BeOne Medicines Ltd.

Good day, everyone. Welcome to B1 Medicine's Q4 and full year 2025 earnings call webcast. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. 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 B1 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.b1medicines.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 on 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 is outlined on slide three. John Euler, 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 Wong, 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 Chalas, 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 B1. From a financial perspective, we delivered on our commitments, achieving significant product revenue growth, gap profitability, and meaningful cash flow generation. In 2025, our foundational BTK inhibitor Brukinza became number one, both in the US and globally. And as you can see on this slide, the gap between Brukinza and the competition is widening. And that's not just a commercial achievement, it's a scientific one. Brukinza'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 one 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. Six-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 six-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 BCL2 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 two continuous BTKIs, albeit with approximately 10% delta in six-year progression-free survival. However, the VI regimen was not approved by the FDA, and the addition of obinutuzumab to Venn has significant safety challenges, which I'm going to touch on later. As good as continuous use of Brutinib was, the molecule was not optimized for potency or selectivity. The second approved BTK inhibitor, Acala Brutinib, was designed to be more selective than Abrutinib and to have a very short half-life of roughly one 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 goals. 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 scatterplot, Acala's six-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 two continuous treatments would be raised yet again by a differentiated foundational medicine. Enter Brukinza. Brukinza 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, Brukinza demonstrated superior efficacy to ibrutinib and a more favorable safety profile. And this includes statistically significant improvement in AFib. And at ASH 2025, Brukinza set a new bar for long-term patient outcomes. Here, we can see six-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 establish Brukinza 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 B1, we believe that true innovation comes from improving upon the best. Rukinza did just that when it demonstrated superiority in terms of safety and efficacy over Abrutinib. No other BTK inhibitor can make that claim. Here we see the Kaplan-Meier curves from head-to-head trials of Brukinza 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, Brukinza showed the greatest early separation from Ibrutinib and remained 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 ElevateRR study, Acala showed early PFS separation from Ibrutinib, albeit less than Brukinza. 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 Pertobrutinib, 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 two-thirds of the enrolled patients in that trial. You can see that PERTO, 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 PERTO may face an uphill battle in showing statistical superiority to Ibrutinib in PFS. Now, if you've learned anything about B1 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 propose three 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, match 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 scatterplot clearly implies the need for further improvements on what's currently available. And we do believe that B1 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 durations? 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 affection risk over continuous BTKI, and be convenient to administer. And we would argue it must be compared to the foundational CLL medicine, Brukinza. 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 Brukinza? In our opinion, not very well. Existing Venn-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 three years follow-up was roughly the same as Brukinza's at six years. And it's quite noteworthy that we haven't seen an updated cut from Amplify for nearly two years. And similarly, with respect to safety, AV and VI have limitations due to VEN, a less potent and less selective first-generation BCL2 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 one 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 one year of VO, severe infections continue to climb for three years while the patient was off treatment. as seen in blue. These infections are serious, often requiring hospitalization and IV antibiotics. Second, even after four years, severe infections were still higher with VO than with continuous ibrutinib, despite the three-year treatment-free period. As a reminder, Rukinza demonstrated roughly one-third fewer grade 3-4 infections versus ibrutinib in the Alpine study. The VO arm also showed a 67% nominally increased risk of death versus abrutinib. 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 six 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 six years, and If I knew that fixed duration wasn't reducing the risk of serious infection over four 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 Brukinza continues to build. Here we can see three recently published match-adjusted indirect comparisons of Brukinza versus AV, VI, and VO, which reach 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 BCL2 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 Venn-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 Xanu 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, Rukinza captures approximately half of the continuous BTK segment of the market. CS will enable B1 to participate in the other half of the market where today we have no presence. In summary, B1 remains the only company with fully owned, potentially best-in-class assets across three foundational MOAs in CLL, Brukinza, Sonro, and our BTK CDAC. As I said earlier, we think it is time to start talking about a cure. All three of these foundational assets, whether as 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.

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. Rukinza global revenues totaled $1.1 billion, growing 38% with strong performance across all geographies. For full year 2025, Rukinza global revenues were $3.9 billion, representing growth of 49%. And as John shared earlier, Rukinza has established itself as the leading BTKI globally by an increasing margin as we closed 2025. In the U.S., Rukinza 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 Brookings' 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, Tovembra reported an 18% increase, reflecting continued market leadership in China. This growth was supplemented by contributions from launch markets. Our in-license 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 Brukinza'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 Brukinza 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 non-recurring $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 non-recurring 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 one-time items, net income reached $287 million 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 Burkina. 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 long 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 and 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 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 and 800 million, and non-GAAP operating income is expected to be between 1.4 and 1.5 billion. In terms of other income and expenses, we expect expenses to be This includes interest expense associated with the royalty pharma arrangement. Turning to income taxes, where we have historically been an evaluation 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 B1 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.

Thank you, Aaron. Hi, everyone. Thanks for joining us today. 2025 has been a standout year for B1 R&D. Most notably, it was a breakout year for Sonos. We achieved our first global approvals in China for RELAS Refractory MCL and CLL. In addition, regulatory submissions for RELAS Refractory MCL are under review in both the US and the EU, with FDA approval expected in the first half of this year. Our BTK integrator continues to advance steadily towards registration. In 2025, we initiated three phase three studies, including a head-to-head trial versus further. In solid tumors, we also made a strong progress. Tevambra delivered a positive phase three readout in HER2 part of gastric cancer in combination with Xanadatimab and chemotherapy. Importantly, the next wave of innovation is here. In 2025 alone, five assets achieved a clinical POC, And over the past two years, we have advanced 17 new molecule entities into the clinic. B1 has moved us through two defining chapters in our history. In the first 10 years, we built from the ground up. With limited capabilities, we delivered the two breakthrough medicines, Bokinsa and Kevembra, and proved that B1 could innovate at the highest level. The second chapter, over the past five years, was about skill and readiness. We invested heavily to build a powerful discovery engine and a truly differentiated global clinical development superhighway, transforming B1 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 B1. Over the next three years, we have focused on four priorities. First, we'll deepen our leadership in CLL, building on our three foundational medicines. Second, we'll expand across hematological malignancies, including indolent and aggressive lymphomas, as well as AML. Third, we'll establish B1 as an oncology powerhouse in solid tumors. with leadership in three 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 cell franchise. We believe we can move faster and do even better across other diseases. With greater skill and a sense of urgency, we can reach far more patients than ever before. In CLL, today Bukinsa is approved for both treatment-naive and relaxed refractory patients, giving us a strong foundation. Looking ahead, in the frontline setting, Bukinsa will serve as the foundational therapy either as continued use for patients who prefer finite therapy as a potentially best-in-class fixed-situation regimen in combination with solo. In the relapsed refractory setting, B1 will offer BTK-CDAC and critical therapies. We see a potential accelerated approval opportunity for our BTK-CDAC as a continuing use model therapy as early as next year. There are three Phase III studies ongoing to establish strong evidence versus current standard care. Beyond that, we believe the BDK-CDAC and the SORON combination has the potential to deliver best-in-class fixed-duration therapy for relapsed refractory patients with strong efficacy, safety, and convenience. A phase 3 study is being planned. Finally, we're also developing an alternative fixed-duration option, combining SORON with anti-CD20 therapies. Currently being tested head-to-head against venetoclax in a phase 3 study. We're also advancing our three foundational hematology assets across non-CL indications. These molecules have demonstrated strong activity across multiple B-cell malignancies, including mental cell lymphoma, water-strong macroglobulinemia, follicle lymphoma, and marginal zone lymphoma. We're particularly excited about the phase 3 interim analysis for ZANU in combination with rituximab in treatment of mental cell lymphoma, expected in the first half of this year. If successful, this would represent the first chemotherapy-free regimen in this study. In addition, we're expanding Soron into multiple myeloma, with plans to initiate a pivotal phase three study in combination with CD30 antibody and dexamethasone by the end of this year. 2026 will also be the year we expand beyond BDK and the BCR2 MOAs in the hematology oncology. A new wave of assets is entering the clinic, led by our proprietary off-the-shelf iPSC-developed 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 cue-managing loss and inadequate or unsustained T cell activation. For ML and MDS, we're building a focused portfolio to address the significance of mathematical needs. Beyond the sorrel, this includes a first-in-indication Cas6 inhibitor supported by strong translational data And at Next Generation, Manning has designed to overcome all known resistance mutations. We also have additional undisclosed preclinical programs on the way that will continue to fuel our future pipeline. In summary, we have built a hematology portfolio defined by durability, differentiation, and the depth. Positioning B1 for sustained impact will be on 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 two years, we have fundamentally re-engineered the portfolio, shifting towards critical oncogenical signaling pathways across breast, gynecological, lung, and the gastrointestinal cancers using multiple therapeutic modalities. As you can see on the slide, We now have more than 20 assets across this focused disease areas. Among them, five programs have achieved the proof concept in 2025. And now I will walk you through this key assets now. First, based on strong emerging efficacy and the safety data from phase one expansion cohorts, we plan to initiate a phase three 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 BGB43395 against the physician's choice of CDK4-6 inhibitor in combination with letrozole, with progression-free survival by central radiology review as the primary endpoint. Beyond the CDK4, we have four additional solid tumor programs advancing rapidly towards registration, all supported by compelling and evolving clinical data. B7H4ADC, encouraging activity in gynecological cancers and the triple negative breast cancer. A phase three study is expected to start within one year. GPC341BB biospecific. The strengths of the positive data from this program has been a pleasant surprise. showing very exciting monocytopenia signals in PD-1 pretreated HCC patients in its first in-human study. A pivotal trial will be initiated before year-end. Piontify inhibitor. This asset stands out with potentially best in class potency, selectivity, and brain penetration. Based on emerging phase 1 data, we're accelerating this program into frontline non-small cell lung cancer. CADC. We are seeing promising monocytopenia activity in heavily pre-treated patients and are planning for the pivotal trials. It is important to note that all four assets have been in the clinic for less than two years, and the three for less than 18 months. This is a level of focus, efficiency, and execution we aim to deliver across the portfolio. Together, these five POC assets represent a step change in B1 solid tumor impact. with multiple modalities, rapid clinical execution, and clear pass-through registration when no longer building a pipeline, while 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 superhighway, designed to deliver industry-leading speed, quality, and reliability. Let me give you a few examples. Over the past two 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 three months. In late-stage development, last year, We're completing enrollment over celestial TN-CLL study with around 700 CLL 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, Soros initial filing with FDA in mental cell lymphoma was completed within one month of top-line data. Industry standards are typically four to six months. Finally, we're equipping the superhighways 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 two to three years, we expect the AI and automation to unlock even greater gains in speed, quality, and decision making. This global clinical superhighway is a core competitive advantage for B1. 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. We just initiated a global phase three study of ZS versus AV in tumor naive CLL, directly comparing two oral fixed duration regimens. Second, in the first half of this year, we expect to file tizolizumab for HER2-positive gastric cancer in combination with standard DATMAP and the chemo. And finally, In immunology, we anticipate multiple proof of concept readouts this year, including BTK-CELEC in CSU and IRAC-4-CELEC in RA. I will now turn it back to John.

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.

Thank you. If you would like to ask a question, please use the raise hand icon, which can be found at the bottom of the webinar application. When you are called upon, please unmute your line and ask your question. We will now take a minute for the queue to assemble. Our first question comes from Michael Schmidt at Guggenheim Partners. Please unmute your line and ask your question.

Hey, guys. Good morning, and thanks for taking our questions. I had a commercial question around the BTK inhibitor market and Brukinza. 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? Thanks so much.

Yeah. Yeah, 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 Brukinza 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, you know, in our mind, best in class product that has demonstrated the translation of its mechanism of action into real clinical results. And I think at this point, you know, certainly there are challenges for those other products. But, you know, 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. So could we jump to the next question, please?

Yes, of course. Our next question comes from Yaron Werber with Cohen. Please unmute your line and ask your question. Great.

Thanks so much and congrats on really a lot of progress. I have a question I think a lot of us have been getting. In the guidance, what are you assuming in terms of competition from AV or Jayapirka is probably sort of late, late in the year. And then maybe secondly, in terms of Sunro for MCL, both in China and in the US, can you just help us think through a little bit, you know, kind of what's the initial opportunity? Thank you.

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

Sure, yeah, I can provide some perspective on Amplify and then JPIRCA 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 Birkenzo. We've outlined, as you heard from John, the importance of meeting some criteria for treatment in CLL, deep and durable remissions. And we see that AAV 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. to some of the cumbersome nature of then utilization. Now, as for JPIRCA, 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 J. Pyrrha after the continuous BTKs. And obviously, in our case, that bodes really well for Brukenza.

So... China, Sorong approved beginning of this year, 2026. And we launched so quickly after that approval. And since launch, this is about six weeks. And the reaction in the market has been very positive. We medicated or doctor prescribed for over 300 patient. And the approved indication is relapsed refractory mental cell lymphoma and CIL. 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 BCR2 market going forward. This is two approved BCR2 in China. One is the Venatoclax, and another one is... China, Loco, Lisa.

Great. Thanks so much, Xiaobeng. Can we jump to the next question, please?

Our next question comes from Zi Chen with Goldman Sachs. Please unmute your line and ask your question.

Thank you so much and 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 four pillars you're going to be working on. Lai mentioned about there are going to be one or two 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 B1 already being 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?

Great. Please lie. Thanks for the question.

Thanks for the question. In our clinical 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 optimistic, looking for potential opportunity to be the first in class or best in class. Our goal is in the next about two to three years to identify one or two 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, you know, the earning course. But there are some very exciting molecules we're really developing at this moment. Some of that is already in the clinical stage.

Thanks so much, Kimmy. Have another question, please.

Yes, the next question comes from Nigal from City. Please unmute your line and ask your question.

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

Sure.

Sure. Aaron's going to jump in tonight. Thanks for the question, Ugal. And you've seen the, you know, different forms of the pie chart that John shared in his slides. You know, 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 PTK-PCL2 combinations are a bit more mature in Europe. You know, about half the market is receiving fixed-dose treatment. and Brutonid 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 Brukinza, we view this as very market expanding.

Thanks.

Yeah, I think the promise is there, and we're hopeful that the data translates as positively as we've seen so far. You know, it really, you know, could fulfill the promise. And, you know, the story that's being told now about, you know, fixed duration, and, you know, were that to happen, that would be a really wonderful thing, but it would place us in a 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, you know, 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.

Thank you.

Thank you. Our next question comes from Rennie Benjamin at Citizens JMP. Please unmute your line and ask your question.

Hey, good morning, guys. Thanks for taking the questions and 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 ASHE. I thought that there was the 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 push out and how we should be thinking about the first approval? Thank you.

Great question. Amit, will you please respond?

Yeah, thank you for the question, Renny. So I don't think there's been a change in terms of, you know, 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 mid-year and file based on our interactions with the FDA. So there's really no change in terms of the timing there.

Got it. Thank you.

Next question, please.

Our next question comes from Sean Laman at Morgan Stanley. Please unmute your line and ask your question. Sean, can you please unmute your line and ask your question?

Good morning, John and team. Sorry about that. And thank you for taking my question. Just trying to understand a bit better, you know, the long runway of growth potential for Brookings 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 growth. So that's about, you know, three and a half billion where Brookings 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 that Calquin share?

Aaron, would you like to answer that? Thanks, Sean. And, you know, as as we've been talking, you know, we certainly feel very confident in the totality of the evidence for Brookings and ultimately the dynamics you're describing in terms of our performance in the marketplace. You know, it's the data that's resonating and ultimately translating to the growth that you've described. You know, as you look at the market share slide, 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 you know, that's the challenge, you know, of course, you know, 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.

Thank you.

Can we jump to a new question?

Our next question comes from Chen Chen with UBS. Please unmute your line and ask your question.

Thank you for taking my question. So my question is on B7H4 ADC. And actually, I think this is not in the model or in the evaluation right now. But I heard that you are going to initiate phase three within the next 12 months. So may I know that 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 phase three trial? And also I think the B7H4ADC is roughly like at least like 12 months like later than our like peers B7H4ADC. So what are the differentiation of this molecule? Thanks.

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 one 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 topo1 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 topo1 conjugated ADC and a good hematologic safety profile. So it's checking all the boxes to be on a path for a phase three study start as soon as possible. And again, we'll be able to share more details about first indication for phase three versus subsequent indications for phase three as we disclose data throughout the year.

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

Yes. Our next question comes from Leonard Timoshev with RBC Capital Markets.

Please unmute your line and ask your question. Hi, guys. Thanks for taking my question. I wanted to ask on the BTK de greater development pathway, specifically on the phase threes. I guess even you're going to have a potential accelerated approval and you're running three phase three studies, I guess what's the incremental value of each of those studies? I guess you need ultimately all three to fully realize the opportunity. Or do you think you're still going to have rapid uptake as the data starts to flow? The win over time. Thanks.

Thank you. Amit, would you like to answer that question?

Yeah, thank you for that question. I think from a BTK degraded 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 three, I think we're answering important questions with the phase three studies that we have right now, particularly with the two global phase three studies. I think, you know, one is in a slightly later line with the investigator's choice as a control arm. And then the other study is really a head-to-head study against pertabrutinib. And so we do see incremental value, especially from that pertabrutinib 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're obviously, as Lai showed, working on a BTK degrader plus Sondra 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. Please unmute your line and ask your question.

Hi. Congratulations on the great results, and thank you for taking my question. 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, um, routine for Kinza and Sunro after sorrow, um, plus Rukinza becomes a viable option. Um, given that now, um, the fixed duration therapy has have the patient share, but obviously much lower commercial sales. So, uh, the net of clacks, for example, only selling, uh, around two to 3 billion. versus the whole BDK 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 two products, even if there's maybe no immediate guidance for the long-term peak sales, but qualitatively the split between the two products?

Thank you. 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 that. 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 then has been very limited by its usability, especially in the community setting. So, you know, I think that having a fixed duration treatment that can replace, you know, 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 and 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... you know, 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, you know, 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, you know, evidence-based therapy that you've seen to date. But, you know, 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, you know, be as efficacious as continuous use for Kenza, it's a high bar. It's a really high bar. And, you know, you just go back and look on that scatter plot where VO is on the scatter plot versus... you know, continuous Ibrutinib, which is the comparison that's made in CLL17. Well, that's not the relevant comparison. The relevant comparison is continuous Brukenza, which of course has much, you know, better looking six-year data, you know, from a patient and physician perspective. So, you know, we need to see how the thing evolves, but it will take time. It'll take more than six 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 Brukinza use? It'd be great if it is, but nobody can be sure of that. At any rate, 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 B1. 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 B1 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 wanna 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, or 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.