Syndax Pharmaceuticals Inc Q1 FY2025 Earnings Call

Good day, everyone, and welcome to the Syndax First Quarter 2025 Earnings Conference Call. Today's call is being recorded. At this time, I'd like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

Thank you, operator. Welcome, and thank you all for joining us today for a review of Syndax's first quarter 2025 financial and operating results. I'm Sharon Klahre. And with me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer; Dr. Neil Gallagher, President and Head of R&D; Steve Closter, Chief Commercial Officer; and Keith Goldan, Chief Financial Officer. Also joining us for the call today for the question-and-answer session are Dr. Peter Ordentlich, Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Strategy 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 the call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, May 5, 2025, only. A replay of this call will be available on the company's website following its completion. With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Thank you, Sharon. Good afternoon, everyone, and thank you for joining us today. Starting with slide three. I'm pleased to report that Syndax delivered another outstanding quarter of execution as a commercial company with two first and best-in-class medicines on the market and a robust pipeline of clinical development programs designed to unlock the multibillion-dollar opportunities for both of our medicines. Starting with the progress on the commercial front. The launches of Revuforj and Niktimvo are both off to very strong starts. In the first quarter of 2025, Syndax recorded $20 million in Revuforj net revenue from the first full quarter of the launch and our partner Incyte recorded $13.6 million in net revenue from the first two months of our joint launch of Niktimvo. Later on the call, Keith will break down the numbers we were reporting for our 50% share of the commercial Niktimvo contribution. This combined $34 million in net sales from Revuforj and Niktimvo reflects the high unmet need, the compelling profiles of our medicine, and outstanding execution across our entire organization. These results also underscore the significant commercial opportunities we have with both our products and the benefits of being first to market. Importantly, we are well funded to deliver on the exciting opportunities in front of us with $602.1 million in cash and equivalents as of March 31. In addition to the progress we have made with the two product launches, we have also continued to advance our position as a pioneer in menin inhibition with the initiation of the first quarter of EVOLV-2, the first pivotal frontline trial of in menin inhibitor. The EVOLVE-2 trial of revumenib in combination with venetoclax and azacitidine is enrolling newly diagnosed mutant NPM1 and KMT2A rearranged AML patients who are unfit for intensive chemotherapy, a patient population with a high unmet medical need. In parallel with ongoing trial recruitment, we will be amending the protocol and analysis plan to include complete remission and overall survival as dual primary endpoints to support potential US Accelerated approval and full approval, respectively. We've also made other major progress advancing our pipeline. In April, we completed the submission of a Supplemental New Drug Application, or sNDA, to the FDA seeking priority review for the approval of Revuforj for the treatment of relapsed or refractory mutant NPM1 AML. If priority review is granted, it would provide a target FDA review period of six months from the date of submission of the sNDA, a two-month advantage compared to the timeline with an NDA. We see it as a significant advantage that our submission builds off of our Revuforj NDA, which was recently approved by the FDA in November of 2024. Like our successful NDA in relapsed or refractory acute leukemia with a KMT2A translocation, the sNDA will be reviewed under the FDA's real-time oncology review or RTOR program, which aims to ensure that safe and effective treatments are available to patients as early as possible. The program provides for frequent iterative communication with the FDA and a rolling submission, which we recently completed. Since 2018 when the program was created, the sNDA applications reviewed under RTOR have had a strong track record of approval. As expected thus far, we have continued to experience robust and timely engagement with the FDA on our sNDA filing and programs overall. Before I hand the call over to the team to provide more color on our recent progress, I want to take a moment on slide four to reflect on the journey that brought us to this point. From the start, Syndax has been focused on generating clinical data that validates promising scientific ideas and research, and this is exactly what we have done with both Revuforj and Niktimvo. Looking at the history of Revuforj as an example, in 2020, Syndax was the first to deliver clinical data that validated the therapeutic benefit of menin inhibition. Since then we have achieved many other important firsts for the field and most importantly patients. We were the first to deliver positive pivotal data in relapsed or refractory acute leukemia patients with KMT2A rearrangements or NPM1 mutations, the first to achieve FDA approval for menin inhibition, the first to have menin inhibition listed in the AML treatment guidelines, and the first to start a pivotal frontline trial of a menin inhibitor. And today, here we stand, having just delivered the largest full quarter of sales for any targeted AML drug in the US to date. We look forward to building off this momentum and achieving additional important firsts as we continue to rapidly advance Revuforj, our best-in-class medicine. In the relative near term, we expect that Revuforj will be the first menin inhibitor included in clinical guidelines for the treatment of relapsed or refractory mutant NPM1 AML. Today we announced that our manuscript detailing our positive pivotal data in mutant NPM1 patients has been accepted by a high impact journal, and we expect this paper will publish imminently. As soon as the paper is published, we intend to submit the paper to the NCCN guidelines for consideration. Further, with our recent sNDA submission, building off our previously approved NDA and the benefits afforded by RTOR, we expect that Revuforj will be the first drug to receive FDA approval in relapsed or refractory mutant NPM1 AML. Looking to the future, Revuforj is well positioned to be the first menin inhibitor approved in the frontline setting. With the EVOLVE-2 trial now underway in close partnership with the HOVON Network, a leading clinical trial group with an outstanding track record of successfully advancing transformative therapies for blood cancers, we are confident that we will continue to lead the development of this new therapeutic class that holds such tremendous promise for patients. With that, I will now turn the call over to Steve to discuss our commercial progress in more detail. Steve?

Thank you, Michael. I'm pleased to report that the launches of Revuforj and Niktimvo are both off to fantastic starts with all the early launch metrics either meeting or exceeding our high expectations. Starting with Revuforj on slide five. As Michael stated, in the first quarter of 2025, the first full quarter of the launch, we delivered an impressive $20 million in Revuforj net revenue. These early results bolster our confidence in the number of acute leukemia patients with KMT2A translocations and highlight the significant commercial opportunity that we have with Revuforj. The rapid adoption reflects multiple factors such as major unmet patient need, the strength of our clinical data and product profile, favorable formulary coverage, and the high caliber of our customer-facing team. Together, these factors are driving the expansion of prescribing as well as strong numbers of new patient starts and robust refill rates which are on track with what we would expect to see roughly five months into the launch. Diving into a bit more detail on slide six. Physician feedback on Revuforj's clinical profile and the overall ease of access to the medicine has been very favorable. This positive experience is reflected in the expanding breadth and depth of Revuforj prescribing, with 44% of our high priority Tier 1 and Tier 2 accounts ordering as of the end of March. That's up from one-third of accounts at the end of February and continuing to grow into the second quarter. Now these Tier 1 and Tier 3 accounts are the centers of excellence in the medium to large academic institutions which represent two-thirds of the patient opportunity. Compared to benchmarks, we have achieved orders at more top-tier accounts over a shorter timeframe than all other targeted AML products. While we have made outstanding progress in these priority accounts in the first few months of launch, there is still significant room for further growth and upside as the remaining roughly 55% of high-priority accounts identify the right patients and initiate treatment. I will also note that we are calling on an entire universe of 2,000 accounts and accounts beyond Tier 1 and Tier 2 are ordering Revuforj, including academic centers of all sizes as well as community practices. Notably, among all the accounts that I've ordered, two-thirds have ordered multiple times as of the end of March. Physicians are prescribing Revuforj to a mix of KMT2Ar patients, which reflects our broad label encompassing adults and children one year and older with any lineage of relapsed or refractory acute leukemia with a KMT2A translocation including AML, ALL and NPM1. We are anecdotally hearing of Revuforj being prescribed to KMT2Ar patients across the treatment continuum, including patients experiencing their first relapse as well as those with very advanced disease. All indicators suggest that the use of Revuforj will move towards first relapse and rapidly become the standard-of-care for the population within our current label. Encouragingly, we're also hearing of several patients going on to receive stem cell transplants after getting into remission with Revuforj, which is the treatment goal for these patients as transplants are the only potentially curative treatment option. We expect based on feedback from physicians that most of these patients, if not all, will ultimately go back on Revuforj post engraftment. As the launch progresses and the relevant data sets mature, we look forward to providing more color and metrics in Revuforj usage, including in the post-transplant setting. Turning to market access. Formulary coverage for Revuforj continues to build very nicely due to the extensive work our market access and medical teams have done educating payers and the rapid inclusion of the product in NCCN guidelines. As of the end of March, formal coverage policies were in place for approximately 72% of all managed care lives, which includes commercial, Medicare and Medicaid lives, up from 53% at the end of February. We have also continued to achieve high payer approval rates with the vast majority of prescriptions reimbursed. We are in a strong position and very pleased with how favorably our formulary coverage is tracking compared to the launches of other AML therapies. We also continue to see the benefits of the limited distribution model we have established to provide patients and clinicians with the best experience possible. Thanks to the infrastructure we have built, combined with the deep experience of our team and all the work we've done with payers, patients are getting approved for coverage quickly and many patients receive their medication within a few days of receiving a prescription, well ahead of industry benchmarks. We and our trade partners are keenly aware that these patients are facing a life-threatening diagnosis and we're deeply committed to ensuring that every appropriate patient can quickly gain access to Revuforj. Moving to slide seven. Our current Revuforj indication provides us with the opportunity to target an estimated 2,000 patients in the US with relapsed or refractory acute leukemia with a KMT2A translocation, a population which represents a $750 million market opportunity. We have high conviction that we'll be able to penetrate a major portion of this market and possibly expand the opportunity given the widespread testing for KMT2A rearrangements, strong enthusiasm for Revuforj and the absence of any other targeted therapies for these patients today or in the foreseeable future. Importantly, based on feedback from clinicians and other data points, we believe the majority of Revuforj revenue to date is from on-label use that we have just started to penetrate the KMT2A opportunity with a lot of room to still grow. Additionally, we're excited about the opportunity for significant future growth including with the potential inclusion of Revuforj in the clinical guidelines for the treatment of relapsed or refractory mutant NPM1 AML followed by the expected approval of our sNDA in this population. We have commercial preparations well underway for anticipated expansion into the second population, a launch that will be boosted by our significant head start into the market with the KMT2A approval and physicians rapidly growing familiarity with Revuforj. To ensure that Revuforj is positioned for near-term and long-term success, we are laser-focused on strong execution against our strategic launch imperatives that we originally outlined on our Revuforj approval call in November. Each day we are focused on ensuring that we leave no appropriate patient behind, engaging all key stakeholders and delivering a best-in-class experience for patients and clinicians. Our strategy is designed to first and foremost meet the needs of patients and secondly, to build long-term competitive immunity ahead of potential me-too products entering the market. Moving to slide eight. In late January of 2025, we and Incyte launched Niktimvo in the US for patients with chronic graft-versus-host disease, or GVHD, after failure of at least two prior lines of systemic therapy. From the first two months of the launch, Incyte reported Niktimvo net product revenue of $13.6 million. This is a very encouraging result which highlights this significant and sometimes underappreciated commercial opportunity that we have with Niktimvo. The robust uptake was driven by multiple factors, including high unmet need, a unique product profile, very strong product awareness, the benefit of co-commercializing with the leader in GVHD and the commercial synergies that Niktimvo has with both companies' product portfolios.

Thank you, Steve. I will now turn the call over to Neil to discuss the progress we are making across our development programs.

Thanks, Steve. It's a pleasure to be able to provide you with an update on development today. Turning to slide 11 and our pipeline. We are aggressively advancing a thoughtful and robust clinical development plan that aims to bring both our assets into additional important populations. Starting with the latest updates on the revumenib program, we have multiple ongoing and planned clinical trials across the acute leukemia treatment continuum, including in combination with standards of care therapies in the frontline setting. Our combination trials build off the positive results from the BEAT AML trial being conducted by the Leukemia and Lymphoma Society and the SAVE trial being conducted by investigators from MD Anderson Cancer Center. Two studies that highlight revumenib's very promising combination potential. We're pleased to have recently initiated EVOLV-2, the pivotal frontline trial of revumenib in combination with venetoclax and azacitidine in newly diagnosed patients with mutant NPM1 or KMT2A rearranged AML who are ineligible or unfit to receive intensive chemotherapy. EVOLV-2 is a Phase 3 randomized double-blind placebo-controlled trial that we expect will enroll approximately 415 patients. As Michael mentioned, in parallel with ongoing trial recruitment, we will be amending the EVOLV-2 protocol and analysis plan to include complete remission and overall survival as dual primary endpoints to support potential US accelerated approval and full approval, respectively. While the trial is open to both NPM1 and KMT2A patients, 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 and/or other comorbidities. Unlike the KMT2A population which tends to be younger and eligible or fit for intensive chemotherapy. We are excited to partner with the HOVON Network in this trial considering their extensive network of leading research institutions across the EU and globally. EVOLV-2 will start outside the US and the majority of sites will be ex-US. Turning to the newly diagnosed fit population. We are planning to initiate two randomized placebo-controlled trials of revumenib in combination with intensive chemotherapy followed by a maintenance phase. One trial for patients with an NPM1 mutation and one for patients with KMT2A. We believe this is the most efficient approach to establish efficacy across these two populations with different expected long-term outcomes and different current treatment goals. We've named these trials reveal ND or newly diagnosed trials. In line with our standard approach, we will share more details on these studies once we have posted them on clinicaltrials.gov which we anticipate doing later this year. In the fit frontline setting, we also look forward to reporting data from a Phase 1 trial of revumenib in combination with intensive chemotherapy in the fourth quarter of this year. With our frontline strategy, we are well-positioned to generate comprehensive data that could support accelerated approvals, full approvals and transform the treatment paradigm for the 40% of AML patients with NPM1 mutations or KMT2A rearrangements. Turning to the bottom half of the slide and axatilimab, we and Incyte are very excited about axatilimab's potential in earlier lines of chronic GVHD and other fibrotic diseases starting with IPF. Together we are advancing several important trials including two ongoing trials of axatilimab in combination with standards of care in newly diagnosed chronic GVHD patients. One is a Phase 2 trial studying axatilimab in combination with ruxolitinib and the other is a Phase 3 placebo-controlled registration-directed trial investigating axatilimab in combination with steroids. Beyond chronic GVHD, we have an ongoing Phase 2 placebo-controlled trial called MAXPIRe which is investigating axatilimab in IPF. Enrollment is proceeding well and we expect to complete enrollment this year with top-line data anticipated in the second half of 2026. We and our clinical collaborators are very encouraged by the preclinical evidence which shows a significant reduction in markers of lung fibrosis with CSF-1R inhibition results which are bolstered by the positive results we observed in patients with BOS or bronchiolitis obliterans syndrome in the GVHD 201 trial. With that, I will hand the call over to Keith to discuss our financials. Keith?

Thank you, Neil. Earlier this afternoon, we reported detailed first quarter 2025 financial results in our press release and Form 10-Q. For today's call, I'll touch upon a few key points on slide 12. For the first quarter of 2025, we reported Revuforj net revenue of $20 million. The vast majority of the revenue was driven by real demand with approximately just two to three weeks of inventory in the channel at the end of the quarter, consistent with levels at December 31 and consistent with what is typical for specialty medicine. We expect channel inventory levels to remain at two to three weeks moving forward. Moving to Niktimvo. For the first quarter of 2025, Niktimvo achieved $13.6 million in net revenue. As a reminder, Incyte records net revenue and Syndax will report 50% of the Niktimvo net commercial profit or loss, which is defined as net revenue less the cost of sales and commercial expenses. For this quarter, a partial quarter, we are encouraged to report that our share of the net commercial loss was only $200,000, as you can see recorded in the line item called Collaboration Loss. Given the strong results from the first two months of launch, we expect that Niktimvo will quickly convert to a positive revenue contribution. In periods where there is Niktimvo net commercial profit, you'll see our 50% share in the revenue section of our income statement under Collaboration Revenue. I will also note that any future milestone revenue we receive from Incyte for various commercial and regulatory milestones will be in a separate revenue line under Milestone and License Revenue. As a reminder, the synthetic royalty we owe to Royalty Pharma is not one of the expenses deducted from the top line Niktimvo net revenue. The upfront $350 million that we received from Royalty Pharma that is liability classified. The capped 13.8% royalty payments that are due are based on US net revenue of Niktimvo and the payments we make will reduce the associated liability on the balance sheet. You will also see on our income statement a new line called Royalty Interest Expense which reflects the interest expense calculated using the effective interest rate method associated with the amortization of the liability principle. With regard to our guidance on expenses, you can find our guidance for the second quarter of 2025 and full year on this slide and in the press release we issued earlier today. Turning to the balance sheet. We continue to maintain a strong financial position with $602.1 million in cash equivalents and short and long-term investments as of March 31. We expect that our cash combined with anticipated Revuforj gross margin contribution, collaboration revenue from Niktimvo, and interest income will enable the company to reach profitability. With that, let me now turn the call back over to Michael.

Thank you, Keith. As you heard today, we have continued to make outstanding progress as a commercial company and Syndax is well-positioned for long-term success. We are in the enviable position of having two derisk medicines with multibillion-dollar potential along with the capital and the right strategy and people to execute on these opportunities. Looking ahead, we remain sharply focused on fulfilling our commitment to patients and shareholders to achieve the multiple upcoming milestones that you can see on slide 13. As always, I want to close by thanking everyone who has made it possible for us to reach this transformational point, including our dedicated Syndax employees and our long-term investors. I especially want to extend my gratitude to the patients and families who have chosen to participate in our clinical trials. On slide 14 you can see a picture of Lilah, one of the young children with acute leukemia who participated in our study. Hearing remarkable stories like Lilah's is what drives our entire organization to deliver for patients every day. With that I would like to open the call for questions. Operator, please.

Our first question comes from Anupam Rama from JP Morgan. Your line is now open.

Hi, guys. This is Priyanka on for Anupam. Congratulations on the amazing progress. Our question is, what are you seeing in regards to the repeat prescribers for Revuforj? Are there certain centers of excellence that have a few high repeat prescribers, or are those prescribers more spread out? Thank you.

Great. Thank you so much for the question. And I'll actually ask Steve to address that regarding repeat prescribers.

Thank you for the question, Priyanka. In the prepared comments, I mentioned that we have a substantial user base. About 44% of our Tier 1 and Tier 2 users have ordered more than once, whether for another patient or a refill prescription. This isn’t limited to just those groups since we know that approximately two-thirds of our business is derived from them. What’s encouraging about the launch is that we are seeing usage extending beyond Tier 1s and Tier 2s. We engage with 2,000 treatment centers, which include oncology practices that have either prescribed or referred patients to other academic centers. Moreover, several small academic centers have also begun prescribing. I believe this provides a strong foundation moving forward. Physicians appreciate the profile and are liking the results they're observing in patients. The user base is expanding, and we are seeing an increase in those who are making repeat prescriptions. We understand that the first prescription can be the most challenging, but once it is established, the process of prescribing, diagnosing, and treating becomes much smoother.

Thank you so much.

Thank you.

Our next question comes from Kelly Shi from Jefferies. Kelly, your line is open.

Hi, guys. This is Clara on for Kelly. Congrats on the great progress. So, for the patients receiving Revuforj, could you comment on whether you are seeing a similar pace of patients receiving transplants to what you're seeing in clinical trials? And maybe whether you're seeing any patients use Revuforj as a maintenance therapy? And how do you expect this dynamic to evolve over time? Thank you.

Thank you for the question. Your inquiry is about patients receiving Revuforj and whether we are observing transplant rates similar to those in clinical trials. Currently, we only have anecdotal information. However, physicians we communicate with are reporting that they are taking patients to transplant, and we anticipate patients will return to post-engraftment in the maintenance phase. It's a bit early to provide extensive commentary on this, but we expect to see developments throughout the year as more patients undergo transplants. What we have observed so far regarding transplants is quite encouraging, but it remains mostly anecdotal at this stage.

Okay, got it. Thanks.

Thanks for the question.

Thank you. Our next question comes from Ellen Horste from TD Cowen. Your line is now open.

Hi, guys. Thanks for taking the question, and congratulations on an awesome Q1. I'm wondering if you can share any color on the month-over-month trends for new patient adds for Revuforj in Q1, as in with patient flow steady through the quarter, or did you see some acceleration throughout? And then can you share any details on the free drug rate and whether you expect that to continue in Q2 and beyond?

Sure. Thanks so much for the question. So, Steve, on month-on-month trends, do you want to talk about that?

Thank you, Ellen, for your question. We are not ready to provide specific numbers yet. It's still early, and our dataset is still being finalized. However, we are pleased with what we are observing. In Q4, we reported net sales of $7.7 million, with approximately one-third attributed to inventory. For this quarter, we anticipate that inventory levels will not exceed 2 to 3 weeks, indicating a positive transition from Q4 into Q1. There hasn’t been a significant surge in patients, as many are quite ill, but we did welcome a diverse group ranging from those experiencing their first relapse to patients in hospice care. We are transitioning into a more stable state. For drugs of this nature, it typically takes at least two full quarters to understand the run rate, but we are satisfied with our progress. We are encouraged by the sales increase from the partial quarter in Q4 to our first full quarter in Q1, and while we have not yet disclosed data from April, we know that our user base continues to grow. Regarding the transplant question, we already have patients who are on their fifth refill in some cases, which is very promising. Concerning free drug, we believe all suitable patients should receive the medication. We have made significant efforts to have the drug covered, and we are experiencing a high success rate as formulary coverage improves. Our patient assistance program is distinct and targets uninsured or underinsured patients. Typically, at the start of the year, there may be changes in deductibles, and Medicaid plans usually become available in the first full quarter following the drug's launch, which occurred on April 1. Therefore, the current rate of free drug is very low, in the single digits, primarily due to effective execution by our team, similar to what you would expect 2 to 3 years post-launch. We are optimistic about our position and the treatment of all patients.

Thank you.

Thanks for the question.

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

Hi. Thanks so much. Thanks for taking the question. I'm wondering if you could speak about any trends that you're seeing in GVHD, in particular, any of the subgroups. Thank you.

Great, Peter. Thanks for the question. So we've got a trend in GVHD in terms of subgroups. I assume your question is regarding the patients that are actually getting the drug and what their specific clinical manifestation is in GVHD. Is that the question?

Yes. Exactly. And then if there's any, kind of, age differences between those. And, again, if there's not, any details there would be great.

Yes, and I maybe I'll turn the question over to Peter, any kind of information relative to that. I don't I don't know that we've reported any of that yet. But, Peter, I don't know if there's much to say there.

No. I think it's a little bit early for us to be able to comment on that. I know that the team's collecting the real-world evidence as it's coming in. But, I think we're just sort of partial quarters so far. I don't think we have that much information.

Got you. Thanks, Peter.

Just a final question just around MSS, CRC, kind of, what's a go-forward signal you need to see for that?

Thank you for your question, Peter. I believe you are inquiring about colorectal cancer. We have been monitoring patients, and the trial is ongoing. We haven't provided an update yet, but we are aiming for prolonged stable disease over a specific time frame, and we plan to follow up on this later this year.

Okay. Thanks so much.

Thank you.

Our next question comes from Michael Schmidt from Guggenheim. Your line is now open.

Hi, everyone. Congratulations on the first quarter results. Could you share your thoughts on how much off-label use in NPM1 patients might have influenced 1Q Revuforj sales? Additionally, I have a clinical question regarding the redesign of the EVOLV-2 study with the inclusion of the CR endpoint. Can you discuss how this might affect the potential timeline for completing the trial? It seems you may have had similar discussions regarding the planned studies in the Fit patient population as well. I would appreciate it if you could provide feedback you've received from the agency on that. Thank you.

Thank you, Michael, for your question. Regarding the off-label contribution for NPM1, from what we're observing anecdotally and based on our data, it appears mainly to involve a KMT2A patient population. We have heard from some physicians that they are using the drug for NPM1, both in combination and as monotherapy, and potentially even in earlier treatment lines. However, most of what we are seeing this quarter is related to on-label KMT2A usage. As for your question about our Unfit trial, now referred to as the EVOLV trial, it was designed from the outset to focus on complete response, and we are updating the analysis plan to prioritize complete response in our endpoints. This means we have two primary endpoints, each with its own success criteria, allowing us to achieve success on either one. This is a favorable configuration for accelerated approval, and we have favorable alignment to proceed. There will be no impact on the trial's progress, which will continue as planned. While we haven't provided a timeline for any potential accelerated approval or early readout, we anticipate being the first menin inhibitor approved in the frontline setting, hopefully by a significant margin. Lastly, regarding the Fit patient trials, we are not commenting on interactions with the FDA at this time, but we believe we are moving positively on all fronts, including the Fit trials.

Our next question comes from David Dai from UBS. David, your line is open.

Great. Thanks for taking my questions, and congrats on the quarter. I also just want to kind of focus on the EVOLV-2 trial in the onset population. So I understand that you just got FDA buy-in to use the dual primary endpoint. So I'm wondering if it's possible if you could provide some additional color around powering for the trial.

Yes, David, thank you for the question. We haven't discussed the powering of the trial in detail. It's a randomized trial involving 415 patients. The powering is based on the NPM1 population compared to KMT2A, as NPM1 has a much larger patient group. Both populations will be included, but the powering will focus on NPM1. However, we haven't publicly shared specific statistics at this point.

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

Yes. Hi, thank you very much. I had a question on the strategy around the Fit studies. Could you just elaborate as to why it seems like you're pursuing two separate trials for NPM1 and KMT2A versus in the Unfit, it's all lumped together? Is there a specific reason for that? Is that set in stone, or is that something that's still subject to discussion with the FDA?

No. Thanks for the question, Yigal. The simple answer is that there are different groups of patients, and we are conducting a trial specifically for NPM1 and another specifically for KMT2A. The outcomes and the standard of care we are implementing in each group are tailored to achieve the best results for both populations. Understanding these differences leads us to design trials that are most suitable for these groups. This is the guiding principle behind our strategy, and we believe it will enhance our chances of success.

Okay. Regarding the use of Revuforj in transplant patients that you mentioned, I’m curious if some of them achieved CRCRH. Are you observing in the commercial setting that physicians are ready to proceed with transplants before seeing CRCRH with Revuforj, if you have that information? I realize that's quite detailed.

Yes, thanks, Yigal. We don't actually know. It really comes down to physician choice. Their main priority is to get the patient into remission, and from there, they decide based on the individual patient whether they have a measurable residual disease negative complete response or just a complete response, which we don't have visibility into. This is within their own domain. We do anticipate learning more over time, but as of now, we lack that information.

All right. Thank you.

Thanks, Yigal.

Our next question comes from Kalpit Patel from B. Riley Securities. Your line is now open.

Yes. Hey, good afternoon and congrats on the net sales for both of these assets. I had a couple of questions for Revuforj. Do you have any color on what portion of the $20 million revenue stems from refill dynamics from those fourth-quarter patients versus new patient starts in the first quarter? And then as a follow-up, do you have an early sense of the median duration of therapy for those patients treated in the fourth quarter?

Yes. Thanks, Kalpit. Thanks for the question. So first question regarding our refill dynamics. Let me ask Steve to comment on that.

Yes. Hey, Kal, good question. I think both are building right now. I'm not going to give a lot of color. I think the dataset is still new. I think we talked about this before. We have decent visibility into maybe less than half through our specialty pharmacies, and our hub, not so much through the other side, which is the specialty distributor side, which is why we are not able with a lot of accuracy to answer some of these questions. But both are filling. And I think from a refill rate perspective, as we talked about getting to transplant. I mean, we've got patients now on their fourth refill. Obviously, there's more patients over time. We're able to track that at least monthly from the data that we can see. We like what we're seeing. We do also, obviously, know when patients are dropping out of treatment; it doesn't mean that it's been a treatment failure. We're hoping that they go to transplant because that's really the only curative option that they have. In terms of patients and new patients, it's been a steady stream, month to month, and that's been building over time. So I'd say the fundamentals and the business are good. We're exactly where we want to be. April's a big month, and, obviously, this coming quarter is going to be big as well. And then your second question?

Median duration of therapy.

The median duration of therapy is still early in the process. We understand that this is a common question, and it will take time for the dataset to mature. The dynamics involve patients going off the drug, ideally moving towards remission, potentially getting transplants, and then returning to treatment after about 2 to 3 months. From a compliance standpoint, we are encouraged by the data we are observing. There will naturally be a decline over time for various reasons, but we anticipate that in a few quarters, we will be able to provide a clear answer regarding the duration of treatment. For now, we are pleased with the data we are seeing.

Okay. Thank you very much.

Thanks, Kalpit.

Our next question comes from Jeet Mukherjee from BTIG. Your line is now open.

Hey. Congrats on the quarter, and thanks for taking the question. Perhaps in line with the previous question, just any color on the month-over-month trend for new patient starts for Niktimvo. Or alternatively, the greater than 1,250 infusions year-to-date, what proportion of that is new patients and just any color on refill rate for Niktimvo? Thanks.

Thank you, Jeet. Another question for Steve here on the on Niktimvo.

Yes. It's quite early, even with the more than 1,250 infusions that Incyte reported earlier this week. That figure is likely based on specialty distributor data, as that's their distribution method. Some patients are enrolled in the Expanded Access Program, although the size of that group has not been specified. Additionally, some patients had been waiting at centers. The drug received its initial approval in August, and new vials were available by the end of January, which created some pent-up demand. Currently, we have mostly new patients, as it's only been a couple of months. We have engaged with nearly all key centers in the country, and as of March, we reported that 95% of the top centers were activated, a number that has since increased. Other centers are also beginning to offer the drug. The onboarding process has been smooth, and patient demand is high. The drug seems to be well received. Regarding the types of patients, it is primarily being used in fourth-line treatments, which is acceptable for our initial phase. Both patients and physicians will gain experience over time, and it will take another quarter or more to establish the true run rate as patients transition through the Expanded Access Program. However, we are off to a strong start, without a doubt.

Great. Thank you.

Thanks for the question. Jeet. Our next question comes from Salim Syed from Mizuho. Your line is now open.

Hello everyone, good afternoon. Thank you for the question and congratulations on the quarter. I have a couple of inquiries, one regarding Revuforj and another about the Niktimvo launch. For Revuforj, can you provide some insight into the SKU distribution between the 25mg, 110mg, and 160mg so we can gauge your blended WAC per patient? Also, regarding the Niktimvo launch, I want to confirm the 1250 infusions year-to-date mentioned on slide nine; is that as of April when Incyte reported, compared to March 31st? I just want to clarify that this figure refers to infusions and not unique patients. Thank you.

Great. Salim, thanks for the question. So maybe I'll turn it to Steve. The first question's related to Revuforj on the sort of breakdown of the SKUs, because we do have three different SKUs, 25, 110 and 160.

We do. We're not going to give a specific breakdown yet. I think as like other things, the data sets mature and we know the majority of prescriptions are going to be at the 110 and the 160. The 25 is new. We launched that in March. But the dosage varies. It's going to vary based on patient weight. Also, on concomitant use of a strong 3A4. The bottles are their 30s. It's twice a day. So, essentially, it's two bottles for most patients. And the majority of patients, that's exactly what they're going to get. If they're not on a strong sip, it's possible they may have to add on a dose. At this point, our guidance is that majority of these scripts are going to be at that 110 and 160 dose.

And then for Niktimvo, I think we were clarifying.

Yeah, 1250, I think it's end of March was what the data was through. And I think the question was it's not patients, that's infusions. So in the time period since launch, it's very likely that some of those were for the same patient. Meaning they've had a couple of infusions. It's every two weeks. And we don't have the mix yet of new patients versus continuing patients.

Got it. Okay. Super helpful. Thanks so much, guys.

Thanks, Salim.

Thanks for your question. Our next question comes from George Farmer from Scotiabank. Your line is now open.

Hi, good afternoon. Thanks for taking my questions. Given the strength of your Q1 Revuforj result, do you think that the total addressable market is accurately reflected in our models? Are you getting the sense of how many patients might be out there? Maybe it's greater than what we've estimated. And also, can you comment if post-transplant use is reimbursed under the current J-code?

Thank you, George, for your question. Regarding the total addressable market, when introducing a new market or a new drug targeting a specific population, we often see dynamics that involve bringing new patients into the market or allowing them to receive treatment. This may apply to Revuforj. As you know, there were no treatment options available for the KMT2A population, which we estimate at around 2,000 patients in relapse refractory cases, but it could be more than that. We'll have to observe how this develops over time. As Steve mentioned, we are making excellent progress in identifying patients and getting them on the drug quickly. We're off to a strong start and wouldn't be surprised if the market exceeds the 2,000 patients we've identified. We'll see how this unfolds. Regarding your second question about post-transplant reimbursement, we have evidence of other drugs being reimbursed for post-transplant maintenance. Physicians emphasize the importance of getting patients back on medication after engraftment to maintain their remission, and this is becoming more recognized by payers as well. Given that these are high-risk patients, we anticipate that post-transplant maintenance will generally be reimbursed, which aligns with our understanding.

Okay, great. And maybe you mentioned this regarding the sNDA for mutant NPM1. Is that going to be based on the 77 patients in the efficacy analysis, or is there a larger data set?

We updated the data set at our ASH event last year. The efficacy analysis included 77 patients. We have submitted all the data to the FDA and the sNDA, so they have access to those 77 patients and all the data we compiled. We expect that they will review the 77 patients, but I can't specify what will ultimately be included in the final data set they analyze for the label.

Okay. Thanks very much.

Thank you.

Thank you, George. And our final question comes from Jason Zemansky from Bank of America. Your line is now open.

Great. Good afternoon. Congratulations on the quarter and really appreciate you fitting us in with our question. In terms of the NCCN guidelines, it looks like the AML panel meets May 19th. Do you think you could realistically get in front of them with your publication by then? Alternatively, if not, is there potential for the committee to meet ad hoc?

So, Jason, thanks for the question. Exciting development as we announced today that we have acceptance of our manuscript in a very good journal. I think the idea is that we would submit it to guidelines quickly. Whether or not we can get it in for the May 19 guideline review is an open question. I think we're optimistic. We'll see. And then, of course, we've had experience where the guideline committee has met on an ad hoc basis. So, we do think that for practice-changing and important new medicines that they would meet in order to accommodate that. So, I think we have both opportunities and we do expect to be included relatively rapidly as the year goes on. So, we're, I think, in good shape either way.

Perfect. So, it's fair to say probably nearer term rather than longer-term.

Yes, we anticipate this in the near term. We had indicated the second quarter as our guidance, and while we don't have full control over it, considering the timing, I believe we have a strong chance of achieving that.

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.

Great. Thank you all. We really appreciate you tuning in today to discuss our recent progress and the exciting milestones ahead. We look forward to seeing many of you at several upcoming investor conferences, including the Bank of America Conference later this month, and Jefferies in early June, as well as other important medical conferences this quarter. And with that, I'd say have a great day everyone.