Syndax Pharmaceuticals, Inc. Price & Performance (SNDX)

Thank you all for joining us today for a review of Synaxis fourth quarter and full year twenty twenty four financial and operating results. I'm Sharon Clari, and with me this morning to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer Doctor. Neil Gallagher, President and Head of R and 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 Doctor. Peter Ardentlich, Chief Scientific Officer and Doctor. Angelie Gangoli, Strategy Officer. This call is accompanied by a slide deck that has been posted on the investor page of the company's website. You can now turn to our forward looking statements on Slide two. Before we begin, I'd like to remind you that any statements made during the call that are not historical are considered to be forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result various important factors, including those discussed in the Risk Factors section in the company's most recent report Form 10 ks as well as other reports filed with the SEC.

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.syndex.com Syndax 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 three. 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 the 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 11/15/2024, the FDA approved RevuForge, our first in class menin inhibitor, for relapsedrefractory 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 U. S. Launch of RevivuOrange and are very encouraged by the patient the early patient demand breadth of prescribing and coverage from payers. For the fourth quarter of twenty twenty four, we reported $7,700,000 in ReviForged net revenue from the initial five weeks of the launch. These early results reflect the high unmet need and demand that RevuForge addresses and the strong execution of our organization to deliver the product. We are very excited about the opportunity we have with RevivorGE. Especially given the clinical data supporting the significant opportunity for future label expansions. We recently reported the first positive pivotal data set 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 CAME rearrangements, the MPM1 mutations or NUP-ninety eight rearrangements. We are preparing to file a supplemental new drug application or sNDA next quarter that could expand the indicated population for eForge into mutant MPM1 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 guideline. 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 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. Nick Timbo is the first and only FDA approved treatment for chronic GVHD that targets CSF1R to reduce the drivers of inflammation and fibrosis. Like RevuForge, NIktimbo has significant potential for expansion. To unlock those opportunities, we and Insight are advancing multiple trials. Two trials are underway that are evaluating NIKTYMVO in combination with standard of care therapies in newly diagnosed chronic GVHD patients including a Phase two trial with VACOPHY and a Phase three trial with steroids. Enrollment is also ongoing for Maxpeyr, our Phase two 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, premier company with the largest and the largest buyer of biopharmaceutical royalties. We received $350,000,000 upfront in exchange for a capped royalty on U. S. Net sales of NIKTIMBO, a deal that highlights NIKTIMBO's multibillion dollar potential.

We are in a strong financial position with the 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 RevuForge. And Nixinvo. Starting with Slide four, it has been incredibly rewarding for me our entire team to be a part of bringing ReviForged 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 $7,700,000 in net revenue. 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 Syndax. 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 Revivorged prescription to the patient actually starting medication. Turning to Slide five. 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 twenty twenty five 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 RevuForge prescribing. As of the February, 33% of our high priority or Tier one and Tier two accounts have ordered RevuForge. 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 also calling on the entire universe of 2,000 relevant accounts across The U. S. And are seeing orders from accounts beyond our Tier one and Tier two accounts.

Including from community practices, which reflects the high unmet need and the ease of use of Revuford. Notably, the majority of accounts [indiscernible] 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 is proving to be an effective approach. We're seeing a mix of patients prescribed ReviForge, which is consistent with their broad label which includes both adult and pediatrics, as well as patients with any lineage of relapsed or refractory acute leukemia with a KMT2A translocation ALL or MPAL. As expected, Revi Forges 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 Revuforged 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 RevuForge and the NCCN guidelines for AML and ALL.

Payers recognize the urgent on Menneed and the clinical value RevuForge we're seeing reimbursement in all payer channels, including commercial, Medicare Part D as well as Medicaid. [indiscernible] Roughly three months into the launch, and we're seeing very strong formulary uptake with formal coverage policies in place for approximately fifty six percent of commercially covered lives and fifty three percent 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, ReviForge is being approved through the medical exception process when formula 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. 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. RevuForge 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 two thousand patients in The U. S. With relapsed or refractory acute leukemia with a KMT2A translocation. When you take the price of Revuforged into account and an estimated average treatment duration of about nine months across various patient experiences, this initial opportunity represents a $750,000,000 market opportunity. With positive pivotal data and relapsed or refractory mutant NPM1AML, we have a near term opportunity to receive a second indication that could expand our target population in The U. S. To five thousand to six thousand five hundred KMT2A and NPM1 patients which together represent a $2,000,000,000 market opportunity.

ReviForge is the first and only FDA approved menin inhibitor on the [indiscernible] our teams are working with urgency to capitalize on the advantages of being first to market. We know that once physicians become familiar with the new therapy, they tell us the bar is high to switch to another product, with the same mechanism. Reviforge is also the only menin inhibitor with positive pivotal data in both relapse or refractory to a rearranged acute leukemia and mutant NPM1AML in both adult and pediatric patients. The consistency and breadth of the data supporting REVUFORGE 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 that is designed to unlock a total market opportunity that exceeds $4,000,000,000 in The U. S. Across the relapsedrefractory and frontline settings. Moving to Slide seven. [indiscernible] In mid January, we and our commercialization partner EnSight announced that the FDA approved NIKTYMVO in nine milligram and twenty two milligram vial sizes In late January, we launched the product and received our first orders. Encouraged by the level of interest in Nectimbo which speaks to the high unmet need the product's compelling clinical profile.

Together with Incyte, we are working to bring this new option to the approximately six thousand five hundred chronic GVHD patients in The U. S. 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 belimosidil or Rezorock, another drug indicated the same line of treatment as Nektenvo, net sales continue to grow in the high double digits. And so suggest that the drug is now annualizing at over $500,000,000 in U. S. Sales. With a new mechanism of action and strong data showing remarkable responses in heavily pretreated patients, We believe that NKTIMA will be able to capture a significant portion of the $1,500,000,000 to $2,000,000,000 estimated total addressable market for third line or later chronic GVHD treatment in The U. S. We are confident that we have just started to scratch the surface of the opportunity with NIKTENVO and are thrilled to be working with Incyte on trials designed to move the product into earlier lines of treatment for chronic GVHD 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 ReVuenem for the treatment of acute leukemias across the treatment continuum.

Thanks, Steve. I'm pleased to provide an update on the revumeneb development program starting on Slide eight with the near term opportunity we have to expand into our lapsed or refractory mutant MPM-one AML. The high unmet need and lack of approved therapies that target this population, we are pleased to have reported the first positive pivotal data set In November 2024, we announced that the primary endpoint was met in the protocol to find efficacy population of sixty four adults with relapsed or refractory mutant MPM1 AML in the Phase two cohort of the AUGMENT-one hundred and one trial. Among a heavily pretreated population, including seventy five percent with prior venetoclax exposure, nearly half of patients achieved a response and twenty three percent achieved CRCRH. Consistent with other data sets, the responses were deep with sixty four percent of CRCOH responders achieving MRD negativity. Additionally, seventeen percent of responders proceeded to stem cell transplant, which is a 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. On the positive pivotal data, We reported results in December 2024 from a larger post hoc analysis, which included additional mutant MPM1 patients from the Phase two cohort who met the efficacy evaluable criteria.

These results were highly consistent with those for the primary analysis with an overall response rate of forty eight percent CRCRH rate of twenty six percent among seventy seven efficacy evaluable patients. Looking ahead, we expect 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 MPM-one data and believe this could serve as a basis for the expansion of the listing Avimena in the NCCN guidelines for AML ahead of the potential FDA approval in this Turning to Slide nine, we're advancing Revumana 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 relapsedrefractory and newly diagnosed patients. In combination with standards of care. The front line, we're advancing a thoughtful combination of Syndax sponsored and investigator initiated trials of 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 inclusion of the NCCN guidelines.

Moving to Slide 10, [indiscernible] In collaboration with the HOVON network, we are initiating a pivotal randomized placebo controlled trial of revuatumum with venetoclax and azacitidine in newly diagnosed patients with MPM1 mutations or KM2A 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 BEATAML, a Phase one trial evaluating revumab with venetoclax nasocitin in newly diagnosed mutant MPM1 or KM2A rearranged AML patients 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 twenty twenty five from an ongoing Phase one trial of revumenib with seven plus three or intensive chemotherapy. 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 twenty twenty five. We are confident that we are poised to lead and win in the frontline setting 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 Menon space, we will continue partner with the Foundation for the National Institutes of Health 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 $7,700,000 of revenue Forge net revenue in the fourth quarter of twenty twenty four. Operating expenses in the fourth quarter were $104,000,000 and included $65,500,000 of research and development expense and $37,700,000 of selling, general and administrative expense. Turning to the balance sheet.

We continue to maintain a strong financial position. We $692,400,000 of cash equivalents and short and long term investments as of the end of the year. We continue to expect that our cash enable the company to reach profitability. For the first quarter of twenty twenty five, the company expects R and D expenses to be $65,000,000 to $70,000,000 and total R and D plus SG and A expenses to be $105,000,000 to $110,000,000 For the full year of 2025, the company expects R and D expenses to be $260,000,000 And total R and D plus SG and A expenses to be $4.15 $435,000,000 which includes an estimated $45,000,000 in non cash stock compensation expense. The company is not providing revenue guidance at this time. Ahead of reporting the first sales for NIKTIMO, our first quarter twenty twenty five 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 NIKTIMBO 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 credit to both, as in the top example on the slide, our 50% share of the net profit will be recognized on our P and L as collaborative arrangement revenue. Of note, the expenses that are deduct to arrive at the collaborative revenue will not include the synthetic royalty owed to Royalty Pharma. The upfront $350,000,000 that we received from Royalty Pharma is liability class 8% royalty payments will be reflected on our 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 loss would be included in operating expenses designated as a separate line called share of collaboration [indiscernible] Any milestone revenue from various commercial and 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 U. S. And our 45% share is included in the income statement as part of our R and 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 U. S. Sales. With that, let me now turn the call back over to Michael. Yes.

Thank you, Keith.

It has been a very successful start to the year for Syndax Syndax we are poised for another exciting period as we advance the launches of RevuForge and Nick Timbo 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 through out the development, approval and commercialization of our first two medicines. 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 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? The first question will come from Anupam Rama with JPMorgan. Please go ahead. Hey, guys. Thanks so much for taking the question and congrats on the launch progress here. The early innings.

Quick one from me. I know in the press release you talked about a third of the 4Q revenue forged sales were inventory. Just wondering how we should be thinking about inventory level throughout 2025? And then I know also that you said you're about a third penetrated into your Tier one, two accounts. KMT2A? Thanks so much.

Anupam, thanks for the question. So two questions.

So first, first question, I'm going to direct to Keith, which is related to inventory levels. Keith, Yes, good morning, Anupam.

Good question. Thank you. I think our inventory levels as you think forward through the 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. 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 will could be expected to grow.

Great. And Steve, do you 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 one and two 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 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're already used the product moving forward and we feel really good about where we 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 one, two accounts that have not yet ordered, What do you expect for the cadence and extent of activation over the next ten months? And then second, now with a few months of commercial experience under the belt, how do you see Revuforged tracking with some of the historic AML targeted therapies? Launches Okay. Thanks, Brad. Appreciate the question. So first, I'll direct to Steve.

So thanks, Brad, for the question. And I like 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 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 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 one and Tier two. There's far more Tier one accounts that have activated. And fewer of the Tier two 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. And maybe the second question relative to Panalas. Yeah. 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 product like RevuForge, identifying Kanti2AR patients, which may not have had as readily speaking to other targeted therapies. So urgent on Menitidis high. Patient 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 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 Phil, great about where we are. Just one partial quarter in and a couple months in, to 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. Thanks so much. Thanks for taking the questions.

And thanks for all the updates. I guess firstly around preview forward, like how that's being used, if you're seeing off label use, how much for MPM-one 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 mentions less than 10 patients transitions. Just kind of how many patients are left on that extended access program? Thank you. 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's anecdotal. We know we're getting use, some use in NPM1, some use in 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 AP 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 2025?

The momentum is good. I mean, I think if you remember, we started this back in the fall initially with the MPM-one 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 REVIEWFORGE as well as in the Menon space. So that momentum that we saw at ASH continues to this day. Very high excitement levels.

Our field team has 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 get it through the payer system. Great. Thanks so much. Thank you, Peter.

The next question will come from the line of Chris Chibbutani with Goldman Sachs.

Line is now open.

Great. Thank you very much. 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, 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 02/1930? Many arguments were 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 and now commercial presence Do you have a vision to that?

Are you going to share that? If not, why not?

Well, Chris, what a a big question here. So thank you for asking. I think the vision for the company is is ambitious. I think we have done wonderful things to get to this 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 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 target 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 you know, a larger pipeline and to build the company over several years by 2030, we expect to be, you know, extremely advancing and rapidly advancing company with multiple commercial products. In our bag, so to speak, and have 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 U. S. And focused in oncology. And look to partner external and ex U. S. As we build business. But I'd say I think we would hope to be a a formidable specialty oncology company by twenty third. And yes, the Board and management are quite aligned in this approach.

Perfect. Thank you for the insights. Thank you, Chris.

The next question will come from the line of Kelly Jefferies.

Line is now open.

Congrats on a great quarter. Thank you for taking my questions.

Although it's still early days, but curious for patients bearing co mutations such as FLT3, of the additional sequence therapies. And what would be the reasons that a physician prioritize RevPORATE? And also curious on 50 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 someone why would a physician use amen 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 three trial that we're currently initiating in the unfit population, there is no selection for for FLT3. We will include patients, as I mentioned, in our in the prepared remarks, patients with both MPM1 and KAM-two twenty eight, there is 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 MPM1.

Mutations at the same time. And this is a 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 [indiscernible] 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 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 forty eight hours of the drug being prescribed. So it's a lot of handholding and helping physicians and their associated staff through through treatment. And dosing is clear, wide age population AML ALL. So I'd say things are very good. There's really nothing getting in the way of physicians putting patients on RevivorGE. Thank you, Kelly.

The next question comes from the line of Michael Schmidt Guggenheim.

Your line is now open. Hey guys, good morning. Thanks for taking our questions. Had a couple more on the RebbeForich launch. Keith, perhaps could you comment on early trends in gross to net adjustment as well as potential use of a free drug program, etcetera. And then in terms of early feedback from the market, what have you heard about or seen around transplant dynamics? Perhaps a lot Thanks, Michael. Sure. So first, first question related to gross to net, maybe I'll direct to Keith. [indiscernible] Good morning, 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 for those reasons and a few others, the gross to net on Ready Forged has been and we expect it to continue to be very tight.

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 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 to 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 MPM-one as well, but but most of these patients are on the younger side for KMT2A.

And so transplant is an objective transplant. So they're going 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 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 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 Mandovitz with Citi.

Your line is now open. Hi, Michael on CING.

Thank you and congrats on the first quarter of 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 one versus Tier two centers, And then third for Neil perhaps, you mentioned some of the Foot three dynamics I'm just curious if you could be a little bit more granular as far as how those Phase III trials could look I could imagine four studies, a KMT2A study for those with a foot three and those without generally NPM1 for those with in foot three and those without, this would be in the in the fit population. So would you have a 7.3 plus the FLT3 control arm in those studies respectively. Great. Good questions, Yigal. Thank you. So let me turn the first in one hundred and twenty five to one hundred and thirty patients.

Net of inventory roughly six percent of the population That's your math. So I'll make some comments on that, Steve. Go ahead. [indiscernible] the math, doll.

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 will take us some time to do that. And I think the second is it's just early from a patient perspective. I think the second question was around Tier one and Tier two definition. And it's roughly combined about 200 accounts. Those accounts represent about two thirds of the patient opportunity. Tier one, you can think say biggest of the big MD Anderson, Dana Farber, those are typical Tier one accounts. Tier two 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.

So examples there could be, like a St. Jude's or a Tampa General, just to give you some examples to put it in perspective.

Great. And then I guess the third question goes to Neil, which is related to the the trials of the FIT population specifically around 10. 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 fact that speed to date is important. There are, of course, multiple population within the FIT. It's not an homogenous population, including patients with FLIP and MPM1 commutations. 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 Okay.

Thank you so much. Thanks, Hugo.

Our next question comes from the line of David Dye UBS. Line is now open.

Great. Thanks for taking my questions. And I also want to congrats on the great quarter. So two from me as well. So the first one just around the relapse refractory MPM-one pivotal data. You're planning to submit for NCCN guidelines in quarter this year. Could you maybe talk about the timing of the inclusion of [indiscernible] We think about the inclusion of the NCCN before the [indiscernible] And then second question is just around the frontline locational trial in unfit AML.

Where you said that you're planning to meet with the regulators to use MARTIN activity as a set of endpoint just talked a little bit more about the timing around that and how should we think about your engagement with the regulators on the time for MARTINETYLE:] CR. Thank you.

Great, David. Thanks for the question. So the first question is related to realized refractory MPM-one 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 a very nice advantage for being the first to have guideline coverage for MPM-one and we believe to get the drug approved as well. So I think that's the timing for MPM1 and the strategy there. The second question, I think there maybe Neil is going to clarify a little bit.

Related to the MRD and meeting with regulators. Go Yes. 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 negative MRD negativity as a biomarker is long standing. And 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. Excellent. 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 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 MTM 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 are couple of 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 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 it. 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. Payor 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 a year and a half advance of approval calling on payers. Activity on NPM1 in the payer space will proceed that of the customer facing sales team.

And what I mean by that, once we file we'll begin talking about MPM-one with payers, making sure they're prepared just like they were for the KANTi2AR launch. I think in the interim, Justin, claims are being paid regardless of indication, for all 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 MPM1 relapsedrefractory. 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 at first mover advantage isn't something that SyneX 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 in a couple of days. And anybody who takes longer is just a payer may be giving us some challenges upfront, which you 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 will 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 and possibly more of us being alone on market, might as well be ten years. That's the kind of muscle memory that accounts gain and that's what our goal is.

Thanks for taking my questions and congrats again. Thank you, Justin.

Our next question comes from George Farmer with Scorsabank. Line is now open.

Hi, good morning. Thanks for taking the 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 with what you have [indiscernible] 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 IC?

Thanks. Great. Thanks, George. So in terms of your question, your first question was strategy for listing for MPM-one.

And have we point to some other products that were listed in potentially in a similar capacity? I think that was the question. Angelie, maybe you want to take Yes. Thanks, George. I think a couple of examples in the space. So I think the first example is sorafenib on Phase two data set. They were granted NCCN guideline listing for foot three treatment. In frontline and then I think more recently, giltretinib in combination with VENAZA off of Phase two data set single arm trial was granted compendium listing as well. So I think there is plenty of examples. I mean, even our our therapy for KMT2A has gotten continued listening as well. So I think in highlights our confidence for being able to get there.

And then the second question Sorry, George. I think the second question relates to the combo for with chemotherapy and the dose and and how this lecture 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 that we've been testing, RevuMen have been. The drug has been actually well tolerated at both doses test one hundred and sixty.

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 were more later in the year.

Excellent. Thanks very much. Thank you, George.

Our next question will come from Saleem Saied line is open. Hi. This is Eric on for Salim.

Congrats on the the nice ramp for ReviForge. So I wanted to try to get some color on what you think of the timing and the total addressable size of ex U. S. For Rebyforged, What Are Your Thoughts There On What The Gating Factors Are That We Would Need To See For You To To Go For Ex U. S. Regulatory submissions and what that might look like if it's a collaboration that outlays something like that? Great. Thanks, Eric. For the question. So first, I think you had asked about timing for ex U. S. And I think the We haven't announced all of our plans regulatory and development wise for ex U. S. I think they do come together rather nicely around our frontline strategy in getting the drug approved ex U. S. Will be tied to not only the frontline trials but there may be other opportunities as well. So we have we're we haven't been specific about the timing. I think the addressable market is probably about half of The U. S, ex U. S. It's a very 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 RevuForge outside The U. S. That will come in time as well as we look to commercialize and develop more extensively.

As outlined. So I think that's a ongoing development with our story. As you know, for NIKTIMVO, we do have a partner in Insight and they'll commercialize and develop the NIKTYMBA outside The United States.

So over the next couple of years, I think you'll see, you know, a lot more development and and plans to move globally.

All right.

Thanks.

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 Hoven 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? More important opportunity for revenue, especially considering the evolving competitive landscape?

Great. 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 in the prepared remarks, we are positioned and we'll 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 of our discussions with Health Authorities.

Right. And maybe maybe first line fit versus unfit prioritization was the second I could take that one. Look, I think we're the unfit population, Venza combination trial with HoldOn, I think that 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 data set in that population to distinguish ourselves. So I think that is a 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 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 global registration trial in that population. So it's again, it's around unmet need and it's around the [indiscernible] to capitalize on all of these market opportunities.

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. 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.