Okay, great. We'll get started. Good morning, everyone. I'm Tara Bancroft. I'm one of the Senior Biotech Analysts here at TD Cowen. I wanna thank you so much for coming to TD Cowen's 46th Annual Healthcare Conference. For our next session, we have a fireside chat with Day One Pharma. From Day One, we have Charles York, the CFO and COO, and Mike Vasconcelles?
Vasconcellas.
Vasconcelles, the head of R&D. It's a privilege to have you both here. Thank you so much for joining me. Before I get started, I wanna say to everyone in the audience that if you have questions, please feel free to jump in, raise your hand, jump up and down, whatever it takes, I'll make sure that you get heard. But I guess Charles, to start, can you give us some high-level thoughts, maybe on the OJEMDA launch, how it's going, the progress that you're seeing and highlights of the year?
Of course. Thanks to the TD Cowen team. Thanks to Tara Bancroft for inviting us to the conference today. Of course, always a pleasure to be here. A couple of things I think that we'd note on first, for those of you that are unfamiliar with Day One, we're a company that is developing and commercializing medicines for patients of all ages that is anchored in our primary program, OJEMDA, which is approved for pediatric low-grade glioma. We'll talk I'm sure a fair amount about OJEMDA throughout the course of today in the fireside chat here.
Note a couple of things, though, you know, from an overall fantastic year that the team delivered in 2025, showed up in a lot of the results that were put forth financially. We ended with over $155 million of revenue for the year. It was our first full year of launch. Over 170% growth year-over-year from that standpoint. The back half of the year was even more strong than we saw in the front. We ended the fourth quarter with over $52 million of revenue and 37% growth quarter-over-quarter. It really just positioned us in a fantastic spot, and we're really excited about what we delivered for that year.
More importantly, though, I think Mike and I, as we sit here today, would probably tell you we're even looking more forward to 2026 and what we have on the horizon. Some really key activities. OJEMDA will be the driver of durable growth over time for us, and you'll see that both in our revenue guidance that we'll touch on later today, I'm sure. You'll also see that in the pipeline, a couple of key activities that are going to occur. First, to continue to expand OJEMDA itself, we have anticipated the completion of the frontline enrollment in the frontline trial in the 1st half of this year, and we'll expand into the other pipeline programs that we have.
First of that on the timeline perspective, excuse me, is our Emi-Le program, which is a B7-H4-targeted ADC for adenoid cystic carcinoma. We expect data in the middle of this year, coming soon, at a medical meeting for that and be remiss if I didn't also mention our first clinical data out of our DAY301 program, which is a PTK7-targeted ADC, which we expect to have in the back half of the year. It's been enrolling patients now for about a year now, so we're really excited about those things.
Great. Yeah. Are we. We'll definitely get to both programs, both datasets, I guess we could start on the OJEMDA launch.
Sure.
You guys have given a lot of metrics over the last year, and maybe you could talk about the most important factors that you guys are looking at in terms of tracking the launch and how we should be interpreting those metrics that you update us on every quarter.
Great. Yeah. The way we work to drive additional growth, and this is really focused on a couple of two key metrics, I would say for the most part. There's a lot of underlying activities that we'll do.
Mm-hmm
we can touch on as well. There's two key metrics that we look at from our standpoint. Growing new patient starts, NPS. We've been able to do that over the last year. In 2025, our second half new patient starts as compared to our first half new patient starts grew on label new patient starts, grew about 25%. We're really starting to see a pickup, and we think that was driven by additional data and education for our KOLs and physicians. That was primarily driven out of some additional data that we provided at ASCO. That's one, the new patient starts. The second piece of it is duration of therapy or persistence. It's how we measure it.
We continue to see durations of therapy in this patient population in the commercial setting, you know, 17 months approximately on a mean basis, and 19 months on a median basis. We believe that is really helpful in building what we think is that durable growth that's sustained and stacking over time. Those are the two key metrics which are really kind of...
Okay. Maybe we can get into the duration of therapy a little bit more, the median 19 months. That's obviously very long. That's very promising. What does it take to get that higher from here, and what do you think could be the eventual ceiling for that?
Yeah. I'll answer at a high level, then kick it over to Mike to talk a little bit about the therapy and patients themselves. I think there's a couple of key things to note on that. One, you know, median's anticipated at this time. Two, just given the short time in the commercial market, you know, end of year was about 20 months in total, we do expect the mean to continue to increase over time. Unsure exactly what that'll look like, but we do see some good duration overall and are generally very positive about that. I think from an overall of the activities that we do in order to influence that, what we see a lot is additional data. Unsurprising, right?
The more data we show to the longer term for the clinical trial itself, the more engagement we get with KOLs and physicians. I think there's just a piece of continued experience in the market as well. For these physicians to be able to have the therapy, to be able to use it and start moving it towards second line for them is really the key for us overall and how we look at it as a company, is to make this the second line standard of care in the relapse setting for PLGG. Is there anything you wanted to add, Mike, from a physician perspective?
Yeah, I think. Thanks, Charles. I think, a couple of things just to sort of underscore Charles's points. With respect to persistence in second line pLGG, as Charles mentioned in the initial parts of the launch and through the FIREFLY-1 pivotal trial, we saw a patient population who had had a median of three prior therapies. Increasingly, as there's familiarity with the medicine, by physicians, patients, and families, we see increasingly, looking to OJEMDA in the second line. That's important, because that prepares us and sets us up nicely for the frontline data that will become available as early as the middle of next year.
When we look at persistence in the context of either second or third line, our commercial team and our medical affairs team have done a really nice job sort of deconstructing the elements of what might be the impediment of persistence in the current label. That'll be a really nice focus for our teams in 2026 to look at closely. For example, we know that if there's familiarity with the use of the medicine already from prior exposure of use, that's helpful obviously to understanding how to administer the medicine over a longer term.
Secondly, we know that there are certain demographics of patients where because of one of the side effects, which is rash, which is very manageable, but you can imagine if you're an adolescent with a rash that getting on top of that rash early, making sure that it's well controlled, that can help a patient stay on therapy longer, increase in persistence. These are the factors that when you look very carefully allows us to utilize, like I said, our medical affairs expertise and support our commercial team in helping physicians and families with the benefit of staying on therapy. Dose reductions is another one.
The other thing to make note of is the design of the frontline study is a little bit different than the FIREFLY-1 study design in that it's purposefully designed for treat to progression. Again, as physicians get used to whether it's in the current label or if they're investigators in the frontline study, having patients stay on therapy till progression versus the way that the FIREFLY-1 design was sort of structured for approximately 26 cycles or 2 years, that's also gonna be helpful over time.
Okay. In mentioning that second line use could increase more with more familiarity, with education on rashes, maybe you could talk about what are the top one or two priorities, and ways to actually get an increase in density in second line use. You know, I know you just had, last year the NCCN guidelines were updated in adult glioma. Like, to what extent is that contributing? Maybe just a little bit more in terms of specific efforts that you guys are doing, to increase that segment.
I would focus in a couple of things on what Mike said too, and boil it down. One, we're already seeing increased second line use in the data that we have, which is very positive. As physicians seem to be gaining more experience, it appears that they're moving more towards second line with more recent patients. It's pretty expected overall, but it's also nice to see that play out in the dataset and in real life. Additional education, I'll let Mike touch on a couple of things here. We had ASCO data that was very important for growth velocity and also for the rash management topic that Mike had highlighted here.
But I think the forward-looking opportunity that we have there, is on these opportunities here in regards to one, down dosing. We do see greater persistence when patients are down dosed. You know, from a financial aspect, that is because we have flat pricing, that's the equivalent from our perspective. The second piece that Mike noted here is the opportunity for more data. Mike, there's a presentation or, excuse me, a publication you're anticipating right the first half of this year approximately. Do you wanna give some details on additional information associated?
Sure. Yeah. Thanks, Charles. Just to again reinforce, it was just a few months ago at ASCO last year where this, sort of, a bit of an overhang on unanswered questions, so to speak, with respect to OJEMDA as it relates to inhibition of continued sort of normal growth for children, was really asked and answered quite nicely in data that was presented at ASCO. In fact, when you look at catch-up growth or annualized growth velocity off of therapy, we very nicely shown in virtually all patients that they assume sort of a growth based on a normalized growth pattern for their age once patients come off therapy. That's obviously very reassuring to physicians, patients, and family. That was sort of asked and answered last year. At the end of...
In the middle of the year, at the end of last year, we were able to present longer-term follow-up data from FIREFLY-1, at a neuro-oncology conference just at the end of last year. Obviously our most intimate experts in the field are aware of those data, but this is really an important year for us to share those data more broadly.
The reason those data are important is because when we look at endpoints such as the time to next therapy after OJEMDA therapy or the treatment-free interval off of OJEMDA before another therapy is needed, because physicians are managing really what's a chronic tumor until patients enter early adulthood, that was really important data to see, to see a time to next therapy that was pushing almost 43 months as a median or a, or a treatment-free interval off of therapy over a year.
When we had asked physicians ahead of those data what would be like a nice treatment-free interval that you could expect with OJEMDA once a patient has that two or more year course, physicians said, "Well, you know, if we could keep a patient off therapy so they can just be a kid, right, for, you know, about a... If even half of them could be off of therapy for a year, that would be, that would be great." The data showed very nicely that actually nearly 80% of children were staying off of therapy after a year, after a full course of OJEMDA. Really important data just becoming available at the end of last year.
As Charles said, those data were presented in a scientific meeting. It's gonna be super helpful to have those data in publication. We've already submitted that up a paper to a peer-reviewed journal. We would expect or hope to have that available for physicians to really dig in and understand by the middle of the year. That'll be a key growth driver as we think about ongoing education about the importance of persistence of therapy when we know that if we can get patients through that therapy, well, there's gonna be a really nice treatment-free interval at the back end.
It's a, it's a really intentional cadence of information. you know, started in the middle of last year, 2025. Additional information out of the back half of 2025 and into 2026 to really drive that continued education and show the long-term potential of the therapy. Very important for us personally.
Okay, great. Well, speaking of cadence, maybe you could talk about all the assumptions that underline your guidance, which implies actually really great growth this year and cadence expected throughout the year per quarter.
Sure. Yeah. We've really focused intentionally on the guidance of $225 million-$250 million for the year 2026 of net product revenue. A couple of things that we get questions on. The biggest one from our standpoint is, you know, how do you represent the top end versus the low end, and what's the difference between those two things? If we just break it down a touch, if you look at the midpoint of that guidance, that's about 50% growth year-over-year, a fantastic spot for us and continues to show that durable growth trend. When we think about the guardrails, you know, the lower end of the range represents where we believe we can continue to drive through.
How we get to that top end of the range is really driven by the things we just talked about here, right? It's continuing to grow new patient starts, improving persistence through additional data, additional education of physicians, that allows us to get to that top end of the range. Pretty straightforward. You've heard us all say all of these things before, those are really the things we have to influence the market to do so.
Okay, great. you know, I know with Mike, you mentioning the frontline trial, and could you tell us based on your peak assumptions for second line, to what extent do you think that the frontline could add to that peak opportunity and approximately when that could be meaningful to you guys?
Sure. Let me say a couple words around what we know about the tumor frontline trial, and then Charles may wanna dovetail that with some comments around sort of peak expectations. The first thing to keep in mind, this is a low-grade glioma. It's unfortunately, it has the opportunity to extend a lot of morbidity and occasionally mortality to children because of its location in the central nervous system. The fact that I bring this up is important because to date, both clinically and in any sort of preclinical models, we've not seen acquired mutations following exposure to certain therapies. Why is that important? That's important for a couple reasons.
One is, we already know from the FIREFLY-1 study that we have patients who've come off therapy, gone onto a treatment-free observation period, and been retreated with OJEMDA and tolerated that well and had nice antitumor responses. That's in the relapsed refractory setting. Now let's think about it in the frontline setting, where we have the largest randomized controlled trial ever undertaken in this disease, asking the question of the benefit of tovorafenib compared with investigator choice chemotherapy. We have a high expectation that that study will be successful given the data we've already generated in the relapsed setting. When those data come to fruition, they end up available to the community and the product label, et cetera.
I think you very easily can imagine the day where a patient will be treated with tovorafenib in the frontline setting. They will have that treat to progression period that we think will extend at least two or more years, have a treatment-free observation period, and then subsequently will have OJEMDA therapy again if and when their tumor begins to regrow. Like I said, we already are generating data in the relapsed refractory setting that supports that hypothesis. That's really important to understand. When we look at the available number of patients on an annualized basis in the U.S., in terms of patients who would be eligible for OJEMDA in the frontline once those data become available, and the number of patients that are eligible for treatment in second or subsequent lines, it's roughly the same number of patients.
If the data continue to hold up, that there's really no acquired resistance and the tolerability is so manageable with a once weekly pill, you can see very nicely how the frontline data are gonna make a big impact for patients with the disease and for the brand.
It's an important point. Some of the time to next treatment data, treatment-free interval data that Mike team recently put out, and are a little bit different than you do often see in other oncology settings. It does take some time to go through it, and we do get the question from investors, like, "Don't you want patients on therapy forever?" type of thing. That's not how we weight in this setting. It's not how we get to the point of standard of care, either, you know, on an approved frontline scenario or in the second line.
It's an opportunity for patients to make sure that they use OJEMDA, to manage their life, and when they have the choice of taking some time off of therapy, when they decide to go back on or need to go back on, that that choice can be OJEMDA.
Okay, perfect. I really wanna make sure we get to both of the.
Totally.
pipeline candidates. I think starting with your own DAY301. You're gonna have data this year. It's initial data. You've started dose escalation at the end of December 2024.
Yeah, that was very right. Yeah.
Maybe you could just set some expectations there in terms of number of patients, how many cohorts that you've dosed, and what kind of safety and efficacy bars that you're looking at?
Yeah. Let me high level on the program, and I'll turn it over to Mike. This is a program. It's a PTK7-derived ADC that we in-licensed in the middle of 2024. Dosed our first patient really the back half of 2024. It's been in the clinic for about a year now. One we're very excited about when we're seeing activity and the safety profile that we think is consistent with other ADCs. We think it is an important program that can expand for us into indications that we think are really truly meaningful. I'll let Mike talk through some of the things that he sees and what we're looking for the back half of the year.
Yeah. I think just a couple of things to keep in mind, right? In my view, PTK7 as a target or an antibody-drug conjugate is established. There are two programs that preceded us that were MMA-based therapeutics. They're not continuing in development. One, we have some insights into, the other not so much. Let's set that aside for a minute because DAY301 is a topoisomerase inhibitor-based ADC. When you have a target that's validated with respect to antitumor activity, regardless of the molecule, and then come in with a new approach, I think you're well-positioned for early development signals that warrant, you know, further investment. That's the backdrop.
I think, you know, you may or may not ask this, Tara, but we also know that others think that that's relevant or important because we know that other folks are looking at this target also with topo-based payloads. That said, an ADC is not an ADC is not an ADC. So you really have to be smart about how to think about the development of that and obviously the context of what the contribution of the molecule is. We have a very stable linker, which we think is important in this context because of the expression pattern of PTK7. As Charles has said, we've really nicely moved through dose escalation. We're at the point where we see antitumor signal even prior to having reached a recommended Phase II dose for expansion.
I think that's an sort of important point to make, as well as the safety profile that we see a clear path to moving forward into later development. Tara, to your question about what to look for at the end of the year, I think what I'd look for is the sort of demonstrable signal from us that we have taken all those data, integrated that in a way that we can articulate at least the first step towards histology-specific or tumor-specific expansion cohorts. Obviously, we'll do our best to summarize everything that I just said in greater detail. What is the sort of profile of the tolerability? What is the specificity around the anti-tumor signal?
What do we know about pharmacokinetics and any PD markers that may or may not be sort of helpful to anchor what we're seeing clinically? Those are the sorts of things.
Just to clarify, when you say anti-tumor activity, do you mean are you gonna be showing response rate? Are you gonna be showing, just, you know, waterfall plots?
Yeah
... tumor shrinkage?
Yeah. We haven't gotten to that.
Yeah
... degree of specificity, but like I said, what are we sharing that supports or buttresses our investment decision to expand into tumor-specific cohorts, and we'll get into all those details near the end of the year when we have them.
Okay, that sounds great. All right. I think we can move to Emi-Le. I know you guys acquired this from Mersana and, you know, I used to cover that, very familiar with the development progress of that asset. I think the biggest question that I'm getting from folks and that I would love to hear as well is why ACC and not TNBC?
This is a great question. From our standpoint, how we looked at it from an investment hypothesis was really anchored on the ACC program. What we saw was a substantial set of data, clinical data that gave us confidence that there was a path to a new medicine there in a relatively short timeframe. A lot of pattern recognition for us in regards to the development of that program versus what we had already achieved in OJEMDA. When we looked at it from a corporate perspective, a meaningful market that we believe can add real growth to OJEMDA over the long term. That was the real anchor. We get this question too from a number of investors.
I would say that the development path that we'll focus on originally and the value that we attributed to it was solely based on ACC. We do see the fact that there's some potential opportunity in triple-negative breast cancer in a post-topo resistant setting, possibly, right? Just not anchoring it, development plans going to that. I'll let Mike talk about what he sees in ACC.
For me, this is an easy question.
Yeah.
I think it's yes and possibly yes. The reason I say that is because, as Charles said, ACC is, it's not a common cancer, but it's a dire clinical situation. The median age of presentation of aggressive ACC is somewhere around 50. A lot of young adults are afflicted. There is really no available therapy. There's certainly no approved therapies, survival is poor. There's a signal coming forward with Emi-Le that says, "This is a medicine that we have to get to patients as quickly as possible." I've been involved in a lot of acquisitions and integrations. This is the most seamless, focused effort to bring the team in and keep pushing as hard as we can, as quickly as we can for patients with ACC. That's an absolute yes.
Possibly yes is because there is, exactly to your question, Tara, an emerging unmet need for women with triple-negative breast cancer. As topoisomerase-based ADCs move earlier lines of therapy, women essentially have nothing, and there's a really nice signal in, again, phase 1 development with Emi-Le that we are well aware of. We're not going to leave women with TNBC to the side. We just need to do this in a sort of a rational, sort of sequential manner. Yes and possibly yes.
Okay. In the update that you'll have this year, are you updating any of the TNBC cohorts even in terms of safety or just focusing on ACC?
Again, yes and possibly yes. We will absolutely be sharing updated data of which we saw a fair bit more than even what was presented at ASCO last year as we did the diligence around the Mersana acquisition. That will absolutely be front and center for the scientific presentation we bring forward as well as improved safety, which by the way, I think we really need to underscore this, especially kind of with the backdrop of the first generation of the linker payload from Mersana. I'm absolutely convinced and I give the team a whole lot of credit for innovating in the context of sort of what their first clinical experience was.
When you look at a proprietary Auristatin with a novel linker, and importantly, the clinical safety data, which we'll update mid-year, showing really no hematologic toxicity, no neuropathy, no ocular toxicity with an Auristatin-based linker payload, that's really important in the context of the anti-tumor signal in ACC. All of that we'll share this year and mid-year, and like I said, when we focus on TNBC, we'll share those data at that point.
Okay, great. Thank you. I know we're up on time, but hopefully maybe briefly, Charles, you can just let us know what do you think is the most underappreciated aspect of Day One right now?
Yeah. Two things. One, I think we have a company set up with a durable growth story that has the potential to be standard of care in second line and beyond, to be fair. Two, we have great employees. The team actually listens to a lot of these things. They work hard listening to these things, and I think it's worth saying that from our perspective, as Mike noted, demonstrated during the Mersana acquisition, just really fantastic effort and work by them. They continue to execute for us, and we really do appreciate it.
Okay, great. With that, we are up on time, but thank you both to Charles and Mike, and everyone for listening.
Thanks, Tara.
Thank you.