Day One Biopharmaceuticals, Inc.

Hello, ladies and gentlemen, and welcome to the day one biopharmaceuticals fourth quarter and full year 2025 financial and operating results conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. Please be advised that this conference call is being recorded. I would now like to turn the call over to Joey Peroni, Senior Vice President of Finance and Investor Relations. Please go ahead.

Thank you. Hello, everyone, and good afternoon. Welcome to Day One's fourth quarter and full year 2025 Financial and Operating Results Conference Call. Earlier today, we issued a press release that outlines the topics we plan to discuss today. You can access the press release and the slides to accompany this conference call in the Investors and Media section of our website at www.dayonebio.com. An audio webcast with the corresponding slides is also available on the website. Before we get started, I'd like to remind everyone that some of the statements that we make on this call and information presented in the slide deck include forward-looking statements as outlined on slide two. Actual events and results could differ materially from those expressed or implied by any forward-looking statements. We encourage you to review the various risks, uncertainties, and other factors included in our most recent filings with the SEC and any other future filings that we may make with the SEC. These forward-looking statements are based on our current estimates and various assumptions and reflect management's intentions, beliefs, and expectations about future events, strategies, competition, products and product candidates, operating plans, and performance. You are cautioned not to place any undue reliance on these forward-looking statements, and as accepted as required by law, day one disclaims any obligation to update such statements. Today, I am joined by Dr. Jeremy Bender, Chief Executive Officer. Lauren Marandino, Chief Commercial Officer, Charles York, Chief Operating and Financial Officer, and Dr. Michael Vasconcellos, Head of Research and Development. I will now turn the call over to Jeremy.

Thank you, Joey. Good afternoon, and thank you for joining us. We are proud to present today our fourth quarter earnings and full year financial results for 2025. 2025 was our first full year as a commercial company. With the launch and uptake of Ojemda, in pediatric low-grade glioma, we've now demonstrated we can deliver on our mission to develop new medicines for people of all ages with life-threatening diseases. Importantly, we've also now taken the initial steps needed to repeat this success with meaningful pipeline advancements. Together, the day one team achieved seminal commercial and clinical milestones in 2025 that have positioned us for accelerated growth in 2026. Ojemda continues to be the primary revenue and growth driver for the company. Enthusiasm for Ojemda among the healthcare professionals, caregivers, and patients in the PLGG community expanded throughout 2025. I'm confident we're advancing and improving the PLGG treatment paradigm and moving towards establishing Ojemda as the standard of care therapy in second-line PLGG. For the year, we reported $155.4 million in net product revenue, which is up 172% year-over-year. We achieved double-digit sequential quarterly growth throughout 2025. That translates to more than 4,600 total prescriptions for the year, which is more than 180% growth compared with 2024. We'll dive further into that performance shortly. The momentum we're seeing has given us confidence in the path forward, and as such, we are reiterating our 2026 agenda net product revenue guidance of $225 to $250 million for 2026. We are just beginning to shape the market for PLGG, and we see considerable opportunity ahead for us to continue agenda growth. This will be driven in part by the three-year data we presented at the Society for Neuro-Oncology meeting, which Mike will review in a moment. As the community gains experience with and confidence in Ojemda, we are in parallel on track to establishing a strong scientific basis for use in the frontline setting in PLGG through the Firefly 2 trial. We expect to complete enrollment in Firefly 2 in the first half of this year, with a top-line readout occurring in mid-2027. These data represent an important opportunity to define our path towards standard of care across all lines of PLGG therapy, which would open up not only the opportunity to advance patient care earlier in the treatment paradigm, but also to broadly accelerate our growth. We also anticipate global expansion for Agenda this year, with our partner Ipsen preparing for ex-U.S. regulatory approvals, including in Europe. Beyond Ojemda, we are advancing numerous potential growth drivers with our expanding pipeline. We closed the acquisition of Mursana in January and are now integrating the lead program, MLE, into our pipeline. This is a promising antibody drug conjugate with early evidence of activity in adenoid cystic carcinoma, or ACC, a challenging and rare cancer with few therapeutic options today. This program represents a very real opportunity to extend our mission into a disease area with significant medical need. We'll share a bit more about this in a few moments, and additional clinical data on MLE will be reported in the middle of this year. We also continue to generate progress with day 301, a promising antibody drug conjugate with opportunities for development in multiple pediatric and adult indications. While we are still early in development, we are seeing encouraging signals of an efficacy and safety profile that could address persistent unmet medical needs as well. We are actively advancing the program and look forward to sharing an update on that trial later this year. Finally, we've maintained a strong financial position throughout this dynamic year, ending 2025 with more than $440 million in cash. We have no debt. Our disciplined approach has and will enable us to continue investment in high-value programs that can deliver meaningful impact to additional patient communities. Taken together, we are on a promising trajectory for 2026 and beyond. Let me now turn it to Mike to review the three-year data on Ojemda.

Thanks, Jeremy. Our mission at day one is well represented by our ongoing clinical development with Ojemda in pediatric low-grade glioma, or PLGG. Notably, long-term follow-up data from our registration trial, Firefly 1, has provided critical insights to the contribution Ojemda is providing to patients with relapsed or refractory PLGG. Referred to as the Firefly 1 three-year data, these updates were presented in November 2025 at the Society for Neuro-Oncology Conference. With a median on-study duration of 40.6 months, these data confirm earlier reported results, strengthening our understanding of the durable clinical impact of GEMDA is providing patients. I'd like to summarize the highlights of these three-year data, beginning with safety. The three-year data summarized on this slide are notable for no new safety signals identified in comparison to data at the time of our initial approval. Specifically, adverse events leading to treatment discontinuation are low. In addition to rash, other low-grade adverse events include fatigue and gastrointestinal events, such as nausea or vomiting. As noted on this slide, adverse events of higher grade and frequency include decreased growth velocity, anemia, and occasional more severe rash than usually observed, and certain asymptomatic lab abnormalities, such as elevated CPK or ALT. This profile remains consistent with the current product label. Let's turn now to the efficacy data. These updated three-year data confirm the meaningful responses in patients with relapsed or refractory BRAF-altered low-grade glioma in second or subsequent line of therapy, as initially reported in Firefly 1. In fact, the 53% objective response rate is slightly higher than the 51% objective response rate at the time of the OJEMDA approval. Response durations were also meaningful, with a median of 19.4 months. The median time to response is 5.4 months. The three-year follow-up data have also revealed insights into clinical decisions taken by investigators when radiographic-only tumor progression was observed on therapy with Ojemda. Consistent with general practice patterns, the Firefly-1 study has allowed for continued Ojemda treatment despite tumor progression. All 38 patients experiencing progression while receiving Ojemda continued treatment for a median duration of 9.3 months. Of these patients, 45% demonstrated further tumor reduction after initial documented progression had been observed. These data prompted us to undertake further analyses to better understand the clinical impact of treatment decision-making in patients on Firefly1, and I'd like to walk you through those on the next two slides. This slide illustrates important endpoints designed to reflect real-world treatment decisions. In addition to objective response and response duration, progression-free survival, or PFS, was assessed in Firefly 1. PFS is a composite endpoint encompassing either tumor progression or death. And in many settings, PFS is a meaningful measure of clinical benefit. However, the data I've just shared with you challenges this assumption in pediatric low-grade glioma, where treatment often remains ongoing despite radiographic evidence of tumor progression. In PLGG, other time-to-event endpoints may better reflect clinical benefit compared to PFS. Two other important time-to-event endpoint assessments are introduced on this slide. Let's focus on time-to-next treatment, or TTNT, which is shown across the top of the slide. Like PFS, TTNT is a composite endpoint measured from the date of onset of the first dose of Agenda. However, unlike PFS, TT&T defines the initiation of the first subsequent anticancer therapy as an event versus tumor progression. The next slide shows these endpoints analyzed using the three-year Firefly1 data. There are several analyses on this slide, but I'd like to call your attention predominantly to the dark blue, or TT&T, and the gold, or PFS, Kaplan-Meier curves. Physicians, patients, and their families work together to balance treatment of patients' low-grade glioma with meaningful treatment-free observation periods in between therapy. For some patients, this clinical balancing act may go on for a couple of decades. The three-year Firefly1 data demonstrate this critical aspect of patients' optimal care. Let me walk you through these points. The gold curve illustrates progression-free survival in Firefly1. The median PFS is 16.6 months. The light blue curve sitting more or less on top of the PFS curve is an exploratory analysis where we've restricted progression to radiographic progression only. We're calling this our PFS. Clearly, most tumor progression events in Firefly1 are radiographic only events, which is why these curves are more or less on top of one another. In contrast, let's look at the two Kaplan-Meier curves or KM curves at the top. Recall from the prior slide that in the time to next treatment endpoint, tumor progression as an event is replaced by the initiation of subsequent anticancer therapy. When we make this substitution, we can easily see the differences in the two curves. The median TTNT is 42.6 months versus the 16.6-month median PFS previously noted. The purple KM curve referred to as clinical PFS simply confirms the TTNT analysis by showing PFS based upon clinical progression events only. In short, these analyses from Firefly 1 illustrate standard clinical practice in the care of patients with PLGG. In an effort to optimize treatment over extended periods of time, treatment decisions are made based upon clinical tumor progression, not simply measurable change in tumor size based upon radiographic imaging. These data show that Ojemda meaningfully contributes to physicians' treatment armamentarium by extending patients' time to next treatment, thus improving their ability to craft the optimal treatment decisions for their patients. These time-to-event analyses are being incorporated into the ongoing randomized Phase III Firefly 2 trial in the frontline treatment of patients with PLGG, allowing the optimal characterization of the clinical benefit of Agenda for these patients in frontline treatment in comparison to standard chemotherapy regimens, which is the control arm in the trial. As previously noted, we anticipate full enrollment in Firefly 2 in mid-2026. These impactful data strengthen our knowledge of the durable clinical impact of GEMDA's providing to patients. Let me now turn it to Lauren to address how this is translating to the continued strong market uptake of a GEMDA.

Thank you, Mike, and good afternoon, everyone. As the clinical data has continued to mature throughout 2025, we have delivered impressive results throughout the year, culminating in an especially strong Q4. This performance reflects the growing confidence in Ojemda within the physician community and its increasing role as a valued treatment option for patients with relapsed or refractory pediatric low-grade glioma. Let me walk you through the key drivers behind this growth. With less than two years on the market, we are proud of the meaningful progress Ojemda has made in improving the care for patients suffering from pediatric low-grade glioma. Our strong growth across 2025 reflects steady growth in physician experience and adoption and an increasing number of patients persisting on therapy. In the fourth quarter, net product revenue reached $52.8 million, representing 37% sequential growth over Q3. For the full year, net product revenue totaled over $155 million, with double-digit sequential quarterly growth throughout the year, and 172% growth over 2024. This performance was driven by clear and compelling increases in demand throughout the year. Fourth quarter prescriptions exceeded 1300, representing 11% growth quarter over quarter, which is notable given the typical seasonal impact of the holidays. For the full year, we delivered over 4,600 total prescriptions, growth of over 180% versus 2024. Although it's still early, demand is off to a strong start in 2026. We believe the three-year data that Mike just reviewed will continue to strengthen physician confidence in Ojemda and fuel our business growth throughout 2026. We've made meaningful progress in redefining the treatment paradigm, but significantly more opportunity remains for 2026 and beyond. Later this year, we expect to report four-year follow-up data from Firefly One, which we believe will further bolster Ojemda's clinical profile with additional insights into time-to-next treatment and a greater number of patients receiving re-treatment. Based on our momentum in 2025 and encouraging market indicators, we are reiterating our 2026 OGEMDA net product revenue expectation of $225 to $250 million. To date, we've made a lot of progress in expanding OGEMDA's use in the second line setting. Market research shows increasing preference for and use of OGEMDA in the second line. And in 2026, our objective is to solidify it as the second line standard of care. As our base of continuing patients grows, maximizing persistency to provide optimal patient outcomes has become increasingly important. Through detailed analysis, we have identified clear opportunities to further improve persistence, and this is an active area of focus for our team. Since launch, we've benefited from highly favorable payer dynamics, which continues to be an important driver of our business. Coverage rates for PLGG remain above 95%, with more than 90% of patients approved on the first request. With over 95% of PLGG patients receiving paid drugs, there is minimal reliance on our free drug programs, enabling patients to initiate therapy quickly and efficiently. The work we do now to establish OGEMDA and relapse refractory PLGG lays an important foundation of experience and confidence that will be essential as we prepare for the outcomes of Firefly 2. These data will be a critical enabler to support the potential approval and use of OGEMDA in the frontline and ultimately support its adoption as standard of care across all lines of therapy. Looking ahead to 2026, we are focused on two primary execution levers to drive our growth, driving new patient starts and optimizing persistence. Ojemda is increasingly well-positioned to become the standard of care in the second-line setting. Its clinical profile aligns closely with the attributes physicians prioritize when treating PLGG, specifically rapid and sustained tumor response, long duration of benefit with the potential for retreatment, a safety profile that is manageable in pediatric patients, and a convenient once-weekly dosing schedule. Our three-year Firefly One data reinforce these attributes, demonstrating durable responses both on and off treatment. Physician enthusiasm for Ojemda is reflected in the pace of new patient starts. In the second half of 2025, PLGG new patient starts increased by 25% compared to the first half. This acceleration was driven by growing clinical experience with Ojemda and the growth velocity data presented at ASCO that showed catch-up growth for patients after completing treatment. These data increased physician confidence in the long-term outcomes for patients. Once patients initiate therapy, our focus remains on optimizing persistence. With just over 20 months on the market, median duration of therapy for commercial PLGG patients is trending to 19 months. The quarter-over-quarter stacking effect of long treatment durations was a significant contributor to our strong performance in the second half of the year. I'm proud of what we've accomplished for the PLGG community since launch. and particularly throughout 2025. And I am confident that this focused and disciplined execution will continue to drive sustained growth for Agenda and solidify its position as second-line standard of care. With that, I'll turn it back to Mike to discuss our pipeline progress.

Thanks, Lauren. While we continue to build a strong base of evidence supporting OJEMDA, we're also advancing highly promising pipeline programs that may help us further deliver on our mission, and I'd like to review those briefly today. But let me take just a moment to reinforce our approach to research and development at day one, as this informs how we prioritize and advance our pipeline. We remain inspired by the urgent need of children with cancer. Our sense of urgency brings focus to innovative solutions in areas of unmet need that others often overlook. Pursuing opportunities that are differentiated with the potential for high impact allows us to leverage the internal focus and expertise we've already established with Ogenda to rapidly advance transformative programs through research, development, regulatory approval, and commercialization. This is the lens through which we continuously work to identify, study, and advanced novel programs intended to substantively change patients' lives. Let's touch briefly on Emil Todig Let It Outen, or Emily, our newest addition to the day one portfolio following the closing of our merger agreement with Mursana Therapeutics last month. MOE is a novel antibody drug conjugate comprised of both a B7H4-directed antibody targeting a well-characterized immune checkpoint cell surface protein, widely expressed on multiple cancers, and our proprietary linker payload designed for targeted delivery of a novel R-statin, FHPA. In phase one clinical development, as reported at the 2025 meeting of the American Society of Clinical Oncology, Emily demonstrated antitumor activity in adenoid cystic carcinoma, or ACC, a rare cancer affecting adults across the age spectrum that most often arises in the salivary glands. monotherapy, antitumor activity, and a well-characterized safety profile may support a rapid development path to registration for this uncommon cancer for which there are no current approved treatments. If ACC is confined to its site of origin at diagnosis, then surgical intervention with or without external beam radiation may be curative. However, Some patients present with locally advanced or metastatic disease or recur shortly after definitive local therapy. This aggressive form of ACC may be defined by a combination of clinical and histologic features and represents a subset of the approximate 1,300 patients diagnosed with ACC each year in the United States. The Phase I dataset with EMILY has advanced in both patient number and follow-up. We look forward to sharing an update on the ACC patient cohort and the expanded safety data set since ASCO 2025 at a medical meeting in mid-2026. In parallel, we intend to initiate discussions with the FDA and the United States to discuss our intended approach for accelerated clinical development for this patient population in desperate need of new therapies. Median survival of the expected patient population for registration is estimated at only between two to three years, and no approved therapy exists. As I noted at the outset of my remarks, our focus on life-threatening diseases others may have overlooked is entirely consistent with the unmet need faced by patients and their families with a diagnosis of ACC. Beyond our focus in ACC, if there are opportunities to study MOE and other cancers where B7H4 is overexpressed, we'll assess those carefully, most notably triple negative breast cancer. However, our primary focus at the present is to ensure a rapid advancement of the clinical development program in ACC. Finally, I'd like to provide a brief update on our early pipeline program day 301. Day 301 targets PTK7, a transmembrane protein in the pseudokinase family of receptor tyrosine kinases. We've harnessed a high-potency topoisomerase 1 inhibitor with a novel, hydrophilic, highly stable linker to deliver a drug antibody ratio of 8 with this molecule. PTK7 is overexpressed in a wide variety of adult and pediatric cancers, in particular, gynecologic cancers and squamous cell cancers of the head and neck. Our phase one program has been progressing through dose escalation and schedule optimization, such that we anticipate sharing data and a program update in the second half of 2026. We are encouraged by early signs of anti-tumor activity, even at this relatively early stage of clinical development. With these summaries of our current programs, I trust you share the same degree of enthusiasm as I do about each one. I look extremely forward to sharing updates across the board as the year progresses. In the meantime, I'll turn it over to Charles, who will provide our financial update.

Thank you, Mike, and good afternoon, everyone. Earlier today, we reported our fourth quarter and full year 2025 financial results. I'll focus on a few key takeaways that highlight the growing strength of Ojemda's commercial trajectory, our disciplined investment approach, and the durability of our financial position as we enter 2026. In the fourth quarter, U.S. Ojemda net product revenue reached $52.8 million, representing 37% sequential growth over the third quarter. This strong finish kept a very successful year. with full-year 2025 net product revenue of $155.4 million, an increase of 172 percent year-over-year, and double-digit sequential quarterly growth throughout the year. As Jeremy and Lauren discussed, this performance reflects sustained demand, increasing prescriber confidence, and the cumulative impact of longer treatment duration. Importantly, this growth has been achieved while maintaining disciplined channel management. Channel stock increased modestly at year-end, consistent with the typical seasonal ordering patterns, and remains at approximately the midpoint of our targeted two to four weeks of days on hand. For the fourth quarter and full year, gross to net remained within our previously communicated 12% to 15% guidance range, reflecting continued stability in payer dynamics. Total costs and operating expenses were $81 million in the fourth quarter of 2025 and $286 million for the full year 2025, as compared to $95 million in the fourth quarter of 2024 and $348 million for full year 2024. The year-over-year decline is primarily driven by the absence of one-time expenses related to the in-licensing of day 301 in 2024. As we continue to grow the top line, we also remain determined to invest at a pace that supports long-term financial stability for day one. We reached an important milestone in 2025. In just about 20 months since our approval of OGEMDA, revenue exceeded the combined cost of sales in SGA for the full year. This highlights both the growing contribution of the product to the enterprise and the scalability of our operating model as revenue continues to expand. and Ojemda is just getting started. Ojemda is supported by both composition of matter and a broader patent portfolio consisting of issued and pending applications that we believe provides meaningful layered exclusivity extending into the 2040s. We see Ojemda as a foundational program that will deliver cash flow for investment and increasing value for shareholders. We ended 2025 with approximately $441 million in net cash and no debt, providing a strong financial foundation to support our commercial growth and our pipeline advancement. This balance does not include the impact of the Mursana acquisition, which closed in early January of 2026. Yet we maintain ample capital to fund our current plans without the need for additional financing. Looking ahead, we are guiding to 2026 Ojemda net product revenue of $225 to $250 million, with a midpoint implying greater than 50% year-over-year growth. Where we land within that range will depend primarily on continued persistence on therapy and the pace of new patient starts. We continue to have a favorable gross net profile for Ojemda, and in 2026, we see gross nets in the range of 16 to 19%. Finally, business development continues to be an important strategic priority. The acquisition of Mursana was anchored on the value we see in the MLE program, particularly in ACC. The transaction is also a framework that is representative of how we think about continuing to grow day one. We look for opportunities that are rooted in oncology or select rare diseases where unmet medical need and clinical impact are the highest, have the potential to be first in class or clearly differentiated, supported by strong biology and early clinical signals, offer a clear line of sight to near-term revenue or meaningful value creation, and can be developed and commercialized at a scale and cost that is appropriate for a growing company while maintaining financial discipline and flexibility. The MELE program embodies all of these traits and has the added benefit of the potential for a favorable accelerated regulatory pathway. We are thrilled to have that platform on board and are excited about the data release plan for mid-2026 and the future announcement of what we anticipate is our path to registration. I'll now turn it back to Jeremy to wrap up and share a few closing remarks.

Thank you, Charles. As you can see, our momentum at day one is palpable. We delivered on our goals for 2025, and our success to date has further fueled our ambitions for 2026. We are well positioned for growth both in the near term and in the long term with well-defined commercial growth plans, upcoming strategic pipeline data sets, and a consistent and disciplined plan for managing our finances. I'd like to extend our sincere thanks to the entire Day One team for an outstanding year of execution and a warm welcome to those new colleagues from Mursana who've recently joined us. We're excited to have them on board as we drive the next phase of growth together. I'd also like to thank our partners and shareholders, and most importantly, the investigators and patients who generously participate in our clinical trials. All of the progress we've shared today is in service of our ambition to deliver life-changing new medicines to people of all ages. Together, we are delivering on this mission. I'll now hand it back to the operator for Q&A.

Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. We ask that all participants limit themselves to one question with an opportunity to have a follow-up. We will now open the line up for questions. Our first question comes from Anupam Rama with JP Morgan. Please proceed with your question.

Hey, guys. Thanks so much for taking the question and congrats on the quarter. You talked about persistency on the agenda here in the commercial setting. You know, how do you maintain the persistency that you've seen? And to your comments, Lauren, earlier, How do you improve it as duration of therapy increases? Thanks so much.

Anupam, thanks for the question. This is Jeremy, and I'll ask Lauren to address the persistence topics directly. Thanks.

Yeah, thanks, Anupam. First of all, I just want to reiterate that our current persistency is really great, so Our median duration of therapy is trending towards 19 months for our commercial patients, so that's really robust persistence already. But we recently did some additional analysis that helped us identify some groups of patients that do better from a persistency perspective, and we think that that creates opportunity for us that can result in increased persistency. Some of those groups, first of all, earlier line relapse refractory patients, which, as you know, were already driving towards establishing Ojemda as the standard of care in second line. So that's consistent with what we're doing already. But those earlier line patients do tend to stay on therapy longer. We also found that physicians with more experience with Ojemda were had patients that stayed on for longer. So that makes sense because they're likely better able to manage any AEs that may pop up, right? And so that really aligns with the depth that we're driving with our prescriber base, right? The more patients they have, the more adept they will be at managing the AEs and keeping patients on therapy. Another group that came out of this analysis were dose-adjusted patients. And remember, all of our doses are priced the same. So regardless of what dose they're on, it doesn't have a revenue impact. However, if they stay on longer, obviously that will have a positive revenue impact. And so we believe there's room for us to further educate physicians on the importance of dose adjustment in AE management. And then the final group that we identified were those patients who were enrolled in our patient support programs. So these are programs where nurses have calls with the patient along the way and help them through their journey. And we found that those patients stayed on for longer. So it creates an opportunity for us to increase enrollment in those programs. So these are all important areas of focus for my team this year, and we believe that this will help us to drive longer persistency over time.

Thanks so much for taking our questions. Thanks, Anupam. Our next question comes from Tara VanCroft with PD Cohen and Co.

Please proceed with your question.

Hey, guys. This is Nick for Tara. Thanks for taking our question. With the updated ME lead data coming mid-year, what are you looking for to support moving into a registrational trial? Also, you mentioned potentially looking at other indications. Do you plan to release data from additional indications mid-year, potentially TMBC, since Mursana looked at this indication initially? Thanks.

Thanks, Nick. One quick comment before I hand to Mike, and that is that I want to reemphasize the importance of Emily to our portfolio and to our strategic plan. It's really critical as an additional growth driver in a relatively short period of time and, of course, underpin the deal. And that's, though, there could be opportunities beyond ACC for development, as Mike mentioned. Go ahead, Mike.

Thanks, Jeremy. Nick, thanks for the question. This is Mike Vasconcellos. A couple of reminders just for you and the folks listening. In the context of the diligence we undertook for MRSANA, we were already able to see a substantial body of data that went beyond what MRSANA was able to present last year at ASCO. 2025, and that pertains to both the anti-tumor signal from the phase one experience as well as the safety data set. We've continued to advance the study in the context of closing the MERSANA acquisition earlier in January to further generate data that will strengthen that body of evidence that will support registration as well as provide the data to firm up our confidence in the dose and schedule that'll be taken forward in registration. We'll aggregate all that information and not only share as much of it as we're able to mid-year this year externally in a scientific conference, but also bring that forward to discussions with the FDA. I think the second part of your question was whether to expect data beyond Beyond ACC, we haven't, in a disclosure later this year, we haven't been specific about that. But I can tell you that certainly the safety data set will be comprehensive. And again, just reiterating what I said in the prepared comments, that our core focus right now is on adenocystic carcinoma while we continue to evaluate other opportunities.

Thanks very much. Appreciate it. Thanks, Vic. Alec, are you there? Yeah, sorry. I cut out there for a second. Can you hear me? Yeah, we can hear you, Alec.

Okay, great. Yeah, thanks for the questions. Just two from me. Great to see the strong progress to close 25. I guess looking to 1Q, just back over the past two years, we've seen some fairly incremental consecutive growth in the first quarter of the year following a strong closure to the year. Any early 2026 trends you could highlight directionally at this point, or maybe anything you think that might be unique to 4Q, and then I've got to follow up.

Sure. Thank you, Alec, for the question. I'm going to ask Lauren to comment, but what I would start with is really to focus on 2026 in total as a year and our our reiteration of the guidance that we provided of $225 to $250 million in net product revenue for the year. We're quite confident in that through the early experience of 2026.

Yeah, and thank you for the question. As you know, we generally don't comment on the details of our current quarter, but I will say that demand continues to be strong in Q1, and as Jeremy mentioned, we're reiterating our guidance and we're confident that we'll be able to continue to grow throughout 2026.

Okay, that's really helpful. And then maybe one on the TNTT analysis. I thought this was pretty interesting. Curious if it's possible to break this down further between patients that continue to receive TOVO after progression versus ones that, I guess, discontinued post-progression. Just trying to better understand sort of what's happening in that window between progression and subsequent treatment. Thank you.

I think, Alec, of course, thank you for the question. I think you're referring to the data that we published at Snow on the three-year follow-up data on Firefly One. Mike, any comments there?

Yeah, Alec, if I tracked with your question correctly, I think you're exactly right. onto the critical point that these analysis are looking to help interpret, which is that if there is a radiographic tumor progression in the context of therapy, that often does not lead to the discontinuation of that therapy. And that statement extends beyond the way in which the Firefly The Firefly 1 investigators have administered tovirapinib, but it's generally an approach that is taken certainly with targeted therapies in the disease. So the analysis that I summarized and shared earlier in this call doesn't differentiate the question that you're asking, which is, which is what's happening to those patients who might have had radiographic progression in the time to next treatment analysis versus those that did not. But as you will see in the upcoming publication of those data, which go into a lot more detail, in fact, you do see that patients who are continuing on tovirafenib that have evidence of radiographic progression often will then have some measurable tumor improvement or certainly tumor stability for an extended period of time. And so it just, you know, again, reinforces the criticality that clinicians are making with respect to the initiation of new therapy, which is driven by overt clinical signs and symptoms and not simply relatively, often relatively small changes in the measurement of tumor on a radiographic assessment.

Okay, very helpful. Thank you. Thanks, Alex. Our next question comes from Ami Fadiyah with Needham & Co.

Please proceed with your question.

Hi, this is Poonam on for Ami. Thank you for taking our question. For day 301, from the initial data update that's expected in second half of 26, how many dose cohorts can we expect the data from? And have you reached any DLTs or MTDs? And how many doses are you seeking to take forward in the phase two expansion? Thank you.

Of course, thank you for the questions. Let me comment kind of broadly on the day 301 program status and what you can expect with respect to the data later in the year. You know, first off, we haven't defined the specific parameters that will be included in that data update at this stage. You know, the program is in dose escalation. We have been backfilling at certain doses to evaluate those doses more comprehensively and to enrich for specific patient populations that we think may benefit. As Mike emphasized, we are seeing both an efficacy and a safety profile consistent with continued development, and we're enthusiastic about what that prospective set of studies may look like. Beyond that, we haven't said much and won't until we put those data out. And, you know, you can look forward to seeing those details, you know, once there's just a more comprehensive data set available.

Got it. Thank you. Thank you.

Our next question comes from Andreas Maldonado with HC Wainwright. Please proceed with your question.

Hi, everybody. Thanks for taking my questions. First one from me is, thank you for, again, for providing us with, you know, incredible amounts of detail, really mapping out the patient journey. So as you guys think about kind of maybe two buckets of patients, one that have a finite treatment course of duration versus maybe ones that are more chronic intermittent, in the chronic intermittent therapy group, I guess, help me understand some of the puts and takes that put some of those patients in one bucket or the other. So help me triage, is one weighted more towards depth of initial response versus, you know, maybe a better retreatment outcome? Help us understand kind of, you know, a little bit of those two kind of patient buckets with the data that you've generated so far.

Thanks for the question, Andre. Let me provide some, just an overview of how I think about how this medicine is going to be used over time based on what we do and don't understand today about treatment patterns. You know, my first comment is that, of course, in Firefly One, you know, we have a fairly regimented approach to how agenda is administered and the potential for a break in treatment at 24 months, right? That is one paradigm that In the commercial or the real world setting, what we're observing is so far quite consistent with an approach that's fundamentally at this stage treat to progression, which is why, as Lauren has emphasized, we're seeing really strong persistence and durations of treatment at the median that are consistent largely with our expectations, if not exceeding those. What I think we expect to see going forward, and this is based on the three-year data is that, you know, we will continue to see that persistence and, you know, certainly durations of treatment that are consistent with it, if not increasing. But we may also see some treatment breaks for patients that have a highly stable tumor. And for that reason, we may very well see retreatment as well because these tumors are genetically stable. There's evidence, and this comes from the three-year data, but other anecdotal descriptors as well, that patients don't develop resistance in those tumors and can be retreated if they've had clinical benefit before. They're likely to have that again. So how that nets out in terms of the specific populations, which is what I think you're asking about, I think is to be determined. But what I can tell you is that what we're expecting, and again, this is based on data you've already seen, is that you will see relatively frequent retreatment for patients who do take breaks and a really good pattern of lengthy durations of treatment followed by reasonably significant for your average patient tumor stability. And I think beyond that, it's just too early to say exactly what the patterns will be and which patients will fall into which kind of patterns of overall treatment.

Great. That's very helpful. And just as a quick follow-up question for maybe one for Emily, you know, what is the magnitude and, I guess, durability of response in AACC that you kind of have set as an internal bar? And I guess, you know, what would regulators likely consider sufficient for accelerated approval? Thank you very much.

So one quick comment, and then I'll hand to Mike on what we hope and believe we'll see for Emily and ACC, and that is a clinical data package that is really consistent with an approvable package in a setting like ACC, where you have really very few treatment options, a rare population, and an important potential new medicine with a pretty clear efficacy and safety profile that's, again, consistent with a lot of clinical benefit. Beyond that, let me ask Mike to comment further.

Yeah, so this is Mike. So just exactly keeping the context that Jeremy nicely summarized in mind, this is a patient population that is really in urgent need of new therapies. There's no approved therapies for aggressive adenocystic carcinoma. And when we look at what we would consider quote-unquote benchmark data, it's essentially old chemotherapy regimens with very poor responses. And we know from a variety of sources that the survival is poor. So when you put all that into context and think about... a development program, our expectation would be, and this is what I would expect until we can give you specifics following our conversation with regulators, is that we would look to a sufficiently robust single arm data set that would define the monotherapy objective response rate with sufficient durability, with patient numbers where the confidence intervals would clearly delineate the performance of a new medicine like Emily in contradistinction to the available therapy, which is very poor in the range of response rates and as low as single digits in some series.

Thank you. Thanks, Andrej.

Our next question comes from Kelsey Goodwin with Piper Sandler. Please proceed with your question.

Good afternoon. This is Brittany Stopa on for Kelsey Goodwin. Thanks for taking our question and congrats on the quarter. Our question is regarding, our questions regarding Ojemda sales. What are you hearing from physicians in your conversations following the presentation of the three-year Firefly data? And with the data having been presented mid-fourth quarter, How much of the fourth quarter growth do you attribute to that data, and when do you expect the bulk of the impact to be seen in the sales figures? Thank you.

Thank you, and I'll pass to Lauren to answer your question.

Yeah, so the three-year data for Firefly 1 was presented at Snow, and that's a conference that many of our KOLs attend. And so we did have opportunities to speak to them at the conference, and their response was very positive to the data. I think, you know, many of them were positively surprised with the length of time-to-next treatment that we're seeing with Ojemda. So a very positive response in every conversation that we had. I will say that aware so you had a few questions in there one is around the timing of it So that was just prior to Thanksgiving And and I would say the awareness is mainly in the KOL community that attended the conference So as far as the impact of that on q4 Performance, I would say it's minimal and it's going to be important that we continue to educate a broader group of physicians on this data in 2026 because it is so compelling. And Mike's team, our medical team, is working on a peer-reviewed publication, and that will be a really important part of sharing this information more broadly. So since it's only been presented at a conference, we're not really able to promote it actively today, right? And won't be able to promote it actively. So we really need that publication in order to broaden the exposure to this data. But we do think that when that time comes, it will be a compelling part of our story for a broader group of physicians to hear.

Super. Thank you so much. Thanks, Kelsey.

We have reached the end of our question and answer session, which concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.