Syndax Pharmaceuticals - Earnings Call - Q2 2025

Executive Summary

• Q2 2025 revenue was $37.96M, up 89% q/q and ahead of S&P Global consensus; EPS of $(0.83) beat expectations as commercial traction in Revuforj and initial collaboration revenue from Niktimvo outpaced OpEx growth. Estimates context: Revenue $26.64M*, EPS $(1.01); Actual: $37.96M, $(0.83) — both beats.
• Revuforj net revenue rose 43% q/q to $28.6M with strong demand, earlier-line use (≈50% in 2L; ≈70% 2L/3L), and an estimated one-third of KMT2A patients proceeding to transplant; physicians plan to restart maintenance post-transplant for 1–2 years, supporting duration expansion.
• Niktimvo’s first full quarter delivered $36.2M net revenue (Incyte), translating to $9.4M collaboration revenue to Syndax; 80–90% of patients remain on therapy and >80% of U.S. transplant centers have adopted the drug, underscoring durable uptake and cash contribution.
• Guidance: OpEx (R&D+SG&A, ex-stock comp) maintained at $95–$100M for Q3 and $370–$390M for FY25, with management reiterating a path to profitability on relapsed/refractory indications alone and a stable expense base over 2–3 years.
• Catalysts: Priority Review for Revuforj sNDA in R/R mNPM1 AML (PDUFA Oct 25, 2025); inclusion in treatment guidelines expected pre-approval; first real-world evidence anticipated before year-end; continued Niktimvo growth and front-line GVHD/ IPF development progress.

What Went Well and What Went Wrong

What Went Well

• Revuforj commercial ramp: Q2 net revenue increased 43% q/q to $28.6M; patient identification robust with >500 patients treated since launch and ~25% of annual KMT2A incidence already penetrated; earlier-line use supports better outcomes and longer duration.
• Niktimvo uptake and profitability: $36.2M net revenue (Incyte) in Q2; Syndax’s collaboration revenue of $9.4M implies 20–30% near-term margin contribution, with 80–90% of patients remaining on therapy and >80% center adoption.
• Regulatory momentum: Revuforj sNDA for R/R mNPM1 AML granted FDA Priority Review under RTOR; PDUFA Oct 25, 2025; management expects guidelines inclusion before approval. “We are prepared for launch… regulatory front is hitting on all cylinders.”.

What Went Wrong

• Continued net losses: Q2 net loss of $(71.8)M despite revenue beat, reflecting heavy R&D and SG&A investment to support trials and commercialization; EPS still negative at $(0.83).
• R&D/SG&A pressure: Q2 R&D rose to $62.2M and SG&A to $43.8M y/y, driven by trial activity, sNDA milestones, and commercial scaling; OpEx remains high even as revenue scales.
• Q4 2024 baseline volatility: Initial five weeks of Revuforj yielded $7.68M with ~one-third inventory; S&P Global Q4 estimates were mis-calibrated vs launch timing, creating optics of an apparent miss historically*.

Transcript

Speaker 2

At this time I would like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

Speaker 3

Great.

Speaker 2

Thank you, operator. Welcome and thank you all for joining us today for a review of Syndax Pharmaceuticals' second quarter 2025 financial and operating results. I'm Sharon Klahre and with me today to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer, Steve Kloster, Chief Commercial Officer, Dr. Nick Botwood, Head of R&D and Chief Medical Officer, 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 Anjali Ganguli, Chief Strategy Officer. This call is accompanied by a slide deck that's been posted on the investor page of the company's website. You can now turn to our forward-looking statements on slide 2.

Before we begin, I'd like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by the statements as a result of various important factors including those discussed in the risk factors section in the company's most recent quarterly report on Form 10-Q as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, August 4, 2025. Only a replay of this call will be available on the company's website, www.syndax.com, following its completion and with that I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax Pharmaceuticals.

Speaker 3

Thank you, Sharon, and good afternoon, and thank you all for joining us today. Starting with slide three, first half of 2025 has been a transformational period for Syndax Pharmaceuticals marked by excellent commercial and pipeline execution. We are well positioned for rapid growth in the second half of 2025 and beyond with its first two first and best in class therapies with a combined market opportunity exceeding $10 billion. Revuforge and Naktimvo sales are growing with nearly $100 million in combined net product sales in the first half of the year, significantly exceeding expectations. Notably, Revuforge net revenue increased 43% quarter over quarter to $28.6 million, even with approximately a third of patients pausing treatment to receive a stem cell transplant.

Importantly, we are on the road to profitability with growing contributions from Revuforge and Naktimvo, a strong balance sheet, and an operating expense base that will remain stable for the next few years while fully funding our strategic priorities. Looking to the future, our leadership in the menin space positions us to be first to the frontline and meaningfully expand the Revuforge franchise. We have a similarly compelling opportunity to bring Naktimvo into earlier lines of therapy and additional patient populations. Turning to slide four, let's dive into more detail on Revuforge, the first and only FDA approved treatment for relapsed or refractory acute leukemia with a KMT2A translocation. The continued growth reflects strong uptake, the high unmet medical need, and physicians' enthusiasm for Revuforge.

It is clear following the recent presentations at ASCO and EHA that revumenib has a best in class profile with compelling activity across multiple genetic subtypes, including efficacy data in relapsed/refractory mutant NPM1 AML that surpass any other results seen in the field. The breadth and strength of our clinical data will be the key to our success in acute leukemia, a market that is efficacy driven given the severity of the disease. As we look ahead, the outlook is very promising with multiple drivers that will further solidify our leading position and ensure sustained growth for many years to come. I will briefly highlight those drivers, and the team will provide additional details. First, patient identification and uptake has been strong since launch. We have already treated over 500 patients with Revuforge, with approximately 90% of usage in KMT2A patients.

In just seven months, we have already reached a quarter of the 2,000 patients diagnosed with relapsed/refractory KMT2A acute leukemia each year. Based on the robust activity we have seen in this population and physician excitement around the drug, we expect the total number of patients treated with Revuforge to grow materially in future quarters, particularly as it is the only approved therapy for these patients. Second, Revuforge is increasingly being used in earlier lines of therapy. Emerging claims data show that the use in KMT2A as of this quarter is already being concentrated in the second line. This trend is especially important in oncology because as patients are treated earlier they generally have a higher response rate, a longer duration of response, and a higher chance of proceeding to a potentially curative stem cell transplant.

Thus, as Revuforge is used earlier, we expect to see an increase in the average time on drug for all patients. We also expect to see a high rate of patients proceeding to transplant, a higher rate of patients proceeding to transplant than was observed in our pivotal trial, which on average enrolled a later line patient population. In fact, early indicators suggest that we are already seeing a meaningfully higher transplant rate in the commercial setting. Third, as the group of patients receiving Revuforge post-transplant increases, it should substantially increase the overall duration of therapy. Notably, prescribing physicians tell us they plan to restart patients on Revuforge post-transplant for one to two years. Given the high risk of recurrence, both patients and physicians tell us they are eager to restart the therapy that induced remission, especially when the drug has an excellent tolerability profile.

These three drivers position Revuforge to transform care for KMT2A patients from an acute treatment paradigm with survival measured in a few months to a more chronic disease with the potential to extend survival from months to years. Importantly, relapsed/refractory KMT2A acute leukemia is just the first opportunity for Revuforge. In the near term, we anticipate both the inclusion of Revuforge in the clinical treatment guidelines and the approval of our supplemental New Drug Application, or sNDA, in relapsed/refractory mutant NPM1 AML. The anticipated approval of our sNDA, which was recently granted priority review and assigned a PDUFA action date of October 25, 2025, would expand our addressable population to over 6,000 patients across both genetic subtypes and increase the relapsed/refractory market opportunity for Revuforge in the U.S. to $2 billion.

Importantly, Revuforge is positioned to become the first and only menin inhibitor with a label that expands to mutant NPM1 and KMT2A translocated patients, both adults and children. Based on resounding KOL feedback, the expected breadth of our label will be a major competitive advantage. Looking to the future, we will further extend our leadership into the frontline setting, a U.S. market opportunity exceeding $5 billion. Enrollment is already ongoing in our frontline trial for patients unfit to receive intensive chemotherapy, and startup activities are well underway to initiate our trials in patients able to receive intensive chemotherapy. With Revuforge's best-in-class profile and a multi-year start into the market versus potential me-too competitors, we will maintain our dominant position in this multi-billion dollar market opportunity.

Shifting gears to slide five, to Naktimvo, our first-in-class therapy for chronic graft-versus-host disease, or GVHD, I am pleased to highlight a very successful first full quarter for sales, with our partner Incyte reporting $36.2 million in net revenue. This is up significantly from $13.6 million in the first two months of the launch in Q1. The $50 million in net revenue generated in the first five months of the launch underscores the substantial opportunity in chronic GVHD. Importantly, Naktimvo is already profitable to Syndax, with our 50% share of the Naktimvo product contribution amounting to $9.4 million for the second quarter.

As sales continue to ramp, the cash flow contributions to Syndax from Naktimvo will only grow in significance, with initial Naktimvo sales tracking with the early benchmark set by Rezurock, another product approved in the third-line chronic GVHD setting, now annualizing at more than $500 million in the U.S. within three years of its launch. We are confident that Naktimvo will be a critical component of our success for many years to come. Finally, before I hand the call over to the team, I would like to highlight that we also strengthened our leadership team this quarter with the addition of Dr. Nick Botwood as Head of R&D and Chief Medical Officer. Nick is a medical oncologist by training with over 25 years of experience leading the development and global commercialization of novel oncology medicines including blockbuster drugs such as Opdivo and Yervoy during his time at BMS.

I would also like to thank Bill Murray for his seven years of service on our board and congratulate him on his new role as CEO of Incyte, our partner for Naktimvo. Bill has been an invaluable member of our board as we developed and launched both drugs, and we look forward to working closely with him and the Incyte team as we continue to unlock Naktimvo's value. With that, I will turn the call over to Steve to discuss our commercial progress in more detail. Steve, thank you Michael.

Speaker 5

Let's dive right into our commercial updates on Revuforge and Naktimvo, starting with Revuforge on slide 6. As Michael said, the launch is going very well with net revenue for the second quarter increasing 43% quarter over quarter to nearly $29 million and $56 million generated over the first seven months of the launch. These impressive results are driven by multiple factors including a high unmet patient need, a robust stream of new patient starts over the quarter, expanding breadth and depth of prescribing, excellent formulary coverage, and a product in Revuforge that is delivering for patients. Physicians are observing excellent activity in clinical practice. Revuforge is rapidly becoming a standard of care in our indicated population. Over 1,300 prescriptions for Revuforge have been written for more than 500 patients from launch through the end of June.

Just midway through the year, we have already penetrated 25% of the annual 2,000 patient incidence and are on track to penetrate 50% by year's end. Next, I'm excited to share some of the emerging data and customer feedback that provide important insights into the population of patients being treated with Revuforge and bolster our confidence that the momentum we have seen since launch will continue well into the second half of the year and beyond. First, Revuforge is increasingly being used to treat patients earlier in their treatment journey. Early claims data show that 70% of Revuforge use has been concentrated in the second and third line settings, with approximately 50% of use coming from that second line, which we can also call first relapse patients alone.

Second, we estimate that one third of KMT2A patients treated with Revuforge have proceeded to transplant based on our analysis of medium to large academic institutions using Revuforge commercially. In contrast, one out of four KMT2A patients proceeded to transplant after treatment with Revuforge in AUGMENT-101, which enrolled a significant percentage of later line and heavily pretreated patients. It's important to understand that patients who ultimately proceed to transplant are typically treated with Revuforge for two to four months to ensure complete disease remission before pausing Revuforge for approximately three months to ensure engraftment of the transplant. Notably, physicians tell us they expect to put most if not all of their patients back on Revuforge post-transplant for one to two years.

In fact, in our clinical trial experience and compassionate use program, we have already seen transplant patients who have been on Revuforge for one to two years and were still on drug at the time.

Speaker 3

Of the data cutoff.

Speaker 5

Encouragingly, in the commercial setting we have started to see the first cohort of patients restart Revuforge. Based on a sampling of our accounts, we estimate that at least a third of transplant patients have already restarted Revuforge, with that percentage expected to grow over time as more patients clear the engraftment period. As Revuforge continues to move earlier in the treatment paradigm, we expect this will translate to a significant increase in the average duration of therapy over time. Specifically, we expect the average treatment duration to build to four to six months in the first year of launch.

According to our assessment of patients who started Revuforge shortly after launch, the average time on therapy is already well within the projected four to six month range and we expect this duration to expand to an average of 6 to 12 months as treatment patterns mature in the second year of launch. I'd now like to briefly review some other metrics that underscore the strong position we're in for continued growth in KMT2A and our anticipated launch into relapsed/refractory mutant NPM1 AML. First, we have a broad and growing prescriber base. From launch through the end of June, we penetrated 65% of our higher priority Tier 1 and Tier 2 accounts, up from 44% of accounts at the end of last quarter and continuing to grow into the third quarter.

These Tier 1 and Tier 2 accounts are the centers of excellence in the medium to large academic institutions which represent two thirds of the patient opportunity. Adoption is also increasing across all other tiers too, including in the community setting. Among all accounts that have ordered, the vast majority have ordered multiple times. Second, we have established excellent market access. Formulary coverage is now complete with more than 97% of all lives covered, including commercial, Medicare, and Medicaid patients. Nearly all prescriptions are reimbursed with very few patients requiring our patient assistance program. The average time from prescription to first fill is less than 4 days, significantly faster than typical industry benchmarks. The best in class customer service we are delivering will be a key factor for our long term competitive immunity and brand loyalty.

Notably, Revuforge performance is outperforming yearly launch benchmarks set by other targeted AML therapies on key metrics including revenue and prescriptions, patients treated, activation accounts, as well as formulary coverage. Further, all indicators give us confidence that Revuforge is delivering for patients. Now we are well positioned to develop this medicine into an industry leading franchise with a market opportunity exceeding $5 billion across the relapsed, refractory and frontline setting as outlined on slide 7. Now turning to key Naktimvo metrics on slide 8. Since the beginning of the launch, over 4,000 infusions have been administered to an estimated 700 patients, representing approximately 10% of the third line plus chronic GVHD total market. Of all the patients that have started Naktimvo, approximately 80% to 90% remain on therapy. Today, more than 80% of all bone marrow transplant centers in the U.S.

are using Naktimvo, reflecting solid execution and the strong commercial synergies Naktimvo has with both companies' product portfolios. Importantly, Naktimvo is poised for further growth.

Speaker 1

Given the high unmet need in the.

Speaker 5

Chronic graft-versus-host disease space and the positive experience physicians and patients are having with the drug. Physicians are reporting rapid and durable improvements across organ systems, including some of the most difficult to treat organs like the lungs and skin. These observations align with the results we demonstrated in our pivotal trial and highlight Naktimvo's unique ability to address both fibrosis and inflammation hallmarks of the condition. As shown on slide 9, Naktimvo has a multi billion dollar market opportunity. Our current indication allows us to target the 6,500 chronic graft-versus-host disease patients in the U.S. who require three or more lines of therapy. This represents a $2 billion total addressable market, assuming an average treatment duration of 12 months, which could be conservative given the chronic nature of the disease and the tolerability of Naktimvo.

Notably, in our clinical trial experience, we have seen some patients stay on therapy for more than three years. To summarize, we are very pleased with the progress we've made with both Revuforge and Naktimvo. Early indicators for both launches drive our confidence and continued growth and expansion with both products. With that, I'll hand the call over to Nick.

Speaker 1

It's a pleasure to be on the call today and to have the opportunity to build upon the exceptional work that Syndax Pharmaceuticals has done, pioneering two new therapeutic approaches. Starting on slide 10 with Revuforge, revumenib, an asset which has the potential to become the menin inhibitor of choice across the breadth of menin-driven acute leukemias. In the second quarter, we advanced our leadership position with a strong presence at EHA and ASCO, including two important publications at EHA. We and our collaborators presented the latest data for Augment 101 and the BEAT AML trial. I'd like to highlight two key takeaways from these. First, the Augment 101 data demonstrate the breadth of revumenib activity across relapsed/refractory mutant NPM1, KMT2A, and mutant NUP98R acute leukemias.

Notably, in the pivotal NPM1 population, nearly half of the patients achieved an overall response, and in a subgrouping analysis, a median overall survival of 23 months was observed among these responders. These data, along with the rate of CR/CRh and duration of CR/CRh, are encouraging results that really stand out in this population. The compelling results are particularly relevant as efficacy is paramount in patients with acute leukemia given the severity of disease and the need for improved outcomes. Data from the pivotal NPM1 population were recently published in Blood, an important milestone that makes these landmark results available to the clinical community. Turning now to NUP98R, Phase 1 data from the Augment 101 trial show an overall response rate of 60% among five patients with relapsed or refractory NUP98R AML, which is an aggressive, difficult-to-treat form of acute leukemia.

While the sample size is small, physicians are encouraged by these data and further trials are underway that will evaluate revumenib in NUP98R as well as other acute leukemias associated with HOX upregulation. The compelling and consistent results observed with revumenib across these genetic subtypes highlight the potential for revumenib to transform the standard of care for potentially 50% or more of all patients with AML. Moving now to the second key takeaway, the BEAT AML data presented at EHA and simultaneously published in the Journal of Clinical Oncology are encouraging. As a reminder, this is a Phase 1b trial evaluating revumenib in combination with venetoclax and azacitidine in newly diagnosed older patients with mutant NPM1 or KMT2A-rearranged AML.

The data support the combinability of Revumenib with venetoclax in the frontline setting and the potential for the triplet to provide high rates of complete remission and MRD negativity, two treatment goals associated with improved clinical outcomes. The overall response rate was 88% and the complete remission rate was 67% in the 43 patient intensive treat population. Importantly, MRD negativity was 100%. By centralized flow cytometry testing, both the CR and MRD negativity compare very favorably to the historical rates reported in the VIALE-A trial of venetoclax. Looking ahead, we have many publications and presentations planned at major upcoming medical congresses, including the anticipated presentation of the first real world evidence before the end of the year. Given the strong clinical interest in real world evidence, we are thrilled to be working with leading cancer centers and physicians to present outcomes for this new therapeutic class.

Turning now to slide 11 and our further work developing Revuforge and Naktimvo into industry leading franchises, I want to highlight three key points. First, we are laser focused on extending our leadership position in menin inhibition into the frontline setting. Enrollment is well underway in the pivotal EVOLVE-2 trial of Revumenib in combination with venetoclax in newly diagnosed patients with mutant NPM1 or KMT2A rearranged AML who are ineligible or unfit to receive intensive chemotherapy. EVOLVE-2 is a phase 3 randomized double blind placebo controlled trial. This trial will have dual primary endpoints of complete remission and overall survival to support potential accelerated approval and full approval respectively. While the trial is open to both NPM1 and KMT2A patients for enrollment, the primary efficacy analysis will be based on the NPM1 population.

This is the population that is more commonly ineligible for intensive chemotherapy due to advanced age or other comorbidities, unlike the KMT2A population which tends to be younger and fit enough for intensive chemotherapy. We are conducting this trial in partnership with the HOVON Group, a leading clinical trial cooperative known for executing clinical trials that deliver practice changing data in hematology. Second, in the newly diagnosed fit population study, startup activities are well underway for two randomized placebo controlled trials with studies of Revumenib in combination with intensive chemotherapy followed by maintenance. We have named these the REVEAL trials. One trial is designed for patients with an NPM1 mutation and one for patients with KMT2A rearrangements. We expect to initiate in the fourth quarter of 2025 in the NPM1 population. The study will have dual primary endpoints of MRD-negative CR and event-free survival.

These are important clinical endpoints in this population and could have the potential to support accelerated approval and full approval respectively. We expect that high awareness of Revuforge and positive experience in the clinic will drive rapid enrollment across our frontline programs in support of our trials in the fit population. We are also looking forward to reporting phase 1 data in newly diagnosed patients treated with revumenib and intensive chemotherapy in the fourth quarter of the year. Lastly, I want to highlight the work underway to develop Naktimvo or axatilimab for additional patient populations in partnership with Incyte. Several important trials are well underway, including a phase 2 trial studying axatilimab in combination with ruxolitinib and a phase 3 placebo-controlled registration-directed trial investigating axatilimab in combination with steroids beyond chronic graft-versus-host disease.

We have an ongoing phase 2 placebo-controlled trial called MAXIMIZE, which is studying axatilimab in idiopathic pulmonary fibrosis or IPF. Enrollment is proceeding very well and we are on track to complete enrollment in the fourth quarter of this year with top-line data anticipated in the second half of 2026. We are optimistic about the potential for axatilimab in IPF and beyond, given the strong mechanistic rationale and preclinical evidence, along with the remarkable lung response observed in the AGAVE-201 trial. With that, I will hand the call over to Keith to discuss our financials.

Speaker 3

Thank you, Nick.

Speaker 0

Earlier this afternoon we reported detailed second quarter 2025 financial results and I'll touch on a few of these key points on slide 12. For the second quarter 2025 we reported Revuforge net revenue of $28.6 million. Quarter over quarter sales growth was driven by demand as inventory levels remained stable to the first quarter at two to three weeks. We expect quarterly growth to meaningfully accelerate over the next year with the potential approval in NPM1 as well as the benefit of a longer duration of treatment in KMT2A-rearranged acute leukemia. Also in the second quarter, Incyte reported Naktimvo net revenue of $36.2 million with inventory accounting for less than 5% of sales. Syndax reported $9.4 million in the Tempo collaboration revenue after deducting the cost of sales and commercial expenses. Importantly, Naktimvo is already a positive cash flow contributor to Syndax in just its.

Speaker 5

First full quarter of sales.

Speaker 0

We expect the Naktimvo margin contribution, defined as collaboration revenue recorded by Syndax as a percentage of Naktimvo net sales, to be in the 20% to 30% range in the near term, and we anticipate this will improve longer term as sales grow and the partnership leverages a largely fixed expense base. We expect continued sales growth. Given chronic graft-versus-host disease remains a chronic disease where there is a high response rate to Naktimvo, the average patient will likely remain.

Speaker 3

On therapy for years.

Speaker 0

R&D expense was $62.2 million in 2Q with the increase versus the comparable prior year driven by costs related to ongoing trials and increased activities to support commercialization. SG&A expense was $43.8 million with the increase versus the comparable prior year driven by costs related to the U.S. commercial launch of Revuforge. With regard to expenses, you can find our guidance for the third quarter of 2025 and full year in the press release we issued today. Notably, we announced today that we expect our operating expenses to remain stable over the next few years. Turning to the balance sheet, we continue to maintain a strong financial position with $518 million in cash equivalents and short and long term investments as of June 30th. As I've said in the past and I reiterate today, we expect Syndax Pharmaceuticals will reach profitability with current funds on hand.

In fact, my confidence is higher today given both drugs are outperforming our original forecasts. We are confident we can execute commercially and also deliver on our integrated clinical development plans for both drugs while keeping operating expenses at today's levels. Our combined cash with increasing Revuforge and Naktimvo cash flow contributions alongside a fixed expense base will drive our path to profitability. Turn the call back over to Michael.

Speaker 3

Thank you, Keith. Before we move to Q&A, I want to take a moment on slide 13 to reiterate how well positioned Syndax is as a company. Revuforge and Naktimvo are outperforming expectations as strong physician enthusiasm drives robust adoption. We have a very sizable cash balance that will allow us to control our destiny and achieve sustained profitability with what we know are two dominant products in multi-billion dollar markets. A few key points to recap on Revuforge: Revuforge is the only FDA approved therapy for KMT2A patients and we have already identified and treated over 500 patients since launch with 90% of those being on label. Physicians are treating earlier relapsed/refractory patients, which portends more favorable outcomes. Revuforge is getting patients to transplant at an even higher rate than what was observed in our clinical trials.

Physicians are eager to put their patients back on Revuforge post-transplant and we have begun to see evidence this is happening. Further, all key indicators of demand remain strong in July, which gives us confidence in the continued momentum of this launch. Ultimately, in the future, KMT2A patients on Revuforge and with the aid of transplant will likely remain on drug for a year or more with the best hope of improved survival in the near term. We are poised to expand into relapsed/refractory mutant NPM1 AML, pending the FDA's anticipated approval of our sNDA. Additionally, we are extending our leadership position to the frontline. With enrollment already well underway in our first pivotal frontline trial, it is important to keep in mind that acute leukemia is an efficacy-driven market and it is clear that Revuforge is a highly effective therapy with a favorable safety and tolerability profile.

Finally, I will also note that we retain worldwide rights to Revuforge and patent protection continues through at least the late 2030s. Turning to a few key points on Naktimvo, in collaboration with our partners at Incyte, the leaders in GVHD, the Naktimvo launch is off to an exceptional start. It is well positioned for growth in a $2 billion market for third-line chronic GVHD treatments. With patent protection extending to the late 2030s, Naktimvo provides a novel option in a market that needs new mechanisms of action. Patients initiating therapy may continue drug for years. We and Incyte continue to advance development programs designed to bring this drug into earlier lines of chronic GVHD therapy and other diseases, starting with IPF. Naktimvo's financial contribution to Syndax is already profitable in its first full quarter. This will grow materially as sales ramp and operating margins continue to expand.

Syndax has never been in a stronger position than we are today and look forward to sharing additional progress with you in the months ahead. As always, I want to close by thanking everyone who has supported us on this journey, including most importantly, the patients and families who have placed their trust in us as well as our dedicated Syndax employees and long term investors. With that I would like to open the call for questions, Operator.

Speaker 2

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 would like to withdraw your question, press star and the number five. Once again, we'll pause a moment to compile the Q&A roster. Our first question will come from Anupam Rama with JPMorgan. Your line is open.

Hey guys, thanks so much for taking the question. Just wanted to ask a question about this path to profitability. Keith, I know you mentioned operating expenses staying stable over the next couple of years, but what are you assuming in terms of the top line, in terms of treatment settings for Revuforge and Naktimvo, can you get to profitability on sort of the refractory settings alone? Is there some sort of assumptions on frontline expansion baked into getting to profitability? How should we be thinking about that?

Speaker 0

Thanks for the question. We have been pretty consistent since November that we expect to get to profitability with the existing resources that we have today. I would say the only thing that's changed since then is that we have two launches that are both outperforming our expectations. The new disclosure that we provided today is stable operating expenses for the foreseeable future, say the next two to three years. We are doing that because we want to give the buy side and sell side, we want to give the street the appropriate data for them to model our business better so you guys can get to the same answer that we're getting to. We're not giving revenue guidance per se on a Palm.

I will say that given the timelines to get to approval in the frontline setting, you can definitely assume that we are getting to profitability on the relapsed/refractory indications alone. I think I just want to add the guidance that we are giving, stable operating expenses, is not to be taken as we are taking our foot off the gas pedal because we're not. The modeling that we've done allows us to fully invest in the continuing successful launches of two products executing commercially but additionally executing our integrated clinical development plan as Nick.

Talked about.

Both for Revuforge and Naktimvo. I think we're in a pretty unique position to control our own destiny. We have two launches that are both outperforming and a stable expense base. The team has worked extremely hard to put ourselves in this position to specifically reward our shareholders for their investment. Thanks for the question.

Thanks so much for taking the question.

Speaker 2

Our next question will come from Corinne Johnson with Goldman Sachs. Your line is open.

Hi, this is Kevin Strangon for Corinne. Good afternoon. I had a quick question on the patients moving on a transplant. After how many cycles is that typically occurring, and for patients that are going back on drug, you said that it was about a third of patients so far. What are your expectations for the ultimate proportion of patients that will move on to maintenance therapy?

Speaker 3

Is this something you'll report quarterly?

Thanks.

Kevin. Thanks for your questions. I think we're very encouraged by what we're seeing with patients going to transplant. As we had noted early on when we first started developing this drug, patients do respond very quickly to Revumenib, and that's usually within the first few cycles. That generally is preceded by a transplant thereafter. That transplant can happen very quickly. It can happen within a couple of weeks. That's usually for KMT2A patients a goal to get them to transplant as quickly as possible. A few cycles, certainly two to three, getting into remission, moving to transplant. That's how it generally works. We do see in our trial about a third, in our commercial experience, rather, about a third of patients getting to transplant. We expect that number to accelerate. The reason for that is we are treating patients earlier and earlier in the treatment paradigm.

Physicians had told us they would put patients on Revuforge in sort of second line or first relapse. We see a vast majority of our patients being treated now in second and third line, which is a great outcome for them. Generally needs patients to stay on drug longer, do better, and have a better chance of going to transplant. We do think that that one third number could go up from here and we expect it to. Ultimately, we will continue to track this over time. It's early days in the launch and we do expect to report on that metric at some point going forward. In terms of maintenance, I think your last question, patients are coming back on maintenance. We know that.

We've reported that based on the earliest patients, earliest cohort of patients that we've seen, about a third of patients have already come back, again early days of launch. That's a very good indicator. Physicians have told us repeatedly that they expect to put the vast majority of their patients back on maintenance. That could range anywhere, 70%, 80%, 90% of the patients assuming that they're eligible for maintenance. That's, I think, a goal for us and we'll see that play out over time.

Speaker 2

Thank you for taking my questions. After the second full quarter of launch, could you comment on the latest observation of treatment duration for Revuforge in real world practice, and also how do you expect the treatment duration to evolve over time, especially now when you have more earlier second lines of patients on the treatment?

Thank you, Kelly.

Speaker 3

Thank you for the question. First question, duration in the real world, what are we seeing? I'm going to hand that to Steve to answer that.

Speaker 5

Yeah, thanks Kelly, for the question. You know, we'd always predicted this first year would be roughly in the four to six month range for average duration, and based on data that we've been able to see, we're very confident that's the case. We take a look at the earliest cohort of patients, and they're certainly within that range that will improve over time. Appreciate the mention of the earlier line patients, which were also in our prepared remarks, and that's a real phenomenon. This happened very, very quickly. The first patients at launch were not these patients. They were likely more third, fourth line patients, but it moved earlier very, very quickly. That portends well in terms of treatment duration. Better chance of success of getting to a transplant and more likely, as Michael just described on the previous question, the concept of returning to drugs.

That will build over the course of this year. We would expect in 2026 that that average treatment duration will be six to 12 months and could skew towards the latter end of that as the launch matures and we're able to move patients earlier and physicians gain more experience.

Speaker 2

Thanks very much. Just one more question if I may. On the cost side, how could we expect a change quarter over quarter for the rest of the year?

Thanks.

Speaker 3

Thanks Kelly.

Speaker 0

I'm going to ask you the cost side.

Speaker 3

The costs just change over quarter to quarter.

Yeah.

Speaker 0

Yeah, Kelly, thanks for the question. We gave guidance today that we expect—we changed the way we gave guidance. Actually, we used to give guidance with respect to OpEx inclusive of non-cash, but we heard from investors that they were more focused on our cash consumption.

Speaker 1

Today we changed the way we.

Speaker 0

Gave guidance to focus on our operating expenses less non-cash. We said that for the third quarter we expected that to be $95 to $100 million and reiterated our full year guidance that we expect that to be now $370 to $390 million. We implicitly gave fourth quarter guidance because we have two quarters of expenses, give third quarter guidance. The fourth quarter guidance that is implicit through the math is almost exactly even with our third quarter guidance for research and development plus selling, general, and administrative expenses less non-cash.

Speaker 2

Thanks very much. Congrats on the quarter. Great quarter.

Speaker 0

Thank you, Kelly.

Speaker 3

Thanks Kelly.

Speaker 2

Our next question comes from Phil Dodell with TD Cowen. Your line is open.

Good afternoon. Congrats on the two successful launches. A couple questions from us. First on the KMT2A launch for Revuforge, you suggested, I think, that 25% of patients with KMT2A for a year have initiated therapy in the second quarter, which suggests in the incident population that the penetration is probably quite high. Can you give us a sense of where you think the penetration is in the incident KMT2A population here today in Q2 of 2025 and kind of where could that go at peak? I guess we're trying to understand how much growth could be left over the next couple quarters before the label expansion. Second, on the NPM1 label expansion, any update on inclusion of NPM1 in the NCCN guidelines?

Speaker 3

Yeah, Phil, thanks for the questions. The first question related to KMT2A and penetration in 2025, I think we're going to clarify that. I'm going to ask Steve to clarify.

That a little bit.

Yeah.

Speaker 5

Hey Phil, thanks for the question. Yeah, I mean, we've treated over 500 patients since launch. We often measure ourselves versus that overall available market of 2,000 KMT2A relapsed/refractory AML and all patients. Since launch, we estimated we've covered about 25% of that population. I think one thing to think about is 2,000 patients over the course of the year, not at any one point in time. There's going to be some variability as those patients are identified and diagnosed. We feel great about finding patients. Revuforge is very early. It's become the standard of care. Physicians are, you know, diagnostic testing is prevalent, so they're finding patients. Over the course of the quarter, the number of new patients coming in has been strong and robust. We expect that to continue for the rest of this year. We'd expect to finish the year roughly at 50% of the identified population.

We think that would be a great launch, doing a lot of good for patients, but also really filling the funnel for Revuforge in our initial indication.

Speaker 3

In terms of your second question, Phil, about label expansion, NPM1, you had asked about the guidelines. Comment is, you know, we've submitted to the guidelines, we published in Blood. The data is available. Very helpful to our medical team to help educate in advance of launch guidelines. We don't have perfect information about when the guidelines will be updated. Could be any day. We do expect it before we get approval in NPM1, and that will help aid our launch even more by having guidelines. I think that's important for payers as well as physicians. Looking forward to that. Everything is all set up and ready for launch. We're just eager to continue to make progress.

Great. Can I just follow up on the first one? There's 2,000 patients in a year. It's reasonable. Assume 1,000 patients in six months. It's been six months since launch. 500 patients have started therapy. It's 50%. You're suggesting 50% of the identified population by the end of the year. Obviously, more and more patients will go on over time, but this is a very sick population, so some are going to fall off. Are you kind of at peak penetration now? Therefore, revenue growth over in the KMT2A population, specifically revenue growth over the next 6 to 12 months, will be basically dependent on patients living longer and the duration of therapy increasing.

Speaker 5

Phil, there's a lot of upside. What we're saying is over the first year, there's 2,000 eligible patients. We're going to get to 1,000 of them over the year, right through the end of 2025. We can go higher than that. There is definitely some upside. I'd say we're not at peak penetration right now. There are more patients that will ultimately be diagnosed. We have a great deal of momentum executing at a very high level. There is a lot of upside still on KMT2A. The next driver of growth on top of that is going to be NPM1.

Speaker 3

Right.

Speaker 5

the PDUFA date in late October, that'll be the next leg of the stool. That's obviously a much larger patient population, but that's how I would think about growth on the new patient side.

Speaker 3

Yeah. I would just add, Phil, obviously other part of this is duration. As you brought up, the duration of therapy is going to be a key driver for KMT2A. As you treat patients earlier, more patients are going to transplant. We're seeing that evidence in our commercial experience. You're going to be able to put more patients back on therapy. We're seeing that early evidence as well. We expect those to be major drivers year over year. As you've added, you're adding new patients, so new patient starts, plus the compounding effect of duration of therapy for these patients who come back and stay on mean. I think there's quite a bit of growth left to do.

That's very helpful. Thank you. Thank you, Phil.

Speaker 2

Our next question comes from Peter Lawson with Barclays. Your line is now open.

Thank you so much. Congratulations on the call to think about the looming FDA approval. What can you tell us around any remaining open items or feedback you've got from the FDA and anything that helps add around the confidence around the FDA approval? The second question would just be around the maintenance setting and what % of patients do you think you can eventually get on the maintenance setting? Thank you.

Speaker 3

Yeah, Phil, thank you. Sorry, Peter, thank you for the questions. First, on FDA approval, I'm going to turn it over to Nick. Are we learning anything new?

Yeah.

Speaker 1

Thank you. The submission is progressing very well. We have our PDUFA day. We've been working very closely with the FDA. It's a team we know well now, and things are progressing very well according to plan. We're looking forward to the PDUFA as guided on October 25th.

Yeah.

Speaker 3

With regard to your second question, maintenance, what % do we think we can put back on? I think we had heard from physicians, we continue to hear from physicians, the vast majority, if not all of their patients, they'd like to put back on maintenance. We know that not every patient will be eligible for maintenance, but with physicians treating patients earlier and the majority of the treatment being concentrated in second line, even at this early stage of launch, that's a very good sign that physicians will drive hard to take more patients to transplant, which gives us more opportunity to put them back on once they clear their transplant and graft. I can't give you exact %, but it should be a very high % of patients.

Thank you. Maybe I circle back on the first question just around the FDA. I know there's always level of uncertainty, and it seems to be a pipe and level of uncertainty. Have you seen any changes in that dialogue, any moving targets?

Yeah, Peter, I think that's clearly, that's not what's. There's nothing to indicate that it's anything other than really very good progress. We have priority review. We're under our tour. We're having consistent quality dialogue with the agency. The feedback has been very good. We have a PDUFA date that's coming close and we're prepared for launch. I think everything on the regulatory front is really hitting on all cylinders. No indication that it's anything other than that.

Perfect. Thank you so much. Thanks, Peter.

Speaker 2

Our next question will come from Michael Schmidt with Guggenheim. Your line is now open.

Hey guys, this is Paul. I'm from Michael. Thanks for taking a question. I have two on the frontline combo opportunities. First, on the recent EHA updates from the AML, it seems pretty clear that revumenib is enhancing the CR and MRD compared to venetoclax alone. We'd love to get your thoughts on the degree of OS improvement you're seeing and whether or not you plan to provide another survival update in the study with additional follow up. Secondly, just looking ahead to the intensive chemo combo, can you sort of talk about how we should think about CR and MRD benchmarks for that combo and what to expect for the update later this year?

Speaker 3

Thank you, Paul. Thank you so much for the questions. I'm going to turn it over to Nick to touch on the B AML.

Speaker 5

Piece of this first.

Speaker 1

Yeah, thank you for that. Firstly, very encouraged by the BEAT AML study. I mean, this was an important study. We were able to confirm a dose to take into F3 and show that the dose was tolerable and also, as you say, report out some early efficacy measures. I think the efficacy measures that are probably most important in this setting are the complete response rate and MRD negativity. Because remember, this is a relatively small 43 patient phase 1b study, so interpretation in that context is quite difficult. The CR rate and MRD negativity were very high. There were 67% and 100% MRD negativity, which as I said in the earlier comments, are really a step change above what you expect from historical controls. Now, when you look at the overall survival, you have to remember that the median follow-up is quite short.

Currently, the median follow-up was only around seven months and it's over 20 months in the RDA. Certainly, we expect as those data mature, you'll see some changes in the median OS. There's a lot of steps in the Kaplan currently which suggests the median is quite unstable and it's therefore very difficult to estimate. Having said that, it's already very comparable or somewhat similar to VRE, which you must also recall is a very heterogeneous group of subtypes of AML with a variety of different genetic mutations. When you actually benchmark against NPM1, you probably find the median overall survival is a little less than was reported and closer to 10 months.

In summary, we remain extremely confident in the profile of the combination of venetoclax and I think it gives us a very high level of confidence that the EVOLVE-2 study that we're doing in collaboration with HOVON will read out well in due course. With regard to the intensive chemotherapy and the MRD negative CR, we think both CR for unfit and MRD negative CR for both plasma and bone marrow are important endpoints in this setting. They've been shown to predict for improved outcomes around event-free survival and OS and believe that they could serve as.

Speaker 3

Surrogates to support accelerated approval.

Speaker 1

Those are obviously discussions we have had with the agency and have refined those. They are built into the protocols as dual primary endpoints, which means that they are independently powered. You could have either the surrogate CR endpoint or the time to event endpoint, whether that be OS or EFS, to give a positive study. We remain quite confident that both of those should read out favorably. As previously indicated, we will be updating data for our combination with intensive chemotherapy for fit patients, specifically the seven plus three regimen from our own sponsor study, the 708 study. We will also likely hear from the study we're doing in collaboration with the NCI, which is also a combination of intensive chemotherapy in the latter part of this year.

Those data should both confirm the dose tolerability and also early signs of efficacy to support our phase 3s with intensive chemotherapy. Overall, we feel very confident about the programs and we really have very good momentum going into the latter part of this year.

Thank you, Paul. Thank you.

Speaker 2

Our next question comes from Yigal Nochomovitz with Citi. Your line is open.

Hey Michael and team, thank you. On the 1/3 of the patients that have restarted after the transplant and then the 2/3 that don't, could you just clarify. Of those 2/3, are they not expected to restart or is it simply that they're not ready to restart and the expectation is that most of them in fact will restart.

Speaker 3

Thanks for the questions. It's the latter. Right. Clearly we said early days, one third have restarted already, which is very encouraging to us. This does leave 2/3 of those patients who could restart, and we expect a very high proportion of patients to restart out of that cohort as well. It's an ongoing, evolving landscape of patients coming back from transplant and going on to maintenance. We haven't excluded that 2/3. We're actually waiting for those to come back.

Okay, and then just can you clarify on the mechanics? Do they need to get a reimbursement approval again when they come back after the transplant, or is it seamless and they just start Revuforge again without a second need to request the reimbursement?

Steve, you want to just—yeah, our expectation, you got.

Speaker 5

It's pretty seamless. I mean, there's typically in this industry, I mean, it's six-month renewals, which are pretty standard, that may be the case here. Typically, if you're within that window, they'll restart without any challenges from payers. Even when there's a restart or a reinitiation of a prescription, we have not heard of any challenges with doing that. Payers' coverage, the formulary coverage is over 97%. Claims are being reimbursed on a regular basis. I'm not expecting any challenges with restarting at all.

Speaker 3

Okay.

I'm just curious if you could speak in a little more detail about this first wave of the real world evidence that you're going to have at the end of the year. Can you expand on that a little, please?

Maybe Nick can take that.

Speaker 1

Yeah, I'd be happy to. We're obviously working with leading centers across the U.S. and leading thought leaders, and we're at the point now with the drug being used in clinic from commercial supply. We're getting some interesting series of data from physicians' experience in the real world. We're collaborating closely with them to collate those data and look forward to presenting those real world experiences from those centers in the latter part of this year. I think we're uniquely well placed to be able to do that with these new therapeutic classes. We're now available commercially in the clinic and can actually report real world experience versus just clinical trial experience. I think those data and how the drug is getting used in the real world will be very insightful, and we're looking forward to those reporting out.

Later in the year. Thanks. Thank you.

Speaker 2

Our next question will come from Justin Zelin with BTIG. Your line is open.

Congrats on the strong quarter. Looking ahead to the October 25th PDUFA day for NPM1 label expansion, can you walk us through how you're preparing the commercial organization for launch readiness, and do you anticipate a meaningful incremental uptick in the population right out of the gate, or would it be more gradual?

Speaker 3

Yeah, thanks Justin for the questions. I'm going to turn it over to Steve to touch on the launch readiness, launch maintenance. Yeah.

Speaker 5

We're in market, Justin. Appreciate obviously with another indication, which would be different from someone who's entering the market. Here's how I would think about this launch. Part of the success or the preparation is doing a great job right now. Physicians, we're leveraging that market experience in KMT2A R patients, understand how to dose the drug. They appreciate the dosing options that they have, how they initiate treatments, how to manage any AEs that might occur in treatment initiation, getting through them, what they expect from efficacy, and how to bring the drug in. How do they as a treatment center prefer to bring the drug in? That's one piece.

Speaker 3

I think the other piece is we're

Speaker 5

In the same audience right now. When we think about treatment centers that treat KMT2A, they're the same ones that treat mutant NPM1.

Speaker 3

We are already there.

Speaker 5

We've got a best-in-class customer-facing team. They have excellent relationships. They understand the space, they understand how these treatment centers treat. They've already got a leg up once the indication is granted on the PDUFA. The last piece is just a great drug, right. We believe we've got a best-in-class profile with NPM1 data. Any physician would tell you most important across any of these types of agents is does the drug work and does it work better than anything else that's out there. We believe we've got a winner in Revuforge. The efficacy data really screams, physicians tell us that. I think as Michael may have pointed out in his comments, the fact that we've got multiple indications for one menin inhibitor, that is a big deal. That is not something that's minor and that holds for treaters. It also holds for payers.

Right.

Payers. When looking at a second indication like they are with Revuforge, it's an easy add and that will get us ahead.

Speaker 3

Those are the, those are the.

Speaker 5

Things I think about in terms of uptake. Absolutely, we're expecting a bump.

Speaker 3

Right.

Speaker 5

We know that right now the usage outside of KMT2A translocation is small. We maintain it's about 10%. We'll call it spontaneous or off label use. The biggest bang for NPM1 is going to be at the indication granting.

Right.

When promotionally, commercially we can stand behind a drug, we think it'll make a big splash. Physicians are ready for it, so we'll expect a decent driver at that time later this year.

Speaker 3

I'll just add that, adding NPM1, you know, you take your patient population from about 2,000 patients to 6,000 patients, that's a big difference. We expect it to be a really important driver not only starting in the end of the year, but going into next year and beyond. It's important to be first. It's important to have the best profile. We have both. We're in good shape.

Great. Thanks for taking the questions.

Thanks, Justin.

Speaker 2

Our next question will come from Saleem Syed with Mizuho. Your line is open.

Great. Hey guys, congrats on the quarter. Mike, Keith, maybe just a couple from us. One on Naktimvo. I apologize, this is going to be another math question, but when I look at 2026 consensus currently I think around $240 million or so on the end user sales number and just kind of like looking at some of the numbers that have been released between yourselves and Incyte. There were $45 million of sales, I think or so ex inventory. That's our number. I think 4,500 infusions. I think they mentioned that on their call. I know you guys are saying over 4,000, but they said 4,500. It looks like about $10,000 net price per infusion. Assuming you know the trial duration of 10.3 months, you start to get to this price of $225,000 before the 22 infusions that would take place.

Assuming you're, you know, they talked about having 1,000 patients at the end of this year perhaps. You start to get to these numbers of $225,000. Again that's using the 10.3, not the 12 month duration. No additional inventory impact, no additional penetration, no growth. Is it just me or is that number just incredibly light? The 2026 Naktimvo end user sales number, just based on that math. Is there something I'm missing?

Speaker 3

Thanks for the question, Celine. We're tracking with your, we're trying to track with your math here. Keith, bunch of comments.

Speaker 0

Yeah, trying to track you with your math. I mean, I think going back to some of the comments that Mohamed and Bill made on the call that Incyte had last week, I think they were asked a question about peak sales and there was a response that included an estimate of, you know, looking at, you know, looking at the Rezurock launch and comparing the Naktimvo launch to that launch. You know, we think we and Incyte both think that that could be a.

Speaker 3

Low watermark for us.

Speaker 0

If you just look forward, you know, Michael made comments in his prepared remarks that that third full year of launch, Naktimvo's annualized in over $500 million U.S. only. Again, we think, you know, looking forward to 2028 when we'll still only have a relapsed/refractory, you know, we don't expect to have necessarily frontline indications by then, but you know, we definitely think this can be several hundred million dollar product in the next few years.

Okay. Yeah, I mean they did talk about the 1,000 sort of at the end of the year from the current 700 or so. That's sort of the basis for the map. I understand your point. Just quickly, I guess on your slides it looks like you updated your EPPE data for the NPM1 from 3,000 to 4,500, just to 4,500. Is there something you guys did on the EPPE to make you more confident around the upper end of that range, the one that's $5 billion TAM?

Speaker 3

Yeah, thanks for the question. The only thing that, you know, a lot of things give us confidence, I think when we think about the epidemiology, we're treating patients now really much more in the second line. You're going to capture the operating of that number if you continue to treat in that capacity. That's how physicians tell us they want to treat, they want to treat earlier. That gives us, you know, confidence to kind of capture the upper end of that range. Just making a comment. I want to go back for a second to your Naktimvo question. You mentioned duration at 10 months. I would just point you to the fact that this is a drug that physicians intend to keep patients on potentially for years. I mean this is a very efficacious drug. We believe that there's potentially a lot of upside in duration of therapy.

I would be thinking about your assumptions there and we'll track with that obviously over time. I think that's one thing that stood out to me in your math that you might want to take a look at.

Oh yeah, it was meant to be conservative. Yeah.

Yes. No, I think it's as a conservative estimate, understand where you're coming from. I think we are encouraged by duration here and what this category and what specifically this drug and mechanism can bear. I would just pay attention, especially.

Speaker 0

Five months into launch, Incyte made comments that 80% to 90% of patients that started on therapy are still on therapy.

Very good point. Fair enough. Thanks so much, guys. Appreciate it.

Speaker 3

Thanks, Elaine.

Speaker 0

Thanks, Elaine.

Speaker 2

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

Speaker 3

Great.

Thanks for taking my questions. Noticeable graphs on the quarter. A couple for me, one just on the $20 million Revuforge revenue, could you talk about the percentage of revenue that is inventory, and also how much of that is coming from new PatientStart versus refill.

Thanks, David.

Speaker 0

David made comments that I made, said that you know, that only. I'm sorry, let me back up. The demand in the quarter was driven by patient growth. Patient demand inventory stayed level two to three weeks, and we expect that to be the case going forward. You know, it's pretty typical of a drug that's used, you know, distributed, using specialty pharmacy, specialty distributors, two to three weeks of inventory. We don't expect that to grow.

Got it. Okay. Just another question on the patients on the stem cell transplant. Right now you have about 33%, a quarter of it or one third. I'm just curious, do you expect this to increase given that you have 50% of patients currently treated in the second line? How should we think about this going forward in terms of the increase in stem cell transplantation?

Speaker 3

David, thanks for the question. We tried to get at this a little earlier. Look, I think the transplant rate at a third. Remember in Augment 101 we were at about a quarter of patients going to transplant. Now we're at about a third. If we're treating patients a lot earlier, instead of third and fourth line, more second and third line. 70% of our prescriptions are in that second and third line. Transplant rate could go 50% higher, we don't know. We are expecting it to materially change over time and get better. What gives us confidence is that we know if we treat patients earlier, they tend to get to a higher level of response, higher rate of response and are more eligible or will be eligible for a transplant. I think that's what's giving us confidence.

We don't have the upper bound of that, but we do expect it to grow over time.

Thank you for taking my questions. Thank you, David.

Speaker 2

Our next question will come from Jason Zemansky with Bank of America. Your line is open.

Good afternoon. Congrats on the quarter and thank you so much for taking our questions. A couple from us, if we may, based on your earlier comments. First, being of the 2,000 or so relapsed/refractory KMT2A patient, can you give us any color on your assumptions regarding the overall peak penetration here? Similarly, given the comments regarding the overall opportunity in relapsed/refractory, at least as far as your cash runway goes, any color on your insights or assumptions as far as the competitive split in the NPM1 population look like? Thanks.

Speaker 3

Thanks, Jason. Thanks for the question. First question related to peak penetration, our estimates on peak penetration for the 2,000 KMT2A patients. Steve, do you want to take a shot at that?

Speaker 5

Yeah, I think we can. As we said, we've already covered 25% of the population. We'll get to 50% of that. There's some upside to that. We haven't guided to a number on.

Speaker 3

Peak, I think we'll.

Speaker 5

Be at levels at a thousand that are close to the upper end of models that some of you may have. We think there's some, you know, beyond that. Treating earlier, I think, as Michael said, brings more people in. Just remember, Jason and everyone, that in KMT2A there's no one in the near term coming to market. It is really white space, and Revuforge is already the standard of care after just seven months on market, and physicians are using it that way.

Speaker 3

Yeah, Jason, I would just say there's penetration into a market. It never happens within one year, always takes in oncology more than that. I think we expect, as Steve said, within 1,000 patients this year. We have more work to do next year and the year beyond. That's, I think just in terms of new patient starts, in terms of really building this market. I'll say it again, duration of therapy is going to be key.

Right.

Physicians treating earlier, we know that that's going to give us the best outcomes. Patients are going back on therapy post transplant. That will ultimately compound the revenue as it goes forward. Patients staying on drug for long periods of time. I think those are the real drivers, those two things, it's actually pretty simple. It's not just about how many patients you could penetrate on KMT2A. It's how long they stay on drug as well and then overall opportunity. You had mentioned the second question being what do you, what's your estimate for competitive split in NPM1? Look, I think we're first, first to market. We know we have best profile. I think the data speaks for itself. We're feeling very confident about that. We would expect to have a significant percentage of that market and dominate in NPM1 as well as KMT2A.

We feel very positive about the fact that we're entering the market first and that's essentially how we see it. We can't guide exactly to what the split would be, but we would expect to have a big share.

Fair enough. Appreciate the color. Thanks, guys.

Speaker 2

Our next question will come from George Farmer with Scotiabank. Your line is open. Hi, this is Chloe on for George. Thank you for squeezing us in, a couple from us. Can you talk a little bit about the monitoring that's happening in the real world right now for potential cardiac AEs, how they're being managed, and to the extent that you're privy to this information, what % of these cardiac AEs, like the QT prolongation, is due to revumenib as opposed to any concomitant medications, and how many of those have resulted in discontinuations in the real world? Number two, if you could give some color on how to model the Royalty Pharma interest expense in the P&L moving forward, that'd be super helpful.

The last one, on Naktimvo in IPF, could you please speak to the unmet need, how big that opportunity is, and how you're thinking about positioning in a market that's dominated currently by generics.

Speaker 3

Thanks for your questions. I counted three, let's start with the first one. Nick will take that. How is monitoring being done?

Speaker 1

Yeah, thank you for the question. Firstly, we've shown in our extensive clinical trial experience now that management of QT is done very simply. There are clear guidelines in the label now for QT in the first month. We know that almost all patients that have any sign of prolongation happens early and is monitored and managed appropriately. That's very consistent with our real world experience. As I said, we'll be reporting on some of that later in this year. We of course have very extensive safety surveillance systems in place, but we're really not hearing any evidence of concerns with standard guidelines and management of those patients. Things are progressing very well. The physicians are very happy with the profile and not flagging any concerns.

Great.

Speaker 3

Keith, you want to talk about the royalty, please?

Speaker 0

Yeah, Chloe, with respect to your question about how to model the Naktimvo, we've already achieved profitability. First full quarter sales, we mentioned that $36 million in net revenue. We reported $9 million in collaboration revenue. We're already in a range of 25% to 30% from a gross contribution perspective. Like I said in my prepared remarks, we only expect that to grow. With respect to the royalty, it's really easy. It's simply 13.8% of the net revenue that is reported by Incyte. In the second quarter, that represents $5 million in royalties paid on $9.4 million in collaboration revenue. We're using the effective interest rate method. The cash paid to Royalty Pharma won't exactly match what we report on.

Speaker 3

The P and L. Lastly, I think you asked about IPF. IPF, very important indication for us. We have a phase 2 trial ongoing. Expect to fully enroll that trial this year, data next year. That's a big market opportunity. As you pointed out, there's some entrenched competitors, different mechanism of action brought by this drug. We think a very impactful one. About 150,000 patients incident market in the U.S., 280,000 worldwide. It's a big market. Patients are still in absolute need of new therapy and we think we bring that with Naktimvo, potentially with this mechanism. We'll have those trial results and we think we'll meaningfully differentiate over time if those are obviously positive. More to come on that, but it's a, we think a very big opportunity for us to exploit as a second indication.

Speaker 2

Great, thank you very much.

Thank you. Thanks, Claude.

Our last question comes from Mayank Matami with B. Riley Securities. Your line is open.

Yes, good afternoon team. Thanks for taking our questions and congrats on the progress. Could you just clarify, and sorry if I missed that, if there's any real world evidence you're planning to generate as you strengthen the case for Revuforge use as maintenance therapy post transplant, and what's your expectation for duration of therapy there, say relative to the four to six months you're seeing in pre transplant? I have a quick follow up.

Speaker 3

Yeah, thank you. Thanks so much for your question. I'm going to let Nick address the real world part.

Speaker 1

We'll be presenting some relatively preliminary data from the series we've been monitoring towards the latter part of this year.

Speaker 5

Second half of this year.

Speaker 1

We're looking for presenting that will obviously include, you know, patients' demography, how they do on therapy, and importantly also the proportion of patients that go on to transplant in the real world from these series and also those patients that then start chart on, you know, on Revuforge after transplant. I think those will be important data. Obviously, as time goes by and our commercial experience increases, we'll be able to add to those data. I think it'll be interesting preliminary data and we'll look forward to reporting those as and I think they'll shed some light on some important questions.

Speaker 3

I'll just make a comment, I think as you asked about what our assumptions are on post-transplant maintenance, what % of patients are likely to go onto transplant and then of course on what time frame. I think we commented earlier about high % of patients going to transplant. I think that's obviously very clear to us now and exciting. In terms of staying on therapy, physicians have repeatedly told us a year to two years is what I said in my prepared remarks. A year to two years is pretty consistent, could be longer. Some physicians say that they will keep them on indefinitely without a real compelling reason to take them off. Obviously these patients are at high risk of relapse. You want to keep them in remission as long as possible. That's the key goal.

I think an assumption you can make on average for maintenance is that physicians are thinking about a year to two year timeframe.

Very helpful, thank you. On Naktimvo, can you just remind us what development milestones to look out for as you think about that therapy? Moving into earlier line GVHD, I believe on the label it's third line, fourth line, but the uptake is in earlier lines. I was curious if any additional clinical data milestones you should be on the lookout for. Thanks for taking your questions.

Yeah, thank you, Nick, if you want to take the question.

Yeah.

Speaker 1

Just to recap, we haven't guided specifically on the timelines. We have two important studies in the frontline setting, one in combination with dexamethasone, that's a phase three with registrational intent. Again, you have guidelines for the typical timing when that study will read out, and an important phase two study as well in combination with Naktimvo. Obviously, our idiopathic pulmonary fibrosis randomized phase two study, which is around 135 patients, we're anticipating more complete enrollment towards the latter part of this year and data in the second half of next year. A number of important milestones are reading out both in early lines of chronic graft-versus-host disease and in idiopathic pulmonary fibrosis.

Thank you.

Speaker 2

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

Speaker 3

Thank you all. We appreciate you all tuning in today to discuss our recent progress and the exciting milestones ahead. Look forward to seeing many of you at several investor conferences and events in the third quarter. With that, have a great evening.

Speaker 2

The call has now concluded. Thank you for joining. You may now disconnect.