Syndax Pharmaceuticals Inc Q3 FY2024 earnings call

Milestones

• In August, FDA approved Niktimvo, the first and only CSF-1R antibody for chronic GVHD. AGAVE-201 trial results published in NEJM and Niktimvo added to NCCN guidelines.
• Revumenib expected FDA approval in December 2024 for relapsed/refractory KMT2A rearranged acute leukemia. AUGMENT-101 trial topline readout for mutant NPM1 AML expected in Q4 2024.
• ASH conference presentations with latest data on revumenib, including updated AUGMENT-101 trial data and SAVE trial results.

Niktimvo

• Partnered with Incyte for commercial launch, targeting ~200 transplant centers in US. Ongoing trials in earlier lines of cGVHD and IPF.

Revumenib

• Anticipated FDA approval, AUGMENT-101 trial data showing strong efficacy in KMT2A rearranged acute leukemia. SAVE trial in children/adults with relapsed/refractory AML showing promising results. Frontline Phase 3 trial with HOVON network planned, enrolling ~400 patients for overall survival endpoint in mutant NPM1 AML.

No detailed segment performance with revenue contribution percentages provided in the transcript.

Full Year 2024

• R&D expenses expected $245M-$250M, total expenses $365M-$370M.
• Royalty agreement with Royalty Pharma provides capital to fund through profitability, support launches of revumenib and Niktimvo. Anticipated FDA approval of revumenib in December 2024, topline NPM1 data from AUGMENT-101 in Q4 2024.

No detailed discussion of specific risks in the transcript beyond general forward-looking statement disclaimers regarding potential differences between actual results and forward-looking statements.

Q: Post the potential approval of KMT2A and pending positive NPM1 data for revumenib, can you remind us of the process to get into guidelines and potential timeline considerations we should be thinking about?

A: Michael Metzger stated that timing to get into guidelines involves having an approved drug, publishing data, and submitting to guidelines, with NCCN guideline panels meeting twice a year or ad-hoc. Example of axatilimab was given where approval and contemporaneous publication led to being in guidelines within 2-3 weeks.

Q: For AUGMENT-101, in the updated data, you noted nine of 21 or 43% of transplanted patients restarted revumenib maintenance. Is that a maintenance percentage rate you expect in the commercial setting, or could it be higher? And also, what have you seen so far on durations? And then, congratulations on the HOVON collaboration for frontline AML. I think you do point to BEAT AML updates in 4Q '24. Help us understand what you're looking for in those data to finalize and initiate that pivotal trial?

A: Michael Metzger said that the maintenance percentage in AUGMENT-101 is trial-driven and physicians elected to put patients back on therapy, expecting it to continue once approved. Neil Gallagher mentioned that BEAT AML update in 4Q '24 will have more patients, specifically more patients treated at dose level one, and they are on track to initiate the Phase 3 study by year-end.

Q: Post the potential approval of KMT2A and pending positive NPM1 data for revumenib, can you remind us of the process to get into guidelines and potential timeline considerations we should be thinking about?

A: Michael Metzger stated that timing to get into guidelines involves having an approved drug, publishing data, and submitting to guidelines, with NCCN guideline panels meeting twice a year or ad-hoc. Example of axatilimab was given where approval and contemporaneous publication led to being in guidelines within 2-3 weeks.

Q: With the sale of some of the royalty strength of Niktimvo, does that accelerate any programs under the development?

A: Michael Metzger said the royalty agreement brought ~$350M cash, strengthening the balance sheet to ~$750M, allowing aggressive execution on trial initiations for revumenib, Niktimvo, and other pipeline programs.

Q: The timing of the NPM1 data and is that -- or after a publication, how we should be thinking about that and kind of if it's in the direct NCCN guidelines or you kind of thinking supplemental?

A: Michael Metzger said for NPM1, you publish data and submit to guidelines independently of approval, with the plan to move quickly to get it into guidelines, potentially preceding approval on NPM1.

Q: Can you give us any sense early in terms of how we should be thinking about the trajectory of an initial commercialization of Niktimvo? And what we can think about how the results from the NPM1 data may impact the level of spending that you have, particularly from the SG&A start -- aspect?

A: Steve Closter discussed Niktimvo's commercial trajectory, noting Incyte's market presence and preparedness, with a small targeted group of transplant centers already profiled. Keith Goldan mentioned SG&A spending will grow incrementally as A&P costs increase with approvals and launches, but the field force is fully built out.

Q: Curious your view on the clinical bar for CR/CRh rate for the pivotal NPM1 data? And also, how do we think about the correlation with OS benefit and what is the OS benefit of -- what is the OS benefit expectation relative to KMT2A subgroup?

A: Michael Metzger said clinical bar for NPM1 is 20%-30% CR/CRh rate, duration of response 4-6 months, similar to precedent. Anjali Ganguli mentioned OS for NPM1 is ~4-5 months, while KMT2A is shorter (~2-3 months) in third-line settings.

Q: The updated KMT2A AUGMENT-101 data that we saw in the abstracts today, is that the most recent analysis that the FDA has? Is that what was submitted to the FDA? And is that what the FDA is reviewing? And then second, we noticed on your slides describing the pivotal trial in combination with ven/aza in the frontline, there was no revumenib dose listed. Have you determined with the FDA's input what that dose is likely to be?

A: Michael Metzger said the updated KMT2A data is highly consistent and supportive of approval, but not confirming if it's what FDA was specifically looking for. Neil Gallagher said health authority approvals are in process, and the study is initiating on 160 milligrams.

Q: Just on the KMT2A data on the 13-months' duration of response that you've disclosed today in the ASH abstract in AUGMENT-101, would you expect a similar duration in NPM1-treated patients once you have longer follow-up from that cohort? And then, as we think about the menin inhibitor competitive landscape, there's been greater focus recently on differences in drug product characteristics as investors are looking to project how combinable the different agents are, particularly on PK or drug exposure metabolism. And as we continue to look at the emerging combo data at ASH, are there any learnings you can highlight where you feel confident about potential advantages for revumenib over others in the field?

A: Michael Metzger said can't speculate on NPM1 duration yet, but SAVE trial data is highly encouraging with high overall response rate, good tolerability, and efficacy in heavily pretreated patients.

Q: Hi, guys. This is Ashiq on for Yigal. Thanks for taking my question, and congrats on all the updates here. I just wanted to ask a follow-up on the maintenance setting questions asked earlier for revumenib. I guess for the AUGMENT-101 KMT2A cohort, there was nine out of 21 patients that got maintenance therapy, but three out of 12 in SAVE. I'm just curious if there were differences in the way those studies were run or maybe awareness among physicians -- differences among regarding awareness between physicians in terms of whether or not they could use revumenib in a maintenance setting. And I'm just -- I'm also just curious to what degree are you aware of how physicians are sort of deciding how or when to use relumenib in the maintenance setting and what sort of incision matrices there are in place today. And then, one more quick clarifying question on the frontline revumenib plus ven/aza study, looks like the primary endpoint is overall survival in just the NPM1 population. It looks like you're enrolling both NPM1 and KMT2A. So, I'm wondering why just the focus on NPM1. Is that related to more population dynamics or something else?

A: Michael Metzger said maintenance is a work-in-progress and physicians will learn how best to administer it over time. Neil Gallagher said the study is powered for the NPM1 population as the predominant mutation in older patients not suitable for intensive chemotherapy is NPM1.

Q: For NPM1, curious as what you're thinking about the potential for breakthrough therapy designation. Have you requested this? Has FDA given you any indication, particularly given they awarded it in KMT2A? And then, maybe just to circle briefly back on your previous answer regarding the NPM1 efficiency range or efficacy range, certainly, you mentioned for physicians higher the better, but is that 20% floor you mentioned necessary for approval? Does that still apply, or is that higher?

A: Michael Metzger said they did not apply for breakthrough therapy designation for NPM1 as they didn't have the required data from the Phase 1 at the right dose. For NPM1, a CR/CRh rate north of 20% is a good result, with higher being better but not mandatory.

Q: Hi. Good afternoon. Thanks for taking my questions. I really appreciate your decision to disclose the additional KMT2A data. A question on this 6.4-month duration that you showed in 97 patients with the February cutoff. Are you going to be showing anything more mature than that? And is it possible that we could see something closer to the 13 months that you reported from the first 57 patients?

A: Michael Metzger said they don't anticipate updating the data set beyond what's already provided, focusing on getting the drug approved and real-world performance.

Q: The HOVON trial, when do you anticipate that concluding and to be reporting on data? Maybe I missed that in your primary comments.

A: Michael Metzger said they haven't given a specific timeline to conclude the trial, but it's an OS-driven endpoint and will take time, with the first site to be opened for enrollment by year-end.

Q: With the Royalty Pharma deal, were they looking at the potential of Niktimvo in IPF by any chance when they were contemplating the term?

A: Michael Metzger said Royalty Pharma looked at the potential of Niktimvo beyond GVHD, including IPF, and the deal was aligned with the potential of the drug over many years.

Q: Just one more follow-up on that overall survival endpoint in the frontline triplet trial. I guess I understand the rationale for just including NPM1 patients in that analysis, but is there a minimum efficacy threshold that you need for the KMT2Ar patients to make sure that they will be included on the label? Or do you just need to hit the primary endpoint for NPM1 patients?

A: Neil Gallagher said the study is designed to test the hypothesis in NPM1 patients, with statistical power around that number, and they will look for consistency of effect in KMT2A patients but the study isn't designed to test a statistical hypothesis in those patients.

Q: On the revumenib filing, I understand that patients are regularly tested for KMT2A status, but do you expect you'll need a companion diagnostic for approval?

A: Michael Metzger said they haven't discussed companion diagnostic requirements for approval yet, but there is precedent for companion diagnostics post approval, and there are existing diagnostics for KMT2A.