Right. Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I am one of the Senior Biotech Analysts here at JPMorgan. I'm joined by my squad: Joyce Zhou, Priyanka Grover, and Ratih [Penhay]. Our next presenting company is Day One. Presenting on behalf of the company, we have CEO Jeremy Bender.
Good afternoon, everybody. Thank you, Anupam, and thanks to the JP Morgan team for the opportunity to be here today. I also welcome all of you in the audience, as well as those listening in. My name is Jeremy Bender. I'm CEO of Day One Biopharmaceuticals. Excited for the opportunity to tell you about the company today. Joining me are a few colleagues: Lauren Merendino, our CCO; Charles York, our COO and CFO; and Mike Vasconcelles, our Head of R&D. Quick reminder that I will be making forward-looking statements during the presentation today. We, at Day One, creatively and intentionally develop new medicines for people of all ages living with life-threatening diseases. This is the mission that brings everyone at the company to work every day.
What began with the founding of this company as the hope to help even a single child has now translated into real impact with more than 1,000 children treated with our approved product, OJEMDA, to date. This is progress that reinforces our commitment to do more and bring more new medicines to patients. We start 2026 in an exceptionally strong position as a result of the progress in 2025 that we achieved across all dimensions of the company's operations. We are on our way to establishing OJEMDA as the standard of care therapy in relapsed or refractory pediatric low-grade glioma , or pLGG. With the completion of enrollment in the FIREFLY-2 trial, which we anticipate in the first half of this year, we're preparing to expand into frontline pLGG. OJEMDA's impact will also extend globally through the work of our partner, Ipsen.
Ipsen is pursuing registration for OJEMDA outside of the U.S. and has rights in all of those territories. With this clinical success and regulatory success, of course, will come the opportunity to continue driving OJEMDA revenue growth, which I'll talk about in some detail today. Beyond OJEMDA, we've also recently completed the acquisition of Mersana. This was a deal we announced in the fourth quarter of 2025, and it's now complete as of last week. We're thrilled to have the [Emmy Lee] program in our portfolio. With Emmy Lee and DAY301, a program we licensed a year and a half ago, we now have two new potential medicines beyond OJEMDA, and we're going to provide updates on both of those in 2026. Finally, we've maintained a very strong financial position that allows us to continue investing in high-value and high-potential programs.
We ended 2025 with more than $440 million in cash, and we have no debt. Our focus is, and always will be, on programs that have the clear potential to become new medicines and to establish new standards of care for patients. We're far down that path with OJEMDA. OJEMDA anchors our growth and our momentum today, and, as I've mentioned, is positioned to become the standard of care therapy in second-line plus pLGG. Success in our frontline trial, FIREFLY-2 , will also allow and represent a clear path to standard of care status across all lines of therapy, including that frontline opportunity. Emmy Lee, our newest pipeline addition, mirrors what we observed in the early tovorafenib or OJEMDA opportunity. Emmy Lee has a clear and unequivocal early signal of monotherapy efficacy. It has a focused and easily identifiable patient population with extraordinary medical need.
It has a potentially rapid path to approval, and it represents a first-in-class commercial opportunity. All very attractive features from our perspective with respect to the Emmy Lee investment and the Mersana deal. We're also making great progress on the DAY301 program. Based on our early clinical results, I'm encouraged that DAY301 will also become an important new medicine for adults and for children living with cancer. We'll share those early clinical updates from DAY301 later this year. Day One is on a clear path to achieve more than $1 billion in revenue based on the potential sales from OJEMDA and Emmy Lee alone. OJEMDA's current approval in the relapsed or refractory pLGG setting represents a product opportunity of greater than $400 million here in the U.S. Critically, the opportunity to expand into frontline pLGG represents additive opportunity of more than $500 million.
On top of that, the Emmy Lee program in ACC, or adenoid cystic carcinoma, represents a near-term opportunity in the next several years to add a program that has the potential to bring in $300 million or more. Unlike OJEMDA and Emmy Lee, we've not yet disclosed data for DAY301, but DAY301 has the potential to increase our revenue growth even more dramatically, and that's because there are multiple potential adult indications for DAY301 that each represent billion-dollar-plus opportunities. Let's take a quick look at OJEMDA, which is the foundational program for the company. We now have little less than two years of launch experience, and we have a deep understanding of the pLGG population, as well as how physicians currently and seek to treat these patients. Importantly, we are still very much actively building this new market.
This is the first approved product in this patient population. Based on the clinical results we've achieved for OJEMDA and what we're observing for market adoption, OJEMDA is on a clear path to become the standard of care in second-line plus pLGG. Physicians are increasingly turning to OJEMDA as they gain experience with this new medicine. The product profile and the clinical benefits observed for OJEMDA align closely with the attributes that physicians seek when treating pLGG patients. So let's look at what those attributes are in more detail. OJEMDA provides and, in many cases, exceeds what physicians are seeking for a standard of care therapy, and that includes extended durations of treatment to fundamentally control this tumor, prevent it from growing and causing functional problems in the brain.
It involves durable responses, the ability to both take patients off treatment and observe that tumor stability, and then also retreat feasibly, as well as data on the safety and tolerability side that are consistent with significant long-term and chronic off-and-on use. The three-year data that we shared in November of 2025 at the Society for Neuro-Oncology Conference further reinforces OJEMDA's benefit along these attributes. I'm going to highlight a few of the key data elements from that presentation here because they align so closely with those attributes. First, what we observed in this three-year analysis is 19.4 months' duration of response for patients being treated with OJEMDA and 42.6 months' median time to next treatment. That's the median time from initiation of OJEMDA therapy to a required next treatment. Quite a durable period of time.
Most importantly, after 24 months of therapy, patients in this trial were allowed to take, at physician discretion, a drug holiday. And among those patients who elected to take that drug holiday after 24 months of therapy, three-quarters of them remained treatment-free for the 12-month period after that drug holiday initiated, showing real tumor stability off treatment as well as on. That's important because it really gives physicians the choice of a therapy that allows children to be children and not to be treated at all times. We also have early retreatment experience from this three-year data. That is experience for those patients who took a drug holiday and did require a new therapy. Nearly all of them went back on OJEMDA, and the experience early showed that that clinical setting resulted in significant tumor reduction, in this case, a 38% average tumor reduction with relatively short-term follow-up.
We will submit these data this quarter for a manuscript and expect publication of that manuscript as soon as possible this year. So overall, these data really support OJEMDA's continued use in the second-line plus pLGG setting. They also lay important groundwork, both clinical and commercial, for expanding into the frontline setting through the FIREFLY-2 trial, and that is a critical next step in building out this important new medicine for pLGG patients. OJEMDA's commercial results in 2025 were exceptional. They exceeded analyst consensus estimates. Our preliminary Q4 and full year unaudited results underscore this performance. Q4 net product revenue reached $52.8 million. That represents a 37% sequential growth over our Q3 net product revenues. full year 2025 net product revenues totaled $155.4 million, up 172% year-over-year. We observed in 2025 double-digit sequential quarterly growth throughout the year. Our underlying demand and volume also remained robust and growing.
Our fourth quarter total script increased to approximately 1,400 total. That was up 11% quarter-over-quarter versus Q3, and our full year total scripts reached more than 4,600, representing 181% growth versus 2024. Our revenue growth continues to be supported by both expanded patient utilization and, importantly, extended treatment duration or persistence, and these results in Q4, in particular, are even more dramatic considering the holidays that happen in Q4, and that often results in lower growth for rare disease medicines in particular. I want to make a note on persistence or duration of treatment. This has been a really important component of OJEMDA's growth as we've moved further into the launch. The quarter-over-quarter stacking effect of long OJEMDA treatment and the duration associated with that contributed substantially to our second half growth, and we anticipate will continue to contribute substantially in 2026.
With 20 months on the market now, the median duration of therapy for commercial new patient starts is trending to 19 months. The mean or average duration of therapy is currently at 17 months, but we expect this will increase over time as we get further from our launch date of April 2024. Our channel stock did increase modestly at year-end. This is typical and consistent with seasonal ordering patterns that you see for many brands. Our channel stock at the end of the year remained at the midpoint of our targeted two to four-week range of days on hand. New patient starts also grew substantially in the second half of the year.
NPS in the second half outpaced the first half by approximately 20%, and this highlights the impact of continued market development, in particular physician education efforts and experience with OJEMDA as a product, and it also highlights the importance of our two-year data, which have been available from FIREFLY-1 , that is, which have been available since May of 2025. So our future growth opportunity in this setting, the relapsed refractory pLGG setting, remains quite bright. We believe the long-term revenue opportunity is 2x-3x our current run- rate and that that growth will extend not just to 2026, but to years beyond that. For 2026, we are guiding to OJEMDA net product revenue of $225 million-$250 million.
The midpoint of this guidance reflects our projections associated with continued growth in adoption and new patient starts, in persistency or duration of treatment, and in highly favorable payer dynamics, all of which is driven by commercial execution. Physicians are gaining significant confidence in multi-year treatments, and that's going to allow us to continue pushing up that persistence amount. Beyond the U.S., we see additional growth through global expansion as led by our partner Ipsen. We're anticipating an [EME] approval decision in 2026, which, of course, will enable ex-U.S. revenue contributions shortly thereafter. I want to make a quick note about the eligible patient population every year for OJEMDA in this second-line setting. Based on all of our experience to date, we estimate there are approximately 1,100 treatment-eligible relapsed refractory pLGG decisions annually.
This analysis, which we're presenting for the first time at this conference, highlights that we are still early in the development of this market and that we have continued meaningful growth ahead as we drive adoption into the relapsed refractory pLGG setting. FIREFLY-2 represents an opportunity to expand OJEMDA and the impact into the frontline setting for pLGG patients. A first-line approval is how we move from building a market to scaling it. A successful FIREFLY-2 outcome has the potential to more than double the OJEMDA commercial opportunity here in the U.S. We view frontline and frontline use as additive. I want to make that as clear as possible that approval in that frontline setting will not only increase use in the frontline, but will also, we anticipate, increase use in the relapsed refractory pLGG setting.
Unlike other oncology settings, we do not expect cannibalization because retreatment is frequently observed in pLGG largely on the basis of the absence of the development of resistance to therapies through genetic means. FIREFLY-2 enrollment is expected to be complete in the first half of this year. This is a critical milestone. It starts the clock on the availability of data, which we expect will be in the mid-2027 timeframe. And of course, that data set is designed to serve as the basis for a potential approval in the frontline setting, which we anticipate will occur in 2028. So far, I've talked about OJEMDA, which has provided a very strong and significant opportunity to be both selective and strategic about how we expand our portfolio, which brings us to our latest program, Emmy Lee, one that we acquired last month.
This program follows a very familiar blueprint for us, one that investors who know this story will recognize immediately. The Emmy Lee program looks and feels like the early days of tovorafenib. It's a focused, high-impact market opportunity in a disease with significant medical need. It offers, we're convinced, a relatively short timeline to becoming an approved new medicine. And with clinical and regulatory success, we anticipate a three-year path to potential approval and then to subsequent meaningful commercial contribution on the order of $300 million here in the U.S. We also expect a relatively rapid adoption curve for the Emmy Lee program given the aggressive clinical course of ACC and the lack of approved therapies in this disease setting. Emmy Lee itself is a B7-H4-directed antibody-drug conjugate. It's shown exciting early evidence of activity in ACC.
I want to note that B7-H4, the molecular target for Emmy Lee, is highly and uniformly overexpressed in ACC tumors, and we have clear evidence of monotherapy activity for Emmy Lee based on the phase I trial that Mersana ran with a substantial number of patients. The enrollment criteria in that trial include a group called ACC1 subtype patients, and that is based on a molecular signature of ACC tumor cells. However, those enrollment criteria were also inclusive of a non-ACC1 clinical subtype that is defined solely on the basis of clinical criteria instead of molecular diagnostic criteria. So the target patient population here is broader than the ACC1 subtype alone. Expanded phase I data from that phase I trial will be presented in the middle of 2026. This data set is substantially larger than what was observed and presented at ASCO 2025.
Of course, that clinical data will inform dose selection, patient strategy, and the design of our next trial for Emmy Lee and ACC, which we expect will be registration-enabling. We view the data, and we've reviewed the data that will be presented in some detail during the course of our deal as compelling, and we expect to progress rapidly to approval. I want to emphasize that this is a pathway that we know how to execute. We have successfully done that before with OJEMDA, and we will apply all of the learnings and capabilities we developed to do so to Emmy Lee. DAY301 is a PTK7-directed ADC that's in phase I dose escalation as well. It has the potential to become a transformative new medicine across multiple adult and pediatric indications. The DAY301 early clinical profile is emerging from those phase I-A efforts.
Our upcoming data in the second half of 2026 will offer a first look, of course, at the direction and the potential for this program. As a DAY301 is a TOPO1 inhibitor-containing ADC that targets PTK7. The biological rationale for targeting PTK7 with an ADC is very clearly established. Our early clinical results have been encouraging. The safety profile that we're seeing is consistent with expectations for a novel ADC. And while we continue to optimize the dose and schedule in this phase I-A, we are seeing clear evidence of antitumor activity. We'll provide updates on both of those, of course, in the second half of 2026. When I opened today, I spoke about our mission and commitment to develop new medicines for patients of all ages facing life-threatening diseases. With OJEMDA, that commitment has translated into real impact.
What we've built at Day One is a dual growth model. Durable, growing commercial revenue from OJEMDA provides a strong foundation, while our clinical catalysts with frontline pLGG, with Emmy Lee and DAY301 will drive the next phases of growth. All of that is a clear path forward with the right programs and the financial strength to deliver the next wave of growth. Most importantly, we remain focused on what brought us here in the first place, continuing to make a meaningful difference for patients and families who need improved and better therapies. With that, I'll thank you for having us here today, and we'll now take questions.
Thanks so much, Jeremy. I'm going to ask the first couple of questions, but there's going to be an opportunity for the audience to also ask questions, so feel free to raise your hand when prompted. On your new frontline analysis on the market, Jeremy, I had a quick question on if you could talk a little bit about the levers there, right? Having a frontline opportunity to be just a little bit bigger than the refractory opportunity. So what are the dynamics there, right? Because in the refractory setting, you've got this prevalent pool of patients that are out there, and the frontline is an incidence. So is it the duration?
Yeah, it's mostly duration. Our estimates of the patient population in frontline and all of relapsed are equivalent, really, around 1,100 patients per year. In the frontline opportunity, though, we are anticipating a slightly longer duration of treatment. The protocol for that frontline trial includes a treat-to-progression approach that is distinct from what we established in FIREFLY-2, and we do anticipate that just being earlier in lines of therapy will also lead to longer durations.
And then on your guidance, which came in kind of ahead of consensus estimates for the year, just wondering, you had the three levers there. What's contributing, if you had to rank order the contributions to the guidance?
You know, I think that the biggest levers are really the new patient starts and maybe more so just treatment persistence or duration of treatment. Those two largely account for the spread in the range that we've provided, and where we net out in 2026 will, on those two elements, really, the duration and the NPS will really drive where we anticipate ending up within that range. I do want to note, though, that the access dynamics here are extraordinarily favorable for this medicine. We have high 90% reimbursement rates and very solid and low gross to nets, which we anticipate will continue into 2026.
Questions from the audience? Yeah.
Sorry, you may have said this already, but when do you anticipate? Thank you. When do you anticipate the readout for the first-line versus chemotherapy trial?
For that trial, we'll complete enrollment in the first half of this year, and then per protocol, that analysis on the primary, which is response rate, will occur 12 months later. And so that analysis we anticipate will be available in mid-2027. The data itself, yeah.
Additional questions from the audience?
So, on OJEMDA, and just when you think about those levers, what are you seeing currently on OJEMDA uptake in the second-line setting versus right now about how we should be thinking about it in 2026?
Yeah, ask Lauren to answer that one.
Yeah, so as we look at second-line uptake quarter-over-quarter, we have consistently seen a growing trend, and so we anticipate that we'll be able to continue growing that trend with the three-year data that came out in November. It's very compelling, and it's differentiating because no other product in this market has data that shows that after two years, patients can get a year or more off therapy, and that's really important for these children who physicians are trying to give time for them to enjoy their childhood in addition to treating their cancer.
Then on the guidance, the third bullet, second bullet was maximizing persistency. So how does some of the recent data that you've presented, not just two-year, three-year, help you kind of optimize that persistency? And what exactly are you optimizing for?
Lauren again.
Yeah, so from a persistency perspective, there's a couple of drivers here. One is growing experience, right? So when physicians use a product for the first time or the second time, they aren't very skilled at managing the AEs. So they're gaining that experience naturally over time. In addition to that, our team has really increased our efforts on proactive AE management, setting expectations with patients and their caregivers so that action can be taken quickly. I think one of the mistakes that some physicians made out of the gates was they see the patient every three months, and they would wait three months before they really got a follow-up. And by then, rash is the first AE that usually appears. And oftentimes, it was pretty extreme by the time the patient came in. And so I think physicians have gotten savvier.
We have also done better educating of both physicians and parents, and then we also think that there is room for physicians to look at down-dosing as well as part of AE management strategy, and we think that that can increase persistency as well.
And then the final driver to growth on that slide was favorable payer dynamics. What are you seeing now? How do we be thinking about OJEMDA dynamics? Because there's a little seasonality there and then the rest of the year.
Yeah, absolutely. So I've been in oncology for over 15 years. I have never had a brand that has the payer coverage that this brand has. We have coverage in the high 90s percentage. Patients get their drug filled quickly and easily, often on the first try. And we do not do payer contracting, and so that leads to a very favorable gross to net as well. And in addition to that, impacting the gross to net is that we also have a fair percentage of patients, about 40% of patients are Medicaid patients, and we were granted a reduced discount rate as a result of being a pediatric medicine. So all of those factors really lead to a very positive access story as well as gross to net story. And to your point about the new year, so every year, of course, benefits reset.
We have a very generous copay card program that helps patients get through that deductible, and so our team actually really prepares for that and ensures that patients have a smooth process in January to continue therapy.
Questions from the audience?
Maybe final one from me. You've got kind of two early-stage updates, DAY301 as well as Emmy Lee. So how should we think about the size and scope of those updates, and what would you be looking forward to that could get you excited about both programs?
Let me ask Mike to answer those questions, and I'll come back in with a couple of final thoughts.
The door closed and I couldn't hear. Can you repeat?
What's anticipated for the updates for Emmy Lee DAY301 in terms of scope of data? Why are we excited?
Oh, got it.
What would get you excited when you flip the card?
I'm already excited, but.
I can see that, right?
I can see that.
But let's take Emmy Lee first because on the calendar, we're going to see updated data sooner. As some of you may know, Mersana had presented an early, relatively small data set last year at ASCO in this cancer, Adenoid Cystic Carcinoma, which arises in salivary glands. There's a very aggressive subtype that's a substantial proportion of the disease. No approved therapies and available therapies have single-digit response rates with poor survival. So it's a patient population with a relatively young median age. So a lot of young adults are affected, and so we're keen to progress that through development. What we expect to see mid-year of this year is an expanded cohort of those patients that have been treated over the past several months, obviously updated outcomes with respect to antitumor activity and durability, and more mature safety data set.
It's a phase I experience, but it's a phase I experience that has been quite broad. And so there's a safety data set already that is pushing up against 200 patients, which is, as you know, a bit unique for that phase of development. So safety, updated numbers, and some durability of that cohort of patients with ACC mid-year. Then later in the year, we're equally excited, though it's slightly earlier data set with DAY301, which is the PTK7-directed ADC, where we have been nicely working through dose escalation, and we expect to see, hopefully, a dose escalation data set that is pretty complete with respect to thinking about honing in on a dose for further development. Obviously, safety will accompany that, and the extent to which we have backfill data will be sharing that as well.
Any final questions from the audience? Thank you, Jeremy and team.
Thank you, Anupam . Thanks, everybody. Appreciate you all being here.