Okay, great. Welcome to the next session, everybody. We have Day One here with me. My name is Kelsey Goodwin. I'm one of the Piper Sandler, analysts. With me today I have the CEO, Jeremy Bender, and the CFO and COO, Charles York. Welcome. Thanks for joining.
Thanks for having us.
Of course. Let's start with a quick one to two-minute summary of Day One and where we stand heading into 2026.
Sure. So Day One, is a company that is really focused on developing new medicines for patients that have life-threatening diseases, with a particular focus on cancer. We're very much inspired by work that allows us to move into children who are living with cancer in addition to adults. And if you look at our portfolio, that is the focus. It's really targeted therapies that have, you know, real transformative potential for cancer patients. And the focus for the company today remains on our most advanced program, which is OJEMDA. This is a new medicine approved in 2024, in April 2024, for relapsed or refractory pediatric low-grade glioma. And the launch of OJEMDA, has been a real success for the company, and it's exceeded the expectations that we had for it. It has really driven a lot of growth, not just in 2024, but in 2025.
I'm sure that'll be the focus of much of our discussion. The next program that's in the portfolio is Day 301. This is a PTK7-targeted antibody-drug conjugate. Again, it targets PTK7, but the payload for that program is a Topol 1 inhibitor. That's in a phase I A trial now. We continue to move forward, so it's in dose exploration. And then earlier this quarter, we announced a definitive agreement to acquire Mersana Therapeutics, for a program called Emi-Le, which is also an antibody-drug conjugate. That program we're really excited about because we think it will become a new medicine in adenoid cystic carcinoma, which is a rare but really important indication and one where we think there's really significant unmet need in a rapid time to approval through an accelerated pathway.
Great. Like you said, we'll start with OJEMDA. We'll work our way through all of that. So it was approved last year, continues to gain traction. Remind us a bit about the disease course, of PLGG and maybe the treatment landscape prior to OJEMDA kind of entering the scene.
As I mentioned, OJEMDA's approved for relapsed PLGG patients. The clinical course of treatment, or clinical progression for patients that have PLGG is relatively straightforward but has some nuances, compared to other oncology indications. This is a tumor that arises in different parts of the brain. Frontline therapy, for patients for whom a total resection is not possible, right? If there is a total resection that's possible, that can be effectively curative. But the majority of patients, that's not achievable, and they require a systemic therapy. In the frontline setting, that is typically chemotherapy, and that remains a fairly clear standard of care. Once patients progress following that chemotherapy, however, there really isn't a clear standard of care for the vast majority of those patients. And that's where OJEMDA comes in.
I should also mention that the specific patients we're talking about are those who have tumors that are driven by BRAF alterations. The majority of those patients have BRAF fusions, what they're called, but there are a small percentage, 15%-20%, who have BRAF V600E changes. And we're approved in the relapse setting for both of those. And it's really our goal to make OJEMDA the standard of care in that second-line setting and beyond. Now, there are other therapies that are used, in that relapse setting, even though they're not approved, for the patient population that we have approval for. Those therapies are typically, most frequently used MEK inhibitors. So that's another, inhibitors. None of them are approved for this indication, but there are approvals out there for other, other indications in cancer. And you do see some use of MEKs in those settings.
but it's not a clear standard of care at this stage and much less data available than what we have for OJEMDA about both efficacy and safety in that, in this population.
Mm-hmm. So now with OJEMDA being formally approved, you know, what have been kind of the key learnings you're seeing as the market evolving with, you know, the entrance of a new approved therapy? And how does it, you know, what have you learned so far in the launch?
So, the learnings have been pretty significant. And I think the pace of our launch experience and the commercial performance have been, I'd say, pretty consistent with our expectations with a few important notes beyond, you know, just meeting expectations. One is that our access has been extraordinary. The ability to drive reimbursement for on-label patients and to a large extent off-label patients, as well, although we, of course, don't promote any off-label use, has been, you know, really exemplary and probably exceeded even our fairly high expectations. So that's an important note, because it does kind of translate to revenue and growth.
I think the other observation is that this is a group of physicians, and we had this expectation coming into our launch, who are very accustomed to making clinical decisions on the basis of their prior experiences.
Mm-hmm.
Not on the basis necessarily of data sets that are published and available. That's because it's been a neglected area. It's an indication for which there hasn't been significant clinical research, certainly by industry, and certainly with the level of rigor that is required to achieve an approval, you know, whether it's the FDA or other regulatory authorities outside of the U.S. The physician experiences are really critical to, you know, trial use and adoption. We knew that coming in. That's very much been the case since we've been approved and on the market. It's where additional data sets can be so meaningful and driving that trial and use. That's what we're seeing with the follow-up data that we've now published. This includes our two-year data set, which has been in our field force's hands since late Q2.
that data, both efficacy and safety, have been important updates around the performance of OJEMDA and the target product profile. But the most important aspect of those data have been the follow-up data we have on growth velocity changes that can be observed when treating with OJEMDA. And in particular, in addressing some of the concerns just because of uncertainty around the reversibility and the catch-up growth that you see off treatment for OJEMDA, both of which have been reinforced by those data sets, and were captured pretty well by our ASCO presentation on that very topic. So that's an important element. And we saw some real increase in new patient starts.
Mm-hmm.
In our third quarter, which we attribute largely to having had those additional data available for promotional efforts. Looking forward, the three-year data cut, which we just published at the Society for Neuro-Oncology Conference, a couple of weeks ago, will be important as well for addressing the next set of questions that I think physicians are starting to ask, which is, what is the long-term efficacy for PLGG patients who are treated with OJEMDA look like? And what can we expect when patients come off treatment? Will they go back on? If so, you know, do patients respond if they go back onto treatment? And our three-year data set is really helping to answer those questions in a way that I think reinforces how important a medicine this is for those patients.
Mm-hmm. Maybe then shifting to the three-year data set, I guess, what do you think were the key takeaways and what do you think would be, you know, most compelling for physicians to hear about, you know, the longer-term follow-up, watching patients come off, watching patients go back on? How does that kind of help tell the story?
Yeah. So the most important single observation from the three-year data from the perspective of prescribers, and I think families as well, is the observation that those patients who received a full 24 months of treatment on OJEMDA on our trial, this is from trial results from FIREFLY-1, and then took a break in treatment, that group of patients, when you look a year after they've stopped treatment, more than three-quarters of them, 77%, in this case, did not require an additional systemic therapy.
Mm-hmm.
What that allows for a physician to do is two things. One, it's have a conversation with families at the outset about what to expect in terms of treatment duration, in this case, 24 months, and the fact that that will, you know, provide a reasonable likelihood of that patient not requiring, you know, or their child not requiring that therapy in the next year. That's a we hear very clearly from physicians, very differentiating relative to how they think about other treatments that are available to them. So I'd emphasize that as the first component.
I think the next piece of that element is for those patients that did go back on therapy within that one-year period, those patients, A, elected to go back on OJEMDA, which we think is encouraging that retreatment, and B, we're seeing a clinical benefit.
Mm-hmm.
So it's they're responding again as they did previously.
I guess any thoughts on how long patients would then go back on therapy for those that do retry it?
No, no, we don't have any experience that would inform on that question. But I do think that the duration of treatment is one of the key questions that of course, you and others, you know, who are looking at OJEMDA as a product, have questions about. And what I would say is that what we're observing to date in the commercial setting is fairly similar to what we've seen in our FIREFLY-1 trial. In our FIREFLY-1 trial, we saw a median duration of treatment of 20, just under 24 months. And we're not far enough into the launch yet to have a true median treatment for the full group of patients that are on commercial product, who have PLGG. But we do have a cohort of patients that started our expanded access program.
Mm-hmm.
Before launch. And in our third quarter call, we provided an update on what we've observed in that EAP cohort with respect to treatment duration. And there, what we see is a 20-month median duration of treatment. And importantly, we're seeing a fairly substantial portion of those patients who reach 24 months of treatment continue on past that 24-month period.
Mm-hmm.
Those are our data elements for the EAP that really reinforce the lengthy durations of treatment we expect for OJEMDA in the real-world setting.
Okay. Got it. I guess in terms of actual prescribing physicians, what do you kind of note as different between, you know, high-volume prescribers or prescribers that are willing to, you know, treat multiple patients and are more than just, you know, "Let me try it once," versus the physicians that maybe are a bit more hesitant to even start it in the first place?
What I would emphasize overall is that the physicians who have the most experience with OJEMDA are the biggest champions.
Mm-hmm.
For OJEMDA. And so those physicians who were investigators in FIREFLY-1 and have treated many patients for years now have real conviction that this should be a standard of care. And physicians who have less clinical experience, for whatever reason, whether they're at high-volume treatment centers or whether they are not and they've.
Mm-hmm.
They've tried with one or two patients or those who are less convinced. And when I say less convinced, I mean exactly that. It's not that they're skeptics per se.
Mm-hmm.
But they have less experience than, you know, those who've really been using the medicine for a long time now. And that experience is the best correlate for, you know, how committed and how clear a standard of care physicians think OJEMDA should be in this setting.
Mm-hmm. And I guess for those that have yet to try OJEMDA, do you think it's mainly just their own idea of what off-label use with other drugs can do? Like, they have a benchmark in their head of what the performance is like versus being able to call back on specific published literature saying, you know, "Here's the reason why I'm choosing this.
So, yes. The reality is that there are not significant and rigorously run data sets for other agents in this setting in the same way that there is for OJEMDA now that it's available. So the comparator they're making in their own minds is to their own experiences with other agents more so than reference to a specific data set that they, you know, view directly and compare with OJEMDA. And so that does mean that in many ways what we're doing is engaging with physicians on the basis of their perceptions.
Mm-hmm.
Of product as opposed to true product profiles that are available and can be genuinely compared in any analytically rigorous way. That's fine, by the way. I think in the end, that's the nature of commercialization and is true in any setting where you have new medicines that are approved for a given indication. There's always physician experience with other options, that is part of the sort of commercial process and the adoption process.
Mm-hmm. Understood. Before we move on, it's the FIREFLY-2 trial in the frontline setting. I guess how do you think that could potentially expand the market opportunity and also kind of what growth levers exist from now until then?
The FIREFLY-2 trial is on track for completion of enrollment in the first half of 2026. That's been our guidance for quite some time and hasn't changed. We're expecting data from the trial in mid-2027. That's because per protocol, the analysis on the primary endpoint, which is response rate, will occur 12 months after that last patient's in. You know, with respect to growth drivers between now and then, I think there are a number. First, there is, you know, continued growth and performance for OJEMDA, commercially. And though we have not guided to any 2026 numbers, we will be providing, you know, guidance for 2026 at a later date. And there's also going to be some updates on the Day 301 program. We expect to provide, you know, clearly published data on Day 301 in 2026.
Mm-hmm.
And then beyond that, with the acquisition of Mersana, which we're anticipating to close in early Q1, Emi-Le, which is the B7-H4 antibody drug conjugate that's part of the portfolio and the real impetus for that deal, will have updates on the data for that program in ACC in 2026, as well as guidance around the regulatory timelines and path to approval in that setting.
Mm-hmm. Okay. Understood. We'll do quick on Day 301 and then leave some time for the Mersana acquisition. But for Day 301, PTK7 is the target for this ADC. I guess maybe just remind us, you know, how compelling of a target this is and how might, you know, Day 301 be differentiated from others we've seen in the space.
That's Charles to take those.
Yeah. Sure.
Perfect. So, from our standpoint, and the reason why we brought the asset in, was it was a target that we really found really interesting, potential to be first-in-class, always some opportunity to be best-in-class. We had clinical data out of a previous Pfizer program, cofituzumab, that showed some real responses in patients. And, our theory and the way we brought that in was a more modern linker payload, a topo I-based linker payload, could provide us with an opportunity when paired with the PTK7 ADC or antibody, to have an ADC that could be really unique in the field. That continues now, still remain in dose escalation as we are currently sitting here.
And we continue to do work, at that point, haven't provided guidance yet on when we'll have data, but we are planning, in the 2026 time frame, to give a better understanding of when we expect that to be.
Got it. And I guess how should we think about kind of that initial data set? You know, will there be enough kind of sample size across tumor types? How should we think about that?
I think the important thing that we are trying to establish in the initial study is to determine where we want to go for expansion arms.
Mm-hmm.
Having the clinical trial as we've designed it right now on dose escalation allows us to get to dose and schedule, of course.
Mm-hmm.
But does allow us to also test the molecule in high-expressing PTK7 tumors, of which that will determine where we're going to go for expansion arms. So we'll really use the initial dose escalation to determine some of that. It's likely to be in a lot of the indications you've probably seen before, a lot of gynecological cancers, endometrial, maybe some head and neck, a couple other areas that we think could be interesting as well. But we'll really let the data drive that.
Okay. Great. Perfect. Just enough time to switch to Mersana acquisition recently announced. Maybe just remind us the rationale for the deal. What kind of drove, you know, you choosing that as an acquisition target?
Yeah. So look, we've talked about this before, but we're active in business development. The way the company is set up for us to drive growth, we need to license or bring in additional programs that we think are interesting. This is exactly one of those programs for us. If you think about the way it's set up, it looks a lot like the program we had for OJEMDA. There's a clear unmet medical need. There's not a lot of other therapies available for these patients outside of chemotherapy. And we saw some clinical data that we think is quite interesting, showing responses, and with a safety profile that we think is manageable, particularly for an ADC. So really set up well.
You pair that with, again, a similar path to OJEMDA in regards to clinical and regulatory, opportunity for, preferred regulatory designations, including the potential for breakthrough, and a clinical path that has a timeline that we find more attractive than maybe a larger adult indication by in and of itself. Put it together, at a deal valuation that we think is really relevant in the ACC population. It was something that we thought was really nice to add to our portfolio.
Great. And I guess, how do you think about the ACC opportunity?
So, really an attractive opportunity to develop a new medicine here in Emi-Le for a patient population that is really underserved. And, when you look at ACC as an overall indication, it really does split into sort of more indolent disease and more aggressive disease. And with Emi-Le , you know, Mersana has been developing in patients that have a more aggressive type of disease. And there really are no good treatment options for those patients. So there's a real opportunity to establish a new standard of care here based on the data that we've seen for Emi-Le in that population. That data set is bigger than what was disclosed at ASCO.
Mm-hmm.
In June of this year, there were nine patients in that presentation for ACC, that is, and in our diligence process associated with the deal, we reviewed many more than that.
Mm-hmm.
We are very excited about those clinical data and do anticipate publishing those data post-close.
Mm-hmm.
In 2026, the way we think about it is, as Charles noted, a really important, rare opportunity, in the cancer setting, one that, you know, we anticipate would be a relatively rapid path to approval, you know, likely on the basis of a single-arm trial.
Mm-hmm.
single-arm phase II. As Charles noted, analogous to the approach that we took with the OJEMDA program in collaboration with the FDA.
Mm-hmm.
Real quick, I just add too, just from an overall perspective on how we thought about it, very much this program that we were looking at, not the rest of the pipeline.
Yeah. Yeah.
From our standpoint, when we view this in ACC as the key indication, we also understand the capital allocation associated with this.
Mm-hmm.
You know, there is, of course, the net cash upfront associated with the company. There's a milestone, a CVR program that has a number of different milestones. But the most recent one will be at the start of a registrational trial that we, of course, anticipate having to work on. But all taking those two, CVRs plus development costs combined, we still think to get to the point of an answer on the registrational trial itself and get the data out of a registrational trial, our investment will be at or below a $200 million point.
Mm-hmm.
So something that works really well for our size of company, with this size of potential opportunity.
Understood. Now we're running a little short on time. So maybe just thoughts on future BD opportunities, or will you pause now post-Mersana?
Go ahead, Charles. Yeah.
Yeah. Sure. So, I think this is an opportunity in the near term to, you know, reflect upon where we are. We understand that growth for us and building, continuing to build the business, means expansion outside of our own walls, given the fact that we don't have discovery. So we will remain active.
Mm-hmm.
I would also say that, you know, the things that are most interesting to us are programs that we can slot into our pipeline that really fit from a strategic perspective if they're earlier, or those that are later stage programs that are generally at or near commercial, where we can see some real accretion of value in the short term and really use and leverage some of the capabilities of the company to create synergy and also for top-line revenue growth for OJEMDA and potentially with Emi-Le as well.
Mm-hmm. Perfect. All righty. One second left with that. We will wrap up. Perfect timing, guys. Thank you so much for joining us.
Thank you.
Thanks everyone.
Thank you, Charles.
For joining us.
Appreciate it. Thank you all for coming in.