Earnings Call Transcript
Syndax Pharmaceuticals Inc (SNDX)
Earnings Call Transcript - SNDX Q3 2023
Operator, Operator
Good day, everyone, and welcome to the Syndax Third Quarter 2023 Earnings Conference Call. Today's call is being recorded. At this time, I would like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.
Sharon Klahre, Head of Investor Relations
Thank you, Operator. Welcome, and thank you all for joining us today for a review of Syndax's third quarter 2023 financial and operating results. I'm Sharon Klahre, and with me this afternoon to provide an update on the Company's progress and discuss financial results are Michael Metzger, Chief Executive Officer; Dr. Neil Gallagher, President and Head of R&D; and Keith Goldan, Chief Financial Officer. Also joining us on the call today for the question-and-answer session are 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 would 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 these 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 may represent our views as of today, November 2, 2023, only. A replay of this call will be available on the Company's website, www.syndax.com following its completion. 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 all for joining the webcast. This continues to be an exciting year for Syndax and I look forward to sharing a number of updates with you on the significant progress we have made. Throughout the third quarter, we delivered on key pipeline milestones that are highlighted on Slide 3, including reporting positive top line AGAVE-201 pivotal data of axatilimab for the treatment of chronic graft-versus-host disease. We also reported positive top line pivotal AUGMENT-101 data for revumenib in adult and pediatric patients with relapsed/refractory KMT2A rearranged acute leukemia. Together these results put us on a clear path to becoming a commercial stage biopharmaceutical company in 2024 with two potentially first and best-in-class products. We are also happy to provide data today from additional relapse or refractory NPM1 patients that were enrolled in the final stages of the Phase 1 portion of the AUGMENT-101 trial. Neil will walk us through the data a little later in this call, but in summary, we are encouraged by the 36% CR/CRH rate and deep responses that we are seeing in the NPM1 population. Responses elicited by revumenib in the NPM1 population are durable with some patients in remission beyond 22-months further supporting the rationale that revumenib can provide a meaningful benefit to NPM1 patients and emphasizing its blockbuster commercial potential across both KMT2A and NPM1 acute leukemia. We continue our positive momentum heading into the end of 2023 with a primary focus on completing two potential regulatory filings by year-end and launching both drugs in 2024. This will put Syndax in a very unique position to create value as a mid cap biotech company. We will have a significant presence at the American Society of Hematology ASH annual meeting, including at our planned investor event and expect to provide several data updates on both these programs at that time. I am pleased to share that as of a few days ago, we initiated the NDA submission of revumenib for KMT2A acute leukemia under the FDA's real time oncology review program or RTOR. We view RTOR as a significant benefit for the revumenib program. It complements our BTD and fast track status for KMT2A and provides a more efficient review process to ensure that revumenib is available to patients as early as possible. Under RTOR, the sponsor has consistent engagement with the FDA throughout the submission process. Drugs accepted for review in this program need to meet specific eligibility criteria, the most important of which is the likelihood of demonstrating substantial improvement over available therapy. In accordance with FDA guidance for AML and in line with the approvals of other AML agents in the relapsed/refractory setting, we anticipate revumenib would be granted full approval based on the results of AUGMENT-101. With our partner Incyte, we also remain on track to complete the BLA filing for axatilimab by year-end. As you saw from our press release earlier today, data from both the AGAVE-201 and AUGMENT-101 pivotal trials including post transplant maintenance data along with revumenib combination data from the SAVE trial will be presented at the ASH meeting in December. Beyond the Congress presentations, we will also have the opportunity to share additional data from ongoing revumenib combination trials at our ASH investor event, which will further reinforce revumenib's compelling clinical profile and meaningfully add to its value proposition. We are well funded with $379 million in cash as of September 30. Our current balance sheet not only supports our planned commercial launches and the trials that we have outlined, but also allows us to expand beyond our core registration indications and pursue select business development opportunities. Now let's dive into revumenib, our highly selective main inhibitor. I will ask Neil to provide a recap of the results from the AUGMENT-101 pivotal trial, speak to the ASH abstracts and review the data from the NPM1 patients in the Phase I portion of the AUGMENT-101 trial. Neil?
Neil Gallagher, President and Head of R&D
Thank you, Michael. I will now review the AUGMENT-101 pivotal data in relapsed or refractory KMT2A acute leukemia beginning on Slide 4. As previously reported, the independent data monitoring committee reviewed the data and recommended that trials stop early for efficacy in accordance with a predefined interim analysis. We are very pleased with the robustness of the data that we reported. Almost two-thirds of these heavily pretreated patients achieved clinically significant responses, enabling many to receive potentially curative transplant. Importantly, a high proportion of all responders in the trial were started on revumenib in the post transplant maintenance setting. The desire for physicians to restart revumenib as post transplant maintenance speaks to its efficacy and tolerability and their belief that it may offer a better outcome for their KMT2A acute leukemia patients. Importantly, the ability of these heavily pretreated patients to both respond to and tolerate revumenib therapy also underscores its potential to be adopted into frontline combinations. Turning to Slide 5. The majority of patients in the efficacy evaluable population, which include adult and pediatric AML and ALL patients, achieve clinically significant responses to treatment with a high overall response rate of 63%. The CR/CRH rate in this population was 23%. The response rates observed in KMT2A AML specifically were consistent with those in the overall efficacy evaluable population, with 65% achieving a response and 24.5% achieving CR or CRH. The MRD negative rate among CR/CRH responders was also impressive at 70%. At the time of the data cutoff, the median duration of CR/CRH response was 6.4 months across both the efficacy evaluable and AML populations, with 46% or six patients remaining in response. Of note, this is a Kaplan-Meier estimate, and the data will continue to mature over time. Therefore, the median duration of response may extend beyond 6.4 months with additional follow-up. Turning to Slide 6. Not only did we observe a high overall response rate of 63%, but 39% of responding patients proceeded to bone marrow transplant, which is notably higher than the historical benchmark in this population of less than 5%. Eight patients were transplanted prior to achieving CR/CRH at the discretion of the attending physician. Clearly, if physicians had decided to wait a little longer prior to transplant, then more of these patients could have achieved the best response CR/CRH. For example, if all 8 of these patients had achieved CR/CRH, then the rate would have been 37%. 71% of these patients, 10 of 14, either restarted revumenib or were eligible to restart as maintenance therapy. At the time of data cutoff, some patients were treated in the maintenance portion for as long as eight months and several are continuing on therapy, which we believe speaks to revumenib's compelling overall clinical profile and the potential for long-term maintenance in this setting. The capacity of revumenib to rapidly induce BLAST-free responses in heavily pretreated patients, thereby enabling them to undergo potentially curative bone marrow transplant followed by post transplant maintenance, represents a potential paradigm shift in the standard of care in this setting. We have a presentation at the ASH meeting that will highlight revumenib for post transplant maintenance, including patients on therapy in remission beyond 18-months. The data from AUGMENT-101 indicate that revumenib is well tolerated and the safety profile is consistent with what was previously reported. We believe that the emerging benefit-risk profile of revumenib supports its use not only as a monotherapy in the relapsed/refractory setting before and after transplant but also its potential use in combination with frontline standards of care for which initial data are forthcoming later this year. Turning to Slide 7. Today, we announced encouraging data from 3 additional patients with NPM1 mutated relapsed or refractory AML included in the Phase 1 portion of the AUGMENT-101 trial for a total of 14 NPM1 patients treated at doses meeting the RP2D criteria. These patients are enrolled in Phase 1 to complete the pharmacokinetic characterization of revumenib. Among these 14 patients, seven achieved a response to treatment for a 50% overall response rate, five of 14 achieved a CR or CRH rate of 36%, and 100% of the CR/CRH responders were MRD negative. On Slide 8, you may see that these responses are durable with four of five of the patients remaining in response, three already beyond 6 months, one beyond 22 months, and one over a 30-month at the time of the analysis. Revumenib also enabled 43% of NPM1 responders to proceed to transplant. One of the patients who proceeded to transplant has been enrolled following the AUGMENT-101 protocol update, which allowed patients to restart revumenib post transplant. This patient remains on revumenib maintenance at the time of the analysis. Similar to the Phase 2 results observed, revumenib was well tolerated in patients with relapsed refractory NPM1 AML. There were no grade four or five QT prolongations, no patients experienced more than grade two differentiation syndrome, and no patients discontinued due to treatment-related adverse events. As Michael said earlier, these data continue to support our conviction that revumenib will be an important treatment for NPM1 AML as well as for KMT2A acute leukemias, and we expect that NPM1 pivotal trial results will be consistent with the data generated to date and highly supportive of a first to market approval. The pivotal cohort of the AUGMENT-101 trial continues to enroll relapsed refractory NPM1 mutant AML patients. The trial is designed to enroll 64 patients and up to 20 pediatric patients. While the trial continues to recruit well in the U.S. and internationally, we now forecast completion of enrollment in the late first quarter or early second quarter next year due to a few high enrolling sites in Europe coming online later than we expected in the third quarter. Coupled with the recent events in Israel where we have a high concentration of sites, I would note that Israel accounts for 16% of our enrolling sites, and historically, these have been very high enrolling. We are now looking to make up for any potential shortfall at our sites, but it is difficult to predict the impact that the evolving geopolitical situation may have on enrollment. Nonetheless, we expect to be in a position to report data in the fourth quarter of 2024 and importantly, continue to look forward to a potential approval in 2025 based on an sNDA filing following revumenib's anticipated initial approval in KMT2A. Turning to Slide 9. In addition to sharing the AUGMENT-101 pivotal data at ASH, we look forward to Dr. Issa highlighting his SAVE trial results in an oral presentation on Saturday morning during the meeting. This is an investigator-sponsored Phase 1b trial conducted by Dr. Issa at the MD Anderson Cancer Center, evaluating an all-oral combination of revumenib with venetoclax and a fixed dose combination of azacitidine and cedazuridine in children and adults with relapsed refractory AML or mixed phenotype acute leukemias. At the time of the data cutoff, the trial was enrolling at the current monotherapy RP2D of 163 milligrams every 12 hours with a strong CYP3A4 inhibitor. In total, eight patients with either NPM1, KMT2A or NUP98 mutations were enrolled in the trial, having received 2.5 median prior lines of therapy. Approximately two-thirds of patients received prior venetoclax. All patients on a strong CYP3A4 inhibitor were therefore treated with revumenib at either 113 milligrams Q12 early or 163 milligrams. Seven of eight patients were evaluable for response. All seven achieved a response. Six of seven achieved a CR, and two of seven, 28% achieved a CR/CRH. Importantly, responses were observed across relapsed or refractory NPM1, KMT2A or NUP98 acute leukemia patients. Three patients transitioned to hematopoietic stem cell transplantation following response, and two continue in remission and have started maintenance as of the data cutoff. We are highly encouraged by the compatibility of revumenib with venetoclax and the hypomethylating agent in this trial. This combination was well tolerated at active doses, including the current monotherapy RP2D. I will now turn the call back to Michael.
Michael Metzger, CEO
Turning to Slide 10, we believe that revumenib could form the backbone of treatment for patients with KMT2A rearranged and NPM1 mutant acute leukemias and as demonstrated by its compelling efficacy and safety profile, we have expanded our clinical strategy beyond the relapsed or refractory setting into earlier settings and post transplant maintenance including combinations with approved therapies. In an attempt to accelerate the generation of evidence of clinical benefits seen with revumenib across various settings of KMT2A and NPM1 acute leukemias, we are collaborating with groups and leading investigators in addition to the clinical trials that Syndax is conducting. In addition to the SAVE trial that Neil described earlier, we plan to present initial data from the Beat AML and AUGMENT-102 trials in the fourth quarter at our planned investor event at ASH. The Phase I Beat AML trial is part of our collaboration with the Leukemia and Lymphoma Society and revumenib is being combined with venetoclax and azacitidine to treat newly diagnosed AML patients who are unfit for induction chemotherapy. Enrollment is ongoing in the dose-finding stage of the trial to confirm the RP2D for this combination, and we continue to expect to share data on safety and efficacy from the trial at our ASH investor event. The AUGMENT-102 trial is designed to assess the safety of revumenib in combination with standard salvage chemotherapies for patients with relapse or refractory acute leukemias. We anticipate presenting an update on the initial safety and potential RP2D from the trial at our ASH investor event. We look forward to initiating a trial of revumenib in combination with standard of care intensive chemotherapy known as seven plus three in newly diagnosed patients with acute leukemia in late 2023 or early 2024. This trial will also include an option for maintenance with revumenib monotherapy. Beyond the acute leukemia trials we have laid out here, we are rolling a proof of concept signal seeking phase one clinical trial in metastatic colorectal cancer based on compelling preclinical science supporting the role of the menin-KMT2A interaction in beta-catenin driven tumors. The trial is advancing nicely through the dose escalation phase and we are nearing RP2D. We would perceive responses or prolonged stable disease as encouraging in this difficult-to-treat patient population with the monotherapy, and we expect to follow these patients to gather sufficient efficacy into 2024. We anticipate being able to provide an update on the progress at the dose escalation phase of the trial in the first quarter of 2024. Now to Slide 11. KMT2A and NPM1 acute leukemias represent up to 40% of AML patients, and there are no FDA approved targeted therapies for this population. Including the expansion opportunities, there is the potential to address upwards of 12,000 NPM1 mutant and KMT2A rearranged acute leukemia patients across various settings. We are committed to bringing these encouraging clinical benefits to even more patients as this remains an area with significant unmet need. We believe that relapse or refractory KMT2A acute leukemias alone represent a $650 million to $750 million market opportunity in the U.S. based on the estimated patient population, duration of treatment and current pricing assumptions. KMT2A-rearrangement represents approximately 10% of AML and ALL, which translates into an incidence of approximately 2,600 KMT2A-rearranged acute leukemia patients, a very high percentage of whom are refractory to frontline standard of care treatments. Based on the enthusiasm we are hearing from physicians and the potential to shift the treatment paradigm in KMT2A to incorporate maintenance treatment post-transplant, we believe the median duration of therapy across the treatment population would be approximately nine months, and we believe that the data generated in AUGMENT-101 support pricing competitive with or above other targeted therapies in AML such as FLT3 or IDH inhibitors. With no treatment options approved for these patients and no near-term competition, revumenib could easily become the treatment of choice for all patients with KMT2A acute leukemia based on obtaining the only age and disease agnostic label in KMT2A acute leukemia. We expect that our first mover advantage and experienced physicians will gain treating their patients with revumenib could extend meaningfully beyond KMT2A and allow us to build a formidable franchise in the next few years. Supported by the compelling NPM1 data we presented today, we believe revumenib will also provide meaningful benefit in relapsed or refractory NPM1 patients. Our market research suggests that if approved, oncologists are likely to reach for revumenib as either their second or third line agent of choice for patients with NPM1 mutant AML. We estimate that this population will be slightly larger than the relapsed refractory KMT2A acute leukemia population. And based on our Phase I results, we also believe overall efficacy and treatment duration will be consistent between the KMT2A and NPM1 populations. Having first mover access to two distinct market segments in acute leukemias, KMT2A and NPM1 creates a total accessible population of 5,000 to 6,000 patients in the relapsed refractory setting and an addressable market opportunity of approximately $1 billion to $1.5 billion for revumenib in the U.S. alone. We anticipate that revumenib will begin to carve out a dominant share of the relapsed and refractory NPM1 market starting in 2025. Now let's dive into axatilimab, our monoclonal antibody targeting the CSF1 receptor beginning on Slide 12. In collaboration with Incyte, we shared positive results from the global pivotal AGAVE-201 trial evaluating the efficacy, safety and tolerability of axatilimab in 241 patients with active chronic GVHD whose disease had progressed after at least two prior therapies. As a reminder, the trial met its primary endpoint of overall response rate by cycle 7 day 1 using the 2014 NIH consensus criteria for chronic GVHD across all three dose groups. The overall response rate or ORR was 74% at a dose of 0.3 milligrams per kilogram administered every 2 weeks. The responses were durable with a median duration of response not yet reached at the time of data cutoff and 60% of responders were still responding at one year. Axatilimab was well tolerated in the trial with a low 6% rate of discontinuations and the most common adverse events were consistent with the on-target effects that were observed in prior trials. I want to remind you that robust efficacy was observed despite the patients being very advanced and heavily pretreated. As an example, I would highlight that there are meaningful differences in patient populations between the axatilimab AGAVE-201 trial and the Rezurock ROCKstar trial, both of which targeted patients with chronic GVHD who had received two or more prior lines of therapy. Notably, patients in the AGAVE-201 trial had a longer median time since diagnosis of severe chronic GVHD and had received more prior lines of therapy, including a greater number of patients that received Jakafi than patients included in the Rezurock trial. We believe these points of differentiation underscore how impressive the AGAVE-201 trial results are and point to the significant value axatilimab could bring to patients if approved. These results not only support the promise of axatilimab's safety and efficacy profile but reinforce potential as a first and best-in-class CSF1R monoclonal antibody in chronic GVHD. Axatilimab is the first investigational chronic GVHD treatment to target inflammation and fibrosis through the inhibition of disease-associated macrophages, and the AGAVE-201 data demonstrates the potentially pronounced impact this mechanism alone or in combination with standard of care therapies already available for the management of this disease may have on patients suffering from chronic graft versus host disease. In collaboration with Incyte, we intend to file a BLA by year-end 2023. Additionally, we look forward to showcasing the full results during the plenary session at ASH. Turning to Slide 13, approximately 14,000 U.S. patients suffer from chronic graft versus host disease, 50% of whom require treatment beyond second line due to disease progression, inadequate response or disease manifestations that aren't wholly addressed with current treatments. Unfortunately, there are no cures for this advanced population of chronic GVHD patients. Patients are initially treated with corticosteroids and then cycled through a variety of additional therapies. While patients may be treated with several of the approved therapies, the order in which they are used may depend on the physician's experience with how a given agent may address specific manifestations of the disease. Jakafi and Rezurock have had successful commercial launches which speaks to the unmet need in chronic GVHD that translates to a substantial commercial opportunity. It is our conviction that axatilimab could provide an effective differentiated, practice-changing intervention for this underserved population. Axatilimab suppresses monocyte-derived macrophage activation and proliferation, which may provide more comprehensive control of the disease than currently approved therapies. This is a key differentiator and also towards moving axatilimab earlier in the treatment paradigm to potentially prevent organ damage before it occurs. Because axatilimab is an antibody, drug interactions are expected to be minimal and axatilimab's unique mechanism of action may offer the benefit of being an ideal combination partner with standard of care therapies currently used for the treatment of chronic GVHD. The opportunity to expand to ex-U.S. markets and additional high-value indications as well as combinations in earlier settings in chronic GVHD both in adults and pediatrics could build significant additional value for axatilimab. We are looking forward to the initiation of additional trials of axatilimab, including a 26-week randomized placebo-controlled Phase 2 trial in 135 idiopathic pulmonary fibrosis patients expected to begin by year-end, as well as a combination trial to be conducted by Incyte in chronic GVHD patients with Jakafi in mid-2024.
Keith Goldan, CFO
Thank you, Michael. Let me take a few minutes to discuss our financial results for the quarter ended September 30, 2023. Turning to Slide 14, the results of our operations for the third quarter of 2023 and the 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 2023 report, which was filed earlier today on Form 10-Q. I would like to point out that our net loss for the Q3 was $51.1 million or $0.73 per share compared to a net loss of $35.4 million or $0.58 per share for the comparable period last year. The difference in our net loss was driven largely by an increase in employee-related expenses and professional fees within both SG&A and R&D, combined with increased clinical and manufacturing expenses. We ended the third quarter with $379.3 million in cash, equivalents, and short- and long-term investments, and 69.9 million shares in prefunded warrants outstanding. Our balance sheet is expected to provide runway into the second half of 2025, which allows us to appropriately invest to maximize the value of our pipeline and importantly, it also allows us to transition into a commercial stage organization in 2024. Looking ahead, I would like to provide financial guidance for the rest of this year. For the full year of 2023, the company expects research and development expenses to be $160 million to $165 million and total operating expenses to be $225 million to $230 million, both of which are inclusive of approximately $30 million of non-cash stock compensation expense. Note that this is a reduction from our prior guidance of $160 million to $175 million for R&D expense and $225 million to $240 million for total operating expenses. With that, let me now turn the call back over to Michael.
Michael Metzger, CEO
Thank you, Keith. Before we open the call for questions, I would like to provide a summary of what was presented today. In the near-term, we remain laser-focused on delivering all the data readouts, including the full AUGMENT-101 and AGAVE-201 data sets as well as data from several other combination trials at the ASH annual meeting and our planned investor event by year-end. We are excited to provide positive final Phase 1 results for revumenib treatment in relapsed refractory NPM1 patients, further demonstrating its best-in-class profile in another important indication with high unmet medical need. Pivotal data from these trials will serve as the basis for potential U.S. registrational filings, including an NDA submission in relapsed refractory KMT2A acute leukemia for revumenib and an Incyte initiated BLA submission in chronic GVHD for axatilimab by year-end 2023. Both revumenib and axatilimab have significant market opportunities with the potential to gain considerable market share and have a meaningful impact on the lives of underserved patients in each setting. In addition, we continue to explore ways to capture the maximum value of our current pipeline by expanding into opportunities beyond the initial registration indications and in doing so aim to bring the encouraging clinical benefits of our lead candidates to even more patients in need. It has been a transformational year for Syndax, and we expect to maintain this momentum in the coming months with a number of upcoming value-generating milestones that are laid out on Slide 15. I remain confident that we have the resources and expertise to execute on our goals and the strategic long-term vision that will enable our successful transition into a commercial stage biopharmaceutical organization. As always, I would like to extend my gratitude to the Syndax team, collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical programs. Through your integral work, we are advancing our mission of realizing a future where people with cancer live longer and better than ever before. I would 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 would like to open the call for questions.
Operator, Operator
Our first question is from Brad Canino at Stifel. Your line is open. Please ask your question.
Brad Canino, Analyst
Hi, and thank you for the questions. Looking forward to ASH. I have a two-part on the SAVE trial, actually, the all-oral triplet where you had the abstract. Yes, first, when you speak to AML physicians, do you get the sense they are looking to use off-label combinations in the relapsed practice setting? Because if we on the street that are anchored to your monotherapy data, I guess what might that then mean about the ultimate opportunity in this treatment line in relapsed refractory as we think about efficacy, percent of transplant, maintenance, etcetera? And then I have a follow-up.
Michael Metzger, CEO
Brad, thanks for the question. I'm going to ask Neil to make a comment.
Neil Gallagher, President and Head of R&D
Yes. Look, thanks for the question. Obviously, this is a preliminary dose ranging, and there is more work to be done. We see the value in the data that Dr. Issa is generating in a couple of different ways. So first of all, the demonstration of the combinability of revumenib with venetoclax and a hypomethylating agent, I think it is very important. And the study is ongoing with revumenib being administered at full dose in DL1, as was mentioned in the abstract. The other thing to bear in mind is that historically, if you look at this population, they are quite heavily pretreated. Most have actually failed venetoclax and hypomethylating agents. One would expect the response rate, therefore, to venetoclax plus an HMA to be quite low, specifically probably less than 10%. And here, we are seeing a much, much higher response, a 28% CR/CRH rate. So this is actually incremental progress, albeit based on early data, incremental progress for those patients.
Brad Canino, Analyst
Regarding the safety of the regimen, is there a greater and more prolonged myelosuppression than what would typically be expected from the components? Additionally, how are you considering this as we look at the frontline combination, which may involve a different patient population and how myelosuppression could impact them? Thank you.
Michael Metzger, CEO
Thanks for the question. Just continuing on. So well, as the authors themselves conclude, the safety profile is what you would expect from venetoclax and the hypomethylating agent. So there is no, you know, the triplet, you can call it a triplet. It appears to be extremely well tolerated for pre-treated patients. And just going to your point about what does this mean, as we advance the combinations in earlier stage patients, I think it signals good things because if heavily pretreated patients can tolerate the combination, then it is highly likely that less heavily pretreated patients will also tolerate the combination well. So we are encouraged. As I mentioned during my prepared remarks, we are overall, when we look at the data that are evolving, we are highly encouraged by the opportunity to advance revumenib into earlier stage combination therapies.
Operator, Operator
Our next question is from Anupam Rama at JPMorgan. Your line is open. Please ask your question.
Unidentified Analyst, Analyst
Hi, this is a question for Anupam. Thank you for taking it. What additional data are you planning to present at ASH regarding AUGMENT-101 KMT2A compared to what we already know from the top line data? Thank you.
Michael Metzger, CEO
Thank you for the question. As we previously mentioned, we have shared top-line data recently, and we will be presenting at ASH. An abstract that was released today highlights our upcoming presentation at the event. The top-line data provided is just the initial analysis, and we will have further analyses that offer more specific insights into that data cut. While I won’t speculate on the exact details of what we’ll present, there are significant analyses that will give attendees a deeper understanding of what we have previously shared. So, please stay tuned for more information at ASH and during our Investor Day.
Operator, Operator
Our next question is from Chris Shibutani at Goldman Sachs. Your line is open. Please ask your question.
Unidentified Analyst, Analyst
This is Charlie on for Chris. I wanted to follow up on the last question about the same data cut for the AUGMENT-101 presentation at ASH. It seems we will assume the same 57 patients used for the top line results. I'm curious if the FDA, with the ongoing rolling submission, will require the additional 37 patients that were after that data cut.
Michael Metzger, CEO
You are correct, it is the same data cut at ASH. I mean, we are very focused now on getting our NDA filed. And as you noted, under Arthur, we have a pretty rigorous and short timeline to complete the filing by year-end, so it is a rolling submission. The agency has very specifically agreed to our data plan, which is again efficacy on the 57 patients, with safety on the overall 94, which we outlined when we top-lined the data, and confirmed through our pre-IND meeting at our R/R process. So the data will be they see all the data, but there is no new data cut required from an efficacy standpoint and the safety obviously will be submitted as such. So, that is the way to look at it.
Operator, Operator
Our next question is from an indiscernible speaker. Your line is open. Please ask your question.
Unidentified Analyst, Analyst
I just had one on the post transplant setting data you would shared. It seems like you are getting very long durability in terms of patients staying on drug for long periods of time post transplant, which is great. I guess, how are you thinking about the commercial opportunity sort of on average in terms of duration treatment in the context of the post transplant study?
Anjali Ganguli, Chief Business Officer
Thanks for the question. So we have been thinking about and speak to a number of physicians about how they want to use revumenib based on the data we are generating. And they see that there is an opportunity to treat patients in the post transplant maintenance setting. The drug is able to get patients to deep durable responses, and they see no downside for continuing them on therapy after transplant. And the goal, I think, would be to keep them on as long as possible, but the standard today is assumed to be close to two years. Obviously, not every patient will achieve that and not every patient is able to successfully receive a transplant. So, we estimate that conservatively, that duration on average will be close to 18 months.
Unidentified Analyst, Analyst
I guess, a conceptual question on the same topic. What's the decision-making for the physician behind choosing the woman to end treatment in the post transplant setting? Is it disease progression or is there a point at which they kind of determine the benefit, maybe lowering over time, I would say the risk of disease progression? Thanks.
Michael Metzger, CEO
Yes, good question. So, Neil, why don't you comment on it?
Neil Gallagher, President and Head of R&D
Yes. Thanks for the question. As you noted, we are seeing patients actually remaining on the drug for very protracted periods of time. And that says to us that it speaks to the tolerability profile of the drug, which has consistently been very good. The feedback we have obviously talked to investigators and other physicians about this. And they are very keen when we speak with them. First of all, they wanted this option. Just to remind you, they wanted this option in the study. It wasn't there in the earlier part of the study, and we included it in Phase 2, at the request of the investigators. So that is one point. The other point is as we talk to them now, they see themselves keeping patients on for protracted periods of time, right? So, you know, they talk about two years, right, for instance. But in fact, there is evidence to suggest that patients could stay on longer than that as well. So I don't I think as long as patients and remember, these patients are extremely high risk, very heavily pretreated. The KMT2A cohort that we have presented, that we reiterated today, very heavily pretreated. And therefore, there is no, the way the physicians are looking at it is why take the risk the patients are. The drug is getting the patients into response, getting the patients to transplant, well tolerated and therefore the patients can go back on it after transplant. Why not just keep the patients on the drug? That is the feedback that we are getting.
Operator, Operator
Our next question is from Phil Nadeau at TD Cowen. Your line is open. Please ask your question.
Phil Nadeau, Analyst
A couple of questions from us. First, congrats on the 36% CR/CRH trait with the 3 additional patients. In terms of the pivotal trial in NPM1 for revumenib, can you discuss in a bit more detail what's the implications of the 16% of enrollment coming out of Israel? Is it that there is a chance that those patients will be lost to follow-up or the data will be lost? How does that impact the timelines and the number of patients that you need to enroll?
Michael Metzger, CEO
Yes. Thanks for the question, Phil. Look, I think it is an unfortunate set of events going there. Our trial sites are still up and running in Israel, data is centralized, so we have obviously good control over the data, not the issue. The implications, we think are a little bit hard to predict, but we have a lot of other sites that we are doing quite well with enrollment elsewhere. And so, I think that is something we feel very confident we can pick up and complete the trial by the end of the first quarter or very early in the second quarter. So it is something that is a little bit unfortunate, but these as I said or as Neil said in the remarks, these are typically high enrolling sites and it was just a little bit unfortunate. But we feel very confident that we will be able to get it done on time.
Phil Nadeau, Analyst
And then a follow-up question on the SAVE trial. I believe the abstract said that enrollment continued in SAVE and additional on it or updated data will be presented at the meeting. What can we expect in terms of patients at dose level one at ASH? I think there were two in the abstract. Would there be another four at ASH or could dose level one enroll beyond the 6 that were enrolled at dose level zero?
Michael Metzger, CEO
Yes. Phil, thanks for the question. It is a little bit hard to answer at this point. I think they are continuing to enroll at that dose level, and as you know, there are only a few that were enrolled so far. The results have been quite strong and striking. So they are looking forward to expanding that to additional patients and that will be obviously presented at ASH in the presentation. But I can't give you specific numbers on how many patients will be expanded to; I just don't have that detail.
Operator, Operator
Our next question is from Jason Zemansky at Bank of America. Your line is open. Please ask your question.
Unidentified Analyst, Analyst
Hi. This is Jason Zemansky. Thank you for taking my question. What kind of data do you believe is necessary before the community can start to feel confident about revumenib's compatibility profile? What do we need to observe regarding both safety and efficacy?
Michael Metzger, CEO
I believe the data we've generated so far, both as a standalone treatment and in NPM1 and KMT2A, strongly supports our expectations for the contribution of components when combining drugs, such as in conjunction with chemotherapy. We are very confident that we have leading monotherapy data, which provides a solid foundation. When it comes to combinations, it's essential to ensure these drugs are combined safely and effectively. Achieving full monotherapy doses within a combination is crucial. The recent SAVE trial data reinforces this. At the upcoming ASH conference, we will present information on the BEAT-AML trial, which involves frontline patients, alongside the SAVE trial, which focuses on relapsed refractory patients. The BEAT-AML trial looks at newly diagnosed patients, emphasizing the importance of safely administering patients the full monotherapy dose while also achieving response rates that meet or exceed those seen in doublet therapies. Additionally, minimal residual disease negativity plays a significant role in how physicians choose to treat their patients. We have demonstrated profound and lasting responses marked by MRD negativity, which we will also evaluate in these combinations, even in cases where patients do not achieve full MRD negative status. These are the areas we will focus on, and we anticipate having significant data by the end of the year to clarify our findings.
Operator, Operator
Our next question is from Peter Lawson at Barclays. Your line is open. Please ask your question.
Peter Lawson, Analyst
Just do you have enough data now to file for a breakthrough designation and we can update this data at the Investor Day. And then, are patients going on to transplant and could that cause a downdraft in the CR, CRH rate in a pivotal trial?
Michael Metzger, CEO
Yes, Peter, thank you. You had a couple of different questions. One was about whether patients are going to transplant, particularly NPM1 patients. The answer is yes, as evidenced in our slides; three out of the 14 patients went to transplant, while many others remain on treatment and in remission, which is an important observation. It’s also noteworthy from the pivotal trial for KMT2A, where some patients who didn't achieve complete count recovery were taken to transplant relatively quickly. This affected our CR/CRH rate, which could have been as high as 37% if all these patients had converted without going to transplant so soon. These patients tend to be less fit compared to KMT2A's younger population. The data shows we are not seeing patients at CRP or incomplete hematological recovery points. Instead, all our patients are CR/CRH and MRD negative, with some going to transplant. This suggests that timing may impact achieving full potential for CR/CRH as an NPM1 patient. We don't believe this will significantly affect the Phase 2 results. In fact, the CR/CRH rates might align more closely with our current findings in the mid-30s or higher for NPM1; we’ll have to see what the data reveals. We think the treatment timeline for taking patients to transplant won't hinder us as it did for KMT2A. We will provide an update, and we may have more to share at our investor event on NPM1, but we wanted to present the available data today. We haven’t finalized what else we will analyze for our R&D or Investor Day around ASH. Regarding obesity, as we've mentioned before, about 20 to 30 patients at the RP2D are needed to file for breakthrough therapy designation. Currently, we have 14 patients at the RP2D, so we do not expect to make that application yet. However, it remains an option relative to our upcoming pivotal data.
Operator, Operator
Our next question is from Michael Schmidt at Guggenheim. Your line is open. Please ask your question.
Michael Schmidt, Analyst
In the NPM1 cohort, how many patients had overlapping co-mutations, other genetic alterations and potentially have had received other target agents prior to receiving revumenib and how do you expect that dynamic to play out in the pivotal cohort and ultimately on the market?
Michael Metzger, CEO
Michael, thanks for the question. So we didn't break out that data in the swimmer's lane, but I will tell you, as you noted in the, we did say that a lot of obviously, a lot of prior therapy for these patients. In terms of co-mutations, I think the vast majority, if not all, were co-mutated. So, there were obviously, there are variations on the theme of what we saw, but we didn't break that out. But I think, suffice to say, we had most patients were co-mutated. Yes, and it is obviously representative of what you would think.
Michael Schmidt, Analyst
And in order to how does that affect potential sequencing of therapies? Should the data be replicated in your pivotal study, if approved, in your opinion?
Michael Metzger, CEO
Yes. I think what you are getting at is whether or not physicians will look at targeting these specific mutations for treatment. And obviously, the paradigm for NPM1, at least in the unfit population or the fit population, they get chemo or they get Venetoclax upfront and then physicians look to target their mutations with either a FLT3 or an IDH inhibitor. And we do expect that if these patients have those co-mutations, that is what's going to happen in the real world and in trial as well. So, that is what ends up resulting, and I think the remarks that I made suggest this; that physicians will be reaching for second or third line revumenib after they have taken action against obviously frontline and then they are going after their targeted mutation to the extent they have one. So, I think the data that we presented today shows that, right? It shows that patients do extremely well treated in, call it, the 3rd line, 4th line setting on our drug, and as they progress and get into very, very late lines of therapy, which we have had some patients also like that, they don't do as well. So I think the targeting of these mutations will likely come before revumenib.
Operator, Operator
Our next question is from Kalpit Patel at B. Riley. Your line is open. Please ask your question.
Kalpit Patel, Analyst
Maybe a couple more questions related to the maintenance use of revumenib. Now that you have all the post transplant data here, how are you seeing the median duration of treatment for revumenib between the KMT2A populations and the NPM1 populations? Do you expect them to be very similar to each other?
Michael Metzger, CEO
Yes, I think we do think it is going to be very similar. It is interesting how the data converges a bit. So you have patients in the KMT2A population that a great percentage go get a high, overall response rate, get taken to transplant and put back on drug and stay on drug and do very, very well. The speed at which they get a best response first and best response and then move to transplant is noteworthy in KMT2A. It is a beat slower with NPM1, which probably allows their counts to recover, as I mentioned earlier. But the paradigm seems to be similar. At least in relapsed refractory disease, where physicians are interested in putting them back on, once you get to a CR, you take them to transplant and you put them back on drug. I think that is also new and it is a new paradigm, but it is actually a very positive pattern for the drug in terms of the ability to treat patients for a long time and keep them in remission. So we are actually very encouraged by what we are seeing, both from the efficacy standpoint and the tolerability and safety standpoint to allow this to be the new paradigm. So it is quite interesting how it has turned out to be pretty similar.
Kalpit Patel, Analyst
It is nice to see the additional responses in the NPM1 patient population. I'm just curious if you have any more NPM1 patients after that, I believe July cutoff in that data in that Phase 1?
Michael Metzger, CEO
We do not; this is final data in terms of patients that is all we have. We were looking to complete the pharmacokinetic work in the Phase 1, and we had talked about that in the past, and these were the remaining patients to accomplish that.
Operator, Operator
Our next question is from Justin Zelin at BTIG. Your line is open. Please ask your question.
Justin Zelin, Analyst
Hi, thanks for taking the question and congrats on the progress here. Maybe a question just on the SAVE AML study, I think the abstract showed there wasn't much differentiation syndrome seen here. Can you comment on whether you would expect differentiation syndrome to be reduced in the combination setting moving forward? Thank you.
Michael Metzger, CEO
Yes, thanks, Justin. The answer is yes. I mean, the data, as we have discussed, are highly encouraging. And I think that clearly, the combination with venetoclax and the hypomethylating agent is extremely well tolerated. So there is no reason to speculate that we would see a different pattern as we advance, for instance, as we advance combinations of hypomethylating agents into earlier lines therapy. So I think it is both expected and gratifying to see.
Justin Zelin, Analyst
Thanks. And congrats again on the plenary for axatilimab. Anything additional we should look out for at ASH beyond what we saw at the top line?
Michael Metzger, CEO
Justin, I think, yes, thank you. We obviously have the plenary for axatilimab, which is very exciting. I think we had five abstracts out today, so a lot of information saved, as we talked about, but also some of the combinations. And so, yes, just a lot of interesting information coming your way and obviously, we will have lots to say at our event at ASH as well. So, looking forward to seeing everybody there.
Operator, Operator
Our next question is from George Farmer at Scotiabank. Your line is open. Your line is open. Please ask your question.
George Farmer, Analyst
Hi, good afternoon. Thanks for taking my question. Neil, you mentioned that the 6.4 month DOR in the AUGMENT-1 trial could get better. I'm wondering if it is possible it could get worse? We haven't seen any Kaplan-Meier curves, so just wondering what your thoughts are there. And then also in the SAVE trial, alluded to a previous question about the myelosuppression. Wondering if those patients got any growth factor support and if growth factors were effective. Perhaps maybe revumenib had an impact on recovery or anything like that, if you could comment. Thanks.
Michael Metzger, CEO
So, with respect to the first question, we have modeled it out in our there is a bit of noise in the line, but with respect to you know, our expectation is that, the median DOR can extend over time with additional follow-up. Right? So we have modeled that out, running various, sorry, I'm blanking on the word. But statisticians have modeled it out looking at various different scenarios. And we see multiple different scenarios under which the median DOR could extend over time. The, to the second point, not to the best of my knowledge with respect to stem cell or with respect to growth factor support. You know, that is not our understanding.
George Farmer, Analyst
Okay, great. And then 1 more if I could on axatilimab. The IPF study, can you just speak kind of high level about the design of that trial?
Michael Metzger, CEO
Sure. I will take that. Yes. As Michael said, in his remarks, it is randomized Phase 2. It is randomized 135 patients is the target sample size, randomized two to one, active axatilimab to placebo, on a background of best supportive care. So very succinctly, that is the study design. We think that it is an efficient way to address the proof of concept question.
George Farmer, Analyst
Is that a six-month study, 52 weeks?
Michael Metzger, CEO
26 weeks. That is right, 26-week primary endpoint analysis.
Operator, Operator
Our last question is from Joel Beatty at Baird. Your line is open. Please ask your question.
Unidentified Analyst, Analyst
This is Ben on for Joel. Thanks for taking the question. What gives you confidence that payers would support or cover post-transplant maintenance for revumenib therapy since it is not in the FDA label?
Michael Metzger, CEO
Well, look, I think the experience physicians have in treating patients for AML and providing abatement treatment to those patients who again are at high, high risk of relapse, that seems to be a very important treatment decision, granted, it is given by the or taken by the physician. And none of these relapsed refractory agents that had been approved have a maintenance label. So it is a sort of a tried-and-true experience with other agents that gives us confidence that this is something that physicians can do and payers will abide by. I think there is a pharmacoeconomic analysis, of course, that supports this; these are not inexpensive therapies, but these are very seriously ill patients who aren't able to get to a steady state. And so, if you can keep them in remission for a long period of time and keep them out of the hospital, that is a very positive driver for any payer. So I also mentioned that this kind of experience can get into the guidelines and you see it in the guidelines as well. And so payers tend to abide by those guidelines in making the reimbursement decision. So I think that all kind of factors into the value when we hear from physicians that they do this and they have very little intervention from payers to stop this from happening, there seems to be a supportive setup. So, that is what I can tell you.
Operator, Operator
That completes the Q&A section of the call. I will now hand back to Michael for closing remarks.
Michael Metzger, CEO
Thank you, operator. Thank you all. We appreciate you tuning in tonight and we look forward to seeing you at our planned investor events including The Cowen Fall Oncology Summit tomorrow and the Stifel Conference on November 14th, as well as the ASH meeting in December.