Syndax Pharmaceuticals Inc

NASDAQ:SNDX

Earnings Call Analysis

Syndax Outlines Financial Path and Trials

Syndax Pharmaceuticals projects an addressable U.S. market for revumenib of $1-1.5 billion, with domination expected in the relapsed/refractory acute leukemia market by 2025. The AGAVE-201 trial for axatilimab revealed a 74% response rate in chronic GVHD patients, setting a baseline for a potential BLA filing by year's end. Financially, Q3's net loss increased to $51.1 million, up from last year's $35.4 million, due to higher personnel and clinical costs. Despite this, $379.3 million in reserve supports plans for a commercial transition in 2024 and R&D plus other operating expenses are forecasted between $160-$165 million and $225-$230 million respectively for the full year of 2023.

Continued Progress and Upcoming Milestones

Despite the challenges presented during the year, Syndax has continued to advance its pipeline and is on the cusp of transitioning into a commercial-stage biopharmaceutical firm with two front-running products. They've delivered key pipeline milestones, evidenced by reporting positive pivotal data for axatilimab and revumenib, the latter for the treatment of acute leukemia with KMT2A rearrangement. Syndax is gearing up for a year-end submission of regulatory filings, targeting drug launches in 2024, and establishing a significant presence at the American Society of Hematology (ASH) Annual Meeting.

Advancing Revumenib Through Real-time Oncology Review

Syndax has initiated the NDA submission for revumenib under the FDA's real-time oncology review (RTOR) program. This approach reflects the drug's meaningful clinical potential, promising an expedited process by continuous cooperation with the FDA. With positive outcomes from AUGMENT-101 and collaboration with Incyte, Syndax aims for concurrent BLA filing for axatilimab. These efforts underscore Syndax's robust financial position, with $379 million in cash to support launches and future growth initiatives.

Impressive Clinical Data Reinforcing Revumenib's Potential

The AUGMENT-101 pivotal data shows exceptional results for relapsed or refractory acute leukemia patients with KMT2A rearrangement. Approximately two-thirds of subjects achieved significant responses, with many progressing to potentially curative transplants. Furthermore, an impressive 63% response rate shows revumenib's tolerability and effectiveness, which is promising for its incorporation into frontline treatment combinations.

Promising Data for NPM1 Mutated Acute Myeloid Leukemia

Latest findings from the AUGMENT-101 trial for NPM1 mutated relapsed/refractory acute myeloid leukemia (AML) patients have been favorable, with a 50% overall response rate and the potential for post-transplant maintenance therapy. This evidence strengthens Syndax's conviction that revumenib could become a key treatment option for NPM1 AML, aligning with anticipated approval based on NPM1 pivotal trial results.

Expansion and Collaboration to Broaden Revumenib's Impact

Syndax aims to position revumenib as a fundamental treatment across various clinical settings of acute leukemia. They are actively engaging with cooperative groups and leading investigators to further this goal and will present initial data from collaborative trials like BEAT AML and AUGMENT-102 at the ASH event. This comprehensive approach exemplifies their commitment to optimize revumenib's clinical benefits and potentially revolutionize treatment standards.

Market Potential and Strategic Positioning

With no FDA-approved targeted therapies for KMT2A and NPM1 acute leukemias, Syndax is targeting a significant market opportunity, estimated between $650 million to $750 million in the U.S. alone. Based on the potential efficacy and safety of revumenib, along with a first-mover advantage and enthusiastic feedback from physicians, Syndax anticipates building a strong therapeutic franchise over the coming years. Moreover, the compelling clinical data presented for NPM1 adds to the prospects of revumenib becoming a leading treatment in AML.

Earnings Call Transcript 2023-Q3

[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'd like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

[Sharon Klahre, executive]

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'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 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 made 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 am pleased to turn the call over to Michael Metzger, Chief Executive Officer, Syndax.

[Michael Metzger, executive]

Thank you, Sharon, and thank you to everyone joining us on 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've 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 2 potentially first and best-in-class products.We are also happy to provide data today from additional relapsed 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 22months, 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 2 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 are accepted for review into 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 30th. 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 menin inhibitor. I'll 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 1 portion of the AUGMENT-101 trial. Neil?

[Neil Gallagher, executive]

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 the trial 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 2/3 of these heavily pretreated patients achieved clinically significant responses, enabling many to receive potentially curative transplant.Importantly, high proportion of responders in the trial were started on revumenib in the post-transplant maintenance setting. The desire for physicians to restart revumenib's post-transplant maintenance speaks to its efficacy and tolerability and the 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 combination.Turning to Slide 5. The majority of patients in the efficacy-evaluable population, which include adult and pediatric AML and ALL patients achieved 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 is 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 6 patients remaining in response. Of note, this is a Kaplan Meier estimate and the data will continue to mature over time. Therefore, the median DOR 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 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 a best response of 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 a 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 8 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 ability 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 we'll highlight revumenib for post-transplant maintenance, including patients on therapy in remissions 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 will be forthcoming later this year.Turning to Slide 7. Today, we announced encouraging data from 3 additional patients with NPM1 mutated relapsed/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, 7 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 4 or 5 of the patients remaining in response, 3 already beyond 6 months, 1 beyond 22 months and 1 over 30 months 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 have 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 to its KBT2A population, revumenib was tolerated in patients with relapsed/refractory NPM1 AML. There were no Grade 4 or 5 QT prolongations, no patients experienced more than Grade 2 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 from 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 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 forward to looking to make up for any potential shortfall at our sites, but it's difficult for us to predict the impact that the evolving geopolitical situation you may have an 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 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. Ghayas 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 Counter Center, evaluating an all-oral combination of revumenib with venetoclax and a fixed-dose combination ofDecitabine 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, 8 patients with either NPM1 KMT2A or NUP98 mutations were enrolled in the trial, having received 2.5 median prior lines of therapy. Approximately 2/3 of patients received prior venetoclax. All patients on a strong CYP3A4 inhibitor were on a strong CYP3A4 inhibitor and were therefore treated with revumenib and an either 113 milligrams Q12 early or 163 milligrams Q12 R. 7 of 8 patients were evaluable for response. All 7 100% achieved a response. Six of 7 achieved the CRC and 2 of 7 -- 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 2 continue in remission and have started maintenance as of the data cutoff.We are highly encouraged by the combinability of revumenib with venetoclax and hypomethylating agents in this trial. This combination was well tolerated by active doses, including the current monotherapy RP2D.I'll now turn the call back to Michael.

[Michael Metzger, executive]

Thank you, Neil. 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 relapse 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 cooperative 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 1 BEAT AML trial is part of our collaboration with Leukemia and Lymphoma Society and revumenib is being combined with venetoclax and azacytidine 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 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 and combination with standard salvage chemotherapies for patients with relapsed 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 7+3 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've laid out here, we are enrolling a proof-of-concept signal-seeking Phase 1 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 an 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 of 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 relapsed 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.KMT2Arearrangements represent approximately 10% of AML and ALL, which translates into an incidence of approximately 2,600 KMT2Arearranged acute leukemia patients, a very high percentage of whom are refractory to frontline standard of care treatment.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 9 months, and we believe 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 would be slightly larger than relapsed/refractory KMT2A cube leukemia population. And based on our Phase 1 results, we also believe overall efficacy and treatment duration will be consistent between the KMT2A and NPM1 population.Having first-mover access 2 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 CSF-1 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 2 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 3 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 1 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 trial, both of which targeted patients with chronic GVHD who had received 2 or more prior lines of therapy.Notably, patients in the AGAVE-201 trial had a longer median time since diagnosis more severe chronic GVHD and had received more prior lines of therapy, including a greater number of patients have received Jakafi than patients included in the REZUROCK trial.We believe these points of differentiation underscore just 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 CSF-1R 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 planar session at ASH.Turning to Slide 13. Approximately 14,000 U.S. patients suffer from chronic graft versus host disease 50% of who 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 supports moving axatilimab earlier in the treatment paradigm to potentially prevent organ damage before it occurs.Because axatilimab as an antibody, drug-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.I will now turn the call over to Keith to review our financial results. Keith?

[Keith Goldan, executive]

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'd like to point out that our net loss for the third quarter 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 in the third quarter with $379.3 million in cash, equivalents and short and long-term investments and 69.9 million shares and 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'd 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, executive]

Thank you, Keith. Before we open the call for questions, I'd like to provide a summary of what was presented today. In the near term, we remain laser-focused on delivering quality 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 quickly 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 which 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 would like to open the call for questions. Operator?

[Operator]

[Operator Instructions] Our first question is from Brad Canino at Stifel.

[Bradley Canino, analyst]

Looking forward to ASH. I have a 2-parter on the SAVE trial, actually, the all-oral triplet where you had the abstract. I guess first, when you speak to AML physicians, do you get the sense they're looking to use off-label combinations in the relapsed/refractory 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, et cetera? And then I have a follow-up.

[Michael Metzger, executive]

Yes. Brad, thanks for the question. I'm going to ask Neil to make a comment.

[Neil Gallagher, executive]

Yes. Look, thanks for the question. Obviously, this is a preliminary dose ranging, and there's more work to be done. We see the value and 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 hypomethylating agent, I think, is very important. And the study is ongoing with revumenib being administered at full dose in CL1, as was mentioned in the abstract.The other thing to bear in mind is that historically, if you look at this population, they're quite heavily pretreated. Most of them have actually failed venetoclax hypomethylating agent. And one would expect the response rate, therefore to venetoclax plus an HMA to be quite low, actually probably less than 10%. And here, we're seeing much, much higher response rate from a 28% CR/CRh rate. So this is incremental progress, albeit based on early data, incremental progress for those patients.

[Bradley Canino, analyst]

And then the second...

[Neil Gallagher, executive]

You said you had a second question.

[Bradley Canino, analyst]

Yes. On the safety for the regimen, I guess, is this higher in more prolonged myelosuppression than would be expected from the components? And then how are you thinking about this, too, as we think about the frontline Ven/Aza combo that might be a different patient population in terms of how myelosuppression might affect them?

[Neil Gallagher, executive]

Yes. Thanks for the question. Just continuing on. So well, as the authors themselves conclude, the safety profile is what you would expect from Ven and the hypomethylating agent. So the triplet, we can call it a triplet, appears to be extremely low tolerates, right? I don't have a pretreated patients. And I'm 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, right? Because if heavily pretreated patients can actually 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're -- overall, when we look at the data that are evolving, some of the data that we've presented today, we're highly encouraged for the opportunity to advance revumenib into earlier-stage combination therapies.

[Operator]

Our next question is from Anupam Rama at JPMorgan.

[Unknown Analyst]

This is actually [ Malcolm Cuno ] on for Anupam. What additional data are you planning to present at ASH on AUGMENT-101 KMT2A versus what we already know from the top line data?

[Michael Metzger, executive]

Yes, Malcolm, thank you for the question. So as we had previously said and I think we said in the remarks, obviously, we've presented top line in in recent days. And we'll be at ASH. We have an abstract that came out today that explains that we'll have a presentation at ASH at our investor event. I think the data that's been top line is the data cut, but we'll have additional analyses that I think go into more specific detail around that particular data cut. And not to speculate specifically around what we're going to present. But I think there are some important analyses that will allow people to get an even deeper feel from what we presented previously. So stay tuned, but we'll have, obviously, more data at ASH and then again at our Investor Day.

[Operator]

Our next question is from Chris Shibutani at Goldman Sachs.

[Unknown Analyst]

This is Charlie on for Chris. Just to kind of follow up on the last question, wondering we have the same data cut for the AUGMENT-101 presentation at ASH. So it sounds like we're going to assume the same 57 patients that we had for the top line results. Just wondering with the rolling submission with the FDA currently, are they going to be looking for those additional 37 patients that are after that data cut?

[Michael Metzger, executive]

Yes, Charlie, thank you. You're correct. It is the same data cut at ASH. I mean we're very focused now on getting our NDA filed. And as you noted, under RTOR, we have a pretty rigorous and short time line 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 toplined the data and confirmed through our pre-IND meeting beginning our RTOR process. So the data will be -- they see all the data, but there's no new data cut required from an efficacy standpoint and the safety, obviously, will be submitted as such. So that's the way to look at it.

[Operator]

Our next question is from Yigal Nochomovitz.

[Ashiq Mubarack, analyst]

This is Ashiq Mubarack on for Yigal. I just had one on the post-transplant setting data you shared. It seems like you're getting some 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 of treatment in the context of the post-transplant?

[Michael Metzger, executive]

Yes, Ashiq, thanks for the question. I'm going to turn it over to Anjali to answer that, please.

[Anjali Ganguli, executive]

Thank you so much for that question. So we've been thinking about and speaking to a number of physicians about how they want to use revumenib based on the data we're generating. And they see that there's 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 the month therapy after transplant. And the goal, I think, would be to keep them out as long as possible, but the standard today is assumed to be close to 2 years. Obviously, not every patient will achieve that, and not every patient is able to successfully receive a transplant. And so we estimate that conservatively that duration on average will be close to 18months.

[Ashiq Mubarack, analyst]

I guess, a conceptual question on the same topic. What's the decision-making for the physician behind choosing when to end treatment in the post-transplant setting? Is it disease progression? Or is there a point in which they kind of determine the benefit maybe lowering over time, or let's say the risk of disease progression?

[Michael Metzger, executive]

Yes. Good question. So Neil, why don't you comment on that?

[Neil Gallagher, executive]

Yes. Thanks for the question. As you noted, we're seeing patients actually remaining on the drug for very protracted periods of time. And that's to us that it speaks to the tolerability profile of the drug, which has consistently been very good. The feedback, we've 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's 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 they talk about 2 years, right, for instance. But in fact, there's evidence to suggest that patients could stay on longer than that as well. So I think as long as patients -- and remember that these patients are extremely high risk, very heavily pretreated. The KMT2A cohort that we reiterated today, very heavily pretreated. And therefore, the way the physicians are looking at it is why take the risk 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's the feedback that we're getting.

[Operator]

Our next question is from Phil Nadeau at TD Cowen.

[Philip Nadeau, analyst]

A couple of questions from us. First, congrats on the 36% CR/CRh rate 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 there's a chance that those patients be lost to follow-up or the data will be lost? How does that impact the time lines and the number of patients that you need to enroll?

[Michael Metzger, executive]

Yes. Thanks for the question, Phil. Look, I think it's 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. It's not the issue.The implications, we think, are a little bit hard to predict, but we have a lot of other sites that we're doing quite well with enrollment and elsewhere. And so I think that's 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's something that's a little bit unfortunate, but these -- as I said or and Neil said in the remarks, these are typically high rolling sites, and it was just a little bit unfortunate. But we feel very confident that we'll be able to get it done on time.

[Philip Nadeau, analyst]

And then a follow-up question on the SAVE trial. I believe the abstract said that enrollment continued in SAVE, and additional or updated data will be presented at the meeting. What can we expect in terms of patients at dose Level 1 at ASH? I think there were 2 in the abstract. Would there be another for ASH? Or could dose Level 1 enroll beyond the 6 that were enrolled at dose levels there?

[Michael Metzger, executive]

Yes, Phil, thanks for the question. It's a little bit hard to answer at this point. I think they're continuing to enroll at that dose level. As you know, there are only a few that were enrolled so far. The results have been quite strong and striking. So they're looking forward to expand 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 the detail.

[Operator]

Our next question is from Jason Zemansky at Bank of America.

[Unknown Analyst]

This is [ Alex Hanna ] for Jason Zemansky. What sort of data do you think is necessary before the community can start to feel confident about revumenib's commutability profile? What do we need to see in terms of both safety and efficacy?

[Michael Metzger, executive]

Yes, thanks for the question. Well, look, I think the data that we generated to date, both as a monotherapy and now in NPM1 and for KMT2A really is a good source or I should say, it underpins well what we would expect to see as a contribution of components, right? When you think about combining drugs such as with Ven/Aza and with chemotherapy.So we feel very confident that we have best-in-class monotherapy data, and that's a good starting point. With combinations, first things first, and Neil made comments about this, you need to be able to combine these drugs safely and effectively. But full dose monotherapy dose getting to those levels in a combination is extremely important. And the SAVE information, the SAVE trial information that came out today really supports that. We'll have data at ASH for the BEATAML trial, which is frontline patients, the SAVE trial were -- that's in relapsed/refractory patients. But BEATAML is in newly diagnosed patients and the opportunity to not only safely dose patients, but dose them at the full monotherapy dose. As well as drive response rates as you'd hope to be as good or better than what they see in the doublet. That's what we're looking for.And I would also say, MRD negativity is a big driver of physician choice and how they think about treating their patients. We've been able to show deep durable responses signaled by MRD negativity, and that's something we'll look at in these combinations as well where patients are not necessarily getting to full MRD-negative status. So those are the types of things that we'll look for and we expect to have meaningful data for the end of the year to kind of elucidate all that.

[Operator]

Our next question is from Peter Lawson at Barclays.

[Peter Lawson, analyst]

Thanks for the update for the NPM1 patients. Just do you have enough data now to file for a breakthrough designation and we get an 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, executive]

Yes. Peter, thank you. So I think you had a couple of different questions here. One was taking it in reverse order here. So do we see patients go to transplant? I think the answer on NPM1 patient, I think the answer is obviously yes. You see that in the swimmers lane that we have on our slides as well as we mentioned in the remarks. So patients are going to transplant 3 of the patients of the 14 went to transplant, and many of them are staying on treatment for and also in remission. So I think that is an important fact pattern.Also important to note are what we saw in the pivotal trial for KMT2A, and Neil mentioned in his remarks, the number of patients who didn't reach complete count recovery, so it didn't reach CR/CRh's best response. And we're taking the transplant very quickly. That actually ended up penalizing us a bit on the CR/CRh rate. And as Neil remarked, it could have been as high as 37%, if all those patients had converted and they didn't go to transplant as quickly. What we're seeing with NPM1 is the treatment course is a little bit slower in terms of taking patients to transplant. So these patients are also not necessarily as fit as what you'd see with KMT2A with younger patients. So we're actually not seeing if you look at the data, we're not seeing patients at CRP or incomplete hematological recovery points. And so what you're seeing is all of our patients are CR/CRh and MRD negative and some of them are going to transplant. So it just tells you the time course probably has an impact in terms of reaching your full potential for CR/CRh as an NPM1 patient.So we don't think actually that's going to meaningfully impactful in the Phase 2. In fact, we see it as the opposite. We see that the CR/CRh could actually be more reminiscent of what we're seeing now, which in the mid-30s or higher. On NPM1, we'll have to see what the data bears out. But we don't think that same treatment paradigm in terms of the speed at which physicians take their patients to transplant is going to penalize in the same way for us on the CR/CRh and KMT2A.We will have an update. This is the data. We may have some more to say at our investor event on NPM1, but this is the data that we have in hand. And so we wanted to get it, obviously, out to you today. But we haven't really bottomed out on what else we would analyze for our R&D Day for our Investor Day for in and around ASH.And maybe there was another question on [ obesity ].

[Peter Lawson, analyst]

Yes, [ for obesity, right ].

[Michael Metzger, executive]

Right, Peter. Thank you. So look, I think we've said in the past, you need approximately 20 to 30 patients at the RP2D to file for breakthrough therapy designation. As you see here, this is 14 patients at the RP2D. So right now, we don't expect that we would be able to make that application. Obviously, that's something that's open to us at some point in time relative to our pivotal data, which is obviously coming. So that's it. Thank you.

[Operator]

Our next question is from Michael Schmidt at Guggenheim.

[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, executive]

Yes, Michael, thanks for the question. So we didn't break out that data in the simmers lane. But I'll tell you, as you noticed 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 obviously, there's 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's obviously representative of what you would think.

[Michael Schmidt, analyst]

Okay. And in order to -- how does that affect potential sequencing of therapy should the data be replicated in your pivotal study, if approved, in your opinion?

[Michael Metzger, executive]

Yes, I think what you're 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 and they get Ven/Aza upfront. And then physicians look to target their mutations with either FLT3 or an IDH inhibitor. And we do expect that if these patients have those co-mutations, that's what's going to happen in the real world and in our trial as well. So that would end up resulting and I think the remarks that I may suggest this that physicians will be reaching for second or third-line revumenib after they've taken action against, obviously, frontline and then after they're going after their targeted mutations 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 third line, fourth line setting on our drug. And as they progress and get into very, very late lines of therapy, which we've 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]

Our next question is from Kalpit Patel at B. Riley.

[Kalpit Patel, analyst]

Congrats on all the updates today. Maybe a couple of 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 population and the NPM1 population? Do you expect them to be very similar to each other?

[Michael Metzger, executive]

Yes. Kalpit, thank you for the question. Yes, I think we do think it's going to be very similar. It's interesting how the data converges a bit, right? So you have patients in the KMT2A population that great percentage go get a response 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's a beat slower with NPM1, which probably allows their accounts to recover as I mentioned earlier. But the paradigm seems to be similar, right? 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's also new, and it's the new paradigm, but it's actually a very positive fact pattern for the drug in terms of the ability to treat patients for a long time and keep them into remission.So we're actually very encouraged by what we're seeing both from the efficacy standpoint and the tolerability and safety standpoint to allow this to be the new paradigm. So it's quite interesting how it's turned out to be pretty similar.

[Kalpit Patel, analyst]

Okay. And then it's 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 cut off in that Phase 1?

[Michael Metzger, executive]

Yes. Thanks for the follow-up. We do not. That is it. This is the final data in terms of patients. That's 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 are the remaining patients to accomplish that.

[Operator]

Our next question is from Justin Zelin at BTIG.

[Justin Zelin, analyst]

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'd expect differentiation syndrome to be reduced in the combination setting moving forward?

[Neil Gallagher, executive]

Yes. Thanks, Justin. The answer is yes. I mean the data, as we've discussed the data are highly encouraging. And I think that cure combination with Ven/Aza, revumenib with Ven and hypomethylating agent is extremely well tolerated. So there's no reason to suspect that we would see a different pattern as we advance for instance, as we advance combinations of Ven and hypomethylating agents into early lines of therapy. So I think it's both expected and gratifying to see.

[Justin Zelin, analyst]

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, executive]

Justin, I think yes, thank you. We obviously have the plenary for axatilimab, which is very exciting. I think we had 5 abstracts out today. So a lot of information saved as we talked about, but also some of the combinations. And so we -- yes, just a lot of interesting information coming your way. And obviously, we'll have a lot to say at our event at ASH as well. So we're looking forward to seeing everybody there.

[Operator]

Our next question is from George Farmer at Scotiabank.

[George Farmer, analyst]

Neil, you mentioned that the 6.4-month DOR in the AUGMENT-1 trial could get better. I'm wondering if is it possible it could get worse. We haven't seen any capital minor curve 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?

[Neil Gallagher, executive]

Sure. Thanks for the question. So with respect to the first question, we've modeled it out and there's a bit of noise in the line. But with respect to our expectation is that the median DOR can extend over time with additional follow-up, right? So we've 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. To the second point, not to the best of my knowledge with respect to stem cells are with respect to growth factor support, that's not our understanding.

[George Farmer, analyst]

And then one more, if I could, on axatilimab. The IPF study, can you just speak kind of high level about the design of that trial?

[Neil Gallagher, executive]

Sure. I'll take that. Yes. As Michael said in his remarks, it's a randomized Phase 2. It's randomized 135 patients to target sample size randomized 2:1 active axatilimab to placebo on background of best supportive care. So very succinctly, that is the study design. We think that it's an efficient way to address the proof of concept question.

[George Farmer, analyst]

Is that a 6-month study, 52weeks?

[Neil Gallagher, executive]

26 weeks. That's right. 26-week primary endpoint analysis.

[Operator]

Our last question is from Joel Beatty at Baird.

[Unknown Analyst]

This is Ben on for Joel. What gives you confidence that payers would cover post-transplant maintenance revumenib therapy, if not in the FDA label?

[Michael Metzger, executive]

Yes. Thanks for the question. Well, look, I think the experienced physicians have in treating patients for AML and providing maintenance treatment to those patients who, again, are at high, high risk of relapse. That is seems to be a very important treatment decision given by the or taken by the physician. And none of these relapsed/refractory agents that have been approved have a maintenance label. So it's 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's 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's a very positive driver for any payer.So I'll also mention 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 there are multiple factors in support of this paradigm. And I also mention that these are rare diseases. And so payers not one payer is impacted dramatically or disproportionately, I should say, by a high-priced therapy being given over an extended period of time.So I think that all kind of factors into the fact -- 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's what I can tell you.

[Operator]

That concludes the Q&A section of the call. I will now hand back to Michael for closing remarks.

[Michael Metzger, executive]

Yes. 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 that we talked a lot about today.So with that, I wish you a great evening. Thank you so much.