Day One Biopharmaceuticals, Inc. Q3 FY2025 earnings call

• OJEMDA showed strong growth in Q3 with net product revenue of $38.5M, a 15% QoQ increase. New patient starts and total prescriptions also accelerated.
• The 2-year FIREFLY-1 data included in the OJEMDA label demonstrates manageable safety and durable clinical benefit, with the median duration of response increasing to 18 months.
• Pipeline progress: Ipsen anticipates mid-2026 EMA approval for OJEMDA in Europe; FIREFLY-2 Phase III trial on track for full enrollment in H1 2026; DAY301 PTK7 directed ADC in Phase Ia with dose escalation ongoing.
• Tovorafenib added to NCCN adult glioma treatment guidelines as a Category 2A recommended treatment.
• Priorities for end of 2025: Drive OJEMDA adoption as standard of care in second-line pLGG, advance the pipeline, and maintain disciplined expense management.

In Q3 2025, Day One Biopharmaceuticals achieved $38.5 million in net product revenue for OJEMDA, representing a 15% quarter-over-quarter increase. Year-to-date net product revenue for OJEMDA was $102.6 million. Additionally, revenue from OJEMDA exceeded the combined cost of sales and SG&A for the first time in Q3. OJEMDA's performance is driven by increased new patient starts, total prescriptions, and durable treatment persistence.

• Raised full-year 2025 revenue guidance to a range of $145 million to $150 million, reflecting confidence in OJEMDA's launch trajectory and expecting continued double-digit sequential growth in Q4.
• Total operating expenses in Q3 were $59.6 million, with the second consecutive quarter of declining expenses. Q4 expenses expected to increase modestly for planned commercial and clinical activities.
• Cash position: $451.6 million in cash with no debt, showing continued improvement in quarterly net cash burn.

• Forward-looking statements may not materialize due to various factors outlined in SEC filings.
• Uncertainties related to pipeline progress, including outcomes of DAY301 and FIREFLY-2 trials.
• Potential impact of competition and payer dynamics on OJEMDA's commercial performance.

Q: Curious to what extent you could describe even qualitatively what impact you're seeing on both the rate of discontinuations and duration of therapy, especially in non-EAP patients A: Tara, thanks for the question. This is Jeremy. So first off, it was a great quarter. I think you captured it appropriately. And that was really on both the new patient start dimension, but also the persistence as noted. So let me ask Lauren to comment on the sort of non-EAP commercial use group. Lauren Merendino: Yes. Thanks, Tara, for the question. At this point, the data is still maturing on our commercial patients. So what I can say is it's consistent with our expectations. But I really can't give any details beyond that. But I do think that the median duration of therapy in the EAP patients of 20 months is significant and is a leading indicator for us. That data is not final. There still are a number of patients who remain on therapy who have not yet reached the point of receiving OJEMDA for 24 months yet. So that number may evolve. But the median will likely stay the same, but the additional duration beyond 24 months is an evolving data point.

Q: I just wanted to focus a little bit on the 3-year data for pivotal FIREFLY-1 study that's coming out at SNO later this month. Can you just expand a little bit more on what you're looking for in that data that could inform how we think about treatment duration or other commercial levers for OJEMDA moving forward?

A: Thanks for the question, Anupam. Mike will answer that one for you. Mike? Michael Vasconcelles: Thanks, Jeremy. Anupam, Mike Vasconcelles here. Yes, we're really excited about these data coming up at SNO. I think given the nature of the disease, the long-term follow-up data in our clinical development program is going to be important for a variety of reasons for the foreseeable future. So of course, in addition to update on safety and duration of response, I think what's going to be important to keep an eye out for are the time-to-event analysis that will be shared specifically around the time to next treatment and a treatment-free interval as well as progression. The reason that's important is because it will be important in second and subsequent lines of therapy to really understand that in the context of other available therapies where we know there may be some biologic sort of events that occur when patients come off therapy that we want to see if are going to be distinguishable for OJEMDA. I think we'll also get a sense of perhaps early retreatment information that could be meaningful for clinicians and patients.

Q: Can you speak how the addition of the FIREFLY data to the label has impacted rates of off-label MEK inhibitor usage? And then on the payer side, you noted 90% plus rates of coverage approval on first submission. Is there a reason to think that favorable coverage could impact the rates of off-label MEK inhibitor usage as well?

A: So let me -- I'm going to ask Lauren to answer the second portion of your question. On the first, I want to clarify and make sure I understand. Was your question related to the NCCN listing that we received for OJEMDA in adult gliomas, and off-label uses? Morgan Lamberti: Yes. Jeremy Bender: Okay. Yes, I'd say, first off, we weren't aware that, that was a listing that was going to occur. And of course, we're interested. We think there's potential utility there based on data that we've seen in the past for OJEMDA. It's a little early to say whether or not it will have any material impact on off-label use, but it certainly could, given that in particular, in adult settings, those NCCN listings can be influential as far as physicians electing to try treatments that are not necessarily approved for a specific tumor. So I think it's a stay tuned story. And Lauren can comment on your question around reimbursement. Lauren Merendino: Yes. So just remember that NCCN is an independent organization. And so although they've made their recommendation, that is not reflected in our label in any way. And so the commercial team must remain strictly within our label. So we have no ability to engage with physicians on that topic at all. But I will say that payers do sometimes leverage NCCN guidelines to inform their policies. But again, this is nothing that we can participate in, and that would be completely up to those payers.

Q: Congrats on the strong quarter. Two from us. Curious if you saw any gross to net changes in 3Q? Just trying to pair the different growth rates that you mentioned, both on revenues and scripts. And then second, on DAY301, I guess how has enrollment been going? Is it sort of proceeding as you would have expected? And any updated thoughts on PTK7 as a target given the shifting development landscape for ADCs against the target?

A: Alec, thanks for the question and comment. Let me ask Charles to comment on gross to nets and then Mike regarding 301 and PTK7. Charles York: Alec, this is Charles. So on the gross to net, you should hear from us that we were definitely at the high end of our 12% to 15% range that we've guided on. That's consistent with what we expected going into the quarter. As you recall from previous conversations, we did take a price increase as of July 1, and the result of that is CPIU penalty, which does drive up our gross to net rates. We would expect in Q4 to get some relief on that CPIU. That's pretty consistent with what we've seen in previous quarters, but we were definitely at the high end for this quarter. Michael Vasconcelles: And again, this is Mike. With respect to the DAY301 program, we have a great group of investigators and the DAY301 program continues to move along nicely through -- not just dose escalation, but also the beginning of dose optimization and backfill cohort. So really no issues whatsoever there. With respect to your broader question, I think I'd reframe it just a bit. I'm not so certain there's an issue at all with the target. In fact, I think the target is a really sound target for oncology development. There are distinctions between some of the other therapeutics against the target, especially with respect to payload. But we're focused, obviously, on our own program, which continues to progress nicely through its paces in early development.

Q: Congrats on the quarter. Two from me. First, maybe just any commentary that you could provide in terms of how the patient population breaks down in terms of line of therapy? I know you had some commentary on increases in second-line specifically, but any color there? And then second question. In terms of gaining uptake with a particular physician, how impactful do you think having the longer-term data is, for example, the ASCO data set versus the prescriber just gaining that firsthand experience?

A: Thanks for the questions, Kelsey. Good ones, and I'll ask Lauren to respond to. Lauren Merendino: Yes. Thank you for the questions. So from a line of therapy perspective, first, let me just say that from a primary data perspective, our view is limited. So we don't have a comprehensive data set to look at line of therapy. It's just the nature of our data. So we have to get it from other -- in other angles. And the way that we do that is through market research with physicians. So the data that I reported today was from self-reported physician prescribing behavior. And we have seen this over time. So over the past 12 months, increased significantly in what they are reporting as far as using OJEMDA in the second-line. So we've seen about 60% growth in their reporting of that. But that's the best data that we have at this point. And so that's the lens that we look at line of therapy through. To your question about uptake, it's very hard to split kind of physician behavior into the why they did that. So you were asking what's long-term data versus first-hand experience. I think it's always a combination of both. But when we're talking about the latest data that came out, the one that I wanted to mention not to underestimate is the ASCO data that was reported on growth velocity. So I do think that some physicians, although they may have believed in the efficacy, and I don't think that most of them were surprised by our efficacy update, it was consistent with what they expected. I do think that some of them may have been more cautious in using OJEMDA than even they would admit, because they had unanswered questions about growth velocity. That ASCO data set answered those questions. So it showed reversibility in the large majority of patients. And many of the physicians who saw that data reported to us that, that was meaningful to them. And then that really made them more confident in using OJEMDA in their patients. Did that answer your question?

Q: Congrats on the nice quarter. My question is about the 3-year update that's coming up. And I heard sort of your remarks about at least in the EAP patients, you're seeing sort of a median of about 20 months of duration of use. With the 3-year update coming up, do you think -- are you expecting to see some patients sort of -- or sort of that median go up in that study? Or is it more meant to inform when to restart treatment and inform growth velocity while the patient is sort of off treatment? So help us understand sort of what we should be focusing on when we see that data. And then separately, if I may -- I can stop and ask the second question later.

A: No problem, Ami. Thanks for the question. So let me walk you through what we know today already from the FIREFLY-1 study and then what we're expecting from the 3-year data. And I'll ask Mike to add anything to my comments. So in the trial of FIREFLY-1, we know already that the median duration of treatment was just under 24 months. And we've known that for some time. And that's an important data point. That actually informed our expectation around what we may see as a median in the commercial setting. We're not there yet in the commercial setting, but we are for that EAP component, and that's why we reported out that 20-month median for the EAP cohort. And that's highly consistent with our expectations and benchmarks. So really encouraging. For the 3-year data set, we're really focused on what happens as you follow patients out for longer periods of time. In particular, what we're focused on, as Mike noted earlier, are these time-to-event kind of end points. But to make it really simple, what we're really laser pointed on is what physicians have been asking us, which is what happens after you give patients 24 months of therapy of OJEMDA once they come off treatment. And they can come off for a bunch of reasons. It can be they simply want a break. It could be some focus on releasing that growth velocity delay. But regardless, in this physician community and in this patient population, there's always a desire to limit treatment if it's at all possible. And their specific question for us, there really are 2, has been, one, do you see tumor rebound growth? Meaning short-term increases in the tumor growth right after you stop that therapy after 24 months. And the reason they're focused on that question is because of their observations reported to us, this is not published, but their own observations around what happens with MEK inhibitor treatment when you stop MEK inhibitor treatments. That's the first question they're interested in. The second is independent of that growth rebound, do you also see stability of the tumor for a significant period of time after that 24-month treatment period. And the way they think about that is what do you see 1 year after you stop treatment. So patient is treated for 24 months and then followed for another year, what portion of those patients that have that 3-year time horizon have required another therapy, and what patients have not required another therapy? And what they report to us is that any percentage greater than about 50% not requiring therapy in that 1-year period is very encouraging. So that's what we're really focused on, Ami, at the 3-year data cut -- that you'll see at SNO. And I think that frames the two big things that we're looking at. I don't want to minimize the substance of what Mike also mentioned, which is the more detailed assessments of time to next therapy as well as treatment-free interval.

Q: Congrats on all the progress thus far. Two quick ones from us. I want to dig into a little bit the new patient starts as a key revenue driver. Obviously, the question是, do you guys view new patient -- all new patient starts as equal? And are you seeing differences in persistence or dose modification needs based on particularly the reason for switching, elective switch toxicity or progression? And then the second question. On the FIREFLY-2 study, given that it includes rechallenge and crossover, curious how you're framing expectations on efficacy, if the crossover leads to a potential compression of the perceived delta versus standard of care for that study?

A: Thanks, Andres. Let me ask Mike to start with your FIREFLY-2 question, and then we'll come back to the question about the commercial setting and Lauren can address. Michael Vasconcelles: Thanks, Jeremy. Yes. Just a couple of key points to keep in mind with FIREFLY-2. The primary initial efficacy endpoint is objective response rate between the 2 study arms. And the primary time to event endpoint is a measure of progression. And so -- and the third point I'd make is that the opportunity to cross over, to receive tovorafenib is very tightly managed within both the study design and the operationalization of the study. So it's our expectation that, that component of the study -- first of all, it will be really helpful and meaningful data, clinical data that we'll generate with respect to the subset of patients that do receive tovorafinib after first-line treatment in that construct. But for the primary endpoints of the study, we don't really see any concern given the way that we've designed the study and operationalized its oversight. Lauren Merendino: And then back to your NPS question. So first of all, NPS is a key revenue driver for us beyond the quarter, right? Because obviously, these patients stay on for long periods of time. So although they may start in this quarter, they actually have a greater impact in future quarters because they'll get 3 refills in a quarter as opposed to -- if they came on in the later half of the quarter, they don't get 3 this quarter, right? So NPS is important for our long-term trajectory. Your question about whether they're all equal and dose modification, I would say, we look at patients by line. And so we do think that second-line is a more desirable place to be, number one, because the patient is likely less complicated from a health perspective. But secondly, because it's a larger pool of patients than the later lines, right? And so I would say that's how we're looking at patients. We're not really categorizing them in other ways. But to your point about dose modification, I just want to point out that our price is the same regardless of dose. So actually, dose modification is an important part of AE management, and we see that patients that get dose modification actually do better. So we think that's an important thing for physicians to be comfortable doing and it doesn't, in any way, impact our bottom line -- our top line.