Good day, everyone. Welcome to BeOne Medicines Q4 and Full Year 2025 Earnings Call. [Operator Instructions] At this time, I would like to turn the call over to the company.

Hello, and welcome. Thanks for joining us today. I'm Dan Maller, Head of Investor Relations at BeOne Medicines. Before we begin, please note that you can find additional materials, including a replay of today's webcast and presentation on the Investor Relations section of our website, ir.beonemedicines.com. I would like to remind all participants that during this call, we may make forward-looking statements regarding, among other things, the company's future prospects and business strategy. Actual results may differ materially from those indicated in the forward-looking statements as a result of various factors, including those risks discussed in our most recent periodic report filed with the SEC. Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation. Reconciliations between GAAP and non-GAAP financial measures discussed on this call are provided in the appendix to our presentation, which is posted to our Investor Relations website along with our earnings release. And all information in this presentation is as of the date of this presentation, We undertake no duty to update such information unless required by law. Now turning to today's call as outlined on Slide 3. John Oyler, our Co-Founder, Chairman and CEO, will provide a business update, including commentary on our foundational CLL franchise; Aaron Rosenberg, our CFO, will provide an update on our fourth quarter financial results and 2026 financial guidance; and Lai Wang, President and Global Head of R&D, will discuss our R&D and pipeline progress. We will then open the call to questions. Joining the team for the Q&A portion of the call will be Xiaobin Wu, President and Chief Operating Officer; Matt Shaulis, General Manager of North America; Mark Lanasa, CMO for Solid tumors; and Amit Agarwal, CMO for Hematology. I'll now pass the call over to John. John?

Thanks, Dan, and thank you, everyone, for joining us today. Q4 marked another solid quarter of execution and a really strong finish to the year and what a year it was. 2025 certainly lived up to its promise as a year of inflection for BeOne. From a financial perspective, we delivered on our commitments, achieving significant product revenue growth, GAAP profitability and meaningful cash flow generation. In 2025, our foundational BTK inhibitor, BRUKINSA, became #1, both in the U.S. and globally. And as you can see on this slide, the gap between BRUKINSA and the competition is widening. And that's not just a commercial achievement, it's a scientific one. BRUKINSA's long-term data have consistently raised the bar in CLL, setting a new standard for efficacy and safety. These results are reinforced by an expanding body of clinical and real-world evidence, all of which support the program's best-in-class hypothesis. CLL is a $12 billion and growing market due to remarkable therapeutic innovation and improvement in patient outcomes over the past 15 years, but it wasn't always that way. As recently as the mid-2000s, patients with CLL received fixed duration chemo and outcomes were quite poor. In fact, the median progression-free survival for patients taking chlorambucil was less than 1 year. In 2008, bendamustine was approved and used in combination with rituximab and the use became widespread, providing substantial benefit over the first chemo-based regimens. 6-year progression-free survival increased to 32%, which was better, but still not great. The FDA approval of ibrutinib in 2016 marked the first chemo-free option and a seminal innovation for patients. Anchored by data that were superior to chemo, the field switched away from fixed duration approaches to continuous BTK inhibition. Why? Because it provided the best long-term outcomes for patients. You can see ibrutinib's 6-year progression-free…

Thanks, John. I'm pleased to share our fourth quarter and full year results as we delivered against all of the financial commitments that we established in the beginning of 2025. Product revenue reached $1.5 billion in the fourth quarter, representing 32% year-over-year growth. BRUKINSA global revenues totaled $1.1 billion, growing 38% with strong performance across all geographies. For full year 2025, BRUKINSA global revenues were $3.9 billion, representing growth of 49%. And as John shared earlier, BRUKINSA has established itself as the leading BTKi globally by an increasing margin as we closed 2025. In the U.S., BRUKINSA fourth quarter sales were $845 million, driven by volume growth of approximately 30% versus Q4 2024. Our leadership is directly linked to the differentiated breadth, quality and consistency of BRUKINSA's clinical data, including those shared at ASH 2025. Pricing dynamics in the United States were consistent with commentary provided last quarter with a mid-single-digit pricing benefit on a year-over-year basis. These results include the previously mentioned typical seasonality benefits seen in the fourth quarter of the year for both current year performance and the 2024 baseline. Meanwhile, TEVIMBRA reported an 18% increase, reflecting continued market leadership in China. This growth was supplemented by contributions from launch markets. Our in-licensed products also showed continued strength, growing 9% year-over-year. We continue to observe solid execution across geographies. The U.S. remains our largest market, generating $850 million with year-over-year growth of 38% China revenue totaled $399 million, an 11% increase compared to the fourth quarter of 2024, supported by TEVIMBRA and BRUKINSA's market leadership and growth from our in-licensed assets. Europe contributed $174 million, with 53% year-over-year growth as we continue our launch trajectory with BRUKINSA with increased share across all major markets. And Rest of World markets grew 74%, driven by market expansion and new…

Thank you, Aaron. Hi, everyone. Thanks for joining us today. 2025 has been a standout year for BeOne R&D. Most notably, it was a breakout year for sonro. We achieved our first global approvals in China for relapsed/refractory MCL and CLL. In addition, regulatory submissions for relapsed/refractory MCL are under review in both the U.S. and the EU, with FDA approval expected in the first half of this year. Our BTK degrader continues to advance steadily towards registration. In 2025, we initiated 3 Phase III studies, including a head-to-head trial versus pirto. In solid tumors, we also made a strong progress. TEVEMBRA delivered a positive Phase III readout in HER2 positive gastric cancer in combination with zanidatamab and chemotherapy. Importantly, the next wave of innovation is here. In 2025 alone, 5 assets achieved clinical PoC. And over the past 2 years, we have advanced 17 new molecule entities into the clinic. BeOne has moved through two defining chapters in our history. In the first 10 years, we built from the ground up. With limited capabilities, we delivered two breakthrough medicines, BRUKINSA and TEVEMBRA and prove that BeOne could innovate at the highest level. The second chapter over the past 5 years was about scale and readiness. We invested heavily to build a powerful discovery engine and a truly differentiated global clinical development super highway, transforming BeOne from a company with isolated wins into one capable of repeatable success. Today, we're positioned better than ever to deliver a continuous stream of innovation. 2026 marks the beginning of a new era for BeOne. Over the next 3 years, we are focused on four priorities. First, we will deepen our leadership in CLL, building on our 3 foundational medicines. Second, we'll expand across hematological malignancies, including indolent and aggressive lymphomas as well as…

Thank you so much, Lai, for the comments. Really appreciate it. I think with that, we're going to jump to Q&A. And operator, please limit the number of questions to ensure we have time to hear from as many attendees as possible, but please go ahead.

[Operator Instructions] Our first question comes from Michael Schmidt at Guggenheim Partners.

I had a commercial question around the BTK inhibitor market and BRUKINSA. Specifically, could you comment some more on how you think about potential net pricing development in the BTK inhibitor market longer term, especially as we see your competitor products enter the CMS drug price negotiation program this year and next?

Yes. Thank you. Nice to hear from you. I think from the perspective in this space, as we've tried to lay out, this is a very differentiated value proposition with BRUKINSA versus any of the current therapies that are on the market, whether it's safety profile or whether it's just the long-term PFS and overall survival. This is, in our mind, a best-in-class product that has demonstrated the translation of its mechanism of action into real clinical results. And I think at this point, certainly, there are challenges for those other products, but we're just standing by the value that the products are creating for patients, and it's there. That's why we're showing it to you. Can we jump into the next question, please?

Yes, our next question comes from Yaron Werber with Cowen.

Congrats on really a lot of progress. I have a question that I think a lot of us have been getting. In the guidance, what are you assuming in terms of competition from AV or Jaypirca probably sort of late, late in the year? And then maybe secondly, in terms of sonro for MCL, both in China and in the U.S., can you just help us think through a little bit kind of what's in the initial opportunity?

So Matt, perhaps you can answer that a little bit, and then we can jump to Xiaobin.

Sure. Yes. I can provide some perspective on AMPLIFY and then Jaypirca as well. As you know, AVO was not approved. And as we've discussed before, AV, while approved, was studied only in a very young and very fit patient population, which had a median age of around 61. So we think those are some natural limitations there. Moreover, I think that we continue to be very confident in the clinical profile of BRUKINSA. We've outlined, as you heard from John, the importance of meeting some criteria for treatment in CLL, deep and durable remissions, PFS, safety and convenience. And we see that AV doesn't live up to that standard. Certainly, on MRD and PFS, it's very straightforward with safety and tolerability. I think that situation holds true. And then the convenience is still tied to some of the cumbersome nature of utilization. Now as for Jaypirca, we have seen some data back at ASH. And overall, that body of evidence doesn't yield the level of compelling data that we think is going to really change the treatment paradigm in the earlier lines of therapy. Particularly, we continue to hear from clinicians that, that evidence does not rise to the level of burning a line of therapy with a continuous BTK and that they will continue to position Jaypirca after the continuous BTKs. And obviously, in our case, that bodes really well for BRUKINSA.

So China approved beginning of this year, 2026. And we launched so quickly after that approval. And since launch, this is about 6 weeks and the reaction in the market has been very positive. We medicated or doctor prescribed for over 300 patients. And the approved indication is relapsed refractory mantle cell lymphoma and CLL. And so far, the safety profile has been also very good. So no major safety concern observed. So there's a very positive experience from all the major China hematology centers. It looks like very positive. And we are aiming definitely to be a market leader for the BCL-2 market going forward. This two approved BCL-2 in China. One is the venetoclax and another one is China local lisa.

Our next question comes from Ziyi Chen with Goldman Sachs.

Congrats on the results. I got one question on the immunology pipeline you mentioned about. I think this is probably the first time during the earnings briefing, you mentioned about immunology is going to be the next thing out of the 4 pillars you're going to be working on. So Lai mentioned about there are going to be 1 or 2 cornerstone therapies that you could potentially pursue and move into pivotal studies for immunology. Could you elaborate a little bit more about what's going to be the strategy for the immunology beyond hematology and solid tumor that BeOne already been very strong at? And what's going to be over the next few years, what's going to be the path and a journey towards becoming some meaningful player in immunology?

Please, Lai. And thanks for the question.

Thanks for the question. In our preclinical pipeline, we have roughly about 20% of our assets are focused on immunology. We acknowledge we're still a young player in the immunology space. For us, we're going to be opportunistic, looking for potential opportunity to be the first-in-class or best-in-class. Our goal is in the next about 2 to 3 years to identify 1 or 2 molecules, which we feel like can be a cornerstone assets for us to build around. So we're looking forward to share with you the updates in the upcoming additional earnings calls. But there are some very exciting molecules we're really developing at this moment. Some of that is already in the clinical stage.

Can we have another question, please?

Yes. The next question comes from Yigal Nochomovitz from Citi.

I just wanted to -- you made some excellent arguments regarding the fixed duration and the inferior options today versus continuous BTK. But I just wonder if you could just clarify, if ZS does become the fixed duration regimen of choice and the standard of care in treatment-naive, could you just clarify how you're not going to sacrifice the long-duration revenues with continuous BRUKINSA? I think that would be helpful to understand a bit better, please.

Sure. Aaron is going to answer to that.

Thanks for the question, Yigal. And you've seen the different forms of the pie chart that John shared in his slides. In the current dynamics, that's a view on the U.S. the dynamics aren't too dissimilar outside the U.S., although fixed-dose treatment for BTK BCL-2 combinations are a bit more mature in Europe. About half the market is receiving fixed-dose treatment, half is receiving continuous use. And as you saw in that view, we're currently getting about 50% on a new patient basis for BRUKINSA. So what we're trying to state really clearly there is the combination of sonro plus zanubrutinib opens up 50% of the market where we don't play at all today. So from that dimension, and as we continue to mature candidly in our market share within the continuous use class alone with BRUKINSA, we view this as very market expanding.

Yes. I think the promise is there, and we're hopeful that the data translates as positively as we've seen so far. It really could fulfill the promise and the story that's being told now about fixed duration. And were that to happen, that would be a really wonderful thing, but it would place us in a truly, truly unique position. I think regardless of that for this 50% of the population that is already on fixed duration, if we're anywhere near the data we're showing at this moment, it's just on every one of those boxes, checking what would be required to be a best-in-class medicine. So we're really, really excited about this opportunity. We just need to wait a little bit for a little more data to mature from that perspective.

Our next question comes from Reni Benjamin at Citizens JMP.

Congratulations on a great year and the guidance that's provided. I guess my question is regarding the BTK degrader. You had some pretty encouraging data that was presented at ASH. I thought that there was a potential for an accelerated approval in the first half of this year. I think it's been pushed out to the second half. Can you just kind of confirm that I'm reading that right? And can you provide some color as to what's causing the pushout and how we should be thinking about the first approval?

Great question. Amit, will you please respond?

Yes. Thank you for the question, Reni. So I don't think there's been a change in terms of the timing and kind of how we're thinking about this. Obviously, this is a single-arm approach. And so in terms of what we're looking at there is based on a single-arm trial. And so we're following that data and look forward to having the interactions with the FDA midyear and file based on our interactions with the FDA. So there's really no change in terms of the timing there.

Our next question comes from Sean Laaman at Morgan Stanley.

Just trying to understand a bit better the long runway of growth potential for BRUKINSA here. You did $3.9 billion, I think, for the year at around 40% growth. Calquence did -- I think they did double-digit growth to get to $3.5 billion and IMBRUVICA is growing negative mid-teens, but still did $2 billion. So that's about $3.5 billion where BRUKINSA is not operating, if you like. And clearly winning the battle against IMBRUVICA, but given the compelling data that you have to show best-in-class, what's the tipping point? Or what's the wrestle here to really start eating into that Calquence share?

Aaron, would you like to answer that?

Thanks, Sean. And as we've been talking, we certainly feel very confident in the totality of the evidence for BRUKINSA. And ultimately, the dynamics you're describing in terms of our performance in the marketplace, it's the data that's resonating and ultimately translating to the growth that you've described. As you look at the market share slide that we showed in the deck, on a new patient share, we're currently getting about 50% of the continuous use BTK market. We are the global market leader, but we're not quite at 50% yet because we continue to mature into that profile. So as you think about the growth for our business is the continued maturation into our growth profile. And certainly, we believe having the best-in-class medicine in the continuous use BTK space, there's more than ample opportunity to continue to grow share over time.

And I think our challenge is really just get people to look at the data. It speaks for itself. That is a portion of the data that we're sharing on this call, whether it's the long-term data, whether it's the head-to-head data, whether it's the combination data versus their combination data, every place you look, the story is the same. And there's work being done in real-world data from that perspective, too. But I just think it's this overwhelming body of evidence. And that's the challenge. Of course, we're the only person that wants to share that information. The rest of the industry, it may not be in their best interest. But it's really, really important that we share it for patients so that they're getting the best medicine.

Our next question comes from Chen Chen with UBS.

So my question is on B7H4 ADC. And actually, I think this is not in the model or in the valuation right now, but I heard that you are going to initiate Phase III like within the next 12 months. So may I know that's been -- so the clinical trial would be initiated in the first half or the second half? And also, it has shown some promising efficacy and safety in gynecology and some breast cancers. So may we know like in which indication are you going to initiate a Phase III trial? And also, I think the B7H4 ADC is roughly like at least like 12 months later than our peers, B7H4 ADC. So what are the differentiation of this molecule?

Thanks for the question. Mark, could you address that, please?

Thank you very much for the question. So we're really pleased with the progress that's been made with our B7H4 targeting ADC. This has progressed swiftly through Phase I dose escalation. And as you heard from Lai, we are planning to disclose efficacy and safety data for the dose escalation in the first half of the year at a major medical congress. We recognize that the competitive landscape that there are a number of competing molecules, both within B7H4 and more broadly within the topo 1 conjugated ADC space, particularly in breast and gynecologic malignancies, which is why we're moving with urgency. I think that we will be able to speak in more detail regarding the differentiation of our compound once we disclose the data. But suffice to say, we're very happy with the emerging efficacy data and think that we also have a nice safety profile with no target-mediated toxicities beyond what one would expect for a topo 1 conjugated ADC and a good hematologic safety profile. So it's checking all the boxes to be on a path for a Phase III study start as soon as possible. And again, we'll be able to share more details about first indication for Phase III versus subsequent indications for Phase III as we disclose data throughout the year.

Thanks, Mark. And could we take 2 more questions, please?

Yes. Our next question comes from Leonid Timashev with RBC Capital Markets.

I wanted to ask on the BTK degrader development pathway, specifically on the Phase IIIs. I guess, given you're going to have a potential accelerated approval and you're running 3 Phase III studies, I guess, what's the incremental value of each of those studies? I guess do you need ultimately all 3 to fully realize the opportunity? Or do you think you're still going to have rapid uptake as the data starts to flow in over time?

Amit, would you like to answer that question?

Yes. Thank you for that question. I think from a BTK degrader perspective, again, we're very encouraged by the data that we've seen so far. We do think that this is going to really be a foundational treatment as a BTK asset for the future. And in terms of the Phase III, I think we're answering important questions with the Phase III studies that we have right now, particularly with the 2 global Phase III studies. I think one is in a slightly later line with the investigator's choice as the control arm. And then the other study is really a head-to-head study against pirtobrutinib. And so we do see incremental value, especially from that pirtobrutinib study to be able to show that as far as that population is concerned, the BTK degrader has a really sort of clear role in terms of the monotherapy. And then beyond that, we are obviously, as Lai showed, working on a BTK degrader plus sonro combination as well. And so you'll continue to see us generate more data there.

Thanks, Amit. And are there any more questions? Or should we wrap up now?

We have one more question from Rebecca Liang from Bernstein.

Congratulations on the great results. So you showed a very interesting chart on the patient share between fixed duration and continuous therapies. I'm wondering how you see the future development between BRUKINSA and sonro. After sonro plus BRUKINSA becomes a viable option. Given that now the fixed duration therapy has half of the patient share, but obviously, much lower commercial sales. So venetoclax, for example, only selling around $2 billion to $3 billion versus the whole BTK market at around $10 billion because of the limitation of fixed duration in treatment duration. So how do you see the future commercial -- the sales split between the 2 products, even if there's maybe no immediate guidance for the long-term peak sales, but qualitatively, the split between the 2 products?

First of all, I would clarify that although half the patients in CLL in that pie chart are listed as fixed duration, they're not all getting then. There's all sorts of other things, even chemo surprisingly, that is still being given to patients. So first of all, as we move into that segment of the class, I think ven has been very limited by its usability, especially in the community setting. So I think that having a fixed duration treatment that can replace, I don't know, I'd say, some of these less evidence-based fixed duration treatments in that half that are being used broadly in the community center, I think, is a huge, huge value to patients. And we would expect with the quality of the early data from that, that this really could be a unique product combination within that 50% of the market for sure. To be clear, there's lots of patients that have different prognosis in CLL. And if we jump back to that, you have deletion 17p in unmutated patients. You also have mutated patients. About half of them are high-risk factor patients. And those patients are hard to handle, for sure. And they're very hard for the current fixed duration therapies to address. I don't have the slide number, maybe someone will flash it to me. But when you go back to the slide that showed on the left-hand side, the infection rates associated with VO. On the right-hand side, you could look at the numbers there. When you look at unmutated patients and deletion 17p patients, really, the outcomes are not good at all. And that's because this is a harder disease to fight. And our hope is it would be great if our SZ doublet, which is all-oral and easy to use and…