All right, let's go ahead and get started. Welcome, everybody, to the J.P. Morgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at J.P. Morgan. I'm joined by my squad: Priyanka Grover, Malcolm Kuno, and Ratih Pinhasi. Presenting next is Day One Pharmaceuticals. I'm presenting on behalf of the company we have CEO Jeremy Bender. Jeremy.
Good afternoon. Thank you, Anupam, and thanks to the J.P. Morgan team for the opportunity to be here today. I also welcome all of you in the audience, as well as those who are listening in virtually. My name is Jeremy Bender. I'm the CEO of Day One. I'm excited to tell you about the company here today. Joining me are a few of my colleagues who can answer questions along with me in the Q&A session. That includes Lauren Merendino, our Chief Commercial Officer, Charles York, our COO/CFO, and Elly Barry, our Chief Medical Officer. So let me tell you at the start about the name Day One. Day One comes from the talk that pediatric oncologists have with families on the first day of the diagnosis of a child with cancer. And that's the inspiration we have as a company.
Our goal as a result is really to make all Day One talks involving physician conversations with newly diagnosed cancer patients to be more hopeful. I'll talk a bit more about how that gets translated in the core business that we have here at Day One. Before we begin, I'd like to emphasize that I will be making forward-looking statements during the presentation here. I'm going to start with our mission statement. Inspired by the urgent needs of children, Day One creatively and intentionally develops new medicines for people of all ages with life-threatening diseases. I emphasize all ages because it's important to note that though our initial product, Ojemda, is focused on pediatric cancer patients, our future programs will pursue with equal intensity not just in children, but also in adults. Our initial work has yielded some early but remarkable results.
In 2024, we became a commercial company due to the approval of Ojemda in relapsed refractory pediatric low-grade glioma. I will tell you more about that indication and about our early commercial efforts as we go through this presentation. Our goal is really to expand the number of new medicines that are available for patients and that have the opportunity to become clear standards of care, and we do that through in-licensing efforts and through the advancement of programs that have both first and best-in-class potential. We've been successful to date in those efforts. In a mere six years since our founding, we now have a commercial product on the market, and that comes three years after our initial public offering in 2021. All of the work since our founding and to date has given us a compelling opportunity to work with our portfolio to build long-term growth and sustainability.
That effort has really resulted from two key facets to our business. The first is that we've got an expertise in the oncology development, registration, and commercialization area that we believe is second to none and deeply valuable to our current programs and to our future programs. The second is that we have the processes and the people to identify new programs, in-license them, and establish potential first and best-in-class medicines. That second piece is really critical because as a company, we do not have an internal research and discovery platform. So that capability, paired with our progress in 2024, sets us on a clear path to growth this year and beyond. We made significant progress across all facets of our business in 2024. First and most important was the approval and launch of Ojemda here in the U.S.
We also established an important partnership with Ipsen that will pave the way for patients who are living with relapsed or refractory PLGG outside of the U.S. to access Ojemda. We also made substantive pipeline progress in 2024. We advanced our Firefly II trial. That's a trial of Ojemda in the frontline PLGG setting, and we acquired DAY301, a PTK7-targeted antibody-drug conjugate that's now in a phase 1A clinical trial. We were able to accomplish all of those goals and at the same time strengthen our financial position and our balance sheet. We ended 2024 with over $500 million in cash. Our execution in 2024, coupled with our capabilities, sets us on an attractive path for growth.
That path for growth will be driven by increases in revenue, by potential indication expansion, and by potentially impactful clinical data sets and pipeline programs, as well as continued strong financial performance. Our agenda in 2025 flows directly from those growth opportunities. Our first priority for this year is to continue our commercial success and to continue growing Ojemda revenue. We see continued opportunities to grow the prescriber base for Ojemda, as well as to reach more of the patients who may benefit from Ojemda treatment. I'll provide our net revenue results for 2024 in a subsequent slide, and in our quarterly call for Q4 later in this quarter, we'll provide some additional details around our commercialization performance in that fourth quarter. Our second priority is to continue to invest in and to advance our pipeline programs.
The Firefly II trial has the potential to demonstrate the clinical value of Ojemda in both frontline patients and thereby to allow us to expand the indication for Ojemda here in the U.S. and with our partner Ipsen outside of the U.S. as well. Our newest program, DAY301, has the potential to address medical needs for cancer patients, both adults and pediatric, across a wide variety of tumors. Our final priority is to maintain a strong financial position. Our performance in 2024 provided us with the ability to operate, to invest, and to build a more advanced pipeline. We will take advantage of our cash position and our growing revenue stream to continue investing in and building the company. With that, let's take a look in more detail at Ojemda, our foundational opportunity for growth.
I'll start with an overview of relapsed refractory PLGG, the disease for which Ojemda is approved. PLGG is the most common brain tumor in children, and the majority of cases are driven by changes in the BRAF gene product. BRAF fusions and rearrangements account for approximately 80% of these alterations, and BRAF mutations, V600E mutations, account for approximately 20% of those changes. It's important to note that at the time of diagnosis, the vast majority of children will have biopsies to determine the underlying cause of tumor growth, and that allows us to prospectively identify those patients who may be able to benefit from Ojemda at the outset. The clinical course of PLGG is distinct from what you see in other oncology settings. This is a tumor that grows slowly and relentlessly.
The goal of treatment is to control that tumor as much as possible and allow the child who has that tumor to get into adulthood with as few neurological and developmental challenges and treatment issues as possible. These children, once they do get into adulthood, typically observe the cessation of growth of the tumor, such that the major goal is to preserve as much function as possible until that point. Though surgery is, wherever possible, an important first step in treatment, the majority of PLGG patients will require systemic therapy and will often require multiple lines of systemic therapy. I'll talk about the patient populations in both that frontline and that relapse setting in a moment. Because this is a disease characterized by relatively high survival rates and because this disease includes the name low grade, there tends to be a misconception that PLGG is a low-impact disease.
This could not be further from the truth. Pictured here is Nora. Nora was diagnosed four years ago at age seven with pediatric low-grade glioma. She was living the life of a normal, healthy child when, on vacation, while reading with a family member next to a lake, the words in the book that she was reading completely disappeared from her vision. Obviously, a very startling experience, and within days, Nora was diagnosed with PLGG. This, of course, transformed her life and also the lives of her family members. For a couple of years, she endured intensive treatments to manage the impact of her tumor. That tumor impact included severely impaired vision, as well as challenges to walking and gait due to pressure by the tumor that she had in her brain on her optic nerve.
Nora's family's lives were transformed by this diagnosis as well due to frequent MRIs, what seemed like endless physician treatments, blood draws, EKGs, and other tests. She also experienced social challenges due to changes in her appearance. That was driven by her glasses and by the fact that she has real struggles walking at that point. Fortunately, Nora's tumor is stable now, though her family members carry with them the fear that the tumor will regrow, and that's because the majority of patients with PLGG will experience tumor progression and need additional treatment throughout their childhood. This is the reason that we focus on not just the treatment at any one given point, but the ability to have an impact on the full treatment journey for patients like Nora, as well as looking for solutions that don't cause both short and long-term toxicities.
In April 2024, Ojemda was approved by the FDA for patients like Nora for the treatment of relapsed or refractory PLGG in patients six months of age or older harboring a BRAF fusion rearrangement or a BRAF V600 mutation. Ojemda's product profile holds significant appeal for physicians and for patients and their families alike, and the reasons are fairly simple. This is a new medicine that treats both BRAF fusions and mutations. It's the only approved medicine to do so. It can be used at any point in a relapsed refractory PLGG patient's journey, and it's an oral tablet that's taken once weekly with or without food, so no food effect from Ojemda. There's also a suspension formulation that allows for patients as young as six months of age to take Ojemda, which is important because many of these children are diagnosed quite early in life.
It's also a generally well-tolerated therapy. We've had great early progress with physicians and with the payer community since our launch last year. We have a focused and efficient sales force. The physicians who treat PLGG are concentrated in pediatric and academic centers. That accounts for approximately 200 offices or accounts. In those 200 offices or accounts, in which there may be multiple prescribers, about 90% of patients who are treated in the U.S. for PLGG are contained. We have a high level of awareness for Ojemda with physicians. That awareness has grown substantially since launch and is virtually universal among the physicians who treat PLGG patients. Further, our payer coverage has been excellent. Since launch, we've achieved approximately 80% reimbursement approval across all payers. Remarkable early progress for a product like this, an oncology product.
So our early execution in the commercial setting has led to steady growth in Ojemda sales. That's come from a steady flow of new patient starts, as well as a high percentage of patients who are staying on treatment once they've started Ojemda in that commercial setting. I'm going to talk about the sales figures, but I also want to talk about the patient population that's addressable with Ojemda here in the U.S. On the left-hand side of this page, you see a breakdown of the incidence of PLGG, and the incidence of BRAF-altered PLGG patients who will require a systemic therapy is 1,100. On the right-hand side is our estimate of the relapsed refractory PLGG patient population. The lack of a previously approved therapy in this disease or an ICD-10 code that specifically describes PLGG patients makes precise estimates of the specific patient population a challenge.
We've spent many years assessing what that population looks like, and we've come to appreciate the substance of the overall opportunity. We estimate that the relapsed refractory BRAF-altered treatment-eligible population is 2,000 to 3,000 here in the U.S. And less than a year into launch, we're confident that we've only scratched the surface of those patients who are already on treatment with Ojemda and who are living with relapsed refractory PLGG. Today, we announced unaudited fourth quarter and 2024 net product revenues. Our 2024 net product revenues total $57 million. This represents approximately eight months of sales, given that Ojemda was approved in late April of 2024. For Q4 2024, this was only our second full quarter post-approval and launch, represented another quarter of consistent and steady growth for Ojemda. Q4 2024 net product revenue was $29 million, which represents roughly 44% growth versus Q3 of 2024.
In the fourth quarter, we also achieved modest improvements in our gross-to-net deductions. And that was driven by CMS agreeing that Ojemda is approved exclusively for pediatric indications, which has resulted in a decrease in the rebate percentage applied to both Medicaid and 340B sales. That decrease is from 23.1% to 17.1%. So important commercial outcome for us for Ojemda. Our commercial plan for Ojemda going forward in 2025 is simple and is focused on really three key efforts. The first is expanding our prescriber base. The second is working to establish Ojemda as the standard of care in second-line relapsed or refractory PLGG patients. The final objective is to support physicians, patients, and caregivers to allow for the optimal duration of treatment with Ojemda. We also continue to focus on enrollment in our Firefly II trial. This is a global phase three trial in frontline PLGG patients.
This slide shows the study design, and what I'll remind you is that this is a randomized phase 3 trial comparing monotherapy tovorafenib or Ojemda with one of several chemotherapy regimens. It is a global trial in many countries. We have over 100 sites globally enrolling. The primary endpoint of this trial is overall response rate as assessed by RAPNO. A key secondary endpoint for this trial is progression-free survival. We made great progress in 2024 with both site expansion and enrollment, and as a result of that progress, we've now guided to the timing for full enrollment for this trial. We anticipate that we'll have this trial fully enrolled in the first half of 2026.
In June of 2024, we also announced the expansion of our pipeline with the acquisition of DAY301, a potential first-in-class clinical stage ADC targeting PTK7 in solid tumors for both pediatric and adult patients. The IND for 301 had been cleared by the FDA at the time that we acquired the program. PTK7 is a highly expressed tumor antigen in a broad range of adult and pediatric solid tumors. It's been validated as an ADC by clinical results for a Pfizer program. We believe that that program is no longer in development due to a narrow therapeutic index resulting from the ADC construct that Pfizer employed rather than from the target. That program was called cofetuzumab pelidotin. DAY301 has been optimized to achieve a wide potential therapeutic index. And that therapeutic index is supported by all the preclinical data that we have available to us today.
This is a program that has both first and best-in-class potential. It's built around a proprietary monoclonal antibody coupled to a novel hydrophilic linker and an exatecan payload. Comprehensive preclinical evaluation showed tumor regression at tolerable doses in multiple patient-derived xenograft models. It's also an ADC that has favorable stability as a construct and a large exposure-based therapeutic index based on data from cynomolgus monkey tox studies. Importantly, last week, we cleared the first dose cohort of the phase one A trial for DAY301. And we're now enrolling patients in the second dose cohort in this trial. Once we have a dose, we'll move towards dose expansion cohorts and anticipate selecting patients based on PTK7 expression. We'll focus on those patient populations that continue to have limited therapeutic options.
And that may include endometrial cancer patients, platinum-resistant ovarian cancer patients, squamous non-small cell lung cancer patients, and other patient populations, including a number of pediatric indications. PTK7 is broadly expressed. And the opportunity for development, if we're able to establish DAY301 as an active agent with a therapeutic index that's favorable, will allow us to pursue a number of different opportunities. In summary, we're poised for a productive year of growth and execution in 2023. OJEMDA remains in the early stages of launch with significant growth remaining throughout this year and the years beyond. We'll continue to execute on our clinical development pipeline.
That includes the FIREFLY-2 trial as well as DAY301. And we'll continue to expand our portfolio through acquisition and in-licensing opportunities with those assets we've used strategic and those assets that have the potential to be differentiated in first or best-in-class. Overall, we are on a path to durable growth, and that's focused on not just the pipeline portfolio, but also our revenue growth and our capital and balance sheet, which is allowed by the efficient capital model that we have, and to that end, we anticipate maintaining a strong capital position with independence from future capital raises. Thanks very much for having us here today. For your attention, we'll now turn to Q&A.
Thanks, Jeremy. I just want to remind folks that there's three ways to ask a question, right? So there's the old-school way where you just raise your hand and I call on you. There's the one where you send me an email and I ask it for you. And then there's the one where you put it in the portal and I'll ask it on your behalf, right? So congrats on the quarter, Jeremy and team. Just wanted to see what you were seeing in the fourth quarter in terms of month-over-month script growth. Were there any impacts on the refill rate around the holidays? Any dynamics that we should be considering?
Yeah. So, upfront, we'll wait for any quantitative discussion on some of those details until we do our full quarterly results. But Lauren, if you want to comment qualitatively on the quarter, that would be great.
Yeah. Overall, Q4 was a strong quarter for us, as you can see from the results that we delivered. Continued to drive growth and penetration into the market. And yeah, just really proud of what we delivered. From a holiday impact, we did not see any significant holiday impact to our overall sales. And yeah, we ended the year strong.
Are there any 340B considerations, though, from a seasonality perspective when you think about reauthorizations and refill rates in this market specifically?
Yeah. So it's hard to say. This will be our first January on the market, obviously, but reauthorization happens in many markets, and so we've been able to prepare for that. One of the ways that we've prepared for that is having a copay card in place, and we have a limited distribution model that leverages two SPs, and they are able to implement that copay card immediately with patients, and so for those patients who have a reset in their deductible and have a higher deductible early in the year, the SPs are able to navigate that by providing the copay card, which brings the patient's copay down to as low as $0.
And then what are you seeing in terms of uptake of the product, say, in academic centers versus, say, more community centers?
Yeah. So thanks for the question. As Jeremy mentioned, this is a market that's very concentrated. So 200 accounts treat 90% of the PLGG patients, which enables us to have a very efficient commercial model. We have a sales team of 18 sales reps, which is relatively small in the oncology setting. But that enables us to reach these accounts. And we've been able to see penetration both on the academic and the community side. Some of these physicians in the academic setting had experience from our clinical trials. But it's important to note that as of our earnings in Q3, we reported that over 80% of our prescribers did not have experience with Ojemda prior to launch. So we have many new prescribers who have tried the product for the first time post-approval.
Question from the audience? Yeah, go ahead.
Maybe I'll just speak loud. So for the ADC program, is it a plan to do some kind of basket trial or do you have any indication?
Yeah, let me just repeat the question in case people didn't hear it online. It's really what the plan is for the development of 301, whether it's a basket trial and how we're proceeding. Elly, do you want to talk about the phase one A and the plan?
Sure, so in phase one A, our dose escalation, it is a number, a range of tumors that are known to highly express PTK7, but from there into dose expansion, we will be going into histology-specific indications based on our phase one A data and some of the preclinical data that we're generating.
Additional questions from the audience? Maybe actually following up on his question, which is, you did get DAY301 from business development. Just strategically, how are you thinking about business development in 2025?
Let me start by saying that we continue to be very active on the BD front, but let me ask Charles to answer the question more specifically.
Great. Thanks, so 2025 for us is really an interesting year from a business development perspective, and that's predicated on the fact of all the work and the achievements that really fell through in 2024, so in addition to the approval, there was capital formation due to a number of transactions that totaled about $400 million. That's led us to a balance sheet that's extremely strong and one that we plan to leverage.
Very consistent to our conversations and our messaging previously, we very much look forward to being very forward-thinking about additional business development opportunities. Being able to build the pipeline is a critical goal for us and one that we will allocate both time and dollars to to ensure that we have continued success there. Having an asset or two additional in the pipeline, we think, is really key to what Jeremy noted earlier in regards to building a company with a foundational Ojemda, but a pipeline for durable growth.
You mentioned that from a cash position standpoint, you are good to profitability. Does that assume some transactions on the BD side?
Yeah. I think, first off, let me nuance my comment a little bit. We do have the ability, we believe, to continue to advance the business and grow it in the absence of future fundraising. Whether or not, or sorry, at what point we would reach profitability under that scenario, I think we're still looking at what our expense basis is. And in particular, I'm hedging on that profitability question on a pump because in the end, if, for example, 301 becomes a program where we have to invest or want to invest across a very large number of phase two expansion cohorts and subsequently randomized trials, it's certainly possible that we'll either raise more capital or defer any profitability to a future date. That being said, we feel like we have a very strong financial position and with growing revenues that we're in a solid long-term financial scenario.
Questions?
Yeah. I want to add anything Charles there on top of that. End of the quarter, Q4, end of the year here with about a little over $530 million, which sets us in a really nice position overall. Important to note too, currently no debt, relatively modest royalty rate on our lead product for Ojemda. So some really nice levers for us to be able to access that capital in the situation like Jeremy described.
Questions from the audience? Yeah, go ahead.
I would like to say thank you. It turns out my grandson Henry had one of these tumors. And at age eight, weighing 34 pounds, going on Ojemda, in a year's time, he was 68 pounds. And since this was a medullary tumor, which compressed his vagal nerve, he, with the course of Ojemda, recovered vagal function, could eat at the dinner table. And because the recurrent laryngeal nerves come off the vagus nerve, his voice improved. His stridor disappeared. And I want to say thank you. It has been amazing.
Wow.
Wow.
Hey. Thank you for sharing that. There's nothing that's more meaningful to those of us up here who are working at Day One and to all of our colleagues at Day One and the investigators who have been involved to hear stories like that. Thank you for sharing it. Yeah. That was a great moment. That was the first time in 17 years that I've heard that. So that's awesome.
Thank you for sharing.
Good for Henry, man.
Yeah.
Thank you. It does make a difference. It's what you do. It does make a difference.
Really appreciate that. It's a gift. I'll take that home for quite a while. Share it with all of my friends and family. Yeah.
Additional questions from the audience? Wanted to maybe just, I guess I'm a little confused on Firefly II timelines. I think you guys have said. Oh, sure. Let me clarify. Said that enrollment expected to complete in the first half of 2026.
Correct. That's right.
But I think your partner has talked about data in 2026.
Yeah. So let me be clear. We anticipate full enrollment in the first half of 2026, which means that data from that trial will be coming 12 months after that last patient end point. There has been discussion of our partner talking about timelines. But in the end, that trial is on track for the enrollment timeline I just described.
Any final questions? Thank you, guys.
Thank you, Anupam. Thanks, everybody.