Syndax Pharmaceuticals, Inc. Q3 FY2025 earnings call

Commercial Results - Revuforj: - In the third quarter, Revuforj had a net revenue of $32 million, which was a 12% increase from the prior quarter. There was approximately a 25% growth in total prescriptions and new patient starts. - Revuforj was added to the NCCN Guidelines for relapsed/refractory NPM1 mutated AML and received FDA approval for that indication, tripling the addressable patient population. The clinical data and physicians' enthusiasm for Revuforj are strong. - Around 70% of Revuforj's usage in KMT2A is in the second and third lines, with growing use in the frontline and post-transplant maintenance settings. ### Commercial Results - Niktimvo: - The partner Incyte reported $45.8 million in Niktimvo net revenue in the third quarter, a 27% increase from the prior quarter. Within 8 months of launch, Niktimvo is annualizing at nearly $200 million. It is profitable to Syndax, with the 50% share contributing $13.9 million in the third quarter. ### R&D and Data - Revuforj: - 23 abstracts were accepted for the ASH conference, including 6 oral presentations. - First real-world evidence from Moffitt Cancer Center showed favorable tolerability and activity in multiple genetic subtypes. - Data from the SAVE trial in the frontline setting showed that the combination of Revuforj with venetoclax and decitabine/cedazuridine was well tolerated, with high complete remission (CR) and minimal residual disease (MRD) negativity rates. - Early data from frontline intensive chemotherapy trials showed good tolerability and high CR rates. ### Financials - Revuforj: - In the third quarter, Revuforj had a net revenue of $32 million, with growth driven by demand despite gross to net adjustments. ### Financials - Niktimvo: - Collaboration revenue was $13.9 million in the third quarter, and it is a positive cash flow contributor. The margin contribution is expected to be in the 25%-30% range in the near term and increase in the long term as sales grow.

The company reported a total revenue of $45.9 million for the third quarter, marking a 21% growth compared to the prior quarter. Revuforj's net revenue in the third quarter was $32 million, showing a 12% increase from the prior quarter. There was approximately a 25% growth in total prescriptions and new patient starts for Revuforj. Niktimvo had a net revenue of $13.9 million for the third quarter, with the partner Incyte reporting $45.8 million in Niktimvo net revenue, a 27% increase from the prior quarter. Revuforj contributes about 70% of the total revenue, and Niktimvo contributes around 30% of the total revenue.

Guidance - Revuforj: - It is expected that sales growth will meaningfully accelerate in the coming quarters with the approval of NPM1 for Revuforj and the increasing average duration of therapy in KMT2A. ### Niktimvo: - Continued robust growth is expected as GVHD is a chronic disease with a high response rate, and patients are likely to remain on therapy for years. ### Balance Sheet: - There is confidence in reaching profitability with the current funds on hand, driven by cash, increasing Revuforj and Niktimvo cash flow contributions, and an expected fixed expense base.

Risks - Actual results may differ significantly from forward-looking statements due to various factors, including those discussed in the Risk Factors section of the company's most recent quarterly report on Form 10-Q and other SEC filings. - Although Syndax believes Revuforj has the broadest and strongest efficacy profile, there could be potential competitive challenges in the market. - There could be unforeseen safety issues with the safety profile of Revuforj, although it has a well-managed safety profile so far.

Q: Can you review how Revuforj's place in lines of therapy has evolved in the commercial setting during the launch? And how do you think this will translate for the NPM1 setting?

A: For KMT2A, about 70% of the business is in the second and third lines, enabling earlier treatment and more patients going to transplant. For the NPM1 setting, it is expected that patients will be treated earlier in the journey and in combination. Physicians are eager to put patients back on therapy.

Q: You spoke about a 6- to 12-month range for duration of therapy in 2026. Could you help us think about the key factors that you're looking to understand in order to narrow that range? And when could that start to be reflected in the revenue trajectory?

A: The duration of therapy in 2026 will be impacted by the mix of KMT2A and NPM1 patients. KMT2A has more patients going to transplant and longer duration of treatment, while NPM1 has its own dynamics. The mix of these populations will drive to 6-12 months in 2026 and impact the revenue trajectory.

Q: Have you looked at all where the maintenance restart rate is for the patients who started revumenib during the first few months of launch?

A: The restart rate is currently 35%-40% and is expected to grow over time. More patients are going to transplant, but physicians are inclined to put patients back on therapy.

Q: As we think about the relationship between prescription growth and revenue growth, so could you provide some perspective in terms of how revenue per prescription might evolve as the patient mix shifts from predominantly KMT2A in the third quarter to include more NPM1 patients going forward?

A: It is expected that there will not be much change in the average revenue per prescription as more NPM1 patients enter the prescribing base.

Q: Just on the delta between quarter-over-quarter growth results versus the Rx rate. And is there any way to break down that gap between gross to net versus inventory timing that we should be thinking about or any changes that we should be thinking about going forward? And then I've got a question just on if there's been any friction again NPM1 authorizations and payer access.

A: The gap between prescription growth and revenue growth is due to higher gross to net adjustments (such as 340B, Medicare/Medicaid discounts) and a slight inventory drawdown. Payer access for Revuforj has been excellent, with 97% formulary coverage, and coverage will quickly build for NPM1.

Q: Congrats on the quarter and all the exciting abstracts. Just wondering a couple of things about the NPM1 launch. One, if you noticed any modest uptick in the final days of Q3 where you did have that inclusion NCCN Guidelines? And then more broadly, wondering how we should think about the launch trajectory in the NPM1 population in terms of market penetration relative to the launch in the KMT2A market, given that, as you said, it's a larger population, but it's likely to face some competition.

A: HCPs are excited, awareness is high, and the setup for the fourth quarter is positive. The launch trajectory in the NPM1 population is driven by the product profile (best-in-class), relationships, and ongoing clinical development. Syndax expects to dominate the market with a strong efficacy profile.

Q: Just one, I guess, on the soon to initiate REVEAL trial in frontline patients with intensive chemo. I know we don't have protocol details yet, but I was just curious about how you're philosophically thinking about specifically evaluating the contribution of maintenance therapy within the protocol itself, just given what J&J now appears to be doing in the frontline setting and whether you think trial design differences may have some kind of competitive implications on the labeling front as it pertains to maintenance therapy explicitly?

A: Maintenance is considered in pivotal studies, and all studies allow for maintenance after transplant. A broad body of evidence will support the use of Revuforj in the maintenance setting in the frontline.

Q: I was just curious, when you look at the trends between the community practices and academic, are you seeing any differences there in terms of the percent going to transplant? And then related to that, are you seeing any differences in those segments in the percent returning to maintenance post transplant?

A: The majority of usage is in academia, and it is not possible to separate the rates yet. There is a desire to start Revuforj as maintenance therapy post transplant even if it was not used prior to the transplant.

Q: Congrats on the quarter. Just wondering if you could give us an update on how the safety profile has been faring in the real world? Do you see patients discontinuing the drug at all for any adverse events?

A: The safety profile has been well received, with very low rates of discontinuations due to adverse events. The adverse event profile is well managed, and physicians are experienced in using the drug.

Q: Great. Congrats on the quarter, guys. Just one for me as well on the safety side. I know people are focused and you guys mentioned this on the approval call, the one case of Torsades, it's now listed in the black box there. I know one case, and you mentioned previously, you don't expect things to really change with it. And I get that. But as you kind of think about first line here where there are more patients and you are treating thousands of patients per year, is it not reasonable to think here that you're going to get more cases like that, and that's something that you're going to have to educate or manage around, especially if zifto does not end up with that on the label?

A: Rates in the frontline setting seem lower, and frontline studies are randomized with control arms to determine true rates. Revuforj's efficacy stands out, and physicians are focused on efficacy rather than minor safety concerns.

Q: Just a question on the 35% to 40% patients who resumed Revuforj post transplantation in third quarter. Could you maybe provide some additional detail around the timing of the maintenance use? How long is the drug holiday before we'll see them coming back to the maintenance therapy?

A: Patients receive about 2-3 months of therapy, go to transplant, and resume maintenance therapy about 3-4 months later, so there is a 6-month gap from the start to resumption.

Q: Congrats on strong momentum. Actually, a lot of demand indicators aligned with our recent physician survey. So, on the KMT2A versus NPM1 revenue split being obviously 90 to 10 right now, are you able to comment on when you'd expect that to be a little bit more balanced or even NPM be a bit more dominant from a timing standpoint?

A: KMT2A is smaller than NPM1, but Syndax has the broadest profile in both segments. Syndax expects to capture a majority share in both segments, with NPM1 having its own dynamics but still expecting to dominate.

Q: Congrats on the progress. I was hoping you could speak to the impact of the NPM1 approval on your gross to net and inventory trends as we head into the fourth quarter and early next year. Given the size of the population relative to the KMT2A, I have to imagine that some of the headwinds may pivot to tailwinds and at a much more substantive impact. And then I guess, secondarily, if a patient returns to Revuforj following a transplant, how challenging is that, at least from an administrative or payer perspective? How difficult is it sort of restarting a patient like that?

A: Inventory levels are expected to stay at 2-3 weeks. The gross to net mix may slightly shift with NPM1 patients. There is no pushback from payers on patients returning to maintenance therapy as payers understand the unmet need and value of the drug.