your telephone. You will then hear a message advising your hand is raised.

To withdraw your question, simply press 11 again. Please note this event is being recorded. Now it’s my pleasure to turn the call over to the CEO and President of Cura Oncology, Doctor. Troy Wilson. The floor is yours.

Troy Wilson, CEO and President, CURA Oncology: Thank you, Carmen, and welcome, everyone. We’re here at ASCO where we’re delighted to have an analyst and investor call to discuss the COMET-one monotherapy registrational data and our ZYPTUMED program. Turning to slide two, I want to remind you that we’ll be making forward looking statements during today’s presentation. And I would refer you to our website or to the SEC’s website for more information about the risks and uncertainties of an investment in CURA Oncology. Turning to slide number three.

I don’t think it’s an understatement to say that even with oncology research and development, AML has proven to be particularly challenging. Approximately twenty two thousand people are diagnosed with the disease each year in The US and even with available therapies, their five year survival rate remains unacceptably low. There’s a desperate need for new therapies and we believe up to fifty percent of AML patients may benefit from menin inhibitor therapy. Turning to slide number four. Today, we will be reviewing the clinical data from the COMET one trial, which evaluated Ziftamenib as a monotherapy for patients with relapsed and refractory AML bearing NPM1 mutations.

Yesterday, we were thrilled to announce FDA has accepted our new drug application based on positive results from the COMET-one trial. The agency granted priority review and assigned a Prescription Drug User Fee Act or PDUFA target action date of 11/30/2025. Along with our partners at Kyokirin, we’re pursuing an aggressive development and commercialization strategy for ziftaminib, and we anticipate the partnership will fully fund Kura’s efforts through the frontline commercialization in The US. Turning to slide five and the agenda. We’ll start with a review of the COMET one registrational data that was just presented by Doctor.

Wang in an oral session here at ASCO, which just ended. Doctor. Maliglioni will briefly discuss how the COMET one trial and results fit within our broader development plan. Then Brian Powell will briefly summarize the market opportunity for ZIFTIMENED in relapsedrefractory NPM1 mutant AML and some of the highlights from our pre commercial activities. And finally, we hope to have plenty of time for Q and A.

We’re honored to be joined by two esteemed key opinion leaders. Doctor. Eunice Wang serves as the Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center in Buffalo, New York, and Professor of Oncology in the Department of Medicine at Roswell Park. She presented the COMET one data in the oral session at ASCO. We’re also delighted to be joined by Doctor.

Amr Zaidan, who currently serves as Chief Division of Hematologic Malignancies, Director of Hematology Early Therapeutics Research at the Yale Cancer Center and Professor of Medicine Hematology at Yale University. Doctor. Zaidan is the principal investigator on the COMMENT seven study, which will be the focus of our presentation at EHA twenty twenty five in a couple of weeks. We’re honored to have Doctor. Wang walk through the clinical data, and then the two of them will be available to take your questions.

With that, it’s my pleasure to turn the presentation over to Doctor. Wang to discuss the COMMENT-one data. Doctor. Wang?

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: Thank you. So, next slide. On behalf of my coauthors, I’m honored to present our abstracts, Ziptomenon in relapsedrefractory NMP1 mutant AML Phase 1btwo clinical activity and safety results from the pivotal COMMENT one study. Next slide. As you can see here, the COMMENT one is a pivotal trial of symptomatically monotherapy in relapsed and refractory NMP1 mutant AML.

As you can see, early study phases in the dose escalation and validation cohorts established the recommended phase dose of zyptomenon of six hundred milligrams once daily and relapsed and refractory NMP1 mutant and KNP rearranged leukemias. The Phase 1b expansion study, which was completed, continued to validate the safety and efficacy of the six hundred milligram daily dosing in patients with relapsed and refractory NMP1 mutant disease, and shown here are the results presented today on the pivotal phase two portion of this study. This is a registration enabling study in relapsed and refractory NMP1 mutant patients, which further evaluated the efficacy and toxicity of Zystamenen. Specifically, the primary endpoint of this phase II registration enabling study was to determine whether the CR CRH rate or complete remission with and without hematologic recovery rate achieved with cystoMetin in these patients was statistically superior to a historic twelve percent CRCRH rate in the same patient population treated with conventional standard salvage chemotherapy. Key secondary endpoints of the study included duration of CRCRH, MRD negativity by molecular analyses, transfusion independence, and adverse events.

Next slide. On this slide, you see the baseline characteristics of the RIIOS three refractory NMP1 mutant patients treated on this study. As you can see, the median age of these patients was 69 years with an age range from 22 to 86 years. This is reflective of the real world experience of newly diagnosed AML patients in the general patient population. Similar to this, we see that the majority of these patients, sixty three percent, were greater than or equal to 65 years of age.

Again, a largely older cohort of patients that represent what we see in our clinical practice in this day and age. ECOG’s performance status was between zero and two. You also see, indicative of other larger studies, that there were several co mutations identified in these patients. Fifty three percent of patients had co mutations in FLT3, thirteen percent IDH1, and twenty three percent IDH2. This was a heavily pretreated patient population with a median of two prior lines of therapy and some patients having received up to seven prior therapeutic interventions.

You can see that a quarter of these patients had prior hematopoietic stem cell transplantation. Sixty percent had prior venetoclax therapy. On the next page, we see here the response data, and you can see here that in the pooled phase 1btwo patient population that the overall response rate in patients was thirty five percent with a CRCRH rate of twenty five percent. Of note, two thirds of these patients, or sixty five percent, achieved MRD negativity by central molecular testing. In the phase two patients of ninety two listed here, the CRCRH rate of twenty three percent was significantly superior by a p value of point zero zero five eight to the historic twelve percent CRCRH rate reported with conventional chemotherapy.

You can see that for these phase two patients after a median follow-up of four point one months, the median time to achieve a CR CRH was two point eight months, and the median time to achieve an overall response rate was one point nine months. Next slide. This study also included prespecified subgroup analysis in responding patients, and as you can see across the board, that there was no difference in response rates in patients depending on age, performance status, and importantly, based on prior therapy. Again, these patients were heavily pretreated, and the fact that some patients had greater than three prior chemotherapy agents and lines of therapy did not impact on the response rate achieved in this patient population. Similarly, prior allogeneic stem cell transplantation and prior exposure to venetoclax therapy in previous lines of therapy did not negatively impact the overall benefit achieved by these patients in terms of response.

Neither did the presence of mutations or mutations. Response rates across the board were similar in all of these patient groups. Moreover, slide, there were other signs of clinical benefit. As you can see here, twenty one percent of patients were converted from being transfusion dependent for red cells and platelets at baseline to becoming transfusion independent after Zipto Menin therapy. Twenty four percent of patients who are dependent on red cells became independent transfusion wise for red cells, and seventeen percent of patients who are dependent on platelet transfusion became independent of transfusions of platelets after receiving ziptylmenin therapy.

About twenty percent of patients who are already transfusion independent also maintained their transfusion independence throughout ziptalmaden therapy, supporting the fact that this therapy is not, in fact, severely myelotoxic. Next slide. The median overall survival of all patients, one hundred and twelve patients in the pooled 1btwo study is shown here and was six point one months. Twenty four patients remain alive on study with nine patients remaining on Vyptomening therapy at the time of data cutoff. Among those patients who achieved a response, meaning they achieved a CR, a CRH, a partial remission or morphologic leukemic free survival clearance, you can see the median overall survival of these responding patients was sixteen point four months as opposed to three point five months in the nonresponding patients in these relapsedrefractory NMP1 patients.

Next slide. Encouragingly, cysto menin was also extremely well tolerated, and you can see here that there were very low rates of cysto related myelosuppression, as mentioned previously. While twenty to twenty two percent of patients developed anemia, febrile neutropenia, and thrombocytopenia, I would argue that these rates of myelosuppression are much lower than we see with similar drugs in the relapsedrefractory setting. Of note, there was no clinically significant Q2C prolongation with three out of one hundred and twelve patients developing what investigators thought was a possible Q2C prolongation due to drug. Among these three patients, one had a grade two QTc prolongation two had a grade three QTc prolongation.

But of note, all three of these patients were on concomitant medications were known to prolong QTc, and two patients had electrolyte abnormalities that could have contributed to these QTc prolongations. None of the investigators deemed any of these QTc prolongations to be significant, and none of the patients ended therapy because of QTC prolongation effects. On the next slide, we see cysto menin related adverse events occurring in greater than or equal to five percent of all patients. As you can see here, differentiation syndrome occurred at any grade in twenty three percent of patients, and fifteen of these one hundred and twelve patients had grade three differentiation syndrome. However, of note, there were no grade four or five events.

There were no deaths associated with the differentiation syndrome, and with the institution of protocol defined mitigation strategies, the majority of these CS events were successfully resolved, with the majority of these patients resuming drug after management of this complication. Only three percent of patients discontinued Ziptaminin due to any adverse events. You can see, although there were instances of nausea, vomiting, pruritus, and decreased appetite, and ALTs, none of these were considered significant or ended up with serious adverse events. Next slide. So, conclusion, the pivotal COMET one phase two study met its primary endpoint, demonstrating that zyptomenon therapy resulted in statistically significantly improved CRCRH rates over historical control of patients treated with salvage chemotherapy.

Of note, these responding patients achieved an overall survival of sixteen point four months. Two thirds of these responses were MRD negative by molecular testing and twenty percent of patients achieved transfusion independence, supportive of the clinical benefit of this agent in these individual patients. And these heavily pretreated patients who had received a median of two prior lines of therapy. There was similar response rates, regardless of the number of prior therapies, prior allogeneic stem cell transplantation and prior venetoclax therapy. In addition, Zipto Menin was well tolerated in these patients with low rates of Zipto related myelosuppression and only three percent of patients discontinuing therapy because of Zipto related adverse events.

There was no clinically significant QTc prolongation, and although grade three and lower differentiation syndrome was observed, with the implementation of protocol specified mitigation strategies, there were no grade four events and there were no DS related deaths. The majority of patients continued to proceed to stifilmenin after resolution of differentiation syndrome. Based on these data, a new drug application, as mentioned by Troy Wilson, was accepted by the FDA for consideration of Zipto monotherapy as a new treatment option for adult patients with relapsed and refractory NMP1, and based on the very favorable safety profile, azithromycin appears to be a very attractive agent for combinatory studies and together with intensive and non intensive chemotherapy backbones in the frontline setting.

Troy Wilson, CEO and President, CURA Oncology: Great. Thank you, Doctor. Wang. Turning to slide 17, we’ll ask, Doctor. Molly Leone if she can, give an overview, quick overview of the ZYPTOMENEM global development plan to help contextualize the results from COMMOD one that Doctor.

Wang just presented. Molly?

Molly Leone, CURA Oncology: Thank you, Troy, and on to the next slide. So together with our partners at KeyWaterin, we are investigating zifomentib across the AML continuum in up to fifty percent of patients for whom we believe the menin KMT2A pathway could be a driver of disease.

Unidentified speaker: On the left hand of this slide, we have a comprehensive development strategy to address patients in the frontline setting, whether

Molly Leone, CURA Oncology: or not they are eligible for transplant, treating along the continuum of their therapeutic intent. On the right hand side, we are building on the data generated by the COMET one monotherapy study to evaluate ziftamenib and other various combination regimens in the relapsedrefractory setting. This comprehensive strategy uses both company sponsored studies as well as investigator initiated studies to provide the greatest number of options and therefore benefit for patients. Moving to the next slide. Previously at ASH twenty twenty four, we presented Phase 1a dose escalation data for the combination of ziftamenib with intensive chemotherapy, or seven plus three.

Ziftamenib was generally well tolerated in combination with standards of care at all dose levels studied. Moreover, the interim analysis from the Phase 1a portion of the dose escalation study showed high CR rates in both the NPM1 and the KMT2A rearranged adverse risk frontline populations. At EHA, we are excited to share an update on the COMET-seven study, where we will see updated results including data from the Phase 1b expansion cohort of zyptomenib at this RP2D of six hundred milligrams plus intensive chemotherapy. It will represent a more mature data cut of the evolving clinical data. As it is a combination of the dose escalation and subsequent expansion, the median time for patients on study is approximately twenty weeks, with some patients from the phase 1a now having been on study for up to forty seven weeks.

As we have discussed, the challenge in the frontline setting is to maintain patients in a durable response, and we look forward to sharing data on the benefit of a targeted agent such as zyptomenen being on board with a focus on these expansion cohorts. Moving to the next slide. We are pleased to have unveiled our strategy to evaluate zyptomenib in combination with standards of care in the frontline AML population with significant leadership roles.

Operator: Please standby, ladies and gentlemen. Please stand by, ladies and gentlemen. We have technical difficulties.

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: Rebecca?

Operator: We can hear you now. Thank you so much.

Unidentified speaker: Can you hear us?

Operator: Proceed. We can hear you.

Brian Powell, CURA Oncology: Yes.

Unidentified speaker: Okay.

Troy Wilson, CEO and President, CURA Oncology: We’re going to apologies for that. We had a technical glitch. We’re going to go back to slide 20 and just pick it up from slide 20. Apologies to all of you in the audience. Molly, want to go ahead?

Slide 20.

Molly Leone, CURA Oncology: With significant leadership roles being played by Doctor. Zaidan and Wang for which we thank them greatly, and with options for both accelerated approval and survival based full approval endpoints. We’re making good progress in study start up, and the COMET zero-seventeen trial remains on track to start in the second half of twenty twenty five. And turning to the next slide. With that, I will turn it over to Brian to talk about the market opportunity in the relapsedrefractory NPM1 mutant AML patient population.

Brian Powell, CURA Oncology: Thanks Molly. Turning to the next slide, slide 22. Along with our regulatory efforts towards the Ziptimedib NDA, we have been conducting pre commercialization activities and market research. Specifically, we’ve sought feedback from both academic and community physicians and investigators on some of the differentiating features of ZYPTO MEDIT. The feedback we’re getting has been very positive, and some of the key highlights are summarized here.

Starting in the upper left, in addition to the twenty three percent CRCRH rate, we’re hearing from physicians and KOLs they are impressed with the overall survival amongst responders, which is longer than many of them would have expected in this population. Turning to the middle, we also hear consistently that physicians are impressed by the combinability and convenience of ZYPTEMEND. Patients can take it once per day. They don’t have to worry about drug drug interactions, and there is no need for weekly cardiac monitoring. Finally, if you look in the upper right panel, another highlight of Ziftaminib is the low rate of myelosuppression.

This allows patients to recover counts more quickly, and they are less prone to infection. Next slide. Turning now to slide 23, we see that physicians highlight the presence of MRD negative responses among patients with or without prior venetoclax, which is seen as an advantage in this patient population. Moving to the middle, the overall safety and tolerability profile was viewed as compelling, particularly the absence of ZYPTOMENEB associated myelosuppression and the lack of a need for cardiac monitoring. Finally, the combinability and convenience are highlighted as key advantages, which will be relevant for both the initial population as well as the ongoing development work in combination.

Next slide. We’re very happy that the FDA has accepted our NDA submission for ZYPTA MEDEV and assigned a PDUFA date of 11/30/2025. We see an attractive opportunity in the relapsed refractory AML population. There continues to be a very high unmet medical need. Among patients twenty percent are primary refractory and fifty percent will relapse within one year.

We see significant potential for Ziftaminib as an active, safe, and well tolerated targeted therapy to support sustained treatment. With an anticipated six months of duration of treatment in the relapsedrefractory setting, we believe Ziftaminib is well positioned to achieve significant share with the combination of clinical activity, best in class safety and tolerability with a once daily dosing regimen. And with that, I’ll pass it to Troy for concluding remarks.

Troy Wilson, CEO and President, CURA Oncology: Great. Thanks, Brian. If we can turn to slide 26.

Operator: Please get closer to the microphone, doctor. We cannot hear you.

Troy Wilson, CEO and President, CURA Oncology: As you know, this is just the first step of our strategy to treat up to fifty percent of AML of all AML patients. With the PDUFA action date of November 30, we’re squarely focused on supporting the FDA and its review as well as preparing for a potential approval and launch in the fourth quarter. We believe Ziftaminib represents potentially best in class menin inhibitor for AML and we think this will be reinforced by the clinical data we’ll share at EHA in two weeks as well as additional data we look to share in the fourth quarter. Beyond AML, we’re looking to create value for patients with menin inhibitors in solid tumors as well as diabetes. And finally, we look forward to sharing data with you from our FTI programs in the second half of the year.

Turning to slide 27, given our focus today on AML, I’ll just highlight for you that we intend to present preliminary clinical data from the seven phase 1b trial in frontline intensive AML at EHA in Milan, Italy in about ten days. We expect to initiate the COMMOD 17 Phase three registration enabling trials in frontline NPM1 and KMT2AR intensive and non intensive AML in the second half of this year. And we expect to present preliminary clinical data from the phase 1b expansion cohorts of COMMID-seven in frontline non intensive AML in the fourth quarter, potentially at ASH. Turning to slide 28. Finally, we’re doing all of this from a position of financial strength.

We had more than $700,000,000 on the balance sheet as of the end of the first quarter. And with the progress we continue to make on the ZIFTOMEND program, we continue to feel confident about our ability to earn up to an additional $375,000,000 in near term milestones. This should allow us to invest appropriately in the research development and commercialization of ZYFTOMENED. That concludes our prepared remarks Carmen and we’re happy to take questions.

Operator: Thank you so much. As a reminder to our audience, if you do have a question, star one one on your telephone and wait for your name to be announced. To remove yourself, press 1 again. One moment for our first question. And it comes from the line of Lee Wotzek with Cantor.

Please proceed.

Lee Wotzek, Analyst, Cantor: Hey, guys. Congrats on the data. Two from me. I guess, first is just given such a prolonged OS benefit in the responders versus non responders, Can you talk a little bit about if there’s any good ways to predict which patients might be more likely to respond to ZEPTOF versus not? And then similarly, I know there are some patients in a trial had pseudo progression.

So I guess just based on your clinical experience, are there any good indicators for that versus actual progression?

Operator: Thanks.

Troy Wilson, CEO and President, CURA Oncology: Thanks, Leigh. Let me ask Doctor. Wang if she could we’ll take your two questions separately. So, starting with the question around DOS. Is there a way that we know of to predict the responders?

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: I don’t know that we know. That’s the $1,000,000 question, is that we’d love to be able to tell which patients are likely to respond versus not. I think that we don’t, at this point, know. When we look at our prespecified subgroups, even patients who’ve gotten three or more lines of therapy do respond, and patients that have gotten prior venetoclax and other prior lines of therapy respond. So that’s a little counterintuitive because some of our other agents in the market, the more pretreatment you have, or if you have prior venetoclax, that tends to build resistance.

So I think at this point I feel that we don’t have a clear signal as to which patients are going to respond. That being said, patients who are responding to ziptylmenon also do very, very well. We’ve had a number of patients I believe there were a number of patients that went on to subsequent allogeneic stem cell transplantation, five patients from the COMET one study, and I believe we have two or three of them still on zyptomenon maintenance. So I feel that zyptomenon provides long term benefit to these individuals and can control their disease with very few side effects. And so I think we’re going to be continuing to explore which of these patients might be predictive.

We did see a small signal in that the patients that had co mutations in IDH1 apparently did very, very well with overall response rates a little bit better than the twenty three percent and the forty percent. So that might be a subgroup of patients where they have further investigation.

Troy Wilson, CEO and President, CURA Oncology: Thank you. And Molly, maybe I’ll ask you on the question of Lee termed it pseudo progression. Can you maybe talk to our strategies as we look across the trials to mitigate the risks of pseudo progression?

Molly Leone, CURA Oncology: So one of the things

Unidentified speaker: is the difference

Molly Leone, CURA Oncology: in response rates, albeit not statistically significant between The US and the Ex US regions, or the North America and ex North America regions where this drug was used, somewhat lower of a response rate in The EU, for example, than in the North American regions, and in part we think this is because these sites came on later. They didn’t have the experience of the phase 1a, 1b, and learning what kind of a pseudo progression looks like with the use of a MEND inhibitor. I think we’ve learned a lot since then. I think we, investigators and KOLs and treaters in general, have learned a lot that there’s more to it in the MEND inhibitor setting than there is in potentially other even differentiating agents. And I think that

Troy Wilson, CEO and President, CURA Oncology: Carmen, can we go on to the next question?

Operator: Sure. One moment, please. Our next question comes from the line of Jonathan Chang with Leerink Partners. Please proceed.

Unidentified speaker: Hi, this is Yen Der Lee on for Jonathan Chang. Thanks for taking my question and congrats on the positive data and also the priority review decision. So my question is, can you share your plan in preparation of the commercial launch of dibtomatinib potentially later this year? And what are the key lessons from rivulminib bonds that might help inform your strategy? Thank you.

Unidentified speaker: Please,

Operator: can you get closer to the microphone while you give the answers? Thank you.

Troy Wilson, CEO and President, CURA Oncology: Yeah. I’ll ask Brian Yander to speak to your question.

Brian Powell, CURA Oncology: Yes. Thank you, Yander, for the question. So we as you know, now that we are granted the PDUFA date, are preparing ourselves for commercialization. We have been building out our capabilities to ensure that product will be available to patients upon approval. And this is supportive across our marketing commercial teams as well as our market access and medical affairs groups to begin the build out of the commercial team and engage with the appropriate customers at the right time.

So we feel that we’ve you know, because we’ve been following the market, and as you mentioned, Revuminav has been on the market for at least one full quarter now, we’ve been trying to track their progress. And we’re glad to see that there is a market for menin inhibitors. And we’re looking forward to taking learnings from their approach to educating around the role of menin inhibition for their particular indication in KMT2A rearranged as we move into the NPM1 population.

Unidentified speaker: Understood. Thank you so much.

Operator: Thank you. One moment for our next question. Comes from the line of Roy Song with Jefferies. Please proceed.

Unidentified speaker: Great. Congrats for the data at ASCO and then the product review for your first NDA. So the question is really interesting, relates to the mechanism, potential mechanistic hypothesis, why vistamatinib seems to having consistent response for the vameda experience versus the naive patient, and also for the heme tox, since you’re significantly lower than other MEN inhibitor, seems to that the manna perhaps the inherent differentiation, which we may not know so far. So, if you can give us some color, that would be helpful. Thank you.

Troy Wilson, CEO and President, CURA Oncology: Yeah. Thank you, Roger. So, Roger’s question is in two parts. One is, do we have any mechanistic understanding of why we see activity in post venetoclax? And then why do we see less heme tox?

Is there any mechanistic explanation? Doctor. Wang, do you have thoughts?

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: Told me the drug isn’t very well tolerated in terms of GI side effects and because of the dose reductions and the twice a day dosing. I think zyptomenon, based on its unique properties, is a different drug. Just like we have different BCRA ABLE inhibitors, different BTK inhibitors, these are different agents. And what we see with ZIF del Mena, and we see an excellent tissue distribution, which allows it to be given once a day. We do not see the Q2C prolongation.

We don’t see the azole effects. And in terms of mechanistically, we have consistently seen through all of the COMET-one data consistent activity and efficacy in the NMP1 mutant patient population, which I think is maybe a little bit different than what we see with revimenin. Whether it’s mechanistic or not, I think in preclinical studies, the mechanism by which it works is similar to the other MET inhibitors, but I just think these are different agents. I hope that answers your question.

Troy Wilson, CEO and President, CURA Oncology: Thank you, Doctor. Wang. Doctor. Zaidan, is there anything you’d like to add to Doctor. Wang’s comments?

Unidentified speaker: Yeah, I think I largely agree with what was said. I think the fact that also what we have seen in the combination studies so far does support the idea that the drug does not exert additional myelosuppression. When we look at the time to recovery after intensive chemotherapy, when it’s combined with ziptominib, we are seeing numbers that not only close to what we actually see with seven plus three, but there’s a suggestion that it could be even a little bit sooner in terms of count recovery, which probably goes with the differentiating effect of zestaminib. Now, how does that compare to other MIN inhibitors? I think it remains to be seen, but it’s my strong belief based on all the data that we have seen so far that this drug is, in my opinion, the best in class agent fuminin inhibitors.

I would also emphasize that monotherapy is only the starting point of kind of seeing the advantage of these drugs. We have a very good paradigm, for example, with FLT3 inhibitors, where in the second line or in the relapsedrefractory setting, you see responses in the range of twenty percent to twenty five percent and some transfusion dependence. But once those drugs have been combined in the frontline setting with intensive chemotherapy, there has been overall survival prolongation and the patients would stay on these drugs for many years. So I think overall, having a drug that is easy to combine, that does not cause myelosuppression, does not have galacto toxicity is very important for chronic use.

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: I just want to make one additional point about the QTc prolongation. So you must remember that on the phase one revimenin studies, the dose limiting toxicity of that agent was QTc prolongation. It was not myelosuppression, and it was therapy. We, in the phase one dose escalation of Ziptomenon, went all the way up to one thousand milligrams a day of Ziptomenon. We did not see any QTc prolongation.

And when you look across the other menin inhibitors in development, I have not seen to date any other menin inhibitors that have that QTC prolonging signal. So that QTC prolongation seems to be unique to the revuminin drug. It is the only menin inhibitor who has listed as of now dose limiting toxicity due to QTc prolongation. So I think it’s not that ZYPTO is different. I think that it’s specifically Revumedin that has that particular side effect.

Troy Wilson, CEO and President, CURA Oncology: Thank you both. Roger, I hope that answers your question. Carmen, maybe we can go to the next question.

Operator: Thank you so much. Our next question comes from Alexander Bullock or Peter Lawson from Barclays.

Peter Lawson, Barclays: Hi. This is Peter Lawson from Barclays. Troy, just had a question around ahead of the PDUFA date. Are there any kind of further regulatory hurdles? Is there a potential of an AdCom?

And then as you think beyond that, kind of the go to market strategy you’re thinking?

Troy Wilson, CEO and President, CURA Oncology: Yeah. So Peter, I’ll address your PDUFA question, and then Brian can address, you know, sort of build on your go to market strategy. And we don’t expect an AdCom at this point based on the feedback we’ve received from the agency as part of their acceptance of the NDA and their assignment of a PDUFA action date. We wouldn’t expect an AdCom. Now the agency of course, can change its mind, but we wouldn’t expect that.

With respect to the go to the market strategy, Peter, I’ll let Brian speak to that.

Brian Powell, CURA Oncology: Thanks for the question, Peter. Yeah, in terms of our go to market strategy, we are have been building our kind of launch strategy based on feedback from both investigators, KOLs, and community physicians that we’ve been working to better understand the profile of our drug relative to other options that are available on the market. And we’re putting together our go to market strategy that will really help to support a potential best in class agent in the relapsedrefractory monotherapy setting. And, you know, all of our teams are working towards building that key communication, but also the ability to get the product available to market as soon as we get approvals. So, we’re working from an access distribution strategy as well to ensure that we will make Ziptamenib available for patients as soon as possible after a potential approval.

Peter Lawson, Barclays: Great. Thank you. Then just on the Grade three differentiation syndrome, if I can squeeze in another question just on how physicians are managing that prophylactically and where do you think that incidence rate can potentially go with that management?

Troy Wilson, CEO and President, CURA Oncology: Did you hear Peter’s

Unidentified speaker: question? Doctor.

Troy Wilson, CEO and President, CURA Oncology: Wang? I’ll just restate his question. How are physicians managing differentiation syndrome? And Peter, I’m going to restate your question. Can we do even better?

Are we happy with where things are? Or can we do better?

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: I think that as Molly alluded to, over the course of the study, the more experienced investigators like Doctor. Zaidan and myself really were experienced enough to utilize mitigation strategies early on, early recognition of potential differentiation syndrome, and keeping patients on study to allow them to get sufficient drugs so that they would achieve a clinical response. As she mentioned, the median time the response was two point seven months. There were some patients that required three point seven months to stay on therapy, but there was a learning curve. The European colleagues that enrolled on the study, when we looked at when they first enrolled, the time that they left their patients on study was relatively brief as compared to more experienced colleagues.

So I thought that over the time of the study and familiarity with the differentiation syndrome led to more comfort and to more consistent institution of these mitigation strategies. As you know, the IDH inhibitors also have a black box warning for differentiation syndrome, but they are widely used in the market now, now that we have all become familiar with it. Acute promyelocytic leukemia, again, has been associated with life threatening differentiation syndrome, and that is actually a success story with over ninety percent of patients going into remission, or ninety five percent over time. So I think it’s a learning curve, but I think that it is something that we are familiar with. And with the very specific protocol guided therapeutic algorithm, which I have to tell you is extremely detailed, and with even initiation of cytoreductive therapies and early initiation of steroids, we’ve not seen the differentiation syndrome in the more experienced hands has been a barrier to giving therapy and achieving the clinical responses.

And I think Doctor. Zaidan can speak onto that, because I think on the combination studies, were brought out to larger sites and more investigators, again, there was a learning curve that improved over time.

Unidentified speaker: Yeah, and I also fully agree with this. And I would actually point just to follow on, I think we have to think about differentiation versus differentiation syndrome because differentiation is on target activity of azithromycin and seeing differentiation is actually something that is expected within the use of these drugs. So the question in my mind really is about the physicians learning And I think this has been already clearly achieved in the monotherapy setting. In the combination setting with, as I mentioned earlier, this is I think where the full potential of MEN inhibitors in general, but in particularly, I think zeftominem will be fully revealed would entail combining it with intensive chemotherapy or Azerbine, which will by itself mitigate the risk of differentiation syndrome because it acts both as a synergistic activity, but also it reduces the risk of differentiation.

So I do agree that on the longer run, I think differentiation syndrome, people will gain expertise. There will be very clear guidance on how to mitigate that. And we, as Doctor. Wang mentioned, we already have done this with APL, with IDH inhibitors, and some FLT3 inhibitors. So it’s not, I don’t expect any difference here.

Troy Wilson, CEO and President, CURA Oncology: Great. Carmen, maybe we can go to the next question.

Operator: Thank you so much. One moment. Our next question is from Jason Simanski with Bank of America. Please proceed.

Unidentified speaker: Thank you for taking our questions and congratulations on the data. Maybe a question for Drs. Wang and Zaidan. When you think about the relapsedrefractory setting in particular, I appreciate it’s a smaller piece of the overall pie here, but in your mind, what’s going to differentiate

Troy Wilson, CEO and President, CURA Oncology: the two

Unidentified speaker: different products? Is, you know, the convenience enough for ZIFTO or are prescribers going to look for something more?

Unidentified speaker: Yeah. No, I think there are many things that will differentiate. I think in my opinion, convenience and safety is a very important aspect. When you have multiple drugs that have potentially comparable efficacy, and we already see this, for example, in the CML world where we have a number of TKIs and the way we choose between them is largely based on the side effect profile and the convenience as well as the comorbidities of the patients. So to have a drug that you can take once a day, and I can tell you for patients, if you are giving a drug for a short term, maybe a few months, maybe doing an EKG every week and taking it twice a day and all of that might not be a big hassle for the physician and the patient.

But once you are talking about administering a drug for years and having to worry about the QTC and having to worry about is the patient taking the drug twice a day, are they forgetting taking the drug, is someone is giving them an antibiotic that might interact with the drug, all of these aspects become very important. So I think you can call it convenience, but I think this is very tied into efficacy because being compliant with the drug, taking it on time, potentially in combination based strategies, I think all of that will ultimately affect efficacy in addition to the safety. So, when you look at all the other inhibitors, I think ziptonib clearly has the advantage here.

Troy Wilson, CEO and President, CURA Oncology: Doctor. Wang, would you like to add anything?

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: Yeah, I completely concur. For example, with revuemenin, there’s a requirement that patients not only have a good baseline EKG, but they also need to come every single week for repeat EKG monitoring, and they have to have all of their drug medications reviewed for potential interactions with a forty percent dose reduction. And it’s very myelosuppressive, so patients will need to come in as well for weekly count checks for transfusion support. Now this is a mostly older age population. So patients in their 60s and 70s, mostly men over women, they’re going to have a lot of cardiac comorbidities, cardiac co medications that are going to preclude them from being able to get revuemenin.

And even if they do get revuemenin, they have to come in every single week to get EKGs monitoring, to get platelet count checked. And there is the issue of safety about them having Q2C prolongation, cytopenia, transfusion support, infections, neutropenic fevers. So I think it’s not just a matter, as Doctor. Zaidan pointed out, of convenience, it’s safety and long term durability of this drug. And I think that those are for the community physician to start a patient on ZiptoMetam once a day and then not have to see them back and to be assured that they were safely tolerating their drug is I think a game changer.

And these are elderly individuals that are not going to want to come in every single week and are not going to want to be able to have to go to their cardiologist and have all of their medications adjusted for these types of drugs. So I think these are not just convenience issues, these are safety, durability, tolerability, and long term maintenance drugs. So, I think those are the things that drive the selection of drugs for patients in the community that are prescribing these.

Unidentified speaker: Got it. Appreciate the color.

Troy Wilson, CEO and President, CURA Oncology: Thank you, Carmen, next question.

Operator: Yes. The next question comes from Philip Nadeau with T. D. Cowen. Please proceed.

Troy Wilson, CEO and President, CURA Oncology0: Afternoon. Thanks for taking our questions and let us add our congratulations on the PDUFA date and the ASCO presentation. Two from us. First, on the average duration of therapy, I think in the prepared remarks, you said you expect approximately six months. We’re curious what’s the math behind that?

So what duration of therapies assumed for responders and what durations are assumed for non responders? That’s the first question. And then the second is on the three IPD patients. There was one discussing who called out that response rate during the session today. Just curious to get the physician’s opinion of using the FLT3ITD patients and any theories as to why that group may have a slightly lower response rate than the other groups?

Thanks.

Operator: Doctor, we cannot hear your answer.

Troy Wilson, CEO and President, CURA Oncology: Sorry, let me ask Molly if she can speak to your question, Phil, around duration of therapy, and then we’ll turn to the FLT3 question from the physicians.

Molly Leone, CURA Oncology: So our understanding of how this drug will be used, as you’ve seen from the data, is that these patients need at least two to three months two to three cycles on therapy in order to achieve a response, which isn’t unexpected with an epigenetic modifying agent that takes time to kind of reprogram the cell and get it to work properly. With regards to how we get to that six month estimate, well then while they’re in their response, we expect them to have at least a median of 3.7 if they’ve hit a CRCRH. Now, the more interesting number would be to look at the ORR median duration of response, because these are still clinically meaningful responses where patients may just have an incomplete recovery of their platelets, for example. And that goes up to a four point seven response rate for a median, and that’s not even discussed in the restricted mean analyses that we’ve performed. So, there’s where you get to your six to seven plus months of patient remaining on therapy.

But I think as the learning evolves, we’ll be able to treat through even any pseudo progressions and even keep patients on longer periods of time. And of course, aiming towards the combination trials, the combinations of these drugs, we’ll see a completely different usage pattern.

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: Thank you so much for the question about the FLT3 mutants ITD patients. So when you look at the subgroup analysis, it is true that there appears to be a trend for a lower CR CRH rate of thirteen percent in patients with FLT3 ITD commutated with NMP1, as opposed to, for example, FLT3 TKD patients that have an overall response of about thirty three percent. Now, it’s hard to parse that data. We do know that these patients were heavily pretreated. So, I imagine that the patients that were FLT3 ITV mutant had probably failed multiple lines of FLT3 inhibitor therapies, as well as, in the upfront setting, allogeneic stem cell transplantation and possibly intensive or non intensive chemotherapy.

So I think that that particular patient population is very difficult to treat. We know that somebody has failed two or three FLT3 inhibitors, their disease tends to be very resistant. The also concern I have is that the more co mutations and the more trier therapies for example, FLT3 inhibitor therapies you build up multiple other mutations and signaling pathways that make it very difficult to treat those individual patients. So based on this in part based on this data, as I mentioned, we actually have initiated on the COMET eight study an arm for relapsed and refractory patients who coexpress both NMP1 and FLT3 ITD to treat them with a combination of a FLT3 inhibitor and zyptomenon. Now, my personal experience is that if that patient is caught early, they have not received prior gilteritinib, and they’re receiving gilteritinib and a menin inhibitor, they’ve done very, very well.

The patients who’ve received prior FLT3 inhibitor therapy don’t do quite as well. I’m going turn it over to Doctor. Zaidan to ask his opinion as well.

Unidentified speaker: Yeah, and again, I fully agree with this. But to kind of again plug it in into the combination front, which I think all these subtypes of acute myeloid leukemia that are very challenging to treat such as a FLT3, ITD mutated disease. When the patient has both mutations, as Doctor. Wein mentioned, there is opportunity to combine in the relapse refractory setting, but also we have within the context of the seven study have initiated a quadruplet trial where we are giving a FLT3 inhibitor in addition to Zeftomineb with intensive chemotherapy. And I think this is a paradigm that we have seen repeatedly on oncology where your best value for the drugs as you move in the frontline setting, this is where you get, I think, the most significant suppression of these clones.

And with that, you make the issue of the emergence of resistance this of a concern because I think your best time to kick these mutations is probably from the frontline.

Troy Wilson, CEO and President, CURA Oncology: Great. Thank you, Carmen. Can we go to the next question?

Operator: Thank you so much. Our next question comes from Charles Zhu with LifeSci Capital.

Troy Wilson, CEO and President, CURA Oncology1: Hi. This is Peter Green on for Charles Zhu. Congrats on the data and especially congrats on the FDA acceptance PDUFA date assignment. Just wondering on MRD negativity, does the central molecular testing method used here in COMET one reflect the accepted endpoint for COMET seventeen MRD testing? Is there any kind of read through to your through that frontline intensive combination?

And any comment on how NRD negative responses relate to overall survival or duration of response as observed so far? Thank you.

Molly Leone, CURA Oncology: Yeah, I mean, would hope that there’s a read through from our monotherapy experience into the combination setting. What we’ve seen is with even intensive induction regimens in the front line, you see in the bone marrow about forty percent MRD negativity rate. So obviously seeing higher in the 60s in the one study with just a monotherapy is extraordinarily encouraging. And we will be using similar methods to detect MRD as we move into our 17 trial.

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: Just wanted to mention on the COMMENT-one study, we did see a difference in overall survival based on MRD status. Patients who achieved MRD negative responses had an overall survival, I believe, over twelve months, as opposed to patients that remained MRD positive who had an overall overall CYBAL of only nine months. So I think that and the importance of achieving an NMP1 negative response has been highlighted by Offman et al, our colleagues at The UK. And they recently published that regardless of whether a patient had NMP1 with or without a co mutation in FLT3, that patients who achieved an NMP1 negative response after two cycles of intensive chemotherapy did not necessarily have to undergo an allogeneic stem cell transplantation for best survival. So as Doctor.

Zaidan highlighted, by moving ziptomening into the upfront setting and rendering some of these patients MRD negative with upfront therapy, there is the possibility that we could forego stem cell transplantation in some of these patients. So achieving MRD negativity is key, we know, for NMP1 mutant patients in the upfront as well as the relapsedrefractory setting.

Unidentified speaker: And adding to what Doctor. Wang has mentioned, MPM1 AML is actually one of the disease subsets where the correlation between MRD negativity by sensitive assays and the long term outcomes has been shown to be the most significant out of different AML subsets. And I actually want to give the CURA team a lot of credit because during the discussion of the zero-seventeen development, the idea of using MRD negative CR as a primary endpoint or a co primary endpoint for intensive chemotherapy was accepted and was discussed with the regulators. I think this is a very innovative way of doing trials in intensive chemotherapy treated patients because it could allow the patients to access the drug at an earlier stage through accelerated approval rather than just waiting for even free survival and overall survival as the traditional endpoints.

Troy Wilson, CEO and President, CURA Oncology: Thank you. Carmen, next question.

Operator: Thank you. One moment please. Comes from the line of Salim Syed with Mizuho. Please proceed.

Unidentified speaker: Great. Congratulations on the data, guys. Maybe three from us, if that’s okay. The first two for maybe Troy, Molly, and then the last one for Drs. Wang and Zaiden.

Troy, Molly, just curious on this line in the press release where you talked about the restricted mean duration of response being four point three months. To my knowledge, this is the first time you guys have used this sort of language of using the mean duration of response rather than the median duration, which has always been the guidance of four to six months. And this came in a little bit lighter at 3.7. So just curious, what was the rationale of including the mean duration of response? Is this an important number, you think, for the FDA or how clinicians view this particular metric?

And then second, just quickly on the just a quick clarification question on defining transfusion independence, how many days to be deemed transfusion independent? And then I’ll follow-up with the doctors on the third question. Thank you.

Molly Leone, CURA Oncology: All right, so the reason, in a very simple fashion, the reason we used the restricted mean is in part because it is recommended by FDA and other statistical experts when you have a small number of events, the duration of response per Kaplan Meier calculations can be quote unquote unstable, which means just a couple of days in either direction completely changes the outcome of the analyses. And so FDA, as well as other statistical experts, do recommend use of this restricted beam, which gives a more cohesive understanding of what these patients are doing, how much time they’re spending on trial. It essentially looks at the area under the curve for these patients and takes away the outliers. So the patients that are spending a very little piece of time in their response,

Troy Wilson, CEO and President, CURA Oncology: and

Molly Leone, CURA Oncology: the patients that are taking spending a very long time in their response. So thus, it’s essentially a way of looking more cohesively at the contribution of all patients to the time on therapy. I know it’s not the easiest answer, that’s the essence of what the restricted mean provides. And if you were your second question, I believe, was about what defines transfusion independence. And again, per FDA guidance, that’s fifty six days.

So to be considered transfusion dependent, they would have had to have had a transfusion within fifty six days prior to starting therapy. And then to be transfusion independent, they would have to have a stretch of fifty six days without a transfusion after starting therapy.

Unidentified speaker: Okay, thank you. Super helpful. Just off to the doctors. Doctor, you mentioned some language regarding game changer, best in class menin. Would you guys be willing to quantify what percentage of your practice you think you would actually put on Zifto versus Revumenib for relapsedrefractory NPM1?

Thank you.

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: All right, so this is Doctor. Wang. So I have to be a little bit biased in that I have not put any patients on Revumenib because we have been involved with the development of the ziptonedin from the onset, and given the very favorable side effects as well as efficacy that we’ve seen in monotherapy and now in combination therapy, I don’t see any need for me to treat my patients with revuminin just because of the concern I have with my patients being more elderly, the need for the EKG monitoring, the transfusion support. There’s issues with nausea, vomiting, myelosuppression. And so I have preferred to use Zifdomenon.

It’s a well tolerated drug in the outpatient setting. And once patients achieve a response, I don’t have to see them for quite some period of time. So I do have that bias. I would turn it over to Doctor. Zaidon if he’s had different experiences.

I do believe that zyptomenon right now is, I think, superior in my hands and my clinical experience to what I’m seeing and hearing from my colleagues with rabbumin.

Unidentified speaker: Yeah, and I fully agree with that. Again, own kind of review of the literature and being very attentive to all of the other MEN inhibitors, as well as my own personal experience with the drug. It’s one of the easiest drugs to give in my experience. Again, we have a number of oral targeted agents that we use in the clinic, and each one of it comes with its own set of either lower level toxicity or need for monitoring, etcetera. But in my experience, it has been one of the easiest drugs to give.

Patients rarely complain about any significant side effects. So I don’t think there is any specific reason in my mind why I would use Rebuminib for an MPM1 mutated patients in the refractory lab setting or in the frontline setting. And we’re actually very excited to open the frontline phase three as well soon so that we treat all of our new patients with the combination with azithromycin as well.

Eunice Wang, Chair of Leukemia Service, Roswell Park Comprehensive Cancer Center, Roswell Park Comprehensive Cancer Center: And so I just wanted to mention that right now, revimenin is not approved for the treatment of patients with NMP1 mutant disease. It’s only approved for its use in KM2 rearrange disease. So I think my preference and PDUFA and the indication for ZYPTOM and NMP1 mutant disease I think is appropriate. I think the data is superior. The tolerability is superior.

I think there’s an opportunity given the number of patients. As you know, NMP1 mutation is much more common, more frequent, and we’re seeing more patients significantly more patients with NMP1 mutant disease than with KMT rearrangements. Revimenin does not have that indication at this time, and I think this is an opportunity to capture a larger market share, a safer drug, a better drug for this mutational subset.

Operator: Thank you. And this is all the time we have for questions. I will pass it back to Doctor. Wilson for closing remarks.

Troy Wilson, CEO and President, CURA Oncology: Thank you, Carmen. I want to thank Doctor. Wang and Doctor. Zaidan for sharing their experience and their wisdom with all of us, as well as my colleagues, Molly and Brian. I want to thank all of you for your attention.

We will see some of you at EHA here in about ten days. We’ll also be at Jefferies as well as at the Goldman conference and look forward to seeing some of you there. If you have any questions, please feel free to reach out. We didn’t have a chance to get to every question today. We’re sorry for that, but we wanted to keep everyone on time.

But we thank you for your time and your attention. And with that, we’ll adjourn. Thank you all so much.

Operator: Thank you. And this concludes our program. And you may now disconnect.

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