Thank you for joining TD Cowen's 45th Annual Healthcare Conference. For this session, we have a fireside chat with Day One. From Day One, we have Charles York, the COO and CFO, Lauren Merendino, the CCO, and Elly Barry, the CMO. Thank you, all three of you, for joining me today. I just want to say to the audience, if you have questions, just shout out, raise your hand, we will get your question heard. I guess to start out, any of you, could you give us a general overview and lay of the land as it is at this moment?
For sure. First of all, thanks to Tara and the rest of the TD Cowen team for having us here at the conference today. Always great to be here. Just to start with Day One itself, Day One is a commercial biotech company focused on delivering new medicines to patients as quickly as possible. We do that through a number of different ways, but we really focus on first-in-class opportunities. You can see that through OJEMDA, our now commercial product, but also through a recently in-licensed DAY301 , our PTK7-targeted ADC. We believe our team has a unique skill set, ability to both develop and commercialize medicines that differentiates us from other people doing this. We do this in a manner that is slightly different.
While we lead with pediatrics with OJEMDA, we also look to the adult patient populations in oncology and look for opportunities where we can develop and commercialize products with equal intensity, both in adults and pediatrics. You will see that going forward throughout the presentation. Also, just to kind of recap on where we are, great momentum leading into 2025. That was really driven by a lot of success and a lot of execution in 2024. Notably, we were able to deliver $57 million of revenue in our first just eight months of launch. You will hear a lot about that from Lauren and the team as we continue here. Built the pipeline itself. We continue to enroll in the FIREFLY-2 trial. It is the front line for tovorafenib and ribociclib, pediatric low-grade glioma. Very excited about the progress there.
In-licensed a clinical ready asset, DAY301 , the PTK7-targeted ADC that we now recently announced is in a phase I dose escalation. We've cleared the first dose cohort, leading to the second now, and continue to keep moving with that as quickly as possible. Did a lot of work on our balance sheet to ensure long-term success of the company and flexibility to execute as we believe delivers value over the long term. Have over $500,000,000 in cash driven by a number of transactions that occurred throughout the quarter. Our ability to focus on and deliver on our pipeline with the currently contemplated cash in our balance sheet, plus plenty of availability, is how we look at things and how we allocate it. I think that sets it up for you.
Yeah, sure does. Okay, I think where we can start is maybe a more qualitative discussion of how the launch is going. Like things that you're hearing from the field team in terms of what is working and doesn't work to reach key high-volume prescribers, other prescribers, and how that's going to impact your efforts in 2025.
Yeah, great. I'll comment real quickly on them, Lauren, to give you a lot of details of what we learned recently. Just in general, you should hear from us that we've been thrilled with what we've been able to deliver in such a short period of time. The reception growth from the market has been really, really positive for us and something we can continue to see as steady growth going forward. I'll let Lauren comment on what we saw for the past year.
Yeah, the reception for OJEMDA has been very positive since launch. We had many physicians telling us even in advance of launch that they found the profile compelling and they intended to use it. Now, eight months into launch, we've seen that play out even to more of an extent than we expected. We shared in Q4 some data on our penetration into our key accounts. We have roughly 200 accounts that treat 90% of the pLGG patients. We've broken them into three priorities: Priority One, Two, and Three, which roughly account for about a third of the pLGG patients. Priority One, obviously, is our highest volume accounts. We now have 100% of those highest volume accounts have utilized OJEMDA since launch. That's not inclusive of EAP. That's just new patient starts. 75% of our Priority Two accounts have utilized OJEMDA.
Tremendous progress in a very short period of time. There is also a lot of potential. We have 25% of our Priority Two that have not utilized yet. Our Priority Three accounts, which are our lower volume accounts, we only have about 35% that have used. We have tremendous opportunity for continued growth. Many of those physicians tell us they intend to use OJEMDA. We are excited to continue to grow their experience in 2025. From a depth perspective, we have also seen great progress, not only in getting them to try for their first patient, but getting them to use in subsequent patients. Generally, the qualitative feedback from physicians is that they are very pleased with the speed with which they see a response for OJEMDA patients.
That is something that encourages them to use more OJEMDA in future patients.
Okay, I would say all of these are early adopters, considering the nascency of the launch itself. To get to those, I guess, third priority or third tier priority and the 25% of the second tier that you haven't reached yet, what additional barriers might there be that your team is focusing on in terms of sentiment or something else? I don't know.
Yeah, no, absolutely. There is generally, for those who have not tried OJEMDA yet, they generally fall into two categories. One category are those who are bought into OJEMDA, find it interesting, want to use it, but they are waiting for an opportunity to use it. For those who have a smaller group of patients that they are treating, this type of market, there really is not a significant amount of switching products. They tend to want to wait until a patient either progresses on therapy or cannot tolerate the therapy to try another drug. We do have a number of physicians who have told us they have a patient in mind for OJEMDA or they have a particular group of patients they have in mind for OJEMDA, and they are just waiting for that opportunity. That is one category. The second category are those who are just more cautious.
In any launch, you have late adopters who prefer to see other physicians gain experience with new products and hear what their experience has been before they try a new product. We provide plenty of opportunities for them to hear from their peers, both through speaker programs, Webexes, and also through publications, et cetera. Their confidence will build over time. From a sales rep perspective, we are seeing all these accounts on a regular basis and are there to answer their questions and address any questions or concerns they have so that that confidence builds over time.
Okay, that makes sense. From what you're saying, it sounds more like it's based on volume, if I mean, like truly actually based on volume, as opposed to like the types of patients. What I'm curious is if you have actually noticed anything like that among types of patients, like maybe someone who's newly diagnosed would wait longer. Maybe those will be later adopters or age, any other factors?
Yeah, actually, interestingly, since launch, when we look at the patients who have received OJEMDA, it's a broad range of patients from every facet. From age, from location of tumor within the brain, from whether they're BRAF fusion or V600E mutation. We've seen actually pretty broad uptake in the product. You mentioned line as well. Generally, physicians who are trying a product for the first time will use it in a later line patient. These are patients who've seen everything already and they try it there. We have seen use of OJEMDA across the gamut. Second line plus, right? We are seeing a broad range of lines as well.
Actually, I'm curious to get into a little bit more context there. Like what is available and how many things are available that could serve as one, two, or three prior lines?
Yeah, so Elly has actually treated these patients, so she can offer some perspective, but maybe I can give the headlines of what we see in the commercial setting. For patients who have a BRAF fusion, generally they're receiving a chemotherapy regimen in the first line, and then they start using targeted therapies in the second line. That oftentimes is a MEK inhibitor, and there are multiple MEK inhibitors that physicians have used. For the fusion patients, they tend to use Dabrafenib combination, which they are approved for that indication. That is now moving more into the front line setting. By the time they get to relapse, many of them have already seen that. A physician could consider going back to chemotherapy, but they are, I think, interested in staying with targeted therapies where OJEMDA is a choice.
I don't know if you have anything to add.
Yeah. In terms of available therapies, as Lauren was, there's very little that's approved per se, except specifically in the V600 mutation space. This is a disease in pediatric oncology in general where there's a lot of comfort around off-label use. Because there are several MEK inhibitors available and other types of targeted therapy, they are comfortably used off-label, particularly the MEK inhibitors, because they've been around for quite some time. The availability of targeted agents, MAP kinase targeted agents, chemotherapy, it's generally been carboplatin, bendamustine, and other medications that may be available on study. Patients tend to cycle through these over the course of their disease because it's such a long, latent disease.
Okay. While we're on physician feedback, have you heard anything good or bad on tolerability?
In general, our tolerability profile is very well received. I think there isn't a lot there that is surprising or something that they can't manage through. The one area that I think is new to physicians is the data about growth velocity. There are some patients who, while on OJEMDA, do see a reduction in the pace of their growth. There has been recent data that Elly can speak more to that shows that growth rebounds after treatment is either paused or stopped. Helping physicians understand that dynamic has been something that I think there's been an educational curve on because it is something they don't experience that often.
Yeah, as Lauren mentioned, we've put out a couple of data sets from FIREFLY-1 and are continuing to follow those patients, obviously, over time. Consistently, as we gather more and more data as patients come off therapy or pause therapy, it's a very consistent story with respect to catch up or increase growth velocity after stopping OJEMDA. Obviously, we'll follow those patients over time to see where ultimately their ultimate height ends up. It's all very encouraging. As I said, we'll continue to follow those data over time. Okay, great. It sounds like the launch is going very, very well. Congrats on that. Now that begs the question of what kind of growth can we expect in 2025? Do you think it's mostly going to be patients continuing on drugs? I know that they can stay on for a considerably long time.
I guess the question that I'm getting at is to what extent do we think that more new patients can add?
In general, when we think about this disease and this disease setting, given some of the differences from adult oncology that we see in the pediatric setting that Elly and Lauren are talking to, overall, you should see consistent, steady growth over time. That's really built on this concept of patients going on therapy, building a base in any one individual timeframe, and layering the additional adds on that base over time. Of course, there'll be some modest amount of discontinuations and/or compliance changes, but that's really how we view this market as a steady growth over time.
Can I just add to that? When you think about the pLGG marketplace, specifically the relapsed/refractory marketplace, we estimate that there are 2,000-3,000 patients at any point in time who are receiving therapy. There is also a larger group of patients that are in watch and wait. Only if their disease progresses will they receive therapy. It is kind of a dynamic population. In Q4, we released that at the end of Q4, we exited the year with 280 active patients on drug. If you do some quick math there, that is roughly 10% of that 2,000-3,000 population. While we are extremely proud of what we have delivered so far, it has exceeded external as well as internal expectations, to be honest. There is so much more potential in this market, and that is what is exciting for us.
The year 2025 is all about continuing to drive for those who have not tried to try OJEMDA and for those who have to build out use in more patients. We expect to continue to grow throughout the year.
Okay. How should we think about or factor into our expectations like patient discontinuations? At what rate are those occurring? Is it consistent with a clinical trial experience? What are the primary reasons that a patient would come off drug?
Yeah, thanks for that. First, from a discontinuation perspective, I think that it's important to remember that in our clinical studies, the median duration of therapy was about 24 months. That means that about 50% of patients were on treatment at 24 months. There are some patients who drop off throughout therapy. Sometimes that is because either they didn't see efficacy. Although we have a clinical benefit rate of 81%, that still means there's 19% that don't see clinical benefit. They're likely to drop off early or if they have an AE that they can't manage through. There are discontinuations along the way. With a long duration, with a median duration of therapy around 24 months, it is much longer than you see in many other tumor types.
Ensuring that patients are supported along that journey so that they can get their optimal duration is important. What we've seen so far, again, we're only eight months into launch. In the early months, you only have a limited number of patients on therapy. We maybe have about six months of discontinuation data that's solid. When we look at that, we do see that it's consistent with what we would have expected based on what we saw in the study. As Charles was describing earlier, we do have a number of patients continuing quarter over quarter. As you think about it, my team is focused on driving new patient starts because that continues the growth trajectory in the future.
The reality is that each quarter, new patient starts represents a smaller portion of the revenue delivered that quarter because we have so many patients continuing from previous quarters.
Yeah, definitely understand. It's very, very early. You do have some patients that have been on for quite some time from the early access program, right? I guess one of the biggest questions that I'm getting from people is, as we're approaching that 24-month, I almost said weeks, that 24-month timeframe, are patients going to come off drug then, I mean, even by choice and take a drug holiday, for instance?
Yeah. There are a few things packed in that question. First of all, from an EAP perspective, at the time that we transitioned those patients to commercial drug, the average duration on treatment was about six months. We had about 15% of the EAP patients with over a year. Some of those patients will reach 24 months in the next year or so. At that point, they have a choice as to whether to continue or to pause and see if their tumor has senesced, right? Elly can speak to the rate at which that was done in clinical trial, but that is yet to be seen from our perspective in the commercial setting.
I think you asked too, what are the reasons for pausing or discontinuing treatment? I think as you're reaching the two-year mark, and it's an individualized decision between the physician and the patient's caregiver. If that patient has been tolerating treatment well, is otherwise doing well, I think there is a critical question to ask around where their tumor is and the sensitivity of structures around the tumor. I think there are some families that the idea of coming off treatment if a patient's doing really well, if they're tolerating the drug well, is absolutely terrifying. They choose to continue. If the patient has done well, tumor has shrunk, even if they're tolerating the therapy fine, there is overall a desire to minimize treatment, especially in young patients.
After two years, it is desirable and acceptable to pause and see how that patient is doing. Then with the idea that you may be able to recapture them with the same treatment if their tumor does start to continue to grow once they come off.
If you had to, I mean, you treated patients yourselves. If you had to put a % to it, of the population, what is the % that would be terrified to come off, and what is the % that likes to minimize treatment?
Goodness. I think it's probably a larger percent that wants to minimize treatment overall. I mean, I think that's just, again, it's the nature of the patient population. I don't know in terms of the percent that's terrified. I can tell you from the FIREFLY-1 data, there's 10%-15% of patients who continued beyond 26 cycles. That's a data point. I can't tell you that's because of fear, but.
It's hard for us to know what's going to happen in the commercial setting, right? I mean, we have clinical data. It's useful, and that's our best data point for now until we can continue duration and have the patients on. There will be some decisions like there are throughout the course of treatment, and it's just hard for us to give concrete answers on now. It's not a desire to not want to. We'd love to, but we need the timeline in the commercial setting to just mature a bit as well.
If you had to pivot.
I wouldn't answer.
I mean, thinking about it just based on the feedback and what you know about the patient population, do you think the ultimate duration of treatment can be longer than 24 months? If so, how much longer would you expect?
Yeah, I think relying on what we know, again, the clinical trial is the best data we have on that. It's that 15%-20% that Elly referred to in regards to that do stay on longer. Tough to know exactly what's going to happen in the commercial setting.
There are some patients who will be reached out. Even if they do choose to stop, if their tumor regrows, they haven't burned through that therapy yet, right? Oftentimes, we've seen physicians go back and use the same therapy. What the lifetime duration is for a patient, I think, is yet to be seen.
Okay. I guess to go back to this growth question, I think it would also be helpful to understand cadence throughout the year. If you expect there are any particular types of impacts that could happen in Q1, Q2, Q3 that we should be looking out for?
As far as seasonality?
Yeah, seasonality, Q1, the insurance resets, vacations in Q3, things like that.
The short answer is no, but Lauren, please remind me.
Yeah, it's still early for us to know any seasonality impact that is consistent year over year. What I will say is that around the holiday season in Q4 with Thanksgiving and the year-end holidays, physicians are human, right? They take vacations and holidays just like the rest of us. With fewer days in the office, there is less opportunity to start new patients. That's true for any product. I don't really consider that seasonality too much, just the way the calendar works. In January, you do have a reset of deductibles as well as patients may opt in for a different payer, right? We have programs in place that help to smooth that. First and foremost, the copay card. We have a copay card that takes the patient's copay for commercial patients down to as little as $0.
We also have coverage interruption programs. If a patient switches payers and that payer is taking time to make a decision on coverage, we can bridge that gap for them so that they have continuous therapy. Both of those programs were in place well prior to January, but certainly play a big role in January.
Okay. I know you're not providing guidance. It's just too early to do so. That's a smart decision. I am more so interested in getting inside your brains to see really what would be the metric that you'd want, that you're thinking internally that would make you say, "Okay, we're ready to give guidance now." Is it just timing? Is it a particular metric that you're actually looking for or something else?
This question comes up a lot, to be honest with you. You're correct. We've been clear about the fact that we don't intend on providing revenue guidance. The underlying reasons for that are really driven by lack of experience in the commercial setting for us and our ability to be able to, when we do provide guidance, be able to discuss it with a level of certainty that we feel more comfortable, even though it's forward-looking and a level of credibility that we want others to rely on, to be fair. It's an important thing for us. When we look at that, what does that mean? How does that get operational without too much into the details of how things work?
A longer timeframe to understand the market, additional understanding of continued growth and how we look at that and how we can articulate that in a manner that helps are all key items. Really just getting comfortable with the data and the patterns themselves that we can use us to analyze and actually drive what we think should happen with the future given the activities that we know, duration that we know, additional items. It is very front of mind for us. We do discuss it internally consistently. We do talk about it on a regular basis of what would make sense and what does not. We're very aware of the ask in regards to that.
Okay. Based on that internal thinking, how comfortable are you with current consensus, which is about $170 million for 2025?
We look at consensus like everyone else does. We make sure we monitor it, make sure we understand it. We talk to our analysts on a regular basis. Hopefully, you believe that. Again, can't comment on guidance. Can't comment on consensus if it ultimately results in guidance itself.
Okay. I understand. All right. We have four minutes left. I do want to get to PTK7, but I also want to touch on the frontline opportunity and how much you think it could actually add on top of current second-line usage. I mean, are you seeing any off-label use in the frontline yet? Even if so or if not, really, how much could that frontline opportunity add to the second line?
Yeah. As we mentioned earlier, the relapsed/refractory, there's about 2,000-3,000 patients on treatment at any one time. In the frontline, every year, there's about 1,100 new patients. We do think it's a significant opportunity, but relapsed/refractory is really important to us as well. As far as off-label use, we don't have complete transparency into that data into line of therapy, right? We only have a subset for those who enroll in our hub services, and there's a voluntary field that they can fill in. We don't have complete transparency, but from what we have seen, it's been very limited use in frontline. We still see that as a significant opportunity. When FIREFLY- 2 reads out, I think there'll be a lot of interest in that data to determine how physicians make their choices in frontline.
I'd just add a couple of key things on top of what Lauren said in regards to how we think about this. Because this is a unique setting, unlike adult oncology settings where often the duration of treatment is less than a year and substantially less than a year in a lot of cases, we expect treatment to be over the course of months and years. Because of that, the frontline opportunity continues to build just very similar to the relapse days. We get a very balanced overall look when you just do basic math in regards to incidence and duration assumptions versus the relapse setting. It's very substantial for us in addition to the fact that clinical trial itself should, we hope, will yield some positive results.
Yes. We're also all very excited to see it. I mean, we're running out of time, but I really want to give you a chance to talk about the PTK7 ADC. It's something that's generating a lot of excitement. Others are picking up their own programs in PTK7. Can you talk about just as quickly as you can, compare and contrast it really to previous ones like Pfizer, AbbVie, and what differentiates this one?
Yeah. Let me start in general with a high level from a corporate perspective of how we viewed it. Elly, please jump in at any moment and add some pieces. From our perspective, this is a unique asset that after looking at hundreds of different opportunities for in-licensing, one that really jumped out to us, clinically validated as far as the antibody target itself with PTK7. You highlighted the Cofetuzumab experience where we thought there was some real clinical data there that showed response in patients and target engagement, but a limited therapeutic index. Our theory and thesis when we looked at this particular asset is that the changes in the linker payload will give us the opportunity to see the same efficacy we saw from the overall standpoint, but not limit the therapeutic index and give us a unique asset here.
I really liked it from that perspective, really liked it from the fact that we can work and target in adult populations that we think have real value and also have a pediatric angle too, which is very important to the company itself. All those things lined up and paired with the clinic-ready nature of it and our ability to drive it into the clinic and control the clinical program, which we think is unique to us, is really important.
Yeah. Just to expand a little further, I mean, I think we think our differentiating characteristic, at least relative to Cofetuzumab, is the linker payload. We think a better tolerated payload with exatecan driving that therapeutic index so that we'll get deeper responses and longer durations of treatment that will benefit patients.
We have seen some nice movement since we have been licensed, we have seen some nice movement with PTK7 ADC specifically with a couple others coming to market or coming to the clinic soon with some assets. Still leaving us with a potential for a first-in-class asset, though. We like our position.
Definitely. Yeah. That is something that is going to generate excitement for a long time to come. Unfortunately, I wish we could talk all day about this, but we have run out of time. I thank you, all of you from the Day One team for being here. Thanks, everyone, for listening.
Thanks, Tara.
Thanks.