Earnings Call Transcript - SNDX Q3 2022

Operator, Operator

Good day, everyone and welcome to the Syndax Third Quarter 2022 Earnings Conference Call. Today’s call is being recorded. At this time, I’d like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals. Please go ahead.

Sharon Klahre, Head of Investor Relations

Great. Thank you, operator. Welcome and thank you all for joining us today for a review of Syndax’s third quarter 2022 financial and operating results. I am Sharon Klahre and with me today to provide you an update on the company’s progress and to discuss financial results are Michael Metzger, Chief Executive Officer; Dr. Briggs Morrison, President and Head of R&D; and Keith Goldan, Chief Financial Officer. Also joining us on the call for the question-and-answer session is Dr. Peter Ordentlich, Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Business Officer. This call is accompanied by a slide deck that has been posted on the Investors page of the company’s website. You can now turn to our forward-looking statements on Slide 2. Before we begin, I’d like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by the statements as a result of various important factors, including those discussed in the Risk Factors section in the company’s most recent quarterly report on Form 10-Q as well as other reports filed with the SEC. Any forward-looking statements represent our views as of today, November 3, 2022, only. A replay of this call will be available on the company’s website, www.syndax.com, following this call. With that, I’m pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Michael Metzger, CEO

Thank you, Sharon, and thank you to those joining us on the webcast. We made significant progress during the third quarter, and I look forward to sharing the updates with you today. I expect this momentum to continue as we advance towards two pivotal data readouts and potential registration filings in 2023 for our two lead drug candidates, both of which are first and potentially best-in-class treatments. I want to repeat that for emphasis. We anticipate having both an NDA and BLA filing in 2023, an almost unprecedented accomplishment for a small-cap biotechnology company which speaks to our focus and determination to realize the future in which people with cancer live longer and better than ever before. We have a strong balance sheet that supports our clinical efforts and enables us to aggressively advance our programs through key near-term milestones. We are also fortunate to have Incyte as a strong partner to help us successfully advance one of our lead molecules, axatilimab. Everyone at Syndax is incredibly excited about the opportunities and important milestones ahead. Turning to Slide 3, we provide a high-level summary of our current corporate priorities. We have designed a broad development plan for both revumenib and axatilimab that is focused on realizing their full potential given their compelling clinical profiles. Starting with revumenib, our highly selective menin inhibitor, our pivotal Phase 2 AUGMENT-101 trial evaluating revumenib in patients with relapsed/refractory NPM1 mutant or MLLr acute leukemia is ongoing. We expect to report top-line data from at least one of the cohorts for the Phase 2 portion in the third quarter of 2023, and we continue to expect to file an NDA by the end of 2023. This morning, we published a press release highlighting positive updates from the Phase 1 portion of the AUGMENT-101 trial that will be presented during two oral presentations at the American Society of Hematology or ASH Annual Meeting this December. Beyond the AUGMENT-101 trial, we see the effect of monotherapy in relapsed/refractory disease as revumenib is the focus of several ongoing and planned trials that present important expansion opportunities in humans. In addition to acute leukemias, we are on track to initiate our first solid tumor proof-of-concept trial in colorectal cancer in the fourth quarter of this year. Moving to axatilimab, our antibody against CSF-1R. Enrollment is now complete in our pivotal Phase 2 AGAVE-201 trial evaluating axatilimab in patients with chronic graft versus host disease, and we expect to report data on the trial in mid-2023. We are working in collaboration with our partner, Incyte, to maximize the value of the axatilimab program, and this includes an expected BLA filing by the end of 2023 as well as initiating a trial testing the combination of axatilimab and ruxolitinib in frontline chronic graft versus host disease. Looking beyond cGVHD, we expect to begin a Phase 2 trial of axatilimab in idiopathic pulmonary fibrosis, or IPF, in the fourth quarter of this year. We also continue to assess potential business development opportunities to complement our existing pipeline. While our bar is quite high for in-licensing drug candidates given the strength of our pipeline, we continue to evaluate potential opportunities to in-license earlier-stage targeted oncology compounds that we believe could become high-value differentiated assets. Let’s now turn to Slide 4 and I’ll provide further details on the revumenib program. First, our pivotal Phase 2 AUGMENT-101 trial is designed as three single-arm Phase 2 trials that enroll independently and can each provide the basis for a co-regulatory filing in the U.S. The AUGMENT-101-2A trial is enrolling patients with relapsed/refractory MLLr ALL; 2B is enrolling patients with relapsed/refractory MLLr AML; and 2C is enrolling patients with relapsed/refractory NPM1 mutant AML. Each trial is designed to enroll approximately 64 adult patients and up to 10 pediatric patients, aged 1 month or older. As site staffing issues industry-wide have impacted start-up timelines in certain geographies, we have updated our guidance for when our first cohort in this trial will be fully enrolled and expect enrollment to extend into the first quarter of 2023. Interest in the trial remains incredibly high with strong enrollment. Investigators are finding it as challenging as we are to deal with the unfortunate resourcing issues faced by some other institutions, and we are working collaboratively to resolve them. We now expect to present top-line data in the third quarter of 2023 for at least one of the three cohorts in the AUGMENT-101 trial. Importantly, we continue to anticipate filing an NDA by the end of 2023. We have agreement with the FDA that for each cohort or trial, the primary endpoint will be the percentage of patients receiving CR/CRh with secondary endpoints, including durability of CR/CRh response, transfusion independence, overall survival, and safety. We also have agreement with the FDA on the statistical design of each trial. Importantly, the trial design allows patients to be treated again with revumenib after bone marrow transplant, a design feature that provides data on the potential role of revumenib in the post-transplant maintenance setting. I will now hand the call to Briggs to provide an update on the ASH abstracts, which were published earlier today.

Briggs Morrison, President and Head of R&D

Thanks so much, Michael. If we turn to Slide 5, I’d like to note that we are excited that revumenib will be the focus of two oral presentations at the ASH Annual Meeting on Saturday, December 10. Dr. Ghayas Issa from MD Anderson Cancer Center will present updated results from the Phase 1 portion of the AUGMENT-101 trial and will also present a second abstract summarizing the outcomes of patients who achieved a response on revumenib and then went on to bone marrow transplant. A copy of the press release with an overview of the ASH abstracts is available on our website and I will take a moment to talk through some of the key highlights of the data that you see on this slide. At ASH in 2021, Dr. Eytan Stein from Memorial Sloan Kettering Cancer Center presented the initial Phase 1 data on 51 patients who had either an NPM1 mutation or an MLLr fusion. This was our efficacy evaluable population. In the abstract released today, there are now 60 patients evaluable for efficacy. The additional patients include 8 patients with MLLr AML and 1 patient with NPM1 mutant AML. All the patients are from Arm A, patients who are enrolled not receiving a concomitant strong CYP3A4 inhibitor. Additionally, all the 9 patients were treated at one of the two doses that had been determined to meet our predefined recommended Phase 2 dose criteria. As you can see, the percentage of patients achieving a complete remission as defined by the CR/CRh rate is now 30% versus the 24% previously reported at ASH last year. In addition, at the time of last year’s ASH presentation, the median duration of response for patients who had achieved a CR or CRh had not yet been achieved. As the data has matured, we now see a very impressive median duration of CR/CRh response of 9.1 months at the time of the data cutoff. I will also point out that we continue to see a high MRD negative rate, 78% among patients achieving either CR/CRh or a CRp, which is quite meaningful in this patient population as it enables patients to proceed to a potentially curative bone marrow transplant. Indeed, the second abstract described on Slide 6 specifically summarizes the outcomes of the 12 patients who achieved a complete response in revumenib and then went on to receive a stem cell transplant. Impressively, 9 remained in remission as of the data cutoff, with a median follow-up of 12.3 months. 2 additional transplant patients were treated with revumenib maintenance in the compassionate use setting following a stem cell transplant or non-myeloablative stem cell boost, both of whom remained in remission for over a year as of the data cutoff. Consistent with the data presented last year, revumenib continues to be well tolerated, and there have been no discontinuations due to treatment-related adverse events. We believe the data continues to support revumenib’s compelling clinical profile and position it not only as a first-in-class but a best-in-class treatment and adds to our confidence in the ongoing pivotal trials. Our principal investigators are highly encouraged by the data and believe that revumenib could play an important role in the treatment of not only these relapsed/refractory patients, but could also play an important role in earlier treatment lines and in combinations, given its clinical profile. I’ll hand it back to Michael to talk more about our programs.

Michael Metzger, CEO

Thank you, Briggs. Slide 7 highlights a few additional opportunities that we are exploring to move revumenib beyond its use as a monotherapy agent in relapsed or refractory acute leukemia. Preclinical data demonstrate the potential benefit of a menin inhibitor in combination with standard regimens and revumenib’s excellent safety and efficacy profile lends well to expanding its use in earlier settings and in combination with approved therapies. Starting with the Phase 1 BEAT-AML trial. As part of our collaboration with the Leukemia & Lymphoma Society, revumenib is being combined with venetoclax/azacytidine to treat newly diagnosed AML patients with an NPM1 mutation or MLL rearrangement who are unfit for induction chemotherapy. Revumenib is the first menin inhibitor to be included in the trial, which will assess safety as well as initial efficacy. Enrollment is ongoing, and we expect initial data from this trial to be available in 2023. Longer-term, we expect that positive BEAT-AML trial results would lead to a Phase 2/3 trial, which could serve as the basis for a future regulatory filing. We are also currently enrolling patients in the AUGMENT-102 trial designed to assess revumenib in combination with standard salvage chemotherapies for patients with relapsed or refractory NPM1 mutant or MLL rearranged acute leukemias. We expect to have initial data available from this trial in 2023. Finally, the INTERCEPT trial. This trial focuses on investigating novel therapies to treat early relapse and clonal evolution as a preemptive therapy in AML and is being conducted as part of the INTERCEPT Master Clinical Trial led by the Australasian Leukaemia & Lymphoma Group. The trial is designed to explore the activity of revumenib as monotherapy in patients with AML who have MRD-positive disease following initial treatment, a group of patients at very high risk of relapse. Of note, revumenib is the first menin inhibitor to be included in the INTERCEPT AML Master Clinical Trial. The INTERCEPT trial is a very creative approach to treating patients early in their disease course. We continue to expect the Australasian Leukaemia & Lymphoma Group to initiate dosing in the fourth quarter of this year. And as detailed on Slide 8, we are committed to unlocking the full potential of revumenib beyond the relapsed/refractory acute leukemia setting by moving it earlier in treatment and in combination. With these expansion opportunities, we see the potential to address upwards of 12,000 NPM1 mutant and MLLr acute leukemia patients across various settings. These two forms of acute leukemia together represent up to 40% of the overall AML population, which to our knowledge will be the largest subpopulation of AML to be addressed by a mutant targeted therapy. We anticipate revumenib will be one of the most important new franchises in the leukemia setting, and we are looking to explore revumenib as a treatment in solid tumors as well. We expect to initiate a proof-of-concept Phase 1 clinical trial in colorectal cancer in the fourth quarter of this year. This trial is designed as a signal-seeking trial in 20 to 30 patients with refractory colorectal cancer to look for responses or disease stabilization. We are excited about this opportunity given the compelling preclinical science supporting the role of the menin-MLL1 interaction and the impact in tumors such as colorectal cancer. Let me now turn to axatilimab, our potentially best-in-class monoclonal antibody therapy targeting the CSF-1 receptor. Slide 9 provides an overview of the pivotal AGAVE-201 dose-ranging trial evaluating axatilimab in patients with cGVHD. We are excited to announce that the trial has now completed enrollment of approximately 240 patients, which exceeds the original enrollment target of 210 patients. We believe this speaks to the enthusiasm that investigators have for axatilimab as well as the unmet medical need among cGVHD patients. The trial enrolled patients whose disease has progressed after two prior therapies, were at least 2 years of age and met overall entry criteria. Patients were randomized to one of three treatment groups, each investigating a distinct dose of axatilimab given either once every 2 weeks or once every 4 weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for cGVHD while secondary endpoints include duration of response and validated quality of life assessments using the modified Lee Symptom Scale. As you may recall, the primary endpoint for the AGAVE trial is response by cycle 7, day 1, measured approximately 6 months after the initial dose. Assuming a few additional weeks for data analysis due to the over enrollment, we are now comfortable guiding to top-line data in mid-2023. By the terms of our collaboration agreement, Incyte will be leading the regulatory filing in cGVHD which we expect will occur in the later part of 2023. This trial is supported by positive Phase 1/2 data in 40 cGVHD patients that we presented at ASH in 2021, where the overall response rate was 68% and the median time on treatment was over 6 months. Along with an excellent safety profile, these results were well received among thought leaders who recognized axatilimab as having a clinical profile that will be beneficial in the treatment of these heavily pretreated patients. In collaboration with our partner, Incyte, we are enthusiastic about expanding the axatilimab program into frontline cGVHD in combination with ruxolitinib. We believe the non-overlapping mechanisms of action of ruxolitinib suppressing T cell activation and axatilimab inhibiting both inflammatory monocytes and profibrotic macrophages may allow for synergistic clinical benefit in patients with cGVHD. The Phase 1 combination trial in patients with newly diagnosed cGVHD is currently in preparation, and we expect the trial to initiate in the first quarter of 2023. Beyond cGVHD, we are excited about the opportunity to expand axatilimab beyond graft versus host disease into fibrotic diseases where the monocyte macrophage lineage plays a key role. We continue to expect to initiate a robust Phase 3 trial in IPF in the fourth quarter of this year. This multinational trial will enroll 170 patients with IPF randomized 1:1 to receive axatilimab or placebo over a 52-week double-blind treatment period. If successful, we believe this trial, along with one additional Phase 3 trial could form the basis for FDA approval in IPF. Slide 10 highlights the broad clinical and commercial opportunity for axatilimab. We believe cGVHD represents a high unmet medical need and an important commercial opportunity with approximately 14,000 patients suffering from GVHD in the U.S. today. The successful commercial launches of Incyte’s Jakafi and Sanofi’s Rezurock are encouraging, both posting meaningful early revenues that begin to speak to the commercial opportunity in cGVHD. Despite recent advancements in this area, to our knowledge, axatilimab is the only agent in clinical development that specifically targets the monocyte macrophage lineage. We and Incyte believe that data generated to date with axatilimab suggests it has the potential to play an important role in the treatment of cGVHD, both as a monotherapy and given its safety profile, in combination with complementary medicines. Through combinations in the frontline setting as well as the opportunity to expand to ex-U.S. markets, we envision the cGVHD opportunity growing meaningfully. I will now turn the call over to Keith to review our financial results.

Keith Goldan, CFO

Thank you, Michael. I’m going to take a few minutes to discuss our financial results for the third quarter of 2022. Turning to Slide 11, the results of our operations for the third quarter of 2022 and a comparison to the prior year’s quarter are included in our press release, so I won’t repeat them in these remarks. Additional financial details are available in our third quarter report, which was filed earlier today on Form 10-Q. I’d like to point out that our net loss for the quarter was $35.4 million or $0.58 per share compared to a net loss of $20.6 million or $0.40 per share in the same period last year. This difference is primarily attributed to $12.4 million in non-recurring license revenue recognized in the third quarter of 2021 as well as higher operating expenses in 2022 driven by increased employee-related expenses as well as higher professional fees. This was partially offset by lower third quarter 2022 clinical development and manufacturing expenses, in large part the result of axatilimab cost-sharing benefits from our partner Incyte. We ended the third quarter with $337.8 million in cash equivalents and marketable securities and 61.3 million shares and pre-funded warrants outstanding, and we continue to forecast the cash runway into the second half of 2024. Our current cash on hand supports our development and pre-commercialization plans for both the revumenib and axatilimab programs during this period and provides us flexibility to decide to engage in business development. I would note that we made a debt repayment in September in connection with the termination of a loan agreement with Hercules. However, this did not have an adverse impact on our cash guidance. Looking ahead, I’d like to provide updated financial guidance for the full year 2022. We now expect R&D expense to be $115 million to $125 million versus our previous guidance of $130 million to $140 million. The reduction is driven largely by higher-than-expected cost offset from our axatilimab development partner, Incyte. And for the full year 2022, we now expect total operating expense to be $145 million to $155 million, including approximately $15 million of non-cash stock compensation expense. The current operating expense guidance is lower than the prior guidance of $160 million to $170 million after accounting for the third quarter financials as well as the updated full year expense guidance. With that, let me now turn the call back over to Michael.

Michael Metzger, CEO

Thank you, Keith. As you can see, we continue to make significant progress executing against our ambitious goals and milestones that we set forth at the beginning of this year. I am confident we have the right plan in place and that we are building the right team to execute on our long-term goals. Syndax has always been focused on delivering new medicines that extend and improve the lives of people with cancer, and we are in a unique position today with two ongoing registration programs with pivotal data within the next 12 months. In addition, both programs offer the potential for broad franchise opportunities beyond their initial registration indication. We believe revumenib could have utility across a wide range of clinical settings in acute leukemia and potentially in solid tumors. Our immediate goal as a company is to be first to market and best in class in NPM1 mutant and MLL-rearranged acute leukemia, and we are pleased to be able to share updated data from the Phase 1 portion of AUGMENT-101 at ASH, which continue to support our ambitions. We are actively engaged with physicians, and we are laying the groundwork for potential launches as we seek to take advantage of our leadership position. We plan to have a large presence at the ASH conference, and we are focused on educating physicians through multiple avenues, such as our disease awareness campaign that kicks off in the fourth quarter. Beyond the relapsed/refractory setting, we intend to drive additional value potential by expanding its use into newly diagnosed settings in NPM1 mutant and MLLr acute leukemias and perhaps into solid tumors. The same franchise potential holds axatilimab where broad opportunity exists in various lines of therapy in cGVHD and across a broad range of fibrotic diseases starting with IPF. We are indeed in a strong financial position with a balance sheet that allows us to deliver on key near-term milestones. I’d like to close the call by expressing our deep appreciation to the Syndax team, collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical programs. It is all of you who help us to execute our mission of realizing a future where people with cancer live longer and better than ever before. I’d also like to thank our committed long-term investors who continue to share in our vision and support us in building Syndax. With that, I’d like to open the call for questions.

Operator, Operator

[Operator Instructions] And we will go right into our first question from Philip Nadeau with Cowen. Please go ahead, your line is open.

Philip Nadeau, Analyst

Hi, good afternoon. Thanks for taking our questions and congratulations on the progress. A couple of questions on the abstract from this morning. It sounds like most of the patients who were added in the abstract are MLLr patients with, I think, you said just one NPM1 patient being added. Why is the enrollment of NPM1 patients still so low? It does seem like that’s a much larger population, we would have thought maybe you’d get more business for that genotype in the trial. And then a related question, I think we are all thinking a 20% CR/CRh rate is necessary, perhaps for filing in that indication. Is that – in any individual genotype, is that a fair assumption?

Michael Metzger, CEO

Phil, thanks for the question. So I guess I’ll take the first one, which is about the number of NPM1 patients. I think we talked about the fact that the enrollment in Phase 1 was initially skewed more towards MLLr patients than NPM1 because the initial patients who came into the trial did quite well and received a response with the MLLr. And of course, we’ve seen patients come on as well in the Phase 1 and 2 quite well in having NPM1. But how the Phase 1 was set up where you have a certain number of slots and so forth has influenced the cadence of enrollment, which has stayed that way throughout the trial. So really no change there with the addition of the new patients. I wouldn’t expect anything to change with the ongoing Phase 1 thus far. Your second question is regarding the 20% CR/CRh rate needed for filing. I think that assumption is based on precedent, right? Our trial statistics are structured such that each of the three enrolling cohorts has the same statistical design and number of patients. We haven't discussed much about the actual statistics and the lower bar that we’re looking to rule out, but you can surmise that the agency has given us guidance around what statistics we need to achieve, and what the point estimates are. Based on precedent, we feel confident that 20% or higher is reasonable to keep in mind, but it’s certainly not absolute. I mean, I'm sure they will take into account both safety and efficacy of these compounds in the risk-benefit analysis that will be part of the package. So 20% is a reasonable assumption, but it’s not a definitive requirement.

Philip Nadeau, Analyst

That’s great. And then one last question from us, just curious whether you mentioned the benefit-risk calculation. In your experience with physicians, what risk of differentiation syndrome is acceptable given the efficacy that we’re seeing from menin inhibitors?

Michael Metzger, CEO

So maybe I’ll turn it over to Briggs. He can address that, please?

Briggs Morrison, President and Head of R&D

Yes. Hi, Phil, thanks for the question. I don’t think we’ve done any market research on that specific question. Obviously, there are other agents that are in clinical use today that have differentiation syndrome as part of their risk-benefit profile. I think the related question we would probably ask is not just what is the percentage that might be acceptable, but what is the severity of those events. As you know, we tend not to see very many differentiation syndrome events, and the ones that we have seen to date in the Phase 1 trial are all grade 2. So, that profile, what we’ve clearly heard from our investigators at least, is quite acceptable.

Philip Nadeau, Analyst

That’s very helpful. Thanks for your perspective, and congrats on the progress.

Michael Metzger, CEO

Thanks, Phil. Appreciate it.

Kalpit Patel, Analyst

Hey, good afternoon. And congrats on the ASH data set today. I guess, first, starting with the ASH data set, can you confirm that the AE profile was comparable to the prior data set as the data matured? And I think you added maybe 9 more patients of efficacy data and particularly the grade 3 or higher QTC rates, did they stay at the 7% range or so?

Michael Metzger, CEO

Yes, Kapil, thanks for the question. I think we can confirm that the safety and new update will be consistent, you'll see the full safety at ASH, but it was consistent with what we’ve shown prior, with no new safety findings in this data cut. We would expect it to be very similar to what you’ve seen in the last time.

Kalpit Patel, Analyst

Okay. And for the efficacy part for the 9 more patients that you added at the recommended Phase 2 doses, if I did the math right, four out of nine patients achieved a CR/CRh, which is obviously a bit better than the overall population numbers. So the question is, if you go back and look at just the patients at the recommended Phase 2 doses, is the CR/CRh rate higher than the 30% that you have reported at the ASH data set?

Michael Metzger, CEO

Yes. Briggs, do you want to take that?

Briggs Morrison, President and Head of R&D

Yes. So again, remember that the vast majority of patients treated of the 60 patients—the vast majority are treated at one of the doses that met the criteria of the recommended Phase 2 dose for the protocol. So, in essence, what you’re looking at is the efficacy that we would anticipate at our recommended Phase 2 dose.

Kalpit Patel, Analyst

Okay. And then maybe a follow-up on Phil’s question, since you did end up enrolling more patients with MLLr, AML in the Phase 1 portion, is it safe to assume that this cohort will likely be the first to read out next year for the trial?

Michael Metzger, CEO

Yes, we haven’t given any particular guidance on which cohort is going to read out first. AML is likely to report before ALL, just based on ALL being a much smaller patient population. We will have more to say about that as we get closer, but I would assume that AML will be first.

Kalpit Patel, Analyst

Okay. Fantastic. Thanks for taking the question and congrats on the data set.

Michael Metzger, CEO

Thank you so much.

Madhu Kumar, Analyst

Yes. Thanks for taking our questions. I wanted to follow-up on Phil’s questions around differentiation syndrome. I guess one we’ve been getting a lot recently is, are there differences in your kind of perspective with using revumenib in differentiation syndrome rates in MLL arranged versus NPM1 mutant disease?

Michael Metzger, CEO

Briggs, would you address Madhu’s question, please?

Briggs Morrison, President and Head of R&D

Yes. So, Madhu, remember the—so I would say we haven’t actually presented that breakdown. But I would say we see relatively little of it. So, it’s hard to say what the determinants are and what it correlates with. Given the relatively few cases we have seen, there doesn’t seem to be a trend between the different mutations.

Madhu Kumar, Analyst

Okay. Great. And then I guess kind of thinking about the axatilimab program in chronic graft versus host disease. How should we think about kind of duration of therapy from the Phase 1 trial? Like could we expect any updates between now and kind of the top-line data mid-year? Like how do you think about kind of the duration of use of axatilimab?

Michael Metzger, CEO

Yes. Thanks for the question, Madhu. I think what we had reported data last year, obviously at ASH, and at that point, patients were on for six months or longer, and so the duration of therapy looks favorable. As to your question about whether there will be an update on that, short of putting out our pivotal data, which of course, we announced today that we have finished the trial, and that data will be coming out in mid-2023. That’s the logical time to update other than a potential publication along the way. But right now, we are gearing up for the top-line data for the pivotal trial.

Madhu Kumar, Analyst

Okay. And I guess one last question is, what kind of things you will be focusing on from the ASH presentation that will be different from the abstracts presented earlier at this point? Like what are kind of key highlights that people should keep an eye on?

Michael Metzger, CEO

You’re asking about what we will be looking for at the ASH presentation itself?

Madhu Kumar, Analyst

Yes, that distinguished from the abstract, yes.

Michael Metzger, CEO

Right. So, just to be clear, this will be—the data cut that we will have at the presentation will not show a new data cut. In terms of updates and additional details, there will, of course, be additional details of what we presented today in the presentation. What those are, in particular, I’m not ready to say now, we are far out from the data. But I would expect that there will be interesting new insights to come from that presentation. Two presentations will be made on the transplant data that we presented as well as the clinical data.

Madhu Kumar, Analyst

Okay. Great. Thanks very much, guys.

Michael Metzger, CEO

Thanks, Madhu.

Operator, Operator

Next, we will go to the line of Yigal Nochomovitz with Citi. Please go ahead. Your line is open.

Ashiq Mubarack, Analyst

Hi team. This is Ashiq Mubarack on for Yigal. Thanks for taking my question and congrats on all the progress. Really great to see. Just kind of going back to the earlier NPM1 enrollment discussion. I guess, would you be able to characterize if enrolling NPM1 patients versus MLLr patients might be different in terms of maybe a competitive dynamic between your trial versus other trials out there? I am just wondering if there are any potential differences there?

Michael Metzger, CEO

Yes. No. Thanks for the question, Ashiq. I think this is—not a dynamic where we feel like there is a competitive reach between one trial versus another for these states. I think we have a trial that’s up and running, and we are enrolling patients well across the three Phase 2s, as I mentioned. The Phase 1 experience was a separate experience for all the reasons I mentioned earlier, from the experience that we are seeing in Phase 2. There are only a couple of sites that overlap with competitors. It’s much more a function of the Phase 1 design and how that was set up to enroll patients versus the Phase 2, which is obviously enrolling independently.

Ashiq Mubarack, Analyst

Okay. Alright. That’s very clear. Maybe I’ll switch over to a question on duration, on the 9.1 months the DOR you reported. Can you maybe give us some color commentary on how compelling you think that duration is? And maybe can you give us a sense of the contribution of the post-transplant retreatment period for that duration number?

Michael Metzger, CEO

Okay, Briggs, would you like to answer that question?

Briggs Morrison, President and Head of R&D

Yes, sure. So, if you look at the other examples, I think Phil asked at the beginning about whether 20% is required for filing for a CR/CRh, the other question that some have asked is, what kind of durability we need. With a 30% CR/CRh rate and a median duration of response exceeding nine months, looking at other approved drugs, I think that’s quite competitive and favorable. And many of our investigators are quite excited about what they are seeing. The question about whether we can separate out what is the duration of response in patients who weren’t transplanted versus patients who were transplanted is obviously difficult to do, because so many of the patients were transplanted. That’s in part why the FDA recommends that people do not censor at the time of transplant since it’s essentially unknowable what the duration of response would have been if they hadn’t been transplanted.

Ashiq Mubarack, Analyst

Okay. Alright. That’s helpful. Maybe last one from me. It seems like you pushed back your expected top-line data release for the pivotal cohorts to the third quarter next year. I guess what’s driving the slight adjustment? Is it that maybe pace of enrollment or is there a need for additional regulatory discussions? Any color there would be very helpful.

Michael Metzger, CEO

Yes. Thanks for the follow-up, Ashiq. So, let me dive into that a little bit more. I would characterize this as really no shift in timelines. What’s important here is the NDA filing by the end of 2023, which is our prior guidance. Data, we expect to fall into the third quarter and enrollment in the first quarter. What I explained in my earlier remarks is that there were some site enrollments, a couple of sites that didn’t come on as quickly as we had projected in the latter part of the year. So that’s put us off a little bit on our expected timeline to fully enroll the first of the three cohorts. Ultimately, through some good efforts with the sites and investigators, I believe we will be back on track now. I would say that enrollment is strong, and the enthusiasm for the trial is really very good. The results of our trial speak to that and support our expectations. What we are seeing across our sites reflects broader industry trends facing site initiation resourcing issues. We’ve really not seen much until we observed a couple of sites get delayed in the last few months. So, that’s the explanation. We are still in excellent shape. Again, we are on pace to deliver on what we think is obviously the most important: top-line data and then of course filing at the end of 2023.

Ashiq Mubarack, Analyst

Good. Thanks for taking all my questions and congrats again.

Michael Metzger, CEO

Thank you so much.

Peter Lawson, Analyst

Thanks. Thanks for taking the questions and thanks for the update. Just wondered if you could make any commentary around any durability differences between the MLLr range and the NPM1 patients? And then as we think about filing in AML, am I right to assume that the FDA is going to look at these as two independent genotypes versus the combined number that you have seen so far in the Phase 1?

Michael Metzger, CEO

Sure, Peter. Thanks for the question. So, let me address the first one and then we’ll tackle your second question. The first one related to differences that we see in durability between NPM1 and MLLr. I think I’ll just point out that we presented last year that the NPM1 patients had all MRD-negative CRs, so they are very strong responders. Two of those patients were NPM1 patients that have done very well and stayed on the drug. So, I think both sets of patients have demonstrated the ability to achieve complete responses and remain in that state for an extended period of time. We don’t necessarily see a difference, albeit the number of MLLr patients is higher than NPM1 in the aggregate. We don’t believe the experience in terms of durability will be any different. The second question was about filing and whether FDA will combine or separate them. We put the trials together as three separate trials. They are enrolling separately, as I pointed out. There are separate statistics, and we designed it that way to potentially enable three separate filings. We could put one or more together due to timing of enrollment, but we are looking to bring the drug to the agency as quickly as possible. We do not want to wait for combined data sets to expedite this.

Peter Lawson, Analyst

Yes. Just regarding the ASH update. Will we see – what additional data will we see in the ASH presentation that will not be available in the abstracts presented earlier at this point? Will key highlights include response rates broken out by dose, durability potentially, or the MRD negativity between NPM1 and the rearranged patients?

Michael Metzger, CEO

Yes. Well, as you know, we have presented some of that information in the past. We’ve tried to be consistent between what we presented from meeting to meeting, so investors can track the data and how it’s improved over time. In terms of detailed updates and what we will present at ASH, I’m not at liberty to say what exactly we will present. Suffice to say, I think it’s interesting information and it will be a great oral presentation. There will be two presentations, one on transplant data and another on clinical data.

Peter Lawson, Analyst

Great. Thank you so much. Thanks for taking the questions.

Michael Metzger, CEO

Thank you, Peter.

Joel Beatty, Analyst

Hi. Congrats on the data. First question is on AUGMENT-101. Does the cohort need to have efficacy data collected on all 64 adults to read out, or could it read out with a smaller denominator than 64% if enough responses are achieved?

Michael Metzger, CEO

Thanks for the question. The way it is set up today, we are targeting 64 patients. That’s how it’s designed. A lower denominator is not contemplated as part of the current protocol. So that’s the target number of enrolling. Of course, we could over enroll, but I don’t believe that there is an opportunity to under enroll at this point.

Joel Beatty, Analyst

Got it. Thanks. Can you discuss the status of initiating clinical trials and doing the work to move into the first-line setting for revumenib?

Michael Metzger, CEO

Right. So, Briggs, maybe do you want to describe the BEAT-AML trial a little bit and maybe some of the other things that we are thinking about?

Briggs Morrison, President and Head of R&D

Sure. So again, I think Joel, your question about early lines of therapy will be separated into two buckets: those who are fit for intensive chemotherapy, tend to be younger patients; and those who are unfit for induction chemotherapy, who tend to be older patients or patients with comorbid disease. For fit patients, the standard of care today, as it’s been for decades, is the so-called seven plus three induction consolidation regimen. There is a keen interest to combine our drug there. The safety profile that we have seen, we think is favorable for combining with chemotherapy. We are in the process of thinking through how—we haven’t yet said when that trial will start or the design, but we are working hard on it. The second population is the unfit population who are in combination with venetoclax-aza. That’s the BEAT-AML trial that’s going on to determine in the Phase 1 portion, what the appropriate dose of revumenib is to give in combination with the label dose of venetoclax. The third group are those with residual disease by sophisticated assays, the so-called measurable residual disease population. There, as you know, the INTERCEPT trial is essentially a single-agent revumenib to see if we can convert those patients to MRD negativity, which would predict that that group will have clinical benefit.

Joel Beatty, Analyst

Great. Thank you.

Michael Metzger, CEO

Thank you, Joel.

Operator, Operator

It appears we have no further questions at this time. I will now turn the program back over to Michael Metzger for any additional or closing remarks.

Michael Metzger, CEO

Great. Thank you, operator, and thanks to everybody on the call today. We appreciate the interest in our story. We look forward to seeing many of you at our upcoming industry meetings, as well as, of course, at the ASH meeting, where we will be presenting data that we talked about today. So, thank you and have a great rest of your evening.

Operator, Operator

This does conclude today’s program. We thank you for your participation. You may disconnect your lines at any time.