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Michael Metzger

Thank you, Sharon. Good afternoon, everyone, and thank you for joining us today.
Starting with slide 3. 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 multi-billion-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 2 months of our joint launch of Niktimvo.
Later on the call, Keith will break down the numbers we're 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 EVOLVE-2, the first pivotal frontline trial of a 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 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 4 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 a menin inhibitor, the first to have a menin inhibitor listed in the AML and ALL 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?

Steven Closter

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 5. 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 6. 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 2 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 have 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 MPAL.
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 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's 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 7. 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 and 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 I 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 me-too products potentially entering the market.
Moving to slide 8. 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 the 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 a leader in GVHD, and the commercial synergies that Niktimvo has with both companies' product portfolios.
Turning to slide 9 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 long-standing 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 REZUROCK, 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?

Neil Gallagher

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 & 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 EVOLVE-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. EVOLVE-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 EVOLVE-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. EVOLVE-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 rearrangements. 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 fifth 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 CSF1R inhibition, results which are bolstered by the positive results we observed in patients with BOS, or bronchiolitis obliterans syndrome, in the AGAVE-201 trial.
With that, I will hand the call over to Keith to discuss our financials. Keith?

Keith Goldan

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 up on 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 commercial profit, you'll see our 50% share in the revenue section of our income statement under collaboration revenue.
I'll 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 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 principal.
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.

Michael Metzger

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 derisked medicines with high -- with multi-billion-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?

Question and Answer Session

Operator

(Operator Instructions) Anupam Rama, JPMorgan.

Priyanka Grover

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?

Michael Metzger

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

Steven Closter

Yes, Priyanka, 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. But 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 refer patients into other academic centers, and we've seen a number of small academic centers prescribe as well. So I would say this, 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.

Operator

Kelly Shi, Jefferies.

This is [Clara] on for Kelly. Congrats on the great progress. So for the patients receiving Revuforj, could you comment on whether you're seeing a similar pace of patients receiving transplant to what you're seeing with -- 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?

Michael Metzger

Yes, 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.
Yeah, Clara, thanks for the question. So, your question relates to, patients receiving every forge and whether they're, we're seeing, transplants consistent with clinical trials. I could just say that. Right now it's anecdotal information. I think we're, 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. 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.

Operator

Ellen Horste, TD Cowen.

Ellen Horste

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? 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?

Michael Metzger

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

Steven Closter

Yes. Thanks, Ellen, for the question. We're not going to provide any numbers yet. It's a little bit early, plus our data set is maturing. But we're happy with what we see.
I mean, if you saw, look at Q -- sorry, the Q4 net sales, we reported $7.7 million. About a third of that was demand -- I'm sorry, a third of that was inventory. In this current quarter, we don't expect inventory levels to go beyond two to three 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 on hospice. So we're moving into steady state zone. I think for drugs like this, you're going to have to wait probably at least two 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, the user base is increasing.
Michael answered the question on transplant. We're seeing patients already on their fifth refill in some cases, 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 a 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. We're at levels that you typically see two to three years into a launch.
So we feel great about where we are and all patients being treated.

Ellen Horste

Thank you.

Operator

Peter Lawson, Barclays.

Peter Lawson

I wonder if you could speak about any trends that you're seeing in GVHD, in particular, any of the subgroups.

Michael Metzger

Great. Peter, thanks for the question. So regarding trends in GVHD in terms of subgroups, I assume your question is, the patients that are actually getting the drug and what their specific clinical manifestation is in GVHD. Is that the question?

Peter Lawson

Yes, yes, exactly. And then, if there's any kind of age differences between those that are getting it versus not. Any details there would be great.

Michael Metzger

Yes. And maybe I'll turn the question over to Peter. Any kind of information relative to that? 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.

Peter Ordentlich

No. I think it's a little bit early for us to be able to comment on that. I know that the team is collecting the real-world evidence as it's coming in. But I think with just sort of partial quarter so far, I don't think we have that much information. Let me -- go ahead.
Just like a final question just around MSS-CRC. Kind of what's a go-forward signal you need to see with that?

Michael Metzger

Right, Peter, so thanks for the question. 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.

Operator

Michael Schmidt, Guggenheim.

Michael Schmidt

Congrats on the first quarter results. 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 the EVOLVE-2 study where you now have the CR endpoint included.
And could you just comment on how that may impact potential timing to completion of the trial? And it sounds like you may have had similar discussions around the fit -- the planned studies in the fit patient populations as well. Just curious if you could share sort of the feedback that you've received there from the agency.

Michael Metzger

Great. Thanks, Michael, for the questions. 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 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 in 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 in terms of your question about the clinical comments about our unfit trial, and that's what we're calling now the EVOLVE 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, I think, an advantaged setup for potential accelerated approval, and we have alignment there to go forward.
So 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 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 front line, hopefully by a good margin. So that's a positive development.
And then on the fit side of the equation with the trials we'll be starting there, we're not commenting, as we generally don't, on FDA interactions and our conversations there. But we are moving, we think, in a positive direction on all fronts, including in the fit setting with additional trials.

Operator

David Dai, UBS.

David Dai

Congrats on the quarter. I also just want to kind of focus on the EVOLVE-2 trial in the onset population. So I understand that you just got FDA buy-in to use the dual primary endpoints. So I'm wondering if it's possible for you to provide some additional color around powering for the trial.

Michael Metzger

Yes. David, thanks for the question. We haven't talked about the powering of the trial. I mean, 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 because NPM1 is far greater patient population. And essentially, that's the -- so it will be -- both populations will be included, but it will be powered off of NPM1. But specific statistics, we haven't talked about publicly at this point.

Operator

Yigal Nochomovitz, Citi.

Yigal Nochomovitz

I had a question on the strategy around the fit studies. Can you just elaborate as to why it seems like you're pursuing 2 separate trials for NPM1 and KMT2A versus in the unfit, it's all lumped together? Is there a specific reason for that? Or is that set in stone? Or is that something that's still subject to discussion with the FDA?

Michael Metzger

No, 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 designed 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.

Yigal Nochomovitz

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

Michael Metzger

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 in their own domain. So we do expect that we'll learn more as we go. But as of today, we don't have that information.

Operator

Kalpit Patel, B. Riley Securities.

Kalpit Patel

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 stemmed 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?

Michael Metzger

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

Steven Closter

Yes, Kalpit, good question. I think both are building right now. I'm not going to give a lot of color. I think the data set 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 to 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. I mean, 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 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 in the business are good.
We're exactly where we want to be. April is a big month. And obviously, this coming quarter is going to be big as well. And then, your second question?

Kalpit Patel

Median duration of therapy.

Steven Closter

Median duration of therapy. So it's early. I mean, I think that we know we get this question a lot. That is going to take time for the data set to mature, just the dynamics of patients going off drug, hopefully, to remission, getting to transplant, engraftment. Usually, two to three months later, they 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 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 see.

Operator

Jeet Mukherjee, BTIG.

Jeet Mukherjee

Congrats on the quarter. 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?

Michael Metzger

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

Steven Closter

Yes, really early. Even the 1,250 -- and it's more than 1,250 infusions. 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, there's an EAP.
I don't think they've given color to how big it is, but there are obviously some patients on 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 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 will take obviously another quarter and then even a little bit beyond that to see the true run rate as the sort of -- these warehouse patients work through, the EAP gets exhausted, but off to a great start, no doubt.

Operator

Salim Syed, Mizuho.

Salim Syed

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 25 mg, 110 mg, and the 160 mg, 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 9 here, the 1,250 infusions year-to-date, that's as of, I want to say, April when Incyte reported versus March 31? I just want to be clear. And that's actually infusions and not unique patients, correct?

Michael Metzger

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

Steven Closter

We do. We're not going to give a specific breakdown yet. I think as like other things, the data set is maturing. 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, right? It's going to vary based on patient weight, also on concomitant use of a strong 3A4. The bottles are -- they are 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 the scripts are going to be at that 110 and 160 dose.

Michael Metzger

And then, for Niktimvo, I think we're clarifying --

Steven Closter

Yes, 1,250, 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 a couple of infusions. It's every two weeks. And we don't have the mix yet of new patients versus continuing patients.

Salim Syed

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

Steven Closter

Yes, how they calculate it -- 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.

Operator

(Operator Instructions) George Farmer, Scotiabank.

George Farmer

Given the strength of your Q1 Revuforj results, 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?

Michael Metzger

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 into the market or have them be able to be treated. And I think that could be true for Revuforj as there wasn't anything available for KMT2A, or the targeted population was, as we said, in relapsed/refractory 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. It 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 -- yes, post-transplant being reimbursed. We have only evidence and there's evidence of other drugs being reimbursed for post-transplant maintenance. I think as physicians say, 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.

George Farmer

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?

Michael Metzger

Yes. So we updated the data set at our ASH event last year. The efficacy evaluable patients were 77 patients, and that's -- in fact, we've submitted all the data to the FDA in 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.

Operator

Jason Zemansky, Bank of America.

Jason Zemansky

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 19. 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?

Michael Metzger

So Jason, thanks for the question. Exciting development as we've 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.

Jason Zemansky

Perfect. So it's fair to say probably near term rather than longer term?

Michael Metzger

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 where we are in the calendar, I think we have a good shot at that.

Operator

All right. 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.

Michael Metzger

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.