Syndax Pharmaceuticals Q2 2026 Earnings Call Transcript

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Provided by Quartr
August 4, 2026

Key Takeaways

  • Positive Sentiment: Commercial revenue grew strongly: Revuforj and Niktimvo generated combined second-quarter revenue of $115 million. Revuforj revenue rose 91% year over year to $54.7 million, while Niktimvo collaboration revenue increased 67% to $18.1 million.
  • Positive Sentiment: Revuforj treatment duration is extending, particularly among patients resuming therapy after stem-cell transplant and those who do not undergo transplant. However, new patient starts declined sequentially in the quarter, which management attributed to normal variability, competition, clinical-trial enrollment and patient availability.
  • Positive Sentiment: Niktimvo continues to expand in chronic GVHD: The drug captured approximately one-third of the third-line-plus market within 18 months of launch, with 60%–70% of patients remaining on treatment for at least 12 months. Phase II readouts in idiopathic pulmonary fibrosis and frontline chronic GVHD are expected in the fourth quarter and could open larger markets.
  • Positive Sentiment: The pipeline has several near-term catalysts. Syndax expects additional frontline AML and post-transplant Revuforj data, NUP98 leukemia data and progress toward pivotal trials; it also plans an IND for its CNS-penetrant EGFR inhibitor by year-end 2026 and a 2027 Phase I start for its next-generation menin inhibitor in myelofibrosis.
  • Positive Sentiment: Financial flexibility remains strong: Syndax ended the quarter with $575 million in cash and investments, including net proceeds from a $250 million convertible-notes offering. Management maintained its 2026 R&D and SG&A expense guidance of approximately $400 million and said the company is funded through profitability.
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Earnings Conference Call
Syndax Pharmaceuticals Q2 2026
00:00 / 00:00

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Operator

Good day, everyone, welcome to the Syndax Second Quarter 2026 Earnings Conference Call. Today's call is being recorded. If you'd like to ask a question following the company's prepared remarks, please press star five during the call. At this time, I would like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

Sharon Klahre
Sharon Klahre
Head of Investor Relations at Syndax Pharmaceuticals

Great. Thank you, operator. Welcome, thank you all for joining us today for a review of Syndax's second quarter 2026 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, Steve Closter, Chief Commercial Officer, Dr. Nick Botwood, Head of R&D and Chief Medical Officer, and Keith Goldan, Chief Financial Officer. This call is accompanied by a slide deck that has been posted on the investor page of the company's website. You can now turn to our forward-looking statements on slide two. 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.

Sharon Klahre
Sharon Klahre
Head of Investor Relations at Syndax Pharmaceuticals

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, August 4th, 2026 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
Michael Metzger
CEO at Syndax Pharmaceuticals

Thank you, Sharon. Good afternoon, everyone, thank you for joining us. Starting with Slide three. The Syndax team delivered another quarter of solid commercial results and progress across our growing pipeline of programs targeting areas of high unmet need and substantial commercial opportunity. The business fundamentals are strong. Sales of Revuforj and Niktimvo grew to a combined total of $115 million in the second quarter. Both medicines are now annualizing at well over $200 million each, and we have just started to unlock their multibillion-dollar potential. Revuforj continued to grow by double digits, with net revenue totaling $55 million in the second quarter, up 91% year-over-year and 12% quarter-over-quarter.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

These results highlight our continued leadership in menin inhibition, robust demand in both NPM1 and KMT2A, and the positive impact of an increasing average treatment duration driven by multiple factors, including a growing number of patients on therapy for an extended period after receiving a stem cell transplant. As the number of patients on therapy post-transplant continues to stack, this reoccurring base will be an important driver of long-term compounding growth. Encouragingly, the average duration of treatment is also increasing among patients who are not proceeding to a transplant. As Steve will describe shortly, the positive impact of an extending average treatment duration, which was partially offset this quarter by fluctuation in the number of new patients initiating therapy, one of several drivers of our business. Today, we are even more confident in the forward trajectory and substantial commercial opportunity with Revuforj.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Our conviction is underpinned by the multiple drivers for continued growth, including a best-in-class profile valued by physicians, an increasing average duration of therapy, a broad and expanding prescriber base, and ample opportunity in NPM1, KMT2A, and other menin-dependent acute leukemias. We are well-positioned to extend our leadership in menin inhibition into the future and continue driving innovation for patients. Building on a long history of landmark firsts, we are positioned to be first to frontline AML, driven by strong global site initiation and patient enrollment in our pivotal trials. With future anticipated indications in frontline AML, we expect that Revuforj could reach in excess of $2 billion in peak annual net revenue in the U.S. alone. We have another data-rich period ahead for revumenib.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

In the second half of the year, we will report additional practice-informing evidence from multiple trials at major medical meetings, expanding on the prominent presence we had at ASCO and EHA in June. We also expect to publish data in relapse refractory NUP98-rearranged acute leukemia in the fourth quarter. These results could inform clinical practice and guidelines in a patient population similarly sized to KMT2A. Patients with NUP98 urgently need new treatment options, including therapies that may reduce the risk of relapse after transplant, as is the case with KMT2A. Physician feedback indicates that NUP98 rearrangements are more common than once thought, occurring in perhaps 5% or more of AML cases, translating into potentially 1,000-2,000 pediatric and adult patients with NUP98 annually.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

As the first and only company to report clinical data showing activity with a menin inhibitor in this subtype, we have a unique opportunity to pursue a guideline listing that could meaningfully expand the patient population treated with revumenib. Switching gears to Niktimvo and chronic GVHD. Niktimvo net revenue grew to $60 million in the second quarter, up 67% year-over-year. This performance reflects robust demand and Niktimvo's unique ability to address inflammation and fibrosis. Niktimvo is positioned for further growth with strong adoption in the fourth line and increasing uptake in the third line, driven by a broad base of prescribers who are enthusiastic about the results they've seen in their patients. We also have multiple expansion opportunities and important upcoming catalysts for axatilimab with phase II data in IPF and frontline chronic GVHD expected in the fourth quarter, poised to unlock new multi-billion-dollar opportunities.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Turning to our pipeline assets. At our R&D event last month, we unveiled two innovative assets we are advancing into the clinic, leveraging our world-class R&D capabilities and experience taking revumenib and axatilimab from IND to FDA approval in about five years. SNDX-4321 is a novel mutant-selective CNS penetrant allosteric EGFR inhibitor for non-small cell lung cancer that offers a new approach to addressing patient populations with high unmet medical needs, such as those with L858R mutations and CNS metastases. SNDX-62122 is a next-generation menin inhibitor we are developing for myelofibrosis, or MF, building on our extensive experience pioneering menin inhibition in hematology. It is the first molecule from our internally developed and wholly owned library of next-generation menin inhibitors, which we intend to advance into promising new areas.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

We are entering into another exciting chapter for the company as we build Revuforj and Niktimvo into major commercial franchises and leverage our proven R&D engine to bring new treatment options to even more patients. We are fully funded to execute on our commercial and R&D priorities and continue to advance towards profitability with growing revenue from the first two medicines from our pipeline. I will now turn the call over to Steve to discuss our commercial results in more detail. Steve?

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

Thank you, Michael. Starting with Revuforj on slide four. We delivered our sixth consecutive quarter of double-digit Revuforj net revenue and prescription growth and continue to track well above launch benchmarks set by other mutation-directed AML therapies. Net revenue totaled $55 million, up 12% from the prior quarter. Total prescriptions were approximately 1,500, up 15% from the prior quarter. These results reflect robust demand and an increasing average duration of therapy, one of several important drivers of our business. We have dominant share of the overall menin business today, having treated over 1,600 patients commercially since launch, including 250 new patients added in the second quarter.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

We saw some fluctuation in new patient starts in Q2 relative to prior quarters, reflecting typical variation quarter to quarter in the number of available patients with a rare disease and market dynamics when physicians have more than one drug in class they can consider using, depending on the patient's mutational profile. To ensure we leave no appropriate patient behind, we have optimized our established customer footprint and targeting, expanded our ability to leverage lab data to engage physicians when they have a suitable patient in their care, and increased our promotional efforts and educational activities. We remain confident we will continue to lead this market with the strongest efficacy profile in an efficacy-driven market and multiple drivers supporting long-term growth. Our business in KMT2A and NPM1 is strong, and it is growing.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

Revuforj is the standard of care for relapsed/refractory KMT2A translocated acute leukemia and remains the only targeted therapy for an aggressive cancer with no other effective treatment options. We continue to expand into our second indication, with NPM1 accounting for at least 40% of new patients in the second quarter and more than 30% of the $55 million in net revenue. All indicators suggest Revuforj will continue to be the menin inhibitor of choice for all menin-dependent acute leukemias. Physicians value having one efficacious and well-tolerated drug they can use across multiple acute leukemia subtypes in both adults as well as children. They appreciate that the efficacy they see with Revuforj in the real world is consistent with, or in fact, even better than the clinical trial results.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

They value individualized dosing, not having to worry about reduced efficacy when their patients are taking commonly prescribed gastric acid-reducing agents like PPIs and H2 blockers, and the lack of any clinically meaningful pruritus, an adverse event that can be impactful for patients and very difficult for clinicians to manage. This combination of efficacy, tolerability, and dosing flexibility is why Revuforj is and will remain the drug of choice for physicians. Turning to slide five. There are two fundamental drivers of our business, new patients and average treatment duration, and both are building. The unique breadth of our indication provides us with the opportunity to target approximately 2,000 patients diagnosed annually with relapsed/refractory KMT2A translocated acute leukemia, plus 4,500 with relapsed/refractory NPM1 mutated AML.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

We've made excellent progress reaching this population, with more than 1,600 patients treated with commercial drug since launching in KMT2A in the fourth quarter of 2024 and NPM1 in the fourth quarter of last year. Importantly, there's still plenty of room to reach more patients each quarter. For instance, of the annual 4,500 relapsed/refractory NPM1 patients, we estimate that less than 15% have received a menin inhibitor, highlighting the substantial opportunity for further growth. Compared to KMT2A, where we saw a steep uptake curve due to the lack of other approved or impactful therapies, we expect our NPM1 business will build over time due to other options that physicians may consider for this population, depending on their co-mutations or other factors.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

The second fundamental driver is average treatment duration, which is increasing due to evolving clinical practice and a product profile that is conducive to patients staying on therapy for extended periods of time. Physicians are reaching for Revuforj early in the relapse refractory treatment paradigm, and are often choosing to use it in combination with other therapies, with the goal of driving responses and extending the duration of effect. Claims data shows 75% of use in the second and third line, and approximately 40% of use in combination. Encouragingly, a significant proportion of patients are proceeding to stem cell transplant after receiving Revuforj, which is the goal in the relapse refractory setting for both KMT2A and NPM1 patients who are fit enough to receive a transplant. We continue to observe approximately 50% of KMT2A patients proceeding to transplant.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

About 50% of those patients have resumed therapy thus far, after pausing for three to six months, up from an estimated 45% last quarter. We expect this % will continue to increase as our colleagues in medical affairs report additional evidence from the post-transplant setting in collaboration with leading treatment centers, building on the encouraging data MD Anderson presented at ASCO and EHA this past June. Over time, we expect that up to 70%-80% of transplant patients will ultimately return to therapy for one to two years based on feedback from physicians and clinical trial and real-world experience. These evolving treatment patterns are increasing the average treatment duration, especially the growing number of patients on therapy post-transplant. This group is already averaging at least nine months of therapy, with this duration expected to steadily increase as we continue to follow patients over time.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

Among patients who do not receive a transplant, over half are still staying on therapy for a significant period, with an average treatment duration that is already over seven months and building. With a significant addressable patient population and an increasing average treatment duration, we are confident in our ability to build a sustainable business with our first two indications for Revuforj. Moving to slide six. We have a solid commercial foundation in place to support the success of Revuforj, including a highly accomplished team with deep and strong customer relationships. Our already robust prescriber base has continued to expand quarter-over-quarter, including our activation of Tier 1 and Tier 2 accounts, the highest volume centers in the U.S., who treat two-thirds of our target population. Nearly 90% of these accounts have ordered, up from 70% prior to the approval of Revuforj in NPM1.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

Overall, more than 580 accounts have ordered Revuforj, up 11% from the prior quarter, reflecting growing adoption from centers of all sizes, including community practices. Our growing prescriber base reflects physicians' enthusiasm for Revuforj and positions us to drive further penetration for both indications. We have excellent payer coverage, and physicians can access the menin inhibitor they prefer. As of the end of Q2, Revuforj's formulary coverage was 98% of all covered lives for both indications, a coverage position that leads the class. In addition to having nearly 100% formulary coverage, Revuforj has preferential coverage on plans representing 17% of all covered lives versus less than 2% of lives for the other menin inhibitor. Turning to Niktimvo on slide seven. Niktimvo net revenue totaled $60 million in the second quarter, up 67% year-over-year and 9% quarter-over-quarter.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

This result reflects strong and consistent new patient starts and solid persistency. More than 300 new patients were added, and about 5,750 infusions were administered in the second quarter. Niktimvo is annualizing at $240 million and continues to track with the launch of REZUROCK, a drug that reached $500 million in annual U.S. net sales within the first four years of launch in the same indication. Moving to slide eight. The fundamentals of our Niktimvo business are strong, with multiple drivers for continued growth. The first is continued adoption in the fourth line and steadily increasing uptake in the third line as clinicians gain experience with Niktimvo. Within one and a half years of launch, Niktimvo has captured approximately one-third of the third-line-plus chronic GVHD market. As the patient mix shifts more towards patients with less advanced disease, we expect this will extend the average treatment duration.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

This is a chronic disease with the potential for patients to stay on therapy for long periods. We've observed solid persistency in the commercial setting, with 60%-70% of patients staying on Niktimvo for at least 12 months. Our clinical trial experience suggests the duration of therapy could be measured in years for a meaningful proportion of patients. Our Niktimvo business benefits from a broad and productive prescriber base and commercial synergies for both Syndax and Incyte. Nearly every bone marrow transplant center in the U.S. has prescribed Niktimvo and become a repeat customer. Physicians continue to report impressive activity in multiple organs, with particularly notable responses in the lungs and skin, some of the most difficult to treat organs. All these drivers position us to expand our impact in third-line-plus chronic GVHD, a $2 billion U.S. market opportunity.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

Looking ahead, the ongoing trials in front-line chronic GVHD and IPF could unlock additional multi-billion dollar opportunities. With that, I'll hand the call over to Nick to talk about our development programs.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Thank you, Steve. Turning to slide nine, I'd like to highlight the progress we've made advancing our scientific leadership in menin inhibition with a strong presence in medical meetings and two landmark publications. At ASCO, we had four revumenib abstracts, including an oral presentation of post-transplant maintenance data from a cohort of heavily pretreated patients with KMT2A/NPM1 or NUP98 alterations who resumed revumenib post-transplant. This analysis showed a two-year overall survival rate of 90%, which is nearly double the historical rate observed prior to the introduction of revumenib. Moving on to EHA, we had 12 revumenib abstracts highlighting the clinical activity with revumenib in multiple acute leukemia subtypes and settings, including in combination with standard of care therapies in the frontline and relapsed/refractory setting. In June, data from the relapsed/refractory cohort in the Phase I/II SAVE trial were published in the "Journal of Clinical Oncology".

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

The results observed with the all-oral combination of revumenib, venetoclax, and decitabine/azacitidine in a heavily pre-treated population of patients with NPM1, KMT2A, or NUP98 AML are impressive. 88% achieved an overall response. 80% of evaluable CRc responders achieved MRD negativity, and 45% of patients proceeded to transplant, with 63% resuming revumenib post-transplant. These results are similar to outcomes observed in real-world cohorts treated with revumenib-based combinations, underscoring the potential to reproduce these results in clinical practice. In July, we and our collaborators published the results of groundbreaking preclinical studies with revumenib, which showed menin is a novel dependency in a proliferative megakaryocytes, major drivers of myelofibrosis. These data provide the basis for our innovative clinical development program in myelofibrosis.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Looking ahead to the second half of the year, we will deepen our scientific leadership with new revumenib data from across the acute leukemia treatment continuum, including from the maintenance and real-world setting. We also look forward to presenting more mature frontline data in the fourth quarter, with updates expected from SAVE and BEAT AML trials of revumenib with low-intensity chemotherapy and from the 708 trial with intensive chemotherapy. We expect these data will be impactful for the clinical community and provide strong support for our ongoing pivotal frontline combination trials. We also expect to publish data in relapsed/refractory NUP98-rearranged acute leukemia in the fourth quarter, followed by submission of this important publication to the clinical guidelines for consideration.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Patients with NUP98 rearrangements have poor outcomes. There is an urgent need for new treatment options, with many parallels to the unmet needs in KMT2A prior to the introduction of revumenib. Physicians are positive about the potential for revumenib to provide a new treatment option for this disease subtype based on the data reported. At EHA, we presented data from 25 heavily pre-treated relapsed/refractory NUP98 patients showing a 28% overall response rate, with 43% of responders proceeding to a transplant and all resuming revumenib post-transplant. Turning to our pipeline on slide 10, I'd like to highlight just a few key points. First, we are rapidly advancing an integrated evidence generation plan designed to establish revumenib as the menin inhibitor of choice across the acute leukemia treatment continuum. Importantly, we maintain good momentum to be the first to deliver pivotal frontline data for a menin inhibitor.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Global site activations and patient enrollment is well established in our pivotal trials, informed by an extensive body of clinical evidence, allowing for optimization of endpoint assumptions and other aspects of the study design. Second, we are nearing two important axatilimab readouts. We are on track to report top-line data from the phase II MAXPIRe IPF trial in the fourth quarter. Positive data would open a transformative opportunity for axatilimab and provide a strong biological rationale for its mechanism in several other diseases where the pathology is underpinned by fibrosis and inflammation. We also anticipate top-line results from the phase II trial of axatilimab in combination with ruxolitinib in frontline chronic GVHD in the fourth quarter. Positive outcomes with the novel combination could begin to unlock the potential for a steroid-sparing regimen in newly diagnosed chronic GVHD.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Third, as highlighted at our recent R&D event, we announced two new pipeline assets, SNDX-4321 and 62122. In line with our focused R&D strategy, these are targeted molecules both with first and best-in-class potential, supported by compelling preclinical data, mechanistic insights, and advocacy of leading researchers and clinicians. With both revumenib and axatilimab, we have demonstrated our ability to efficiently generate clinical data that validates new therapeutic targets, leading to new approvals, a strength we will leverage again as we advance the next chapter of our R&D strategy. Turning to slide 11, 4321 is a novel mutant-selective, CNS-penetrant allosteric EGFR inhibitor. We're developing it for non-small cell lung cancer patients with high unmet needs, such as those with the L858R mutations, CNS metastases, and atypical activating mutations or resistance to current therapies.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

In contrast to ATP site-directed third and fourth-generation EGFR inhibitors, 4321 binds at a pocket adjacent to the ATP site that is only accessible in the presence of L858R and certain other EGFR mutations. The allosteric approach allows for high selectivity and a double lock approach to inactivating the receptor. 4321 and ATP site-directed therapies combine EGFR at the same time at different sites on the receptor, potentially enhancing efficacy and delaying resistance. We expect to submit an IND for 4321 by the end of 2026, with an assessment of monotherapy activity expected in early 2028. 62122 is our next-generation menin inhibitor in development for myelofibrosis that could offer a novel and potentially disease-modifying approach. It is the first candidate from our library of internally developed and wholly owned next-generation menin inhibitors that we plan to advance into new areas.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

We expect to submit an IND and initiate Phase I trial of 62122 in 2027. This program will be informed by a proof-of-principle trial of revumenib in myelofibrosis that will be conducted in partnership with world-leading experts in myelofibrosis. We expect this trial to initiate in the fourth quarter, with initial data anticipated in the second half of next year. In summary, we've made enormous progress advancing our late-stage trials and expanding our pipeline of differentiated assets. We are nearing several important data readouts and have multiple opportunities to transform the standard of care for some of the most difficult-to-treat diseases. With that, I'll turn the call to Keith to discuss our financials.

Keith Goldan
CFO at Syndax Pharmaceuticals

Thank you, Nick. Pardon me. Earlier this afternoon, we reported detailed second quarter 2026 financial results, and I'll highlight a few key points on slide 12. Total revenue for the second quarter of 2026 was $72.8 million, up 92% over the same period last year. This consisted of $54.7 million of Revuforj net revenue and $18.1 million in Niktimvo collaboration revenue, which equated to 30% of the Niktimvo net revenue reported by our partner, Incyte, in the quarter. We expect Niktimvo margin contribution, defined as a collaboration revenue recorded by Syndax as a percentage of Niktimvo net sales, to continue to be in the 25%-30% range in the near term and increase longer term as sales grow. We expect revenue from both Revuforj and Niktimvo to continue growing and advancing the company towards profitability.

Keith Goldan
CFO at Syndax Pharmaceuticals

Our guidance for R&D plus SG&A expenses in 2026 remains approximately $400 million, excluding the impact of $550 million in estimated non-cash stock compensation expense. We ended the second quarter with $575 million in cash equivalents and investments. This includes $244 million in net proceeds from the issuance in June of $250 million of 2.25% convertible notes. That deal provided the lowest cost of capital that Syndax has ever accessed and positions us well to build shareholder value over the long term. We're fully funded to execute our commercial and R&D priorities, including our late-stage trials of revumenib and axatilimab, and the development of our pipeline assets. With relatively modest investments and proof-of-principle trials of 4321 and 62122, we believe we can quickly generate early clinical data that creates significant value for the company and its shareholders. With that, I'll hand the call to Michael for closing remarks.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Thank you, Keith. Syndax is well-positioned for long-term growth and success, with multiple blockbuster opportunities and upcoming milestones as highlighted on slides 13 and 14. We have a best-in-class menin inhibitor that is positioned to be the first to frontline AML and deliver peak annual net revenue in excess of $2 billion in the U.S. alone. We are nearing data readouts in the fourth quarter that could unlock multibillion-dollar upside for Niktimvo in IPF and frontline chronic GVHD. We have a proven track record of successfully developing and commercializing novel medicines and are bringing forward two new pipeline assets with best-in-class and blockbuster potential in EGFR-mutated lung cancer and myelofibrosis. With $575 million on the balance sheet and growing revenue from two products, we are funded through profitability and have the capital to realize our pipeline opportunities and drive significant long-term value.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

I will close by thanking our dedicated employees and the many patients, clinicians, and scientists who support our work and inspire us to pioneer bold, new approaches to some of the most devastating diseases. With that, I would like to open the call for questions. Operator?

Operator

At this time, I would like to remind everyone in order to ask a question, press star, then the number five on your telephone keypad. If you'd like to withdraw your question, press star and the number five once again. We'll pause for just a moment to compile the Q&A roster. The first question is from Anupam Rama with JPMorgan. Your line is now open.

Joyce Zhou
Joyce Zhou
Analyst at JPMorgan

Hey, guys. This is Joyce on for Anupam. Thanks for taking our question. Could you discuss the physician feedback you received at ASCO and EHA on the Revuforj data that you guys presented there, especially the post-transplant maintenance data? How soon could those data have positive pull-through to the launch in terms of what you're seeing with the proportion of patients going on maintenance therapy? Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Joyce, thanks so much for the question. I'll direct the first question to Nick.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Thank you for the question. I think the data was very well received. I think it's a remarkable outcome when you look at the proportion of patients alive at two years, 90%. It's obviously not randomized, but MD Anderson did a very nice job comparing it to the current standard of care, which is considerably less than that. I think they're very encouraged by that. We have significant research efforts ongoing to further elucidate the benefits of giving revumenib in the post-transplant setting. It's really important, I think, to optimize the dose. We're learning a lot about that, and we have a dedicated phase I study ongoing to optimize dose, and we hope to report on that later this year.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

We also actually have the first prospectively randomized study called the MenTain Study that was recently announced on ct.gov in collaboration with Dana-Farber and other collaborators, which will hopefully further elucidate the benefits of maintenance

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Which will be extremely helpful, and it's an important study to do. Generally, however, we are seeing the uptake of maintenance very much in clinical practice, and that will be evidenced by the real-world series we've already reported upon, where you see high rates of both transplant and then patients going back onto therapy after transplant. We'll be updating on those further in the year with more data, which I think support and perhaps even exceed what we've seen to-date.

Operator

Our next question is from Brad Canino with Guggenheim. Brad, you may unmute yourself and ask a question.

Brad Canino
Brad Canino
Analyst at Guggenheim

Hey, afternoon. Thanks for the questions. Maybe two for me. One, just any quantification you can provide on the duration of treatment increasing, either numerical or some estimation of a relative increase the DoT saw? I'm just trying to judge the magnitude of increase. Two, have you seen any indication of an inflection in the maintenance rate? Sounds like it was 50% is what you're up to for this past 2Q, but any inflection in July after showing the maintenance data at ASCO and EHA as you've been going out and talking with physicians? Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Brad, thanks so much for the question. First of all, in terms of the duration of treatment, we're very much encouraged by what we're seeing. I think for patients who are actually going on to maintenance, we know that cohort of patients is out beyond nine months. That's an increase from what we've seen previously, and we feel quite encouraged by that. You might have picked up in my remarks, what's also encouraging are patients who don't go to transplant, who remain on therapy for an extended period of time, are well beyond seven months at this point and building. That's new news and very encouraging for what we think will continue to build the recurring revenue within the franchise. Thank you. In terms of inflection in maintenance rates in July, that was a pretty specific question.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

I'll just say that we are seeing continued buildup in maintenance. I don't think we've quantified it quite for July, but we feel very encouraged by what we've seen coming out of last quarter and into this quarter. We believe that will continue to build. We've talked about reaching 70%-80% of patients getting on maintenance. We believe that assumption will hold as we build beyond the 50% that we saw this quarter. When exactly that will get to the 70%-80% will take a little bit of time, but we do feel quite encouraged by the momentum we're seeing coming out of last quarter.

Operator

The next question is from Faisal Khurshid with Jefferies. Your line is now open.

Faisal Khurshid
Faisal Khurshid
Analyst at Jefferies

Hey, guys. How are you doing? This is Faisal from Jefferies. I just wanted to ask, this looks like the first quarter that you actually took a step down in new starts. Can you give any more specificity on the reasons for this? Also, in terms of modeling this going forward, what are the forward trends that we should expect on new starts, each in KMT2A and NPM1? Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Thanks so much for the question. Maybe I'll turn it over to Steve to make some comments on new starts for this quarter.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

Yeah. Thanks for the question. Appreciate you pitching it to me, Michael. Overall, good performance. It's a sixth consecutive quarter of double-digit revenue and demand growth. I think interestingly, we grew 15% on TRX demand, and that was in the face of what you notice is a falling number of patient starts from Q1 into Q2. The reasons for that there are just multiple drivers to the business. A lot of our prepared comments around the KMT2A business, how it's advancing. It's heading exactly in the direction that we predicted it would. Higher transplant rates, higher restart rates relative to the clinical trials, which is really driving the DOT. I'd say for NPM1, it's still early days, but we know that the business is growing. It's growing nicely. Our revenue and our patients on drug from Q1 into Q2 advanced as well.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

New patient starts are simply just a part of the growth story, but not the only part. Couple things I hit at in the prepared comments, I'll maybe add a different flavor to it as well. This is normal. You're going to see, at least in the larger targeted AML therapy class, new starts do jump around. There's typical variability. We see it month-to-month. You're going to see it quarter-to-quarter. We've been largely immune to that, right? Rev has existed in this space, and we've either had the same number of new starts or grown them quarter after quarter. This is a fundamental aspect of the market that is typically there. Other things that we've mentioned, physicians have more than one drug class to consider, right? There is a big focus on the NPM1 patient.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

Based on that patient's mutational profile, physicians are going to make a choice. I think they're still figuring out where the menins fit. Is it before a FLT3, is it during a FLT3, or perhaps after? That will play its way out, but ultimately, patients will relapse, and Rev will play a role. The last piece are just clinical trials. When you sign up to be in this business, oncology, hematology, you're advancing drugs through the clinic, and you're also commercializing them. We've done that successfully since the launch of Rev, this isn't something that's entirely new. There are new trials that pop up from time to time. As they get established, patient flow will ultimately work its way through, and opportunities for commercial patients are going to stabilize.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

Many of these are placebo-controlled trials, we expect to still treat many of these patients, either when they relapse. Not all patients are obviously eligible for clinical trials. We made a conscious decision about a year ago to go to a much broader audience. As we updated in this call, we're approaching 600 accounts that have prescribed. Many of those are medium-sized to smaller accounts, less impacted by clinical trials, and we find meaningful patient build there as well. These factors can cause some lumpiness and fluctuation quarter-to-quarter, but we are able to flex and change our business as needed. We're confident in the forward. I think one of the questions was, what is the trend moving forward? We look at this quarter

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

As an anomaly, we feel confident about finding patients and getting back to levels that we've seen historically.

Faisal Khurshid
Faisal Khurshid
Analyst at Jefferies

Got it. Steve, if you don't mind, just a quick follow-up. Am I to take your comments to mean that new starts on commercial drug in relapsed AML as a whole were down quarter-over-quarter? If so, are you able to quantify that at all?

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

Probably don't have the full data set to look across all of AML. We're limited in what we can see on our drug. Perhaps that is the case. I would bet that it is. Again, it'll jump around from quarter-to-quarter.

Faisal Khurshid
Faisal Khurshid
Analyst at Jefferies

Great. Thank you.

Operator

The next question is from Phil Nadeau with TD Cowen. Your line is now open.

Phil Nadeau
Phil Nadeau
Analyst at TD Cowen

Good afternoon. Congrats on the progress and thanks for taking our questions. A few commercial questions from us. First, in NPM1, I apologize if I missed this, did you say what you estimate your share of NPM new patient starts was this quarter and how that compared to last quarter? That's first. Second, I think you said 15% of NPM1 patients have been on a menin. That's after approximately three quarters of your launch. Is that trend that we should continue into the future? In another three quarters, should we expect maybe 30% of NPM1 patients will be on a menin? Or is there any reason to think that would either accelerate or decelerate? Finally, on maintenance, can you tell us where maintenance is being used today in terms of what centers and where's the growth going to come from?

Phil Nadeau
Phil Nadeau
Analyst at TD Cowen

What new centers could come online over the next several quarters to drive increased use of maintenance across the market? Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Great, Phil. Thanks for the question. First question I took as what's our NPM1 share, and I think as we stated in our prepared remarks, we're about two-thirds of the business right now. If you think about where we were last quarter is roughly about the same, two-thirds or more of the overall business. We expect that to continue to build over time. We do have a dominant position. I would also say in terms of relapse refractory business, assuming our competitor gets close to their numbers, we're probably 85+% of relapse refractory. We are quite dominant in the space and expect to continue to build that.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

We did make the comment about 15% of the patients, this is your second question, 15% of the NPM1 patients have seen a menin inhibitor, and that's not only our drug, but our understanding of how our competitor contributes as well. That's 15% total. We do expect that to expand meaningfully and from quarter to quarter, we expect that to grow, accelerate. In a year from now, we'll be at 30%. We would hope that it would be even greater than that, and it's supported by all the data that we're generating. Nick mentioned the presence at our congresses and what we've provided in terms of monotherapy and combinations, and that has shown Revuforj to be a very useful drug in a number of ways.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

We expect that we'll be treating NPM1 patients and continuing to penetrate that market very meaningfully, hopefully well beyond 30% in a year. Then maintenance, I'll turn to Nick on this one. Maintenance. Where is it being done? What are those centers? We won't list them all. Academic centers for sure. Nick can make a comment there. Where is the growth going to come from in terms of maintenance? Nick?

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

I think the growth will come from a number of drivers. Number 1 is patients getting treated earlier on. They're getting treated increasingly in combination. That's just driving response rates higher. We know that if a patient gets to response, they're eligible for transplant. Having had a transplant, the likelihood of them going on to post-transplant maintenance. As we gather more data and present more data there, I think physicians are feeling more confident. They understand how to manage the dose better. These patients after transplant are particularly prone to cytopenias generally, so you really do need to manage the dose, and that's something we'll be presenting updated data on later this year, and I think they're getting confidence to do that. Really just the real-world experience from academic centers. We've seen extremely high rates. They're feeling more confident doing it.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Their intent is to treat out to 1 to 2 years. Most of our clinical trials include therapy out to 2 years. Given the high rates of relapse after transplant without any active therapy, they really want to just do their best for the patients and think that revumenib gives them the best chance of a durable remission. We're seeing uptake increase. From a research perspective, it's our efforts to further confirm that benefit, who's most likely to benefit, and how we can make sure that the drug is well-tolerated. I think we're very encouraged by what we're seeing in the uptake, and we'll be presenting more data on that again later this year with a big focus on this whole post-transplant maintenance area.

Phil Nadeau
Phil Nadeau
Analyst at TD Cowen

That's very helpful. Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Thanks, Phil.

Operator

The next question is from Stephen Willey with Stifel. The line is now open.

Stephen Willey
Stephen Willey
Analyst at Stifel

Good afternoon. Thanks for taking the questions and congrats on the progress. Just curious how you're thinking about the near-term growth opportunity for this franchise prior to potential label expansion. Was also just wondering if you can confirm whether the definition of event-free survival, which is being used in the phase II frontline trial that reads out later this year, plus Rox, is the same as the phase III frontline trial that's looking at Niktimvo in combination with steroids. Thanks.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Stephen, thanks for the question. Maybe I'll take the first with maybe a comment on the second from Nick. Niktimvo, look, I don't agree with the characterization that it's flat, first of all. Niktimvo is not flat, it's growing, and we see it tracking very nicely to what REZUROCK has done. We expect it to continue to grow meaningfully. What I'm talking about is third and fourth line. We've penetrated well into the fourth line. third line, we have about a third of the third line population at this point, which is very meaningful about a year post-launch. I think we will continue to build that and be meaningful in third and fourth line. You should expect continued growth there. Of course, we have expansion opportunity with the new data coming at the end of the year with combination with ruxolitinib.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

We feel like that's a obvious expansion opportunity as we're on our way to the front line. We'll also have steroid combination in early 2028. A lot of data to come. I think physicians are eager to see the combinations and how our drug combines with Jakafi. In the meantime, we'll have considerable growth, we believe, over the near term with third and fourth line. Maybe I'll turn to Nick on definition for event-free survival.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Steve, the event-free survival endpoint is in the, for the frontline steroid combination phase III. That does have an event-free survival primary endpoint. For the phase II three-arm study, we're actually going to look at overall response rate at six months. As you recall, this is steroids versus Rux versus the combination of axatilimab and Rux. We expect the benchmark from that based on a publication in 2022 to be about 40% response rate for steroids alone at six months. We're looking for a meaningful improvement over that. I think for the combination, it could be considerably higher than that. It's not formally a comparative study. It's randomized one-to-one-to-one, about 120 patients, you'll recall.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Yeah, we'll look at overall response rate, but I think also the duration of response will be very important to look at in that study to see whether the combination, and Rux alone can offer a meaningful alternative to steroids. That's what we will report on and looking forward to seeing that readout, because I think it could be very informative and potentially practice and guideline informing readout if either or both of those combinations beat steroids alone.

Stephen Willey
Stephen Willey
Analyst at Stifel

All right. Thanks for taking the questions.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Thanks, Stephen.

Operator

The next question is from Etzer Darout with Barclays. Your line is now open.

Etzer Darout
Etzer Darout
Analyst at Barclays

Great. Thanks for taking the question. A quick one for me. Just wondering, for the proof of principle trial of revumenib in myelofibrosis, what is the primary analysis? What will that entail, and what endpoints will you be evaluating there? Just as a potential, obviously read through to the next gen menin inhibitor. Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Great, Etzer. Thanks for your question. Maybe I'll turn to Nick on the proof of concept trial.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Yeah, this is a study we're doing with the MPN Research Foundation with John Mascarenhas and collaborators. It's not under our sponsorship. It was recently posted on clinicaltrials.gov. It's quite a full posting if you want to look at some of the details of the study there, but I'll just summarize it for you. Cohort 1, which is primarily the safety assessment, will look at just dose-limiting toxicities. That's going to be relatively few patients treated, around six. In Cohort 2, where we will look for the combination of rev in combination with Jakafi, we'll be looking at standard response criteria. We'll be using the ELN response criteria, looking at anemia, spleen response, and symptom benefit. We'll be looking at SVR less than 35%.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

In patients that have a suboptimal response on Jakafi alone and are stable on Jakafi for 12 weeks, we'll add in revumenib, and then we will be looking for using standard ELN response criteria, to generate proof of principle data, which will be incredibly informative to our development program and really catalyze, I think, when we go into phase I in 2027 with our next gen menin inhibitor in myelofibrosis.

Etzer Darout
Etzer Darout
Analyst at Barclays

Great. Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Thanks, Etzer.

Operator

Our next question is from Yigal Nochomovitz with Citigroup. Your line is now open.

Joohwan Kim
Joohwan Kim
Analyst at Citigroup

Hi, this is Joohwan Kim on for Yigal. Thanks for taking our questions. I was wondering with regards to your expanded use of lab data, I believe that you had mentioned, to engage physicians when they have a suitable patient. To what extent can that help smooth new start variability, particularly in NPM1, where the population is larger, but co-mutations can help influence the treatment choice? Also with regards to the MAXPIRe trial, just wondering, patients can be on pirfenidone or no background anti-fibrotic. If the study is positive, how should we think about the extent to which the background therapy could help define axatilimab's role, whether it's add-on or potentially for patients not getting much benefit from current treatments? Thanks.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Great. Thanks for the question. First, with the use of lab data, maybe Steve, you want to make some comments on how we identify patients?

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

Yeah, sure. We do use lab data, as pointed out in the question. It enables us to find diagnosed patients. We buy lab data. We can identify patients that may be suitable. It's obviously de-identified. We can target accounts that we know patients exist. It's largely worked since launch. I think that really speaks to why we've been so successful, particularly at the CAN 2-2a launch. We've modified our approach over time. We've been able to bring in new lab data sets. We've been able to apply some applied artificial intelligence and machine learning principles. It still holds. I think specifically the question was, can you use that to smooth out new starts? The market's the market. Patients are going to come in at often a random pace. Over a year, you know what it is, but month to month, it's going to be different.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

We will find every possible patient that we can, right? We've shown we've been able to do that, and we're going to get better simply over time. That's something we remain committed to.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Maybe Nick, do you want to talk about MAXPIRe and the background therapy impact?

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

MAXPIRe has three strata. We stratified by nintedanib, pirfenidone, and then no anti-fibrotic, as you would expect, consistent with previous studies that looked at IPF. By far, the majority of the patients were on a background anti-fibrotic. We will obviously look at subtypes in those strata to ensure there isn't an imbalance between the arms. The study is really not powered. Recall it's two to one randomized. It's not powered to detect differences between the different types of anti-fibrotic. That's something we will look at. In terms of phase III planning, we would plan to include axatilimab on a background of standard of care anti-fibrotics, and potentially other standards of care.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

One of the attractive things I think about the mechanism of action of axatilimab is that it really does treat what we think is the underpinning pathology by targeting specific, these monocyte-derived macrophages, so inflammatory and fibrotic components of the disease. We really think that that could be a very important differentiator and particularly suitable for combination with current standards of care.

Joohwan Kim
Joohwan Kim
Analyst at Citigroup

Understood. Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Thank you.

Operator

Our next question is from David Dai with UBS. Your line is now open.

David Dai
David Dai
Analyst at UBS

Great. Thanks for taking my questions. Just thinking about the Revuforj, new patient starts, and KMT2A penetration. Last quarter, you mentioned that you were 50% penetrating to the KMT2A market. How did the number look like this quarter? How do you envision the peak penetration will look like? How long do you think that's going to take? That's the same question we'll apply to NPM1. What percentage of NPM1 market have you penetrated so far, and what would the peak penetration look like?

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

David, thanks for the question. Maybe I'll address KMT2A first. First of all, we own the KMT2A market. This is a part of a business that where we are firmly established as standard of care. NPM1 is building. We firmly acknowledge that we have best in class profile for both broadest set of opportunities there. For KMT2A, we have said that we were about 50% penetrated, and that continues to build. Peak penetration's likely to get to roughly 80% or maybe even more. We've seen examples in the market of companies launching products into targeted areas where they have dominant position, and they get to those levels. KMT2A should reach a very deep penetration over the reasonably near term. NPM1, I would say is a slower build, mainly because of some of the things that Steve said.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

It is a bigger patient population for sure. More patients are able to be treated, more patients are being treated. They just happen to be on other therapies. Our job is to introduce Revuforj to those patients. It's monotherapy and perhaps combination as physicians want to use the product, and we'll continue to penetrate there. Again, I think Revuforj can have a very high penetration. We already own, as of today, about two-thirds or more of the business in NPM1, and that should continue to build. Our penetration will get to a high percentage over time. Maybe not quite as high as KMT2A, but we do think that we'll have a dominant position in both with best offering as we've talked about. I think there are different kinetics of build between KMT2 and NPM1 as described, but high penetration is the name of the game here.

David Dai
David Dai
Analyst at UBS

That's helpful. Then just a question on inventory stocking. What does the inventory stock look like this quarter? Any dynamics there?

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

I'll give this one to Keith. Inventory.

Keith Goldan
CFO at Syndax Pharmaceuticals

Thanks, David. The guidance that we've been pretty consistent with, very consistent with since launch, still holds. Again, not just for Syndax, but really for any rare disease-targeted oncology product. We're about two to three weeks. It's been remarkably consistent since we've launched the product. We'll let you know if there's any changes, but you can assume that we have about two to three weeks of Revuforj in the channel.

David Dai
David Dai
Analyst at UBS

Thank you so much.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Thanks, David.

Operator

Our next question comes from Salim Syed with Mizuho. Your line is now open.

Salim Syed
Salim Syed
Analyst at Mizuho

Great. Congrats on the progress, guys. Thanks for the question. One from us on the $2 billion revenue expected in the U.S. alone. Mike or Keith, could you maybe I think this is the first time we're formally seeing it in a slide written like that, and I noticed also that I think this is the first time that the bar chart for the TAM has been taken out of the deck. Wondering if you guys are starting to think here that the $5 billion TAM is a conservative number, you're sort of reworking your numbers internally, or what your assumptions were exactly going into $2 billion, how much first-line is in there versus second-line, et cetera. Then one clarification. I think you guys mentioned, I think it was Mike, 85% of relapse is what you guys are getting.

Salim Syed
Salim Syed
Analyst at Mizuho

I presume that's also inclusive of KMT2A rearrange. What percentage of NPM1 starts are you guys seeing? I think Kura on their side, they've said 40% is their shares, which would imply you guys are at 60. Is that ballpark-ish correct in line? Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Salim, lots of parts of your question. Let me see if I can tackle them. First of all, just because I see it on the page here, 85% of what I had mentioned, 85% of the relapse refractory business is KMT2A and NPM1 combined. That's our calculation. If you look at the numbers for the quarter relative to our competitor, we're at least 85% of the business. That's one. When we talk about the estimate of $2 billion plus in revenue peak potential, when we include the frontline, you're right. That is the first time we're talking about this in this way, and I think it's important. Why now? We're more confident than ever, and this is clear to us that this is a very large market opportunity.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

When you look at the data that we've published over the last quarter or two, all things point to growing relapse, I would say, overall survival, days of therapy. The response rates are higher than we've seen previously. The data is all very positive and gives us confidence that we will, once we get to the frontline, have a very supportable market position and dominant position in frontline. We will be the first to get there. With the profile that we have today, we feel quite confident that we will have a very meaningful share, a dominant share of frontline. Thinking probably the most important driver here is days of therapy or time on therapy. What we've said today is that we see that elongating.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

We're quite encouraged by that, which gives us a lot of confidence because it's a very important indicator, a very important component of the calculation for the market, how long patients stay on therapy. So far, even in relapse refractory patients, we're seeing this exceed our expectations. We are quite confident, again, that we can reach that level of sales. When you talk about the breakdown between frontline and relapse refractory, as we've said in our bar chart, nothing's really changed in terms of our evaluation of the overall total addressable market. $5 billion does assume the $2 billion is part of that. We've always been clear about it, that $5 billion is the overall market when you assume that you get to frontline. $2 billion is really our assessment of the relapse refractory opportunity.

Salim Syed
Salim Syed
Analyst at Mizuho

Okay, thanks so much.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

You're welcome. Thank you.

Operator

The next question is from Andres Maldonado with H.C. Wainwright. Your line is now open.

Andres Maldonado
Andres Maldonado
Analyst at H.C. Wainwright

Hi, guys. Thanks for taking the questions and congrats on the progress. First question is a question on slide five. You talk about 40% of Revuforj uses in combination. Curious if, are physicians mainly adding Revuforj to a failing venetoclax-based regimen, or are they beginning a new combination at relapse? How should we be thinking of those variants and approaches, their potential to produce different treatment durations or transplant rates? This is the first question, then I have a follow-up.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Great. Andres, thank you for the question. Maybe I'll turn it to Nick to talk a little bit about combination regimens.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Yeah, what we're observing in the real world is multiple combinations. I think you're right that ven is a common desire, either ven or ven as a combination. Sometimes patients have been exposed to prior ven. There's some interesting data that revumenib may actually synergize with BCL-2 and may even be an opportunity to re-challenge. That's one of the more common combinations, but we do also see other combinations in use. We have, for example, ongoing studies, which I think is important with FLT3 inhibitors. It's not something we hear that it's a high priority amongst the physician community, but we do want to generate data to confirm both tolerability and efficacy with a FLT3 inhibitor, and then potentially other single agent therapies as well.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Certainly ven is one of the more common ones, and what we have observed in our real-world data today is that it does drive response rates up significantly from what you observe with revumenib alone. If a patient's able to tolerate it and they want to treat, we're obviously not promoting in that indication. It's not within our label to treat in combination. We do see, in some cases, 50%-80% of patients actually treated in combination because we know it drives a 60%-80% response rate, which gives a patient a much better chance for durable response and potentially a transplant.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Andres, you have a follow-up question?

Andres Maldonado
Andres Maldonado
Analyst at H.C. Wainwright

Great. Then a quick one on that.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Yeah, go ahead.

Andres Maldonado
Andres Maldonado
Analyst at H.C. Wainwright

Sure. A quick one on MAXPIRe. I think you guys have highlighted in the past some of the expectations of the scenarios, whether you expect the FVC curves to separate earlier or maybe potentially later. In the scenario that the curves maybe gives a modest 26-week FVC result with a longer later slope or biomarker effect, how should we interpret that influence on the potential market there?

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Yeah, nice question, Andres. Maybe I'll turn to Nick.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Yeah, we're pretty confident, I have to say, in that 26-week endpoint. It's been a very good predictor in other studies of IPF. We model that out to 52 weeks because that's the endpoint we would use in a pivotal phase III and is the FDA's preferred endpoint. For a proof of concept study like MAXPIRe, 26 weeks is pretty robust. Some other studies have used 12. We're not anticipating any delayed separation of those curves. We saw in our experience in GVHD, very early onset. Certainly symptoms were responding within a month, and we were observing responses within the first month or two. We are expecting by week 26, the evidence of activity will be very much in evidence. That's what we'll be using. We'll be using the model. We're using a mixed linear regression model out to 52 weeks.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

That's what we will be using if it's positive to inform and power the phase III study. Obviously, the phase III study size and dimensions will be influenced by what we observe in the phase II. We're feeling very confident, I have to say, in everything we've observed to date that would suggest that study will read out well. Obviously, it remains a double-blind, placebo, ongoing study. We don't know what the study will show, but given all of the preclinical and clinical data we've generated and the mechanism of action, we're feeling quite positive, and we're looking forward to that study reading out in the fourth quarter. We think it'll be a very robust proof of concept given its design.

Andres Maldonado
Andres Maldonado
Analyst at H.C. Wainwright

Thank you very much.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Thank you.

Operator

The next question is from Jason Zemansky with Bank of America. Your line is now open.

Analyst at Bank of America

Hi, this is Jackie on for Jason. Thanks so much for taking our question. You previously characterized the decline in new Revuforj starts as an anomaly, but can you quantify how starts change sequentially within NPM1M and KMT2A-R? Clarify whether the decline primarily reflected clinical trial enrollment, competition, or underlying patient availability. Also, could you maybe tell us whether July starts have returned to prior quarter levels? Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Jackie, thanks for your question. First maybe I'll turn it to Steve to talk a little bit about what the decline in new patient starts, what it reflected. That's it.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

I think we talked about the potential reasons why it's difficult to piece out each one and determine the contribution factor from each. I'd say it was an overall drop in all new patient starts. I think there was an earlier question on AML in general. We didn't see a differing change in NPM1 relative to KMT2A. We do believe it's a temporary effect, and we're going to return back to where we were previously. I think there was the question also just-

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

About July. Yeah.

Steve Closter
Steve Closter
Chief Commercial Officer at Syndax Pharmaceuticals

We're not going to comment on July, at least in the quarter forward. We feel good. We feel confident in the business plan and in everything that we have going against the brands as shared on this call.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Yeah. Absolutely. I think we expect to return to growth as Steve mentioned. Look, in terms of the dynamics for NPM1 and some of these other I think there are different things that impact from quarter to quarter, but I think we feel confident we have a plan to make sure that we get back to that positive growth there. Thank you.

Analyst at Bank of America

Great. Thank you so much.

Operator

The final question today is from Mayank Mamtani with B. Riley Securities. Your line is now open.

Mayank Mamtani
Mayank Mamtani
Analyst at B. Riley Securities

Yes, good afternoon. Thanks for squeezing me in. Appreciate it. I will keep it very tight. Did you say the NPM1 relapse segment, how is the duration of therapy tracking, sorry if I missed that, relative to what you had in the trials, given the context of earlier line use in co-mutation patients? Was also curious if there's a year-end exit rate you expect to have in terms of how the split between NPM1 and KMT2A patients you expect to have at the end of the year?

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Mayank, thanks for the question. I don't think we gave a specific number for NPM1 tracking, I'd just say that duration, most of these patients don't go to transplant. As we commented, that very encouraging that the duration for patients who haven't gone to transplant is averaging well over seven months at this point early on. A lot of those patients, of course, are NPM1 or I'd say the disproportionate amount of NPM1 patients don't go to transplant. I think that's a potential indicator of how things are going. We're quite encouraged by the overall, and without breaking it out, that's perhaps an indicator. In terms of the number of NPM1 patients at the end of the year, I don't think we've said or guided to that. All I'd say is that we do have a dominant position in the market.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

We expect that to build over time. We'll continue to use all of our resources to identify patients and build that business, we feel encouraged by what we see both as monotherapy and in combination. That's been what the themes have been at our medical congresses. We're quite in a good position to continue to build and feel good about the forward.

Mayank Mamtani
Mayank Mamtani
Analyst at B. Riley Securities

Understood. Maybe just lastly, we are coming off a busy conference season, obviously you have your biggest conference at the end of the year. If you could just quickly comment on what to expect there, including from the three frontline setting trials we have ongoing, and if there's any enrollment update we can expect to have on EVOLVE-2 or REVEAL-ND would be good to know. Thanks for taking my question.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Yeah, thanks. Thanks for the follow-up. End of the year, Nick, do you want-

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

Yeah, very data rich end of year. Looking forward to the second half of the year. We hope to carry the momentum. I outlined briefly what we saw at ASCO and EHA. The teams have been working very hard. We're going to see multiple data sets. I would expect to see updates to all of our frontline studies. There's several, two studies in combination with BEN and HMA combinations, and then obviously our combination study with intensive chemotherapy as well. That'll be very informative to our ongoing pivotal phase IIIs, which remains a focus for us. Expect to also see, as we've talked a lot about, further data on the maintenance after transplant, informing practice there, combination, and of course, real-world evidence. That will be very important.

Nick Botwood
Nick Botwood
Head of R&D and Chief Medical Officer at Syndax Pharmaceuticals

I think it'll be also important that I know there'll be a lot of interest in looking at how some of the time to event things are coming from our frontline studies, like event-free survival and particularly overall survival. I think we should have sufficient maturity to update on those as well. As I say, very data rich period coming up in the second half of the year we're looking forward to.

Mayank Mamtani
Mayank Mamtani
Analyst at B. Riley Securities

Thanks so much. No problem.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Thank you.

Operator

This concludes our question and answer session. I will now turn the floor over to Michael Metzger for any additional comments or closing remarks.

Michael Metzger
Michael Metzger
CEO at Syndax Pharmaceuticals

Thank you all. We really appreciate everyone tuning in today to discuss our recent progress and the exciting milestones that we have ahead. We look forward to seeing many of you at the upcoming investor conferences in the third quarter. Have a great evening, everyone.

Executives
    • Sharon Klahre
      Sharon Klahre
      Head of Investor Relations
    • Michael Metzger
      Michael Metzger
      CEO
    • Steve Closter
      Steve Closter
      Chief Commercial Officer
    • Nick Botwood
      Nick Botwood
      Head of R&D and Chief Medical Officer
Analysts
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