Syndax Pharmaceuticals Inc Q4 FY2024 Earnings Call

Good day, everyone, and welcome to the Syndax Fourth Quarter and Full Year 2024 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 fourth quarter and full year 2024 financial and operating results. I'm Sharon Klahre. And with me this morning 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 2. 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 Form 10-K, as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, March 3, 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 morning, everyone, and thank you for joining us on the call today. Starting with Slide 3. We made exceptional progress in 2024 with the FDA approval of two first-in-class medicines that address major unmet needs, a truly remarkable achievement, which puts Syndax in a unique category as a biopharmaceutical company. Today marks another major milestone in the company's evolution as we report our first quarter with product revenue. As a reminder, on November 15, 2024, the FDA approved Revuforj, our first-in-class menin inhibitor for relapsed/refractory acute leukemia patients with a KMT2A translocation. Just five days later, we had product in the channel with immediate ordering, a very fast timeline that highlights the caliber of the team that we have built to support our transition into a leading commercial oncology company. We are off to a strong start with the US launch of Revuforj and are very encouraged by the early patient demand, breadth of prescribing and coverage from payers. For the fourth quarter of 2024, we reported $7.7 million in Revuforj net revenue from the initial five weeks of the launch. These early results reflect the high unmet need and demand that Revuforj addresses and the strong execution of our organization to deliver the product. We are very excited about the opportunity we have with Revuforj, especially given the clinical data supporting the significant opportunity for future label expansions. We recently reported the first positive pivotal dataset in relapsed or refractory mutant NPM1 AML and have continued to report data that shows strong evidence of synergistic activity in combination with standard of care therapies across newly diagnosed and relapsed or refractory patients with KMT2A rearrangements, the mNPM1 mutations, or NUP98 rearrangements. We are preparing to file a supplemental new drug application or sNDA next quarter that could expand the indicated population for Revuforj into mutant NPM1 AML around the end of the year. In parallel, we are also aggressively advancing our clinical development strategy in the frontline setting to support label expansions and inclusion in the NCCN guidelines. We are very confident that we are well-positioned to lead in the frontline setting, building off our leadership in this space as the first and only company with an approved menin inhibitor. Shifting gears to our second product, Niktimvo. We are thrilled to have launched Niktimvo in chronic graft versus host disease, or cGVHD, in late January in partnership with Incyte, the leader in graft versus host disease. Niktimvo is the first and only FDA approved treatment for chronic GVHD that targets CSF1R to reduce the drivers of inflammation and fibrosis. Like Revuforj, Niktimvo has significant potential for expansion. To unlock those opportunities, we and Incyte are advancing multiple trials. Two trials are underway that are evaluating Niktimvo in combination with standard of care therapies in newly diagnosed chronic GVHD patients, including a Phase 2 trial with Jakafi and a Phase 3 trial with steroids. Enrollment is also ongoing for MAXPIRe, our Phase 2 trial in idiopathic pulmonary fibrosis, or IPF, with topline data expected in 2026. Turning to our financial position. In November, we further strengthened our balance sheet through a deal with Royalty Pharma, a premier company and the largest buyer of biopharmaceutical royalties. We received $350 million upfront in exchange for a capped royalty on US net sales of Niktimvo, a deal that highlights Niktimvo's multi-billion-dollar potential. We are in a strong financial position with a balance sheet that is expected to fund our operations through profitability. I will now turn the call over to Steve to discuss our commercial progress in more detail. Steve?

Thank you, Michael. It's really a pleasure to be on the call today to provide an update on the launch of Revuforj and Niktimvo, starting with Slide 4. It has been incredibly rewarding for me and our entire team to be a part of bringing Revuforj to patients. We are very encouraged by the progress we have made in the early phase of the launch. As Michael stated in the initial five weeks of launch, we generated $7.7 million in net revenue. We estimate that approximately one-third of the net revenue for this first partial quarter represents inventory at our specialty pharmacies and specialty distributors and the remainder represents patient demand. Patient demand was driven primarily by new patient starts, with only a small number of patients transitioning from our Expanded Access Program, or EAP, to paid drug. All the pre- and post-launch work we have done with HCPs, payers and other stakeholders is truly paying off. We are seeing high product awareness among clinicians and the feedback from our customers has been overwhelmingly positive regarding the product profile and the overall ease of access to the medicine, which really speaks to the efficiency of the limited distribution model that we have established. Our distribution model includes partnerships with two of the leading specialty pharmacies for oncology products as well as a network of specialty distributors and our own dedicated patient support program, known as SyndAccess. Thanks to the systems we have in place, the high quality of our internal team, and the work we've done with payers, we're seeing patients get approved for coverage quickly and a rapid time to first fill, which is the time it takes from initiating a Revuforj prescription to the patient actually starting medication. Turning to Slide 5. As Q4 was a partial quarter of sales, I'd like to provide some high-level color on the trends we're seeing in the first quarter of 2025 that provides additional insight into the health of the launch. Starting with the top of the slide, we are seeing very encouraging early breadth and depth of Revuforj prescribing. As of the end of February, 33% of our high priority, or Tier 1 and Tier 2, accounts have ordered Revuforj. These accounts are the centers of excellence in the medium to large academic institutions that represent two-thirds of the patient opportunity. While we prioritize our efforts at these top accounts, we're also calling on the entire universe of 2,000 relevant accounts across the US and are seeing orders from accounts beyond our Tier 1 and Tier 2 accounts, including from community practices, which reflects the high unmet need and the ease of use of Revuforj. Notably, the majority of accounts that have ordered have written more than one prescription for Revuforj. We're leveraging data from multiple sources to help our field teams identify and engage providers at the time when they may have an appropriate patient in their care, which is proving to be an effective approach. We're seeing a mix of patients prescribed Revuforj, which is consistent with the broad label, which includes both adult and pediatric patients, as well as patients with any lineage of relapse or refractory acute leukemia with a KMT2A translocation, including AML, ALL or MPAL. As expected, Revuforj is being prescribed to patients across the treatment continuum, including patients on their first relapse as well as patients with more advanced disease. Based on feedback from physicians, the dire need in this patient population, and the lack of any other targeted therapies for these patients, we expect to see Revuforj rapidly become the standard of care for patients with KMT2A translocations at the time of their first relapse. Turning to the payer front and market access. We did extensive work educating payers before and after launch and we're benefiting from these efforts as well as the rapid inclusion of Revuforj in the NCCN guidelines for AML and ALL. Payers recognize the urgent unmet need and the clinical value of Revuforj and we're seeing reimbursement in all payer channels, including commercial, Medicare Part D, as well as Medicaid. Roughly three months into the launch and we're seeing very strong formulary uptake with formal coverage policies in place for approximately 56% of commercially covered lives and 53% of all managed care lives, which includes all commercially covered plus Medicare and Medicaid lives. Importantly, we're pleased to report that the vast majority of prescriptions are being reimbursed by payers, despite formulary coverage still building. As anticipated, Revuforj is being approved through the medical exception process when formulary coverage is not yet in place. Day in and day out, our team and specialty pharmacy partners are working diligently when necessary to ensure that patients get the treatment they need with the speed and care we would all want to see if it was our loved one in need. This commitment to delivering a best-in-class customer experience is the right thing to do for patients and delivering on this commitment will be one important factor that drives long-term competitive differentiation. Turning to Slide 6. Revuforj is well positioned for near-term and long-term growth and success. In the near term, our current 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. When you take the price of Revuforj into account and an estimated average treatment duration of about nine months across various patient experiences, this initial opportunity represents a $750 million market opportunity and with positive pivotal data in relapsed or refractory mutant NPM1 AML, we have a near-term opportunity to receive a second indication that could expand our target population in the US to 5,000 to 6,500 KMT2A and NPM1 patients, which together represent a $2 billion market opportunity. Revuforj is the first and only FDA approved menin inhibitor on the market today and our teams are working with urgency to capitalize on the advantages of being first to market. We know that once physicians become familiar with a new therapy, they tell us the bar is high to switch to another product with the same mechanism. Revuforj is also the only menin inhibitor with positive pivotal data in both relapsed or refractory KMT2A rearranged acute leukemia and mutant NPM1 AML and in both adult and pediatric patients. The consistency and breadth of the data supporting Revuforj is a strong strategic advantage, because physicians prefer to have one effective and safe drug that they can prescribe across a wide range of patients. Looking ahead, we are well positioned to extend our leadership in the relapse/refractory setting into the frontline setting, and we have a robust development plan underway that is designed to unlock a total market opportunity that exceeds $4 billion in the US across the relapsed/refractory and frontline settings. Moving to Slide 7. In mid-January, we and our commercialization partner Incyte announced that the FDA approved Niktimvo in 9 milligram and 22 milligram vial sizes. In late January, we launched the product and received our first orders. And in mid-February, we had the opportunity to drive awareness of Niktimvo at Tandem, the largest conference for clinicians who perform stem cell transplants. While it is still very early in the launch, we are encouraged by the level of interest in Niktimvo, which speaks to the high unmet need and the product's compelling clinical profile. Together with Incyte, we are working to bring this new option to the approximately 6,500 chronic GVHD patients in the US who require three or more lines of therapy. Addressing the needs of this patient population represents an attractive commercial opportunity. For example, in the three years since the launch of belumosudil, another drug indicated for the same line of treatment as Niktimvo, net sales continue to grow in the high double-digits and suggest that the drug is now annualizing at over $500 million in US sales. With a new mechanism of action and strong clinical data showing remarkable responses in heavily pre-treated patients, we believe that Niktimvo will be able to capture a significant portion of the $1.5 billion to $2 billion estimated total addressable market for third-line or later chronic GVHD treatment in the US. We are confident that we have just started to scratch the surface of the opportunity with Niktimvo and are thrilled to be working with Incyte on trials designed to move the product into earlier lines of treatment for chronic GVHD and other inflammatory and fibrotic diseases, starting with IPF. With that, I'll hand the call over to Neil to discuss the work we are doing to develop revumenib for the treatment of acute leukemias across the treatment continuum.

Thanks, Steve. I'm pleased to provide an update on the revumenib development program starting on Slide 8 with the near-term opportunity we have to expand into relapsed or refractory mutant NPM1 AML. Given the high unmet need and lack of approved therapies that target this population, we are pleased to have reported the first positive pivotal dataset. In November 2024, we announced that the primary endpoint was met in the protocol-defined efficacy population of 64 adults with relapsed or refractory mutant NPM1 AML in the Phase 2 cohort of the AUGMENT-101 trial. Among a heavily pre-treated population including 75% with prior venetoclax exposure, nearly half of patients achieved a response and 23% achieved CR/CRh. Consistent with other datasets, the responses were deep with 64% of CR/CRh responders achieving MRD negativity. Additionally, 17% of responders proceeded to stem cell transplant, which is a meaningful outcome in a population that is older and less fit for transplant than, for example, patients with KMT2A rearrangements. Overall, the data are compelling and we are confident that they could support regulatory approval, further solidifying our leadership position. Building on the positive pivotal data, we reported results in December 2024 from a larger post hoc analysis, which included additional mutant NPM1 patients from the Phase 2 cohort who met the efficacy evaluable criteria. These results were highly consistent with those for the primary analysis, with an overall response rate of 48% and a CR/CRh rate of 26% among 77 efficacy evaluable patients. Looking ahead, we expect to file the sNDA in the second quarter and believe we could receive approval around year-end. Also in the second quarter, we expect to publish the pivotal NPM1 data and believe this could serve as the basis for the expansion of the listing for revumenib in the NCCN guidelines for AML, ahead of the potential FDA approval in this population. Turning to Slide 9. We're advancing revumenib for the treatment of genetically defined acute leukemias across the treatment continuum and are well positioned to establish it as the preferred menin inhibitor for both relapsed/refractory and newly diagnosed patients in combination with standards of care. In the frontline, we're advancing a thoughtful combination of Syndax-sponsored and investigator-initiated trials for revumenib in combination with standards of care in patients ineligible or unfit for intensive chemotherapy, as well as those who are eligible or fit for intensive chemotherapy. Our strategy prioritizes addressing populations with the greatest unmet needs, speed to data and the generation of a regular cadence of potentially practice-changing evidence that could support label expansion and/or inclusion of the NCCN guidelines. Moving to Slide 10, and next steps in the frontline. In collaboration with the HOVON Network, we are initiating a pivotal randomized placebo-controlled trial of revumenib with venetoclax and azacitidine in newly diagnosed patients with NPM1 mutations or KMT2A rearrangements who are ineligible for intensive chemotherapy either due to their age or comorbidities. Our partnership with the well-established HOVON Network provides significant advantages for trial efficiency by allowing us to quickly enroll patients globally, while conducting the trial with the highest quality. The pivotal trial will build on the encouraging data from BEAT AML, a Phase 1 trial evaluating revumenib with venetoclax and azacitidine in newly diagnosed mutant NPM1 or KMT2A rearranged AML patients who are unfit for intensive chemotherapy. The latest data show that the overall response rate was 100% and the MRD negative rate was 95% among 37 efficacy evaluable patients. These results highlight the potential for revumenib to enhance the responses observed with venetoclax and azacitidine in this population. The data also demonstrate that revumenib can be combined with standards of care in the frontline setting. Turning to the frontline population that is eligible to receive intensive chemotherapy. We expect to report data in the second half of 2025 from an ongoing Phase 1 trial of revumenib with 7+3 or intensive chemotherapy. We also plan to initiate multiple trials of revumenib in combination with standards of care in newly diagnosed AML patients who are eligible to receive intensive chemo starting in the second half of 2025. We are confident that we are poised to lead and win in the frontline setting, and we recognize that speed to data will be key. Furthermore, we will be in a position to avail ourselves of any opportunities that may emerge to accelerate timelines through the use of alternative endpoints. For example, as leaders in the menin space, we will continue to partner with the Foundation for the National Institutes of Health's Biomarkers Consortium on MRD and AML to establish MRD as a validated biomarker in the disease. With that, I'll hand the call over to Keith to discuss our financials. Keith?

Thank you, Neil. Earlier this morning, we reported fourth quarter and full year 2024 financial results in our press release. For today's call, I'll touch on a few highlights from our fourth quarter on Slide 11. We're pleased to report $7.7 million of Revuforj net revenue in the fourth quarter of 2024. Operating expenses in the fourth quarter were $104.0 million and included $65.5 million of research and development expenses and $37.7 million of selling, general and administrative expense. Turning to the balance sheet, we continue to maintain a strong financial position with $692.4 million of cash, equivalents and short and long-term investments as of the end of the year. We continue to expect that our cash, together with our anticipated product revenue and interest income, will enable the company to reach profitability. For the first quarter of 2025, the company expects R&D expenses to be $65 million to $70 million and total R&D plus SG&A expenses to be $105 million to $110 million. For the full year of 2025, the company expects R&D expenses to be $260 million to $280 million, and total R&D plus SG&A expenses to be $415 million to $435 million, which includes an estimated $45 million in non-cash stock compensation expense. The company is not providing revenue guidance at this time. Ahead of reporting the first sales for Niktimvo with our first quarter 2025 results, I would like to take a moment to briefly review how we will recognize revenue for that partnered product. Slide 12 provides an illustrative example of accounting for sales of Niktimvo and is not intended to provide any margin or other guidance. We will record 50% of the commercial profit defined as net product revenue minus the cost of sales and commercial expenses. During a period where there is net commercial profit for Niktimvo, as in the top example on the slide, our 50% share of the net profit will be recognized in our P&L as collaborative arrangement revenue. Of note, the expenses that are deducted from the top line Niktimvo revenue to arrive at the collaborative revenue will not include the synthetic royalty owed to Royalty Pharma. The upfront $350 million that we received from Royalty Pharma is liability-classified on the balance sheet and the 13.8% royalty payments will be reflected on our financials as a combination of interest expense and amortization of the liability principal amount. During a period where there's a net commercial loss for Niktimvo, as in the bottom example on the slide, our 50% share of the net commercial loss would be included in operating expenses designated as a separate line called Share of Collaboration Loss. Any milestone revenue from various commercial and regulatory milestones that we received from Incyte will be recorded as milestone revenue on our income statement. As a reminder, research and development expenses, including regulatory and CMC expenses, are shared 55:45 in the US and our 45% share is included in the income statement as part of our R&D expense. Outside of the United States, Incyte is responsible for 100% of the development and regulatory expenses. We are entitled to receive milestones plus a double-digit royalty on ex-US sales. With that, let me now turn the call back over to Michael.

Yeah. Thank you, Keith. It's been a very successful start to the year for Syndax and we are poised for another exciting period as we advance the launches of Revuforj and Niktimvo and work towards achieving the multiple upcoming milestones that you can see on Slide 13. We are confident that Syndax is well positioned for long-term growth. We are very excited about the derisks and very significant market opportunities we have in front of us with the first two differentiated medicines to emerge from our pipeline. We are laser-focused on unlocking the full value of both products and are set up for success with a strong balance sheet and a highly experienced team that has done an exceptional job executing to plan throughout the development, approval and commercialization of our first two medicines. In closing, I want to thank everyone who has made it possible for Syndax to bring two novel medicines across the finish line in 2024. I especially want to thank the patients, investigators and study sites who participated in our clinical trials as well as our dedicated and talented Syndax team members. I'd also like to thank our committed long-term investors who continue to share in our vision and support our work in building Syndax into a leading oncology company, an objective that we are well on our way to achieving. And with that, I'd like to open the call for questions. Operator?

(Operator Instructions) The first question will come from Anupam Rama with JPMorgan. Please go ahead.

Hey, guys, thanks so much for taking my question and congrats on all the launch progress here in the early innings. Quick one for me. I know in the press release you talked about a third of the 4Q Revuforj sales were inventory. Just wondering how we should be thinking about inventory levels throughout 2025? And then I know also that you said you're about a-third penetrated into your Tier 1/2 accounts. How have you seen any trends on repeat prescribers from some of the docs, given the aggressive nature of KMT2A? Thanks so much.

Yeah, Anupam. Thanks for the question. So, two questions. So first question I'm going to direct to Keith, which is related to inventory levels. Keith?

Yeah. Morning, Anupam. Good question. Thank you. I think our inventory levels, as you think forward through 2025, probably be similar to other specialty launches or rare disease launches. As a result of our limited distribution channel, which Steve talked about, we're not expecting to see more than two to three weeks of inventory in the channel. We mentioned in our prepared remarks that we saw about approximately one-third stocking. And in five weeks, we're kind of right there in the sweet spot. So we wouldn't expect the inventory level to change in terms of weeks, but as revenue grows, obviously, that inventory level, on an absolute basis, could be expected to grow.

Great. And, Steve, do you want to take the penetration into accounts question?

Yeah. Thanks, Anupam, for the comment. We're pretty pleased with where we are. We've got 33%, as you mentioned, of Tier 1 and 2 accounts, our biggest accounts, that account for two-thirds of the opportunity that are getting on board. We're confident we'll go along the list and get others to write as well. In terms of repeat prescriber, something we're looking at carefully and we're not going to provide numbers yet or estimates on that. But I will say the majority of accounts have used more than once, and that's good, whether that's a patient getting a refill or finding new patients. I mean, this is all about building a habit. The better experience they have upfront, the more likely they are to use the product moving forward. And we feel really good about where we are.

Thanks so much, guys, and congrats.

Thanks, Anupam.

The next question will come from the line of Brad Canino with Stifel. Your line is now open.

Good morning, and nice first commercial quarter. Two-parter for me. For the 66% of Tier 1/2 accounts that have not yet ordered, what do you expect for the cadence and extent of activation over the next 10 months? And then second, now, with the few months of commercial experience under the belt, how do you see Revuforj tracking with some of the historic AML targeted therapy launches? Thank you.

Okay. Thanks, Brad. Appreciate the question. So first I'll direct to Steve.

Yeah. So thanks, Brad, for the question. And I like what you're thinking. I mean, I think for us it's a good start to have a little over a third of accounts activate really early. And it's a good mix of accounts. It's not just the biggest. It's not the smallest. It's a broad range. We think it represents a ton of opportunity moving forward. We're not going to comment on the cadence. I think what we are doing is activating across all 2,000 treatment centers. We're going to focus on the top 200. We think it's just a matter of time for those institutions to get experience. We've got a sales team that is perhaps the most experienced and talented in the industry. They've got great relationships. We still have a ton of momentum. So we expect over the course of the year, one by one, we'll pick each one off. As you can imagine, the 33% is a blend of Tier 1 and Tier 2. There's far more Tier 1 accounts that have activated and fewer of the Tier 2 accounts. But over time, with the right type of effort, they will fall. There's unmet need, product is responding well. So we're pretty positive over the course of the coming months.

Great. Maybe the second question relative to analogous.

In terms of analogous, I think we've got a unique setup. I mean I think unlike other targeted therapies in the past, you've got testing for a product like Revuforj, identifying KMT2Ar patients which you may not have had as readily speaking to other targeted therapies. So urgent unmet need is high. Patient diagnostic testing is very high. As mentioned, the product is very well received by clinicians. And on a payer front, things are in a great place. Not all companies look to get paid claims early on in the launch. There's a sense of kind of giving drug away. That's not what we're doing. We're developing a habit for physicians to understand the customer experience they can expect, which we believe is a good one. So it's too early to say where we are relative to those analogous launches, but we feel great about where we are. Just one partial quarter in and a couple of months into the start of 2025.

Great. Thank you.

Thanks, Brad.

The next question will come from Peter Lawson with Barclays. Your line is now open.

Great. Thank you so much for taking the questions, and thanks for all the updates. I guess firstly around Revuforj, like how that's being used, if you're seeing off-label use, how much for NPM1 and if you're seeing it being used in combination? And then just regarding the Expanded Access Program, just maybe a clarification for me. You kind of talked about a rapid transition, but I think it mentioned less than 10 patients transitioned. Just kind of how many patients are left on that Expanded Access Program? Thank you.

Yeah. Thanks, Peter. Maybe Steve again for you, off-label use, first question.

Yeah. Good question, Peter. Obviously, it's not something we promote. We're only going to promote against the primary indication as you'd expect. In terms of off-label use, what we can say at this point, it's anecdotal: we know we're getting some use in NPM1, some use in combination treatment, certainly earlier line types of treatment. And that's anecdotal. Over time, we'll be able to better qualify that. But at this early stage, it's a challenge to do that. And in terms of the EAP question, as pointed out, EAP transitions were in the single digits. All patients that were eligible to be transferred have been and the EAP remains lightly used for off-label indications and oral solution. It's all lightly used there, but no additional patients to transfer from EAP at this time.

Just maybe a final question. How's momentum going in the first couple of months of '25?

The momentum is good. I mean, I think if you remember we started this back in the fall initially with the NPM1 data release followed by approval, followed by ASH. Believe it or not, institutions are still doing their ASH reviews, which is physicians that didn't make it to the conference. They see the data, so they'll certainly see the data on Revuforj as well as in the menin space. So that momentum that we saw at ASH continues to this day. Very high excitement levels. Our field team, as mentioned, is closely connected to the customer community. So opened — welcome arms. Physicians see unmet need. They like what they see in the drug. So, I think, we'll ride this wave really probably throughout the rest of the year.

Yeah. And maybe I'd add that the payer coverage seems to be building really very nicely and I think that's a complement to all the hard work that the team is doing to get it through the payer system.

Great. Thanks so much.

Thank you, Peter.

The next question will come from the line of Chris Shibutani with Goldman Sachs. Your line is now open.

Great. Thank you very much. Congratulations on great progress with the initial part of the commercial launch. Many questions have been asked there. Perhaps if I could ask a little bit more of an intermediate or longer term strategic question. Certainly, the company has gotten to this point finding assets, developing them successfully. Now commercializing. What are your thoughts on what's next? What does this company look like in 2030? Many arguments for saying that if you're making these investments in a fully integrated company that we be soon turning to what else is in the pipeline based upon your experience, capabilities and now commercial presence. Do you have a vision to that? Are you going to share that? If not, why not? When might you? And are you and the Board aligned? Thank you.

Well, Chris, what a big question here. So thank you for asking it. I think the vision for the company is ambitious. I think we have done wonderful things to get to this point not only in-licensing and developing two novel medicines, but bringing them to patients. And I think we'll do quite well commercially. I think the broader vision is to extend these products into earlier line indications and really build on our first-mover advantage. So I think that's a longer-term vision for these particular products and I think the extension to additional products, bringing in additional products in targeted oncology has been our focus. I think we'll continue to build in oncology and build the pipeline ultimately to be able to leverage the organization that we've developed over time. So I think we have an ambitious vision to have a larger pipeline and to build the company over several years. By 2030, we expect to be an increasingly advanced and rapidly advancing company with multiple commercial products in our portfolio and have the opportunity to continue to get drugs approved. That's the vision, long-term vision. As a standalone company, we'll be focused in the US and focused in oncology and look to partner externally and ex-US as we build the business. The Board and management are aligned in this approach.

Perfect. Thank you for the insights.

Thank you, Chris.

The next question will come from the line of Kelly Shi with Jefferies. Your line is now open.

Congrats on a great quarter, and thank you for taking my questions. Although it's still early days, curious for patients bearing co-mutations such as FLT3, how physicians sequence the therapies? And what would be the reason that physicians prioritize Revuforj? And also curious, on safety front, could you share about the physician feedback on their real-world experience? Thank you very much.

Sure. Kelly, thanks for the question. So first one related to the prioritization, why would a physician use a menin inhibitor versus some of the other targeted therapies? I'll direct that to Neil.

Yeah. Thanks for the question. The answer is in fact two parts. It depends on whether or not the patient is considered to be eligible or ineligible for intensive chemotherapy. So in the Phase 3 trial that we're currently initiating in the unfit population, there is no selection for FLT3. We will include patients, as I mentioned in our prepared remarks, patients with both NPM1 and KMT2A. There's no approved therapy for patients with these mutations who are unfit for intensive chemotherapy. In the fit setting, it's slightly different. There are approved therapies and therefore physicians will likely reach for a FLT3 inhibitor for patients who have a FLT3 mutation before anything else, where an approved FLT3 inhibitor exists. And of course, patients can have both FLT3 and NPM1 mutations at the same time, and this is an area of intense interest for us.

Great. Thank you. And then the second question I'll refer to Steve. I think the question, Kelly, was related to physician feedback on the safety profile so far in real world.

Yeah. I mean, I think feedback on the whole profile is great. From an efficacy standpoint, it's got data that's instructive to use in terms of safety and tolerability. As we know we have a boxed warning for differentiation syndrome that's being managed. Other aspects of tolerability are understood by physicians. The label is clear. And I'd say the other thing that we do is have a pretty comprehensive customer-facing footprint. We have oncology clinical nurse educators that are in accounts within 48 hours of the drug being prescribed. So it's a lot of hand-holding and helping physicians and their associated staff through treatment and dosing is clear across the adult and pediatric populations. So I'd say things are very good. There's really nothing getting in the way of physicians putting patients on Revuforj.

Thank you.

Thank you, Kelly.

The next question comes from the line of Michael Schmidt with Guggenheim. Your line is now open.

Hey, guys. Good morning. Thanks for taking our questions. I had a couple more on the Revuforj launch. Keith, perhaps could you comment on early trends in gross-to-net adjustment as well as potential use of a free drug program, et cetera? And then in terms of early feedback from the market, what have you heard about or seen around transplant dynamics?

Thanks, Michael. Sure. So first question related to gross-to-net. Maybe I'll direct to Keith.

Yeah. Good morning, Michael. While we're not providing specific numerical figures on gross-to-net, it's tight. I think if you go back to the comments I made earlier about our limited distribution channel, that allows us to really keep the gross-to-net very tight. Additionally, we've not seen nor do we foresee the need to rebate. So for those reasons and a few others, the gross-to-net on Revuforj has been and we expect it to continue to be very tight.

And maybe, Steve, do you want to talk about the free drug program?

Yeah. So we do have a patient assistance program. It's used for basically uninsured or underinsured patients. Our goal as an organization is to make sure every patient has drug. Our first priority is to get the claim paid. If the patient can't qualify for paid drug, there is that patient assistance opportunity. It's in the single digits. You often may see some pressure at launch as deductibles reset for the beginning of the year. I think we've navigated through that incredibly well. It's going to be in the low single digits.

Right. And then maybe early feedback on the transplant dynamic. I think physicians are obviously very interested in getting patients to transplant, certainly for KMT2A. We've also seen it for NPM1 as well. But most of these patients are on the younger side for KMT2A. And so transplant is an objective and we know patients are going to transplant, so they're getting drug and then going to transplant. And then we expect the vast majority of those patients, especially as they're treated earlier in their treatment course, more like first relapse, have the opportunity to potentially go back on maintenance after receiving their transplant once engraftment happens. So I think we're optimistic about how that's unfolding. It's early days yet to really say much more about it. But as of today, this is how we're feeling. Very good.

Thank you.

Thanks, Michael.

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

Hi, Michael and team. Thank you, and congrats on the first quarter revenues. I have three quick ones, if I may. First, by my math, it seems like you have about 125 to 130 patients on drug net of the inventory, which is about 6% share. Could you just comment on that? Second, if you could be a little more specific regarding how you're defining Tier 1 versus Tier 2 centers? And then third, for Neil perhaps, you mentioned some of the FLT3 dynamics. I'm just curious if you could be a little bit more granular as far as how those Phase 3 trials could look? I could imagine four studies, a KMT2A study for those with a FLT3 and those without. Similarly, NPM1 for those with a FLT3 and those without. This would be in the fit population. So would you have a 7+3 plus FLT3 control arm in those studies, respectively? Thank you.

Great. Good questions, Yigal. So let me turn the first to Steve talking about the math that you've done, 125 to 130 patients net of inventory, roughly 6% of the population. That's your math. So make some comments on that, Steve. Go ahead.

Yeah. Appreciate the math, Yigal. And we're just not going to provide specifics on patient counts just yet. There's really a couple of reasons for it. One is just we have visibility at the patient level in less than half of our limited distribution channel. It's really just to the specialty pharmacy channel. So we want to be accurate, and that'll take us some time to do that. And I think the second is, it's just early from a patient perspective. The second question was around Tier 1 and Tier 2 definition, and it's roughly combined about 200 accounts. Those accounts represent about two-thirds of the patient opportunity. So Tier 1, think biggest of the big—MD Anderson, Dana-Farber—those are typical Tier 1 accounts. Tier 2 just tend to be a little smaller. It's really just defined by patient opportunity. So these are influential accounts, but may not have the patient volume that the Tier 1s have. Examples could be St. Jude's or Tampa General, just to give you some perspective.

Great. And then the third question goes to Neil, which is related to the trials in the fit population, specifically around FLT3.

Yeah. So thanks, Yigal. As we referred to in the prepared remarks, our intention is to initiate multiple trials in the fit setting. We also alluded to the fact that speed to data is important. There are, of course, multiple populations within the fit group, including patients with FLT3 and NPM1 co-mutations. We're not discussing the detailed design of our strategy publicly because it's a competitive space. But we are working aggressively to start multiple trials starting in the second half of this year.

Okay. Thank you so much.

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

Great. Thanks for taking my questions, and also want to congrats on the great quarter. So two from me as well. So the first one just around the relapsed/refractory NPM1 data, you're planning to submit for NCCN guidelines and kudos here. Could you maybe talk about the timing of the inclusion of Revuforj for NPM1 in the NCCN guideline? Do we think about the inclusion in the NCCN before the approval in second half this year? And then the second question just around the formalization of the trial in unfit AML, where you said that you're planning to meet with regulators to use MRD negativity as a set of endpoint. Can you just talk a little more about the timing around that and how should we think about your engagement with the FDA or with the regulators on the timing for MRD negative CR? Thank you.

Great, David. Thanks for the question. So the first question is related to relapsed/refractory NPM1 and our timing relative to submission for NCCN and whether that could happen before approval. We plan to publish the data and submit it for NCCN consideration in the second quarter and we expect that the inclusion in the NCCN could occur in the second quarter as well. That would be in advance of a potential FDA approval toward the end of this year. That timing could provide an advantage for access in that population. The second question relates to MRD as an endpoint and our meetings with regulators. Neil will address that.

Thanks for the question. Typically, we don't discuss the details of our interactions with health authorities. I would point out that our interest in MRD negativity as a biomarker is long-standing. As mentioned in the prepared remarks, we have been part of the consortium led by NIH, which also includes other industry partners as well as the FDA, through the Biomarkers Consortium. Beyond that, we won't discuss specifics of regulatory interactions on this call.

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

Thanks for taking our question, and congrats on the strong commercial start here. Michael, maybe just to follow up on the prior question, can you speak to your confidence of a broad recommendation by NCCN in the second quarter? And any color on payer discussions regarding reimbursement of patients with NPM mutations with support of a broad NCCN guideline recommendation ahead of the formal potential FDA label expansion later this year?

Thanks, Justin. I think we feel very confident the data is supportive and practice-changing and we expect inclusion in the NCCN. That should help access. I'll turn the payer question to Steve.

Maybe even take it a step back. We've had a good start. Payer coverage is growing; it's at 53% for all managed care lives. Importantly, claims are being paid really across the continuum. Because we had an early payer engagement effort starting about a year and a half before approval, we are prepared to talk about NPM1 with payers when we file the sNDA. In the interim, claims are being paid regardless of indication from what we can tell. Payers are not standing in the way of physicians who need a treatment where they otherwise don't have one. So we feel pretty good about where we are and expect payers to be prepared to cover NPM1 when the time comes.

That makes sense to me. And Steve, could you just talk to the importance of being first in a competitive marketplace like this, the importance of being first to market?

I appreciate the question, Justin. Being first to market and first-mover advantage is meaningful. It's about getting the product out, having the right customer-facing field team, trade support, medical affairs alignment, and delivering a consistent, strong customer experience. Time to first fill is critical; we're seeing patients start in a matter of days. That kind of experience and the muscle memory accounts gain is difficult for a follow-on competitor to match.

Thanks for taking my questions, and congrats again.

Thank you, Justin.

Our next question comes from George Farmer with Scotiabank. Your line is now open.

Hi. Good morning. Thanks for taking my questions. A couple from me. Regarding the strategy for attaining compendia listing in the NPM1 population, can you point to other AML drugs in the space that have secured compendia listing based on a similar dataset than what you have today? And then as a follow-up regarding your strategy in the intensive chemo fit patient population, this data that could come in the second half in combination, can you talk about what you think the optimal dose is in combination with intensive chemotherapy? Thanks.

Great. Thanks, George. I'll turn the compendia question to Anjali and the dose question to Neil.

Thanks, George. A couple examples in the space: sorafenib was granted NCCN guideline listing for FLT3 treatment based on a Phase 2 dataset. More recently, gilteritinib in combination with venetoclax and azacitidine off a Phase 2 single-arm trial was granted compendia listing as well. There are several examples, including therapies like Revuforj for KMT2A that have secured compendia listing, which supports our confidence in being able to achieve similar listings for NPM1 based on our dataset.

Thanks for the question. As mentioned, we'll present data later in the year. Across the combinations we've been testing, revumenib has been well tolerated at both doses tested, 110 mg and 160 mg. So we have choices and the data will inform the optimal dose. Currently, we're combining a full chemo dose alongside revumenib in our ongoing studies, and we'll report more later in the year.

All right. Excellent. Thanks very much.

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

Hi. This is Eric on for Salim. Thanks for taking our question, and congrats on the nice ramp for Revuforj. I wanted to get some color on the timing and the total addressable size of ex-US for Revuforj. What are your thoughts on the gating factors for ex-US regulatory submissions and what that might look like if you were to collaborate or outlicense ex-US?

Great. Thanks, Eric. We haven't announced all of our ex-US regulatory plans. Ex-US plans tie to our frontline strategy and global trial activity. The ex-US market is appreciable, roughly comparable to a large proportion of the US opportunity, and we will look to address it as soon as possible. We are open to partnering outside the US, and for Niktimvo we already have Incyte as a partner ex-US. We'll develop our ex-US plans for Revuforj in due course as we progress the clinical program.

All right. Helpful. Thank you.

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

Good morning. Congratulations on the launch progress, and thanks for taking our questions. Two, if I may. Somewhat of a follow-up, but regarding the HOVON-led trial in the unfit population, is there something in the protocol that could support a potential path to accelerated approval? And what would the timelines look like for that? And then maybe from a broader strategic perspective, how are you prioritizing first-line fit versus unfit? What's the more important opportunity for Revumenib, especially considering the evolving competitive landscape?

Great. Jason, thank you for the questions. First, on the HOVON trial and accelerated approval, Neil?

Thanks for the question. As I mentioned in the prepared remarks, we are positioned and will continue to position ourselves to be able to avail of any opportunity for accelerated approval based on intermediate endpoints. However, we do not discuss the details of our discussions with health authorities on this call.

And on the prioritization of first-line fit versus unfit: the unfit population with venetoclax and azacitidine is a high unmet need and the HOVON trial addresses that population globally, so it's a top priority. We will also initiate trials in the fit population later in 2025. In 2025, we'll progress trials addressing both populations, but the HOVON study in the unfit population is a key near-term priority because of the unmet need and opportunity.

Great. Thanks, Mike. Appreciate the color.

Thank you.

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

Great. Thank you, operator, and thank you all. We really appreciate you all tuning in today to discuss our recent progress and the exciting milestones ahead. We look forward to seeing many of you at the Cowen, Jefferies and Barclays conferences this month. And with that, have a fantastic day.