Syndax Pharmaceuticals Inc (SNDX) 2024 Q4 法說會逐字稿

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 factor section in the company's most recent report Form 10-K as well as other reports filed at 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 addressed 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 NPM1 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 the space as the first and only company with 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 II trial with Jakafi and a Phase III trial with steroids. Enrollment is also ongoing for MAXPIRe, our Phase II trial in idiopathic pulmonary fibrosis, or IPF, with top-line data expected in 2026.

Turning to our financial position. In November, we further strengthened our balance sheet through a deal with Royalty Pharma, the premier company and largest buyer of biopharmaceutical royalties. We received $350 million up front in exchange for a capped royalty on US net sales of Niktimvo, a deal that highlights Niktimvo's multibillion-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, with 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 have done with payers, we are 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 are 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 and the medium to large academic institutions that represent two-thirds of the patient opportunity. While we prioritize our efforts at these top accounts, we are 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 ease of use of Revuforj. Notably, the majority of accounts that have ordered have written more than one prescription for Revuforj.

We are 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 are seeing a mix of patients prescribed Revuforj, which is consistent with our broad label, which includes both adult and pediatrics, 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 moving mountains 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 that delivering on this very commitment will be one important factor that drives long-term competitive immunity.

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 relapse 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 relapse 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 relapse 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 relapse/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 miligram and 22 miligram 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 or Rezurock, 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 and 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 II cohort of the AUGMENT-101 trial. Among a heavily pretreated 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 II 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 of revumenib in combination with standards of care in patient's 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 in 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/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 I trial, evaluating revumenib with venetoclax/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/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 I trial of revumenib with 7 plus 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 time lines 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 full-year 2024 financial results in a 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 expense and $37.7 million of selling, general, and administrative expense.

Turn 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 at 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 on 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 receive 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 is 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 regulatory milestones that we receive 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 statement as part of our R&D expense. Outside of the United States, Incyte is responsible for 100% of the development and regulatory expenses, and 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.

Yes, 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) Anupam Rama, JPMorgan.

Congrats on all the launch progress here in the early innings. Just quick one for me. I know in the press release, you talked about, 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, Tier 2 accounts. How -- have you any trends on repeat prescribers from some of the docs given the aggressive nature of KMT2A?

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, Anupam. Good question. Thank you. I think our inventory levels, as you think forward through 2025, probably be thinking about it 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.

And we mentioned in our prepared remarks that we saw about approximately a 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 will -- could be expected to grow.

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

Yes. Thanks, Anupam, for the comment. We're pretty pleased with where we are. We've got 33%, as you mentioned, of Tier 1 and Tier 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 prescript -- repeat prescribers, 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 up front, the more likely they are to use the product moving forward, and we feel really good about where we are.

Brad Canino, Stifel.

Nice first commercial quarter. Two part-er for me. For the 66% of Tier 1, Tier 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 a few months of commercial experience under the belt, how do you see Revuforj tracking with some of the historic AML targeted therapy launches?

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.

Okay. Maybe the second question relative to analogs.

Yes. In terms of analogs, 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 the payer front, things are in a 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 too early to say where we are relative to those analogs, but feel great about where we are. Just one partial quarter in and a couple months in to the start of 2025.

Peter Lawson, Barclays.

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, I think you mentioned less than 10 patients transitioned. Just kind of how many patients are left on that extended access program?

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

Yes. Good question, Peter. Obviously, it's not something we promote against. 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 it's anecdotal.

We know we're getting use. 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, it's -- we're talking 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 also 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.

Yes. 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.

Chris Shibutani, Goldman Sachs.

Congratulations on great progress with the initiative 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, 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 2023? Many arguments for saying that if you're making these investments in a fully integrated company that we'd be soon turning to what else is in the pipeline based upon your experience, capabilities, 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?

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 in 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.

I think that's a longer-term vision for these particular products. And I think the extension to additional products, bringing in additional products, 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 extremely advancing and rapidly advancing company with multiple commercial products in our bag, so to speak, 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 external and ex-US as we build business. But it's a -- I think, we would hope to be a formidable specialty oncology company by 2030. And yes, the Board and management are quite aligned in this approach.

Kelly Shi, Jefferies.

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

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

Yes. Thanks for the question. So the answer is in fact two parts, right? So it depends on whether or not the patient is considered to be eligible or ineligible for intensive chemotherapy. So in the Phase III 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 -- in the prepared remarks, patients with both NPM1 and KMT2A. There's no approved therapy for patients with FLT3 mutations who are unfit for intensive chemotherapy. In the fit setting, it's slightly different.

There are approved therapies, and therefore, until there are approved, other approved therapies, then physicians will reach for a FLT3 inhibitor for patients who have a FLT3 mutation before anything else. 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.

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 real world, so.

Yes. I mean, I think feedback on a 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 black box for DS that's being managed. QT, other aspects of tolerability are understood by physicians.

The label's 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 handholding in helping physicians and their associated staff through treatment. And dosing's clear, wide age population, AML, ALL.

So I'd say things are very good. There is really nothing getting in the way of physicians putting patients on Revuforj.

Michael Schmidt, Guggenheim.

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 perhaps relative --

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

Yes. Michael, while we're not providing specific numerical figures on gross to net, It's tight. I think 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 then maybe Steve, do you want to talk about free -- Michael, had asked about free drug program, so why don't you make a comment on that?

Yes. So we do have a patient assistance program. It's used for basically uninsured or underinsured patients. I mean, 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 a -- that patient assistance opportunity. It's in the single digits. I mean, you often you can't see some pressure at launch. You can see some pressure as deductibles reset for the beginning of the year. I think we've navigated through that incredibly well. It's going be in the low single digits.

Right, and then maybe early feedback on the transplant dynamic. I think we've -- physicians are obviously very interested in getting patients to transplant, certainly for KMT2A. We've also seen it for NPM1 as well, 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 going to 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 transplant -- go back on maintenance after receiving their transplant and the engraftment happens. So I think we're optimistic about how that's unfolding. I think it's early days yet to really say much more about it, but as of as of today, this is how we're feeling. Very good.

Yigal Nochomovitz, Citi.

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 III trials could look. As I could imagine, four studies, a KMT2A study for those with a FLT3 and those without, similarly NPM1 for those within FLT3 and those without. This would be in the fit population. So would you have a seven, three plus the FLT3 control arm in those studies respectively?

Good questions, Yigal. Thank you. 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 I'll make some comments on that, Steve, go ahead.

Yes. Appreciate the math, Yigal. And we're just -- we're 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 -- it's just early, you know, from a patient perspective. I think 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, you can think, we'll say 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 opportunities. So these are influential accounts, but may not have the patient volume that the Tier 1s have. So examples there could be, like a Saint Jude's or a Tampa General, just to give you some examples to put it in perspective.

And then I guess the third question goes to Neil, which is related to the trials and the fit population related, specifically around FLT3.

Yes. 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.

It's not an homogenous population, including patients with FLT3 and NPM1 co-mutations. We're not really talking in detail about our strategy. It's a competitive space, but we are working aggressively to start multiple trials starting in the second half of this year.

David Dai, UBS.

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 pivotal data, you're planning to submit for NCCN Guidelines end quarter this year. Could you maybe talk about the timing of the inclusion of Revuforj for NPM1 in the NCCN Guideline? Do we think about the inclusion of the NCCN before the approval in second half this year?

And then second question just around the frontline additional trial in the unfit AML where you said that you were planning to meet with the regulators to use MRD negativity as a set of endpoint. Can just talk a little bit more about the timing around that? And how should we think about your engagement with the regulators on the timing for MRD negativity CR?

David, thanks for the question. So the first question is related to relapsed/refractory NPM1 and our timing relative to submission for guidelines, and does that will that potentially happen before approval?

So a couple of steps here. First, we plan to publish the data. I think we announced in our prepared remarks, announce or, sorry, submit the data for publication in the second quarter, and we hope to get approval on the guidelines that is included in the guidelines sometime in the second quarter as well.

So that's, certainly, in advance of when the drug would be approved towards the end of this year, which would of course provide us, you know, a very nice advantage for being the first to have guideline coverage for NPM1 and we believe to get the drug approved as well. So I think that's the timing for NPM1 and the and the strategy there.

The second question, I think there -- maybe Neil's going to clarify a little bit related to the MRD and meeting with regulators. Go ahead.

Yes. Well, so thanks for the question. Typically, we don't discuss the details of our interactions with health authorities. I would just point out that our interest in MRD negativity as a biomarker is long standing. As I 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. But as to specifics, we won't get into specifics of discussions with health authorities.

Justin Zelin, BTIG.

Congrats on the strong commercial start here. Michael, maybe just a follow-up on the prior question. Can you speak to your confidence of a broad recommendation by NCCN in the second quarter? And then 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?

Yes. Thanks, Justin. Appreciate it. I think the couple questions. So the first around the confidence of broad coverage in NCCN.

I think our -- we'll see. I mean, I think we feel very confident. The data is supportive of approval. We think it's practice changing, and informative and important. And I think from that perspective, we expect that the -- it will be included in the guidelines, and we'll have very good access as a result of that.

Second one is related to payer coverage, I guess, that follows on from there and whether we expect that to impact our ability to get the drug covered. Maybe, Steve, if you want to make a comment about that.

Yes. Maybe even take it a step back. I mean, we've had a good start. I think, in my prepared comments and Michael's comments on market access, we're off to a good start. Payer coverage is growing.

It's at 53%. Importantly, claims are being paid really across the continuum. I think because we had such a early start with the payer team calling in probably 1.5 years advance of approval calling on payers. The activity on NPM1 in the payer space will proceed that of the customer facing sales team. What do I mean by that, once we file, we'll begin talking about NPM1 with payers, making sure they're prepared just like they were for the KMT2Ar launch.

I think in the interim, Justin, claims are being paid regardless of indication from what we can tell. Some of this is anecdotal, but payers are not standing in the way of physicians who need a treatment where they otherwise don't have one.

And they don't have one, whether it's KMT2Ar or NPM1 relapsed/refractory, these are patients in need, and they see the need to get patients on drug and are paying the claims. So we feel pretty good about where we are and getting to a better place as we near the launch of that indication.

That makes sense to me. And Steve, if I could just ask a quick follow-up. Could you just talk to, in your opinion, the importance of being first in a competitive marketplace like this, the importance of having first to market?

Yes. I appreciate the question, Justin. I think, being first to market and first mover advantage isn't something that Syndax made up. This is just a function of the market and what we expect. The kind of competitive immunity that we're building now, it's about getting drug out, it's having the right customer facing field team, the right trade support, the right medical affairs alignment, doing things right out of the gates, which we are doing, something we didn't -- I mentioned in my prepared comments, but I'd amplify, is time to first fill.

The ability to from prescription to getting patients on, we're seeing patients get on in a couple of days. And anybody who takes longer is just because a payer may giving us some challenges upfront, which we ultimately get through.

So it's that type of great experience, white glove experience that we're trying to provide for physicians and patients. That'll be very challenging for any follow-on product if they make it to market to match what we're doing. The kind of experience that physicians will get in a year and possibly more of us being alone on market might as well be 10 years. That's the kind of muscle memory that accounts gain and that's what our goal is.

George Farmer, Scotiabank.

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 -- with 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 do you think the optimal dose is in combination with IC?

Thanks, George. So in terms of your question, your first question was strategy for listing for NPM1 and have -- do we point to some other products that were listed in potentially in a similar capacity? I think that was the question. Anjali, maybe you want to take that?

Yes. Thanks, George. I think a couple examples in the space. So I think the first example is sorafenib on a Phase II dataset. They were granted NCCN Guideline listing for FLT3 treatment in frontline. And then I think more recently, gilteritinib in combination with ven/aza off a Phase II data set single arm trial was granted compendia listening as well. So I think there is plenty of examples. I mean, our therapy for KMT2A has gotten compendia listening as well. So I think we -- it highlights our confidence for being able to get there.

Right. And maybe this -- thank you. And then the second question relates to the combo for with chemotherapy and the dose and how the selection is going to work. Maybe I'll turn it over to Neil.

Yes. Look. Thanks for the question. As mentioned, we'll present data later in the year. We are -- just to sort of summarize where we are at this point in terms of all of the combinations that we've been testing revumenib have been -- the drug has been actually well tolerated at both doses tested, both 110 and 160.

So we have choices, right? It could be either dose, and the data will indicate to us which dose it could be. Currently, we're combining a full dose. That's what we're doing currently, and as I said, we'll report more later in the year.

Salim Syed, Mizuho.

This is Eric on for Salim, and congrats on the nice ramp for Revuforj. So I wanted to try to get some color on what you think of the timing and the total addressable size of ex-US for Revuforj. What are your thoughts there on what the gating factors are that we would need to see for you to go for ex-US regulatory submissions and what that might look like if it's a collaboration that outlines something like that.

Thanks, Eric, for the question. So first, I think you had asked about timing, for ex-US. And I think the -- we're -- we haven't announced all of our plans regulatory, and development wise for ex-US. I think, they do come together rather nicely around our frontline strategy in getting the drug approved ex-US will be tied to not only the frontline trials, but there may be other opportunities as well.

So we have -- we haven't been specific about the timing. I think the addressable market is probably about half of the US, ex-US it's a very appreciable market opportunity for us. So we'll look to address it as soon as possible. As I mentioned in my earlier remarks, looking for a partner, to help us certainly with Revuforj outside the US, that'll come in time as well as we look to commercialize and develop more extensively as outlined.

So I think that's an ongoing development with our story. As you know, for Niktimvo, we do have a partner in Incyte, and they'll commercialize and develop the Niktimvo outside the United States. So over the next couple of years, I think you'll see a lot more development and plans to move globally.

Jason Zemansky, Bank of America.

Congratulations on the launch progress. Two, if I may, somewhat of a follow-up, but regarding the HOVON led trial in the unfit population, there's 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 Revu, especially considering the evolving competitive landscape?

Jason, thank you so much for the questions. First one relates to the HOVON trial and accelerated approval and timeline. I'm going to hand that over to Neil.

Yes. So 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're -- it is not our practice to discuss, the details over discussions with health authorities.

Right. And maybe first line, fit versus unfit prioritization was the second question. I could take that one. Look, I think we're -- the unfit population ven/aza combination trial with HOVON, I think, that addresses the highest unmet need in the frontline population, and we will be first to initiate a trial there. We also have the only dataset in that population to distinguish ourselves.

So I think that is a very important first trial to initiate. I think we'll have other trials, as Neil pointed out, in the fit population initiated before the end of this year. That will help to kind of drive our strategy and fit. So I think in 2025, we'll take a quantum leap forward in in initiating trials that will address all the important populations, both fit and unfit. But the first trial to initiate will be the HOVON trial, which, again, is a global registration trial in that population.

So it's -- again, it's around unmet need, and it's opportunities in front of us, and we plan to be first to capitalize on all of these market opportunities.

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.