SNDX - NASDAQ

Good day, everyone, and welcome to the Syndax First Quarter 2025 Earnings Conference Call. Today's call is being recorded. [Operator Instructions] 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, www.syndax.com 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 mNPM1 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 relapse or refractory mutant mNPM1 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 relapse or refractory acute leukemia with a KMT2A trans location, 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 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 relapse or refractory acute leukemia patients with KMT2A rearrangements or mNPM1 mutations, the first to achieve FDA approval for menin inhibition, the first to have a 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 relapse or refractory mutant mNPM1 AML. Today we announced that our manuscript detailing our positive pivotal data in mutant mNPM1 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 relapse or refractory mutant mNPM1 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 Hovan 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 and 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 2000 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 relapse or refractory acute leukemia with a KNT2A translocation including AML, ALL and mNPM. 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. Encouraging, we're also hearing of several patients going on to receive stem cell transplants and 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 and 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 relapse or refractory acute leukemia with 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 relapse or refractory mutant mNPM1 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 they 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 me2 [ph] products potentially 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 cocommercializing with the leader in GVHD and the commercial synergies that Niktimvo has with both companies product portfolios. Turning to slide nine and some of the early launch metrics. We're pleased to report that an estimated more than 1,250 infusions of Niktimvo have been administered year-to-date and approximately 95% of top accounts and more than 70% of all bone marrow transplant centers have ordered as of the end of March. The rapid progress we have made in these accounts highlights the advantages of launching into an established market with well identified patients as well as the benefits of Incyte's longstanding relationships with the roughly 200 accounts in the US that perform stem cell transplants. At this early point in the launch, we are hearing of some accounts using Niktimvo in the third line setting, but typically they are fourth line plus patients who have already cycled through several treatments and are in need of a new option. Feedback from physicians has been very positive regarding the responses they are seeing in their patients and we expect this firsthand experience along with their educational efforts will drive more usage in the third line setting. On the market access front, payers recognize the value of Niktimvo and the drug is being reimbursed. Additionally, a permanent J-code was assigned by CMS effective April 1, an important milestone that helps facilitate efficient billing and reimbursement for IV products. Moving to slide 10. Our current Niktimvo indication provides us with the opportunity to target the 6,500 chronic GVHD patients in the US who require three or more lines of therapy, which represents a $1.5 billion to $2 billion total addressable market. Addressing the needs of this patient population is an attractive commercial opportunity. For instance, in the three years since the launch of Revuforj, another drug indicated for the same line of treatment as Niktimvo, net sales continue to grow and suggest that the drug is now annualizing at over $500 million in US sales. Together with Incyte, we are making excellent progress executing on our strategic launch imperatives for Niktimvo and are very excited to continue advancing the launch of this much needed new option for patients suffering from this debilitating and sometimes life threatening disease. With that, I'll hand the call over to Neil to discuss the progress we're making across our development programs. Neil?

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 is 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 mNPM1 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 mNPM1 and KMT2A patients, the primary efficacy analysis will be based on the mNPM1 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 mNPM1 mutation and one for patients with KMT2A. We believe this is 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 mNPM1 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 [ph] 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 31st 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 31st. 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.

[Operator Instructions] 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 excellences that have few high repeat prescribers, or are those prescribers more spurred out? Thank you.

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

Yeah. Hey, Priyanka, a good question. I think in the prepared comments, we've talked about a significantly sized user base. 44% of our Tier 1s and Tier 2s have written about 80% of those folks have actually ordered more than once whether that was for another patient or for a refill prescription. I wouldn't say it's concentrated in only those groups. We know about two-thirds of the business is coming from that group. I think what's very encouraging about the launch is that we're seeing usage well outside the Tier 1s and Tier 2s. We do call on 2,000 treatment centers. There's oncology practices that have -- if they haven't already prescribed, they referred patients into other academic centers. And we've seen a number of small academic centers prescribe as well. So, I would say that it's a good foundation to start. I think physicians like the profile. They like what they're seeing in patients. And that user base is growing and those that are using more than once is increasing. We know the first prescription is often the hardest. And then once we've seen that happen, that muscle memory of how to prescribe, diagnose and treat comes after that pretty quickly.

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 transplant 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.

Yeah. Clara, thanks for the question. So, your question relates to patients receiving Revuforj and whether we're seeing transplants consistent with clinical trials? I could just say that right now, it's anecdotal information. I think we do know from physicians who we speak to reporting that they are taking patients to transplant and we do expect patients to go back on post engraftment in the maintenance setting. I think it's a little early to comment too much on that. And we'll see that kind of go throughout the year as more and more patients do go to transplant. But it's very encouraging what we're seeing so far relative to transplant. We're just -- it's mostly anecdotal information at this point.

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?

Yes. Thanks, Ellen, for the question. We're not going to provide any numbers yet. It's a little bit early, plus our dataset is ensuring. But we're happy with what we see. I mean, if you saw within Q4, net sales we reported $7.7 million. About a 1/3 of that was demand -- I'm sorry, a 1/3 of that was inventory. In this current quarter, we don't expect inventory levels to go beyond 2 to 3 weeks, so there's a good ramp from that period in Q4 into Q1. There wasn't I wouldn't say a true bolus of patients. Patients are too sick for that. But we did get a wide range of patients at the launch all the way from first relapse to patients that were that were on hospice. So we're moving into steady state zone. I think drugs like this, you're going to have to wait probably at least 2 full quarters really to see the run rate, but we're happy with what we see. We're happy with the net sales gain, from Q4 partial quarter into our first full quarter into Q1 and we haven't reported on what we're seeing this month in April. But as you can imagine, user base is increasing. Michael answered on transplant. We're seeing patients already on their fifth refill, in some case, which is very encouraging. And I think another part of your question was just around free drug. So we believe every appropriate patient should be put on drug. We've made every effort, obviously, to get drug paid, which we've had a very successful rate as formulary coverage has improved. Our patient assistance program is very specific. It's really for uninsured or underinsured patients. Sometimes through the first of the year, you'll see some changes in terms of deductibles resetting. Medicaid plans tend to open up the first full quarter, after the drug is launched, so that opened up April 1. So the rate of free drug right now is very low. It's in the single digits, and that's just due to execution and a great trade team where levels that you typically see 2 to 3 years into a launch. So we feel great about where we are and all patients being treated.

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 thanks for the question. So we've got a trend in GVHD in terms of subgroups. I assume your question is, the patients that are actually getting the drug and what their 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 this is not, any details there would be great just there.

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 quarter so far. I don't think we have that much information.

Got you. Thanks, Peter.

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

Right. Peter, so thanks for the question. I think, you're asking about colorectal cancer, and I think we've continued to follow patients, and I think that trial continues. We haven't given an update as of yet. But, I think what we were looking for was stable disease -- prolonged stable disease over a certain period of time and we're looking to follow-up on that sometime later this year.

Okay. Thanks so much.

Thank you.

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

Hi, guys. Congrats on the first quarter result. Could you just comment on, to what degree off label use in NPM1 patients may have contributed to 1Q Revuforj sales? And then, yes, I had a clinical question also on the comments that were made around the change in the design of EVOLV-2 study where you now have the CR endpoint included. And, yes, could you just comment on how that may impact potential timing to completion of the trial? And it sounds like you may have had a similar discussions around the Fit -- the planned studies in the Fit patient population as well. Just curious if you curious if you can share sort of the feedback that you've received there from the agency. Thanks so much.

Great. Thanks, Michael, for the question. So, in terms of off label contribution, for NPM1, I think what we're hearing again anecdotally, I think, and based on some of the things that we can see in our own data, this looks so far primarily to be a KMT KMT2A set of patients. I think there's been some physicians reporting to us that they are prescribing the drug for NPM1. They're prescribing a combination, monotherapy, and also potentially even earlier lines of therapy. But I think the vast majority of what we're seeing, in this quarter is on label KMT2A. And then and in terms of your question about the clinical comments about our Unfit trial, and that's what we're calling now the EVOLV trial. From the start, the trial was designed to collect CR, and we're amending the analysis plan and raising CR in the hierarchy of endpoints. And so, it's pretty straightforward. So these are dual primary endpoints, independent success criteria for both, so we can win on either. So it's a I think, an advantage set up for potential accelerated approval, and we have alignment there to, to go forward. So there's no impact. There's no impact to trial because the trial will simply go forward when we started. But in terms of accelerated approval and how that potentially could be an early an early readout, we haven't given guidance on the timing there. But we do expect, as we are the first to start a trial in the frontline setting, we do expect to be the first menin inhibitor approved in the frontline, hopefully, by a good margin. So that's a positive development. And then on the Fit -- in the Fit side of the equation with, the trials we'll be starting there. We're not commenting, and we as we generally don't on FDA interactions and our conversations there, but we are moving in, we think in a positive direction on all fronts, including in the Fit setting with additional 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, thanks for the question. We haven't talked about the powering of the trial. I mean, it's a -- other than the fact that, of course, it's the number of patients, 415 patients, it is a randomized trial. It's powered with NPM -- based on NPM1 population versus KMT2A a because NPM1's far greater patient population. And, essentially, that's the -- that so it'll be. Both populations will be included, but it'll be powered off of NPM1. But specific statistics, we haven't talked about publicly at this point.

All right. Thank you.

Thank you.

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. 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. I think -- thanks for the question, Yigal. I think the simple answer is that there are different populations of patients, and I think we're having a trial that's specifically for NPM1, a trial specifically for KMT2A. I think the outcomes, the standard of care, the work that we're doing in each population is specific or the trial design is specific to trying to achieve the best outcomes in both of these populations. So, knowing that there are differences, we design trials that would be most appropriate for these populations. So that's the driving force behind the strategy, and we think that obviously will give us the best chances of success.

Okay. And also on the comments around the use of Revuforj in the transplant patients that that you mentioned. I'm just curious, did some of those -- did they achieve CRCRH? Are you seeing in the in the commercial setting that the physicians are willing to go to transplant before seeing CRCRH with Revuforj, if you know. I know that's quite detailed.

Yes. Thanks, Yigal. No. We don't actually know. I mean, I think that's physician choice. Right? They treat. Their first priority is to get the patient to a remission, and then they make a determination based on that individual patient, whether they have an MRD negative CR or just a CR that's completely blind to us. That's -- they're in their own domain. So we do expect that, we'll learn more as we go. But as of today, we don't we don't have 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, who were enrolled or 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 is we talked about getting to transplant. I mean, we've got patients now on their fourth refill. Obviously, there's more patients on 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.

Median duration of therapy. So it it's early. I mean, I think that we know we get this question a lot. That is going to take time for the dataset to mature, just the dynamics of patients going off drug, hopefully, to remission, getting to transplant, engraftment, usually 2 to 3 months later then may be back on treatment. But what we can see in the data from a compliance perspective, we like what we're seeing, right? You're going to see a decay month to month over time for a variety of reasons. But, we think in, let's say, a couple of quarters from now, we'll have -- we'll be able to give a real definitive answer on duration of treatment, and we like where we're at right now from the data that we can't see.

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. Really early, even the 1,250 and it's more than 1,250 fusions. I know that's what Incyte reported earlier this week, and that's really an estimate that they can take from, specialty distributor data because that's how they distribute their drug. And some of those patients that there's an EAP, I don't think they've given color to how big it is, but there are obviously some patients on the EAP. There were some patients that were waiting at centers. As you know, the drug was initially approved in August, ultimately new vials out late January, so there was some, we'll call it, some pent up demand. So largely new patients now since it's only a couple of months in. We've activated against all the -- pretty much all the important centers in the country. I think the statistic we gave was 95% of the top centers. That was as of, I think, March that's higher than that today. There's other centers bringing the drug on board. So, it's been a smooth onboarding. High patient demand, I think the drug is being received well. I think we asked -- someone asked earlier just about the types of patients. It's probably fourth line, which is fine to get started. Patients and physicians will get experience, like what we're seeing. It'll take obviously another quarter, and then even a little bit beyond that to see the true run rate as this sort of these warehouse patients work through the EAP gets exhausted, but off to a great start, no doubt.

Great. Thank you.

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

Hey guys, good afternoon. Thanks for the question and congrats on the quarter. I guess a couple from us, just one on Revuforj and one on the Niktimvo launch. On Revuforj, is there any color you can provide just on the relative SKU split between the 25mg 110mg and the 160mg, just so we can understand what your blended WAC is per patient. And then on the Niktimvo launch, just so I'm clear on your slide nine here, the 1250 infusions year-to-date, that's as of, I want to say April, when Incyte reported versus March 31st. I just want to be clear. And that's not -- that's actually infusions and not unique patients. Correct? Thank you.

Great. Salim, thanks for the question. So maybe I'll turn it to Steve. The first question's related to Rev 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 we're -- 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 a couple of infusions. It's every two weeks. And we don't have the mix yet of new patients versus continuing patients.

Okay, got it. And just quick follow up. If you use two vials, that's still one infusion, correct?

Yeah. Have they calculated this is -- again, it's through the SD channel. So, they just know how much they shipped out to customers. They don't know if it's a new patient, an existing patient. So, the way you calculate it is they'll use an average dose per patient based on the clinical trials and then they would apply that to the product that they've sold to come up with the number of infusions.

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

Thanks, Salim.

Thanks for your question. [Operator Instructions] 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 is post-transplant use reimbursed under the current J-code?

Thank you, George. Thanks for the question. So just -- and Steve may chime in here, but total addressable market. I think when you have a new market or a new drug that addresses a targetable population, you're often experiencing dynamics where you're exposing or bringing new patients to -- into the market or be have them be able to be treated. And I think that's that could be true for Revuforj. As you know, there wasn't anything available for KMT2A or the targeted population was, as we said in relapse refractor, about 2,000 patients. It could be larger than 2,000 patients. I think we'll have to see how that unfolds over time. But we are -- as Steve said, making great progress. Not only identifying patients, but getting them on drug and getting on drug quickly. So, we're off to a great start. Wouldn't surprise us if the market were bigger than the 2,000 patients -- addressable patients. We'll just have to see how that unfolds. And then second question in terms of post-transplant. Yeah. Post-transplant being reimbursed, we have only evidence and there's evidence of other drugs being reimbursed for post-transplant maintenance. I think it's as physicians say, these are important. It's important to get patients back on drug after engraftment in order to maintain them in remission. And I think that is more and more accepted by payers as well. These are high risk patients and so, we expect that post-transplant maintenance will be reimbursed generally. And so that is our understanding.

Okay, great. And maybe you mentioned this regarding the sNDA for mutant mNPM1. Is that going to be based on the 77 patients in the efficacy analysis, or is there a larger data set?

Yeah. So, we updated the data set at our ASH event last year. The efficacy of valuable patients were 77 patients. And that's -- in fact we've submitted all the data to the FDA and the sNDA and so, they have access to the 77 patients. They have access to every data set that we've pulled together. But we do expect that they'll look at the 77 patients. I can't tell you what will ultimately be part of the final data set that they analyze and include in the label.

Okay. Thanks very much.

Thank you.

Thanks, George. And our final question comes from Jason

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 guideline committee is 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. Near term is our expectation. We had said second quarter as our guidance, so that's -- and of course, we don't control that fully. But realizing that we're -- where we are on the calendar, I think we have a good shot at that.

Understand. Thanks for the color.

Great. Thank you.