DAWN - NASDAQ

Greetings, and welcome to the Day One Biopharmaceuticals Q2 2025 Earnings Conference Call. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Joey Perrone, Senior Vice President of Finance and Investor Relations. Please go ahead, sir.

Thank you. Hello, everyone, and good afternoon. Welcome to Day One Second Quarter Financial and Operating Results Conference Call. Earlier today, we issued a press release, which outlines the topics we plan to discuss today. You can access the press release and the slides to accompany this conference call on 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 2. 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 except 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 Merendino, Chief Commercial Officer; Charles York, Chief Operating and Financial Officer; and Michael Vasconcelles, Head of Research and Development. I will now turn the call over to Jeremy.

Thank you, Joey. Good afternoon, and thank you all for joining us. This quarter marks a pivotal moment, 1 full year since the approval of OJEMDA. In just 12 months, OJEMDA has not only met expectations, it has exceeded them. With $113.1 million in cumulative net revenue for the most recent 12 months, we've demonstrated clear commercial momentum, strong physician adoption, and sustained patient demand. With OJEMDA's approval, we've transformed Day One into a commercial organization and laid the groundwork for long-term value creation. We've built a high-performing, focused company with demonstrated execution, a solid financial position, and a portfolio that will deliver durable growth. For the second quarter, we again delivered double-digit top-line revenue growth, generating $33.6 million in net product revenue, up 10% over our first quarter. Our total volume in Q2 exceeded 1,000 scripts for the first time, underscoring OJEMDA's continued adoption in the market. Our continued growth and performance highlight the importance of this medicine to the physicians, patients, and caregivers in the pLGG community. Today, we're also issuing net product revenue guidance for the first time. We project total net revenues of between $140 million and $150 million for full year 2025. This guidance is grounded in strong and persistent demand, deepening prescriber adoption, and consistent payer coverage. Looking forward, we remain sharply focused on OJEMDA commercialization and expansion. We have a clear opportunity to establish OJEMDA as a standard of care in second-line plus pLGG. We also have opportunities in the near term for significant potential indication expansion for OJEMDA in frontline pLGG here in the U.S. through our FIREFLY-2 trial and in second-line plus pLGG in Europe through our partner, Ipsen's filing of an MAA. Our global FIREFLY-2 confirmatory first-line trial remains on track for completion of enrollment in the first half of 2026. And our partner, Ipsen, announced EMA acceptance of the OJEMDA filing in Q1 and potential EMA approval mid-2026. We share Ipsen's commitment to patients and will continue to support their filings to help more patients and physicians gain access to OJEMDA. In Q2, we also welcomed Michael Vasconcelles to the company as Head of Research and Development. Mike brings decades of experience and success in oncology development and will play a pivotal role in driving the next phase of Day One's growth. We are also prosecuting our broader portfolio beyond OJEMDA. We recently discontinued our investment in the VRK1 program we had in-licensed from Sprint Biosciences. Importantly, we are advancing our PTK7-targeted ADC, DAY301, through the dose escalation portion of our Phase Ia trial, and we continue to actively evaluate new opportunities for portfolio expansion. Our strong financial position remains a strategic advantage. We closed Q2 with a strong balance sheet and growing product revenue, giving us the flexibility to execute our plans without reliance on the capital markets. We are focused, well-capitalized, and committed to delivering meaningful value for patients and shareholders through our strategy to develop and commercialize new medicines. I'll now turn the call over to Lauren to discuss our commercial progress in greater detail.

Thanks, Jeremy. OJEMDA continued to demonstrate strong commercial performance in the second quarter, delivering $33.6 million in net product revenue. This reflects double-digit growth over the prior quarter and marks the first time that we've surpassed 1,000 total prescriptions in a quarter. The 15% quarter-over-quarter growth in prescriptions was driven by steady expansion across both the number of prescribing accounts or breadth and the number of patients per account or depth. More details on this in a moment. On a trailing 12-month basis, OJEMDA has now generated over $113 million in net revenue, well beyond initial expectations of where this brand would be at this point in our launch. In addition to strong demand, a high rate of payer coverage continues to be a key contributor to our strong financial performance. Over 95% of patients on OJEMDA are paid patients, with less than 5% receiving free drugs. Additionally, about 90% of patients receive approval upon initial submission, helping to reduce the administrative burden on HCPs and leading to faster time to treatment for patients. Looking at revenue over the past 12 months, we've seen significant and consistent growth with a compound quarterly growth rate of 22%. Even with this growth, considerable opportunity remains. Many eligible patients have yet to receive OJEMDA, and we are just beginning to realize the potential of this brand. In order to fully deliver on OJEMDA's potential and establish a new standard of care in second-line pLGG, we must continue to build the clinical evidence and at the same time, encourage physicians to gain further experience with the brand. Our medical team continues to publish updated data and additional analyses, building a more robust case for OJEMDA and creating opportunities for the commercial team to keep providing valuable information to our customers. We recently introduced 2-year follow-up data from FIREFLY-1 patients. And at ASCO in June, we published additional data characterizing growth velocity recovery and effective rash management. These data provide important long-term insights that reinforce the robust efficacy we reported previously, as well as offering new evidence of catch-up growth in patients after therapy is completed. Physicians have consistently told us that these longer-term data strengthen their confidence in OJEMDA and further validate its broad use in appropriate relapsed/refractory patients in the real world. Prescription growth has remained strong, with total prescriptions increasing by 15% quarter-over-quarter. This growth continues to be driven by a steady flow of new patient starts and strong persistence among patients already on therapy. We're also seeing an evolution in prescribing patterns. With increased familiarity and confidence, physicians are initiating OJEMDA earlier in the treatment journey. Based on recent market research conducted in June, second-line OJEMDA share has grown significantly in both BRAF fusion and mutation patient populations. Our field team has been instrumental in driving this momentum, consistently emphasizing OJEMDA's differentiated efficacy, safety, and dosing profile and why we believe it should become the new standard of care in relapsed/refractory BRAF-altered pLGG. The 2-year FIREFLY-1 data have further strengthened this positioning by speaking to both the durability of response and addressing the growth velocity questions. Following the release of these data, we saw a meaningful ramp-up in new patient scripts in the latter half of Q2, and that trend has continued into July. These data have also helped us to continue to expand breadth and depth of prescribing. So let's take a closer look. This graph shows updated breadth and depth metrics for OJEMDA prescribing. The top line reflects the total number of unique accounts that have initiated new patients, while the layered segments illustrate the number of new patient starts per account. These data reflect commercial patients only and exclude any patients treated through our early access program. We're pleased to report that over 60% of prescribing accounts have now started multiple patients on OJEMDA, with nearly 20% of accounts initiating treatment in 5 or more patients. We believe this strong depth of prescribing is a positive indicator of growing physician confidence and satisfaction with this product. As we look to the second half of the year, our commercial priorities remain clear: drive continued growth through increased breadth and depth of prescribing, expand second-line use, and optimize treatment duration. While these focus areas remain consistent, our approach continues to evolve. We are leveraging the latest prescriber insights, exploring alternate data sources, and leveraging innovative approaches such as AI to strategically target our resources and identify emerging opportunities. At the same time, our clinical and med affairs teams are generating additional data and publications that enhance the OJEMDA value proposition. We're looking forward to the 3-year follow-up data for FIREFLY-1, including additional efficacy and safety analyses that we expect to release in the fourth quarter of this year. As the body of evidence grows, we see increasing opportunities to solidify OJEMDA as the new standard of care in relapsed/refractory pLGG. With that, I'll turn it over to Charles, who will walk through the financials in more detail.

Good afternoon, everyone. Earlier today, we reported detailed second-quarter 2025 financial results in our earnings release. And for today's call, I'll highlight a few key points. As we pass the 1-year point since launch, we see OJEMDA revenue continue its steady upward growth trajectory. In the second quarter, U.S. OJEMDA net product revenue was $33.6 million, which grew 10% compared to the first quarter. Our Q2 results bring our year-to-date net product revenue to $64.1 million and our trailing 12-month revenue to $113.1 million, a fantastic start to our launch. As Jeremy highlighted earlier, we are providing full-year 2025 OJEMDA net product revenue guidance of $140 million to $150 million. The midpoint of the guidance range implies approximately 150% year-over-year growth, which builds on the strong launch results delivered to date. It also reflects continued momentum in the launch trajectory and in achieving our goal of establishing OJEMDA as a standard of care in the relapsed/refractory setting. Where we land in this range will be determined by 2 critical variables: first, persistence on therapy for patients continuing on OJEMDA; and second, the pace of new patient starts. For the second quarter, total costs and operating expenses were $68.9 million, which includes $10.9 million in noncash stock-based compensation. This represents approximately 5% decrease quarter-over-quarter. Additionally, net cash used in operating activities decreased significantly quarter-over-quarter, approximately 50%, reflecting our continued focus on disciplined execution while advancing our investment opportunities. Given today's challenging markets, we see prioritizing a balanced approach to delivering top- line expansion paired with thoughtful cost control as a responsible capital allocation strategy. Finally, we remain in a strong financial position, ending the quarter with $453 million in cash and no debt. Looking forward, our robust balance sheet positions us to advance our priorities and capitalize on the opportunities ahead, including completion of the frontline FIREFLY-2 trial for OJEMDA and advancing DAY301. I'll now hand back to Jeremy for his final thoughts.

Thank you, Charles. To close, I'd like to share a story that captures the essence of what motivates all of us at Day One. The story is of a 4-year-old living with pLGG. Late last year, this child was experiencing vision loss due to his BRAF-altered optic pathway glioma. He was nearly color blind and was also struggling with walking due to his vision loss. This past January, his care team decided to treat his tumor with OJEMDA. His vision, including color clarity, improved after only a month on therapy. It's now 7 months later, and this brave young 4-year-old remains on therapy. His family reports that their son is now having a more typical childhood. He's coloring, playing with friends, and walking without assistance. All of us at Day One, myself included, are here because we are inspired by stories like this young boy's. We are committed not only to enabling as much patient impact as we can with OJEMDA, but also to developing new medicines that bring hope to more children and adults living with cancer. I'll now turn the call over to the operator for Q&A.

[Operator Instructions] First question that we have comes from Anupam Rama of JPMorgan.

This is Priyanka on for Anupam. Congrats on the quarter. Just a quick question from us. So looking at the newly provided 2025 guidance, seems second half is estimated to be around $76 million to $86 million. First half, of course, was $64 million. So what couple of levers in particular will you focus on to increase the growth rate?

Priyanka, this is Jeremy. Thanks so much for joining and for the question. There's really 2 key variables that are critical to defining the range that we provided for guidance for revenue for fiscal year 2025. And they're really continued adoption in the form of new patient starts and persistence on therapy. And we've reached a point in the launch at this stage where we feel that those 2 variables are more predictable than they had been given that we're about a year away from launch, and the trends we're seeing have led to that range.

The next question we have comes from Tara Bancroft of TD Cowen.

So seeing 1,000-plus scripts in Q2, it's really great to see. So I'm wondering if you could maybe tell us what proportion of those are new versus continuing patients. And mostly, I'm asking because you mentioned the increase in new patient scripts in the latter part of Q2. So I'm wondering to what extent maybe the ASCO data might have contributed to the rash management and reversibility of the growth impacts.

Thanks for the question, Tara. So yes, we were excited to hit a milestone, of course. But I think more importantly, as you know, really focused on the trajectory of what we're seeing in terms of growth that really does -- was impacted by the 2-year data that you referenced. Why don't I ask Lauren to comment on what she and her team are seeing in the field to give you a sense of that, at least qualitatively?

Yes. Thank you for the question. So the 2-year data has been received very positively by our customers, as I mentioned. And they're both confirming the efficacy and building confidence in our efficacy with additional follow-up. And then also, as you mentioned, the growth velocity data is reassuring to have additional volume of patients where we have evidence of catch-up growth after stopping treatment. So those 2 things have been compelling for physicians, and we have seen, as I mentioned, an uptick in starting new patients, and we're eager to continue that with continued promotion of these data.

[Operator Instructions] The next question we have comes from Andrea Newkirk of Goldman Sachs.

Jeremy or maybe, Lauren, I was just wondering if you might be willing to speak to what you're seeing with respect to durability or persistence now that you are 1 year into launch and have greater clarity there. What are you hearing from physicians regarding their intentions for how long they'd like to keep their patient on drug? And to what extent do you think the 3-year follow-up will meaningfully change their view versus the 2-year data that they've seen already?

Thanks, Andrea, for the question. Let me start, and I'll ask Lauren to comment on those last elements. We -- what we're seeing in terms of persistence is very consistent with what you've heard me describe previously, and that is for on-label patients, what we're seeing for persistence, or the flip side of that potential for median duration of treatment is consistent with what we expected based on the FIREFLY-1 trial. We have not provided any estimate of what that median duration of treatment will be or what specific persistence values are. But what I can tell you is we still have not yet reached a median duration of treatment for patients since we've launched and been approved. So we're really confident that we're seeing fairly lengthy durations. Let me ask Lauren to now comment on both the 2-year data as it relates to persistence and intent and the 3-year data.

Yes. So you mentioned -- you asked about intent. So as we've discussed previously, many physicians, their intent is to keep a patient on treatment for 2 years, if possible, as long as that patient does not progress. And we continue to hear that from physicians. Many of them are still anchored to this 2-year concept. As we think about the 2-year data versus the 3-year data, the 3-year data will have more evidence of what happens after patients either stop therapy or if they continue on therapy beyond those 2 years. And so I think that will be very informative and additive to the data that we have now.

The next question we have comes from Alec Stranahan of Bank of America.

This is Matthew on for Alec. Maybe just double-clicking on a previous point. Is the distribution of total scripts attributed to repeat versus new prescriptions holding relatively constant between Q1 and Q2? And then second question, curious how dropouts have been trending and whether ASCO updates on skin AEs are helping to sign your strategy moving forward?

Lauren, do you want to take those?

Sure. So as far as distribution of TRx and NRx, I actually haven't calculated the ratio and looked at them comparatively quarter-over- quarter. So I can't be too specific there. But what I can tell you is that we continue to focus on driving new patient stats in NRx, and the 2-year data does seem to be very compelling to our customers. So we'll continue to share that data as we move forward. From a drop-off perspective, it's been fairly consistent with what we've seen previously. And I'm trying to remember if there was more.

Yes. I think let me -- yes, I'll just -- no, no, Matthew, good question. The ASCO data that came out with respect to rash management, I do think is important as far as helping us to manage, especially those physicians who don't have prior experience with OJEMDA, to prevent any dropouts that might be premature and not give the patient a sufficient time to achieve a really good efficacy result. So that is, we think, valuable. I wouldn't say it's showing up dramatically in the data yet, given just how recent ASCO -- recently ASCO occurred. That being said, as we track the sort of overall persistence curves over time, we are seeing positive trends as physicians get more experience with OJEMDA and as all of the tools that we've had available and have made available throughout the launch become better known and understood by treating physicians, by office staff, and by caregivers. And they are pretty significant investments that we've made in those areas, really, since launch.

Yes. And just to add to that, rash tends to be one of the first AEs that is seen early on in treatment. And so it is important that physicians not only manage it, but take proactive steps before the child has a rash in order to lead to the best outcomes. And so I think since launch, we have increased the messaging around that to make sure that physicians are prepared to manage that AE proactively for the best success of their patients.

[Operator Instructions] The next question we have comes from Ami Fadia of Needham & Co.

This is Poorna on for Ami. I guess continuing on previous questions, could you provide additional color on what you're modeling in your guidance in terms of new additions versus discontinuations? I'm just curious, how is your gross to net for this quarter? And separately, for the ADC DAY301, just wanted to get some understanding on how the development is progressing, what phase it is in, in terms of dose escalation? And what's the benchmark that you're looking at?

Certainly. So I'm going to ask Charles to comment on your guidance topic and then Mike to comment on DAY301.

Thanks, Jeremy. So for the guidance range itself, very similar assumptions to how we've discussed this launch previously, and what Jeremy and Lauren had highlighted earlier. In general, in order to meet that, we believe we're going to have to have continued persistence, continued duration for patients, and the steady increase in new patient starts that we've continued to see. Other important factors in there, though, are minimizing the fluctuations on a couple of other items that we have that we've talked about previously. First being channel stock. And in order to meet that range, we'll need to keep the previously guided 2 to 4 weeks of channel stock on hand still in place. And we expect that gross to net range to still remain in that 12% to 15% that we've talked about previously. Those are the main assumptions associated with this, in addition to the work to gross.

Thanks, Charles. And Mike, can you comment on 301?

Sure. Thanks, Jeremy. Thanks for the question, Poorna. We're really doing quite nicely through Phase I dose escalation. We have a really engaged group of investigators, and things are progressing about as we would expect or anticipate for a molecule of this class and target. With respect to the benchmark, I think we'll have to keep an eye on that. We certainly know some early-phase programs against the target. It's been a target of interest for some time, but it's really a target that at least historically, has been a little bit of a challenge, at least with one prior molecule. We think we've got a very innovative molecule against PTK7, and we'll keep an eye on how others progress. There's a broad opportunity in terms of expression patterns. So as we move through Phase I and then define our expansion cohorts, we'll look forward to sharing those details with you.