Ticker: ONC

Quarter: Q4 2025

Date: 2026-02-26 00:00:00

Operator: 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.

Daniel Maller: 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?

John Oyler: 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 survival and overall survival of approximately 61% and 77%, respectively. At the same time, the field was developing new fixed duration treatments that were enabled by the discovery of BCL-2 inhibition and the approval of venetoclax. These ven-based approaches greatly improved upon historic chemo-based regimens, and they began to approach the long-term benefits provided by the 2 continuous BTKIs, albeit with approximately 10% delta in 6-year progression-free survival. However, the VI regimen was not approved by the FDA and the addition of obinutuzumab to ven has significant safety challenges, which I'm going to touch on later. As good as continuous use ibrutinib was, the molecule was not optimized for potency or selectivity. The second approved BTK inhibitor, acalabrutinib, was designed to be more selective than ibrutinib and to have a very short half-life of roughly 1 hour with the hypothesis that these changes would translate to a more favorable safety profile, including fewer cardiac adverse events. And in that respect, acala achieved its goal, demonstrating statistically significant improvement in afib in the ELEVATE-RR study. However, in that same study, acala demonstrated non-inferior PFS compared to ibrutinib. As shown on this scatter plot, acala's 6-year progression-free survival and overall survival of 62% and 76% in treatment-naive CLL is nearly superimposable on ibrutinib. But innovation never stops. The bar set by the first 2 continuous treatments would be raised yet again by a differentiated foundational medicine, enter BRUKINSA. BRUKINSA was designed from inception to be both more potent and more selective than ibrutinib with complete 24/7 target coverage. We took that preclinical hypothesis into the clinic where in head-to-head global Phase III trial, BRUKINSA demonstrated superior efficacy to ibrutinib and a more favorable safety profile. And this includes statistically significant improvement in afib. And at ASH 2025, BRUKINSA set a new bar for long-term patient outcomes. Here, we can see 6-year progression-free survival and overall survival of 74% and 84%. And adjusting these for COVID, those are 77% and 87%, respectively. Now I really appreciate you bearing with me as I know I've spent a lot of time on this slide, but the data, as you can see here, is really important. These data clearly established BRUKINSA as a foundational standard against which all current and all future regimens must be compared and the long-term outcomes that patients and physicians should expect and demand. At BeOne, we believe that true innovation comes from improving upon the best. BRUKINSA did just that when it demonstrated superiority in terms of safety and efficacy over ibrutinib. No other BTK inhibitor can make that claim. Here, we see the Kaplan-Meier curves from head-to-head trials of BRUKINSA and other BTK inhibitors versus ibrutinib in relapsed/refractory BTK-naive CLL patients. And this is as assessed by Independent Review Committee or IRC. In all of these studies, the IRC assessed PFS is the predefined key secondary endpoint to demonstrate superiority over ibrutinib. In the ALPINE trial, BRUKINSA showed the greatest early separation from ibrutinib and remains separated with a hazard ratio of 0.69 and a p-value of 0.001, demonstrating statistical superiority on PFS. We presented longer-term follow-up data from that study at ASH just a few months ago. In the ELEVATE-RR study, acala showed early PFS separation from ibrutinib, albeit less than BRUKINSA, but that early separation was not sustained. As you can see in the middle chart, acala crossed over and became numerically worse than ibrutinib at roughly 33 months. ELEVATE-RR ultimately reported a hazard ratio of 1. And this brings me to pirtobrutinib, a non-covalent BTK inhibitor, which recently reported data from its head-to-head trial against ibrutinib in CLL. On the right, we see the curves from relapsed/refractory BTKi naive cohort of BRUIN-314, which comprised 2/3 of the enrolled patients in that trial. You can see that pirto with only 18 months of follow-up shows the least early separation versus ibrutinib with a hazard ratio of 0.845 and a p-value of 0.4102. We need to see much longer follow-up from BRUIN-314 based on the minimal early separation in these short-term curves, and pirto may face an uphill battle and showing statistical superiority to ibrutinib in PFS. Now if you've learned anything about BeOne Medicines over our 15 years of existence, it's that we're never satisfied with the status quo. And despite the incredible progress the industry has made, it's hard not to dream about the next chapter of CLL innovation. And we think it's time to start talking about a cure. And with that, we proposed 3 aspirational goals for the next wave of innovation in CLL: The first one is an obvious one, life expectancy equal to that of the general population matched for geography and age for any patient diagnosed with CLL. Second, for patients who prefer a time-limited therapy, any regimen must deliver long-term outcomes that are at least as good as the best continuous treatment available. And finally, any treatment designed to offer long-term life expectancy must also deliver quality of life, ease of use and convenience. Applying these aspirations to the scatter plot clearly implies the need for further improvements on what's currently available. And we do believe that BeOne is the only company with the foundational assets in our CLL portfolio and pipeline to take us there. The next chapter of CLL innovation is going to come from options that address the unmet needs and deliver the best long-term outcomes for patients. So what about fixed duration? There's a clear desire from some patients and physicians for fixed duration options that provide a break from treatment. For fixed duration to change the treatment paradigm, it must elicit a deep response, demonstrate sustained progression-free survival, be safe with only minimal infection risk over continuous BTKi and be convenient to administer. And we would argue it must be compared to the foundational CLL medicine, BRUKINSA. Naturally, patients want to be off treatment. But just as they want to know what they're gaining, every patient also wants to know what they're giving up. If that's overall survival, it's important that this is considered in the shared decision-making. So how do current fixed duration options compare to BRUKINSA? In our opinion, not very well. Existing ven-based BTKi regimens have liabilities that have limited their uptake and approval. These include underwhelming efficacy as seen in the AMPLIFY trial, where the AV combination had an inferior depth of response compared to chemo, demonstrating an undetectable MRD of only 34% despite AMPLIFY enrolling a young, fit and low-risk frontline population. In fact, AV's PFS at 3 years follow-up was roughly the same as BRUKINSA's at 6 years. And it's quite noteworthy that we haven't seen an updated cut from AMPLIFY for nearly 2 years. And similarly, with respect to safety, AV and VI have limitations due to ven, a less potent and less selective first-generation BCL-2 inhibitor. In terms of convenience, the low depth of response for AV may result in most patients having to be treated for far longer than 1 year to reach an undetectable MRD. In addition, ven requires cumbersome patient monitoring due to its long half-life and TLS risk, which calls into question the convenience benefit of this all-oral regimen. At the highest level, the primary benefit of fixed duration therapy is the treatment-free interval, during which patients are not exposed to the potential side effects of ongoing therapy. In CLL, this means avoiding the agents that suppress rapid B-cell expansion, which allow for immune recovery and a reduced risk of infection. So fixed duration therapies should lower infection risk over time, not raise it. The CLL17 trial studied fixed duration VO and VI versus continuous ibrutinib, and it was presented at ASH a few months ago. The chart on the left shows the CLL17 trial data, which tells a clear and quite concerning story. First, after 1 year of VO, severe infections continue to climb for 3 years while the patient was off treatment, as seen in blue. These infections are serious, often requiring hospitalization and IV antibiotics. Second, even after 4 years, severe infections were still higher with VO than with continuous ibrutinib despite the 3-year treatment-free period. As a reminder, BRUKINSA demonstrated roughly 1/3 fewer grade 3/4 infections versus ibrutinib in the ALPINE study. The VO arm also showed a 67% nominally increased risk of death versus ibrutinib. These findings are quite consistent with data from other recent studies, such as AMPLIFY, where the AVO regimen was not FDA approved. In fact, the FDA specifically called out the higher death rate due to infections from the AVO arm. In our view, this profile stands in direct opposition to what patients want and deserve from a fixed duration treatment. And if you now look at the table on the right, for the highest risk patients, roughly half of all CLL patients, VO shows notably lower PFS. This data shows that patients have an approximately 50% higher chance of progressing within 6 years. 50%. Look, there's a narrative that the current fixed duration options are good. And if someone I love was diagnosed with CLL, my first inclination might also be towards fixed duration. But if I knew the disease had potentially 50% higher chance of progressing within 6 years. And if I knew that fixed duration wasn't reducing the risk of serious infection over 4 years, just accelerating it into the earlier years, I certainly would encourage them to think twice. The risk-benefit profile of current fixed duration regimens simply does not justify a shift away from established continuous BTKi therapy. The evidence that existing time-limited therapies may not provide long-term outcomes comparable with BRUKINSA continues to build. Here, we can see 3 recently published match-adjusted indirect comparisons of BRUKINSA versus AV, VI and VO, which reached that conclusion. And these reflect the early trends we're seeing in real-world data. Our goal for patients that prefer a fixed duration treatment option is simple. We aim to develop a more efficacious time-limited regimen that does not come with caveats or accommodations. And we believe ZS is that therapy. The clinical data being generated by combining the best-in-class BTK inhibitor with a potentially best-in-class BCL-2 inhibitor just looks different. With all the caveats of cross-trial comparison, ZS has demonstrated the highest undetectable MRD rate, the highest PFS for the respective follow-up when compared to other ven-based fixed duration therapies. ZS shows a favorable safety profile with fewer high-grade adverse events and no deaths. And in terms of patient convenience, we've not yet observed any clinical or laboratory TLS, and we're very optimistic that for most patients, only one clinic visit during ramp-up will be required after zanu lead-in. Today, the CLL landscape is roughly split evenly into patients who receive continuous BTK inhibitors and those who receive some form of fixed duration treatment. And currently, BRUKINSA captures approximately half of the continuous BTK segment of the market. ZS will enable BeOne to participate in the other half of the market where today we have no presence. In summary, BeOne remains the only company with fully owned potentially best-in-class assets across 3 foundational MOAs in CLL: BRUKINSA, sonro and our BTK CDAC. As I said earlier, we think it is time to start talking about a cure. All 3 of these foundational assets, whether it's monotherapy or in combination, represent the next chapter in CLL innovation, raising the bar for patients everywhere. Now I'll pass it over to Aaron to provide the financial update.

Aaron Rosenberg: 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 launches. Now turning to the other components of our GAAP P&L, and my commentary will be on a full year basis, unless otherwise noted. Gross margin improved to 87% from approximately 84% in the prior year. This year-over-year improvement primarily reflects the benefits from favorable product mix, price and product cost efficiencies. Operating expenses grew by 12%, totaling $4.2 billion as we are investing with discipline to support our commercial growth and rapidly advance our innovative pipeline. Income from operations totaled $447 million, showcasing the inflection in 2025 to a company that is at scale and profitable. Bridging from operating to net income, other income and expense included a nonrecurring $40 million equity investment impairment in the fourth quarter. Income tax expense totaled $130 million for 2025, increasing from $112 million in 2024, including $25 million of nonrecurring tax expenses and $20 million of timing-related tax expenses in certain geographies. These effects, in part driven by our valuation allowance status, disproportionately impacted the fourth quarter. Altogether and including these onetime items, net income reached $287 million in GAAP -- with GAAP diluted earnings per ADS of $2.53. Our non-GAAP P&L includes adjustments for typical items with a full reconciliation provided in the appendix. Non-GAAP income from operations totaled $1.1 billion in fiscal 2025, up from $45 million in 2024. And non-GAAP net income came in at $918 million for full year 2025, which translates to diluted non-GAAP earnings per ADS of $8.09. We continued our strong trend of cash flow generation with free cash flow of $380 million in Q4. Full year 2025 free cash flow was over $940 million. Now turning to our 2026 financial guidance. We expect another strong year of revenue growth with continued global leadership for BRUKINSA. We anticipate that the U.S. will continue to see strong demand growth with relatively stable net pricing. Growth is anticipated in all markets and will benefit from continued global expansion in important rest of world markets. We anticipate modest initial contributions from our launches of sonrotoclax and zanidatamab as physicians begin to gain experience with these medicines ahead of launches in their respective larger market opportunities. We are pleased that these practice-changing medicines are becoming available to patients as they fulfill important unmet medical needs. In total, we project 2026 revenue to be between $6.2 billion to $6.4 billion. As you model quarterly phasing for 2026, please recall that we expect similar seasonality in shipping weeks in Q1 2026 as we observed in Q1 2025. And therefore, we believe it is more useful to consider year-over-year growth rates in this upcoming period. Our GAAP gross margin percentage is expected to be in the high 80% range with continued benefit from mix and a full year of productivity from improvements implemented last year. Operating expenses on a GAAP basis are anticipated to be between $4.7 billion and $4.9 billion. This level of investment ensures we are positioned to capture the full value of our commercial and late-stage pipeline opportunities. GAAP operating income is expected to be between $700 million and $800 million and non-GAAP operating income is expected to be between $1.4 billion and $1.5 billion. In terms of other income and expenses, we expect expenses to be between $25 million to $50 million. This includes interest expense associated with the Royalty Pharma arrangement. Turning to income taxes, where we have historically been in a valuation allowance, whereby our accumulated deferred tax assets have a reserve against them. Given our recent history of earnings, we believe that there may be sufficient positive evidence to recognize a portion of these assets in 2026. The exact timing and magnitude are uncertain, but we believe that a potential reversal would result in a material tax benefit to the income tax provision when recognized. When this reversal occurs, we will reflect deferred taxes in our financial statements, and our effective tax rate will become a more meaningful and predictable metric. We will provide additional updates on income taxes throughout the year. In summary, we are pleased with our performance in 2025 and like our setup for continued growth and financial strengthening as reflected in our 2026 guidance. I would be remiss if I did not take this opportunity to thank our global teams across all parts of BeOne for their incredible dedication to our company's purpose and the corresponding results that can be seen so clearly in our financial performance. And with that, I'd like to pass the call over to Lai.

Wang Lai: 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 AML. Third, we'll establish BeOne as an oncology powerhouse in solid tumors, with leadership in 3 strategically chosen subtypes driven by both internal innovation and external partnerships. And finally, we plan to advance one to two potential cornerstone immunology assets towards registration. It took us 15 years to build our foundational CLL franchise. We believe we can move faster and do even better across other diseases. With greater scale and a sense of urgency, we can reach far more patients than ever before. In CLL, today BRUKINSA is approved for both treatment-naive and relapsed/refractory patients, giving us a strong foundation. Looking ahead, in the frontline setting, BRUKINSA will serve as the foundational therapy either as continued use for patients who prefer finite therapy as a potentially best-in-class fixed duration regimen in combination with sonro. In the relapsed/refractory setting, BeOne will offer BTK-CDAC anchored therapies, we see a potential accelerated approval opportunity for our BTK CDAC as a continuous use monotherapy as early as next year. There are 3 Phase III studies ongoing to establish strong evidence versus current standard of care. Beyond that, we believe the BTK CDAC and sonro combination has the potential to deliver best-in-class fixed duration therapy for relapsed/refractory patients with strong efficacy, safety and convenience. A Phase III study is being planned. Finally, we are also developing an alternative fixed duration option, combining sonro with anti-CD20 therapies, currently being tested head-to-head against venetoclax in a Phase III study. We are also advancing our 3 foundational hematology assets across non-CLL indications. These molecules have demonstrated strong activity across multiple B-cell malignancies, including mantle cell lymphoma, Waldenström's macroglobulinemia, follicular lymphoma and marginal zone lymphoma. We're particularly excited about the Phase III interim analysis for zanu in combination with rituximab in treatment-naive mantle cell lymphoma expected in the first half of this year. If successful, this would represent the first chemotherapy-free regimen in this setting. In addition, we're expanding into multiple myeloma with plans to initiate a pivotal Phase III study in combination with CD38 antibody and dexamethasone by the end of this year. 2026 will also be the year we expand beyond BTK and BCL-2 MOAs in the hematology-oncology. A new wave of assets is entering the clinic, led by our proprietary, off-the-shelf iPSC-derived gamma delta T-cell therapy with 12 genetic engineering modifications. This program is highly differentiated and designed to overcome many of the limitations of the existing off-shelf cell therapies. I'm very excited about its potential in the clinic. In parallel, we're advancing T-cell engagers and T-cell boosters for B-cell malignancies particularly for aggressive lymphomas to address challenges such as tumor antigen loss and inadequate or unsustained T-cell activation. For AML and MDS, we are building a focused portfolio to address the significant unmet medical need. Beyond sonro, this includes a first-in indication KAT6 inhibitor, supported by strong translational data and a next-generation Menin inhibitor designed to overcome all known resistance mutations. We also have additional undisclosed preclinical programs underway that will continue to fuel our future pipeline. In summary, we have built a hematology portfolio defined by durability, differentiation and depth, positioning BeOne for sustained impact well beyond our current leadership areas. With that, let me turn to solid tumors. Previously, our solid tumor focus was largely on immuno-oncology. Over the last 2 years, we have fundamentally reengineered the portfolio, shifting towards critical oncogenic signaling pathways across breast, gynecological, lung and gastrointestinal cancers, using multiple therapeutic modalities. As you can see on the slide, we now have more than 20 assets across these focused disease areas. Among them, 5 programs have achieved proof of concept in 2025, and I will walk you through these key assets now. First, based on strong emerging efficacy and the safety data from Phase I expansion cohorts, we plan to initiate a Phase III trial in frontline hormone receptor-positive breast cancer in the first half of 2026. The safety profile suggests potentially best-in-class hematological safety with manageable gastrointestinal toxicity. The Phase III study will compare BGB-43395 against the physician's choice of CDK4/6 inhibitor in combination with letrozole with progression-free survival by central radiology review as a primary endpoint. Beyond the CDK4, we have 4 additional solid tumor programs advancing rapidly towards registration, all supported by compelling and evolving clinical data. B7H4 ADC, encouraging activity in gynecological cancers and the triple-negative breast cancer. A Phase III study is expected to start within 1 year. GPC3x41BB bispecific, the strength of the positive data from this program has been a pleasant surprise, showing very exciting monotherapy signals in PD-1 pretreated HCC patients in its first-in-human study. A pivotal trial will be initiated before year-end. PRMT5 inhibitor, this asset stands out with a potentially best-in-class potency, selectivity and brain penetration. Based on emerging Phase I data, we accelerated this program into frontline non-small cell lung cancer. CEA ADC, we are seeing promising monotherapy activity in heavily pretreated patients and are planning for the pivotal trials. It is important to note that all 4 assets have been in the clinic for less than 2 years and the 3 for less than 18 months. This is a level of focus, efficiency and execution we aim to deliver across the portfolio. Together, these 5 PoC assets represent a step change in BeOne solid tumor impact with multiple modalities, rapid clinical execution and a clear path to registration, we are no longer building a pipeline, we are building a solid tumor franchise, and this is only the beginning. To complement our growing portfolio, we have also invested heavily in clinical execution capability. We now call this our global clinical development super highway, designed to deliver industry-leading speed, quality and reliability. Let me give you a few examples. Over the past 2 years, we have completed around 200 dose escalation cohorts across multiple first-in-human studies with a median of just 1.5 months per cohort. The industry norm is roughly 3 months. In late-stage development, last year, we completed enrollment of CELESTIAL TN CLL study with around 700 CL patients across 20 countries and more than 200 sites in just 14 months. And as you know, CLL is not an easy indication to enroll. On the regulatory side, our most recent NDA filing, sonro's initial filing with the FDA in mantle cell lymphoma was completed within 1 month of top line data. Industry standards are typically 4 to 6 months. Finally, we're equipping the super highways with AI and automation. Today, we can already deliver near real-time data analysis and insights across all early stage clinical trials. Over the next 2 to 3 years, we expect AI and automation to unlock even greater gains in speed, quality and decision-making. This global clinical super highway is a core competitive advantage for BeOne. We look forward to sharing continued progress in future updates. Very quickly, on 2026 catalysts, I have touched on most of them already, so let me highlight a few key ones I haven't mentioned yet. First, we just initiated a global Phase III study of ZS versus AV in treatment-naive CLL directly comparing two all-oral fixed-duration regimens. Second, in the first half of this year, we expect to file tislelizumab for HER2-positive gastric cancer in combination with zanidatamab and chemo. And finally, in immunology, we anticipate multiple proof-of-concept readouts this year, including BTK CDAC in CSU and IRAK4 CDAC in RA. I will now turn it back to John.

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

Michael Schmidt: 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?

John Oyler: 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?

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

Yaron Werber: 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?

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

Matt Shaulis: 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.

Xiaobin Wu: 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.

Operator: Our next question comes from Ziyi Chen with Goldman Sachs.

Ziyi Chen: 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?

John Oyler: Please, Lai. And thanks for the question.

Wang Lai: 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.

John Oyler: Can we have another question, please?

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

Yigal Nochomovitz: 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.

John Oyler: Sure. Aaron is going to answer to that.

Aaron Rosenberg: 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.

John Oyler: 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.

Operator: Our next question comes from Reni Benjamin at Citizens JMP.

Reni Benjamin: 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?

John Oyler: Great question. Amit, will you please respond?

Amit Agarwal: 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.

Operator: Our next question comes from Sean Laaman at Morgan Stanley.

Sean Laaman: 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?

John Oyler: Aaron, would you like to answer that?

Aaron Rosenberg: 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.

John Oyler: 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.

Operator: Our next question comes from Chen Chen with UBS.

Chen Chen: 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?

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

Mark Lanasa: 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.

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

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

Leonid Timashev: 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?

John Oyler: Amit, would you like to answer that question?

Amit Agarwal: 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.

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

Operator: We have one more question from Rebecca Liang from Bernstein.

Rebecca Liang: 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?

John Oyler: 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 seems pretty safe, can treat all patients indefinitely, and that's truly, truly a cure. But we don't have long-term follow-up yet on that. I think the early data makes it appear this is going to be better than any fixed duration evidence-based therapy that you've seen to date. But we need time for that all to mature. And although it could be possible that this therapy even in the highest risk patients is very compelling and can be as efficacious as continuous use BRUKINSA. It's a high bar. It's a really high bar. And you just go back and look on that scatter plot where VO is on the scatter plot versus continuous ibrutinib, which is the comparison that's made in CLL 17. Well, that's not the relevant comparison. The relevant comparison is continuous BRUKINSA which, of course, has much better-looking 6-year data from a patient and physician perspective. So we need to see how the thing evolves, but it will take time. It will take more than 6 years to understand and establish for those high-risk patients. Is this really something that's as good as and competitive with long-term continuous BRUKINSA use. It'd be great if it is, but nobody can be sure of that. And anyway, thank you so much for the question. And I'd like to thank everybody for today's discussion. It really marks the close of a strong fourth quarter, and it's a pivotal full year for BeOne. And I think as you just heard, 2025 was defined by really flawless commercial execution and accelerated R&D momentum across our whole business. And I do believe that our performance reflects what truly differentiates BeOne as a company. It's our commitment to scientific excellence, our exceptional speed, our relentless focus on developing the best long-term outcomes for all patients. And on behalf of everyone here, I really want to thank the broader oncology community, the patients and families who inspire our work, the clinicians who partner with us every day and our almost 12,000 employees all around the world who continue to raise the bar. I truly believe that together, we're how the world stops cancer. And as we enter 2026, we're more confident than ever in the opportunity ahead of us. So thank you again, everyone, for your time today, and have a wonderful week.