BeOne Medicines Q3 2026 Earnings Results & Report

BeOne Medicines EPS Results

• Actual EPS: $3.64
• Consensus EPS: $2.34
• Beat/Miss: Beat by +$1.30
• One Year Ago EPS: N/A
• EPS Beat Rate: 4 of last 6 quarters

BeOne Medicines Revenue Results

• Actual Revenue: N/A
• Expected Revenue: N/A
• Beat/Miss: N/A
• YoY Revenue Growth: N/A

BeOne Medicines (NASDAQ:ONC) Ltd. is a global oncology company focused on discovering, developing, manufacturing and commercializing medicines for cancer patients. Formerly known as BeiGene, the company operates an integrated biotechnology platform spanning research, clinical development, regulatory activities and commercial operations.

Its portfolio includes BRUKINSA (zanubrutinib), a Bruton’s tyrosine kinase inhibitor used in the treatment of several blood cancers, and TEVIMBRA (tislelizumab), an anti-PD-1 immunotherapy approved in multiple markets for certain cancers. BeOne Medicines also maintains a pipeline of investigational therapies targeting a range of solid tumors and hematologic malignancies.

Founded in 2010, the company serves markets in North America, Europe, Asia and other international regions through its global commercial and clinical-development network. John V. Oyler, the company’s founder, serves as chairman and chief executive officer.

BeOne Medicines Q3 2026 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: Q3 revenue and profitability accelerated: Product revenue rose 33% year over year to about $1.9 billion, while GAAP operating income increased 157% to $419 million. BeOne raised its 2026 revenue outlook to $6.9 billion–$7.0 billion and increased its operating-income guidance.
• Positive Sentiment: BRUKINSA continued to drive growth: Global sales grew 34% to $1.4 billion, with U.S. sales exceeding $1 billion for the first time. Management pointed to strong new-patient starts and real-world evidence, while noting that U.S. sales benefited by about $50 million from order timing.
• Positive Sentiment: Pipeline progress broadened across hematology and solid tumors: BeOne reported encouraging early data for several solid-tumor programs and advanced its B7-H4 ADC into a Phase III trial. The company also said its BTK degrader met the primary endpoint in a Phase II CLL study and that its treatment-naive mantle-cell lymphoma application received FDA priority review.
• Negative Sentiment: Some expected returns may take longer, and investment will remain high: After FDA discussions, BeOne shifted its planned accelerated-approval filing for the BTK degrader in relapsed/refractory CLL to mid-2027, citing a request for additional follow-up. Management expects 2027 operating-expense growth to remain substantial, moderating the pace of margin expansion; it also flagged potential revenue pressure for XGEVA and KYPROLIS from biosimilars and possible China VBP inclusion.

Presentation

[Operator]

Good day, everyone. Welcome to BeOne Medicines Q3 2026 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.

[Dan Maller, Vice President of Investor Relations at BeOne Medicines]

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.

[Dan Maller, Vice President of Investor Relations at BeOne Medicines]

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. All information in this presentation is as of the date of the presentation, and we undertake no duty to update such information unless required by law. Now turning to today's call as outlined on slide three. John Oyler, our Co-Founder, Chairman, and CEO, will provide a business update. Aaron Rosenberg, our CFO, will provide an update on our third quarter financial results and 2026 financial guidance. 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.

[Dan Maller, Vice President of Investor Relations at BeOne Medicines]

Joining the team for the Q&A portion of the call will be Xiaobin Wu, President and Chief Operating Officer, Matt Shaulis, our General Manager of North America, Mark Lanasa, Chief Medical Officer for Solid Tumors, and Amit Agarwal, Chief Medical Officer for Hematology. I'll now pass the call over to John. John?

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thank you, Dan, and welcome. I am pleased to present our Q3 results today. Across every dimension of the business, BeOne is executing at the very highest level in our history. The results speak for themselves. Financially, we continue to deliver rapid growth and strong earnings. Aaron will take you through that shortly. In hematology, BRUKINSA's powerful and sustained BTK inhibition continues to translate into clinical and real-world differentiation. Building on BRUKINSA, BEQALZI, and tacabrutideg are expanding our leadership and extending it well into the future. In solid tumors, we are living up to our promise that 2026 would be an inflection year. Last week, we shared data for three of our most promising programs at ESMO. We have now shared differentiated data for five pivotal late-stage solid tumor programs.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

We have reached a level of productivity that I think is very rare in our industry, and the model we have worked so hard to build is already delivering very tangible results, and we have only just begun to scratch the surface of what is possible. Here we see BRUKINSA's performance for the quarter. Sales totaled $1.4 billion, growing 34% year-over-year, with U.S. sales exceeding $1 billion for the quarter for the first time. The underlying fundamentals continue to be very strong. BRUKINSA is not just a leader in CLL. It is a powerful treatment option across four other B-cell malignancies, and we are far from done. BRUKINSA, both as a single agent and in combination, continues to generate the most phase III data across the BTKI class. We often talk about BRUKINSA's clinical differentiation.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

It was designed for complete and sustained BTK inhibition, and it remains the only CLL therapy to show PFS superiority over ibrutinib in a head-to-head trial. The results we see in the clinical trial data for BRUKINSA are increasingly reinforced in the real world, and the picture is remarkably consistent. This slide brings together six independent data sets in CLL, representing tens of thousands of patients across three endpoints: overall survival, time to discontinuation, and time to next treatment. Across all of it, the answer is the same. All 21 hazard ratios favor BRUKINSA. In overall survival versus acalabrutinib, the four large U.S. claims data sets, including Medicare, range from 16%-25% lower risk of death. Versus ibrutinib, the reduction was 27%-36%.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Taken together across U.S. and European patients, claims and health records, survival and treatment durability, and versus both acalabrutinib and ibrutinib, the real-world evidence consistently favors BRUKINSA. BRUKINSA has established a strong foundation in hematology, but it is only the beginning of what we believe our heme franchise can achieve. With BRUKINSA, BEQALZI, and tacabrutideg, we are the only company with potentially best-in-class medicines across the three key mechanisms of action in B-cell malignancies. So whether a patient wants continuous or fixed-duration therapy, or requires an option after progression, we will be able to meet the need with the right medicine, alone or in combination. No other company is positioned to do that. This is not hypothetical. In the pivotal trials for the regimens on this slide, they are already reading out, and the data will be coming fast and furious over the next three years.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Behind these three promising medicines, the next wave of heme assets from our prolific discovery engine is entering the clinic. This includes small molecules, multispecific antibodies, and novel cell therapies. Turning to solid tumors, over the past several months, we have shared differentiated data for five programs: our GPC3 x 4-1BB bispecific antibody, our brain penetrant PRMT5 inhibitor, our CEA ADC, our CDK4 inhibitor, and our B7-H4 ADC. Most companies have just one exciting asset. Some have two. From just the first wave of our solid tumor pipeline, we have five, all advancing towards registration-enabling development in roughly the same time. These programs target some of the most common and deadly cancers in the world, including lung, breast, liver, gastric, and ovarian cancer. Together, they affect millions of patients every year and account for millions of cancer deaths worldwide.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

When we started this company 16 years ago, the goal was simple: to fight cancer and to fight for life, and also to dramatically change how things were done in our industry by building a company that could sustain that purpose. Today, that is no longer a vision, it is a reality. How are we doing this? This slide reiterates something fundamentally different about BeOne. For years, we have talked about our goal to build a lasting oncology company, one that generates higher returns for each dollar of R&D investment by leveraging our global development superhighway. Today, we are seeing the results. Over the last three years, we have brought more new oncology medicines into the clinic than any other company in our industry. We are moving them through the clinic with exceptional speed, behind the power of our global development superhighway.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Our CDK4 inhibitor and B7-H4 ADC programs show what this looks like in practice. Both moved from first in human to pivotal development in just two and a half years, allowing us to rapidly close the gap with the competition. Now we are seeing that pipeline advance into registrational trials, which puts BeOne in an exceptionally select group of oncology innovators. If you look back at any 18-month period in oncology since 2010, very few companies have ever seen this level of late-stage productivity. Our peers on this list are the largest, most accomplished pharma companies in the world, with R&D budgets many times ours. Yet, there we are, among the top. Our scientists are generating more high-quality shots on goal, we are advancing them faster, and importantly, we are converting them into late-stage programs. We are just getting started. At BeOne, we believe we have created something truly special.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

I just want to thank the team again for doing this. After these years of sustained investment and hard work, we have certainly built a model that is unique in the industry and is extremely difficult to replicate. It is built on four competitive advantages: rigorous and prolific internal research, our global development superhighway, global commercial presence, and an entrepreneurial culture driven by a deep sense of urgency, because cancer patients just cannot wait. These advantages create a self-reinforcing feedback loop. Together, they enable us to drive industry-leading R&D returns at scale, turn that innovation into profitable growth, and to fund a growing level of investment in next-generation medicines. Each turn of the cycle strengthens the next. That compounding effect is BeOne’s greatest long-term competitive advantage, and the best way to maximize long-term value is to keep investing behind it.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

As Aaron Rosenberg will discuss later, we think it's important to retain the financial flexibility to fully fund the opportunities we see in the business. We believe this is the right approach to bring more transformative medicines to patients and to achieve our goal of building the world's leading oncology company. With that, I'll turn it over to Aaron Rosenberg to discuss our financial performance. Aaron Rosenberg.

[Aaron Rosenberg, CFO at BeOne Medicines]

Thanks, John Oyler. Our third quarter results demonstrate continued strong execution across the business, with broad-based revenue growth, expanding operating income, and strong cash generation. Starting with our commercial performance, we delivered another strong quarter across the portfolio, with product revenue growing 33% year-over-year to approximately $1.9 billion. BRUKINSA global revenues reached approximately $1.4 billion, representing 34%, with sustained global leadership and growth in all regions. U.S. BRUKINSA sales exceeded $1 billion in the quarter, representing growth of 36%. Growth was driven by continued strong demand, with trends consistent with those that I discussed last quarter. These include sustained high level of new patient starts, meaningful growth from all approved indications, improved patient adherence, and duration of treatment compared to relative historical benchmarks. U.S. BRUKINSA sales did have an approximate $50 million tailwind due to order timing, inclusive of an extra shipping day in the quarter.

[Aaron Rosenberg, CFO at BeOne Medicines]

TEVIMBRA generated approximately $243 million, growing 28% year-over-year. We maintained our leadership position in China and saw launches in other markets increasingly contributing to growth. Since the August U.S. approval and launch of the HERIZON regimen, we have seen encouraging early prescriber reception, reflecting the strength of the triplet's differentiated profile in first-line HER2-positive GEA. Our Amgen in-license portfolio generated approximately $167 million, growing 26% year-over-year. Overall, we are pleased with the breadth of performance across the portfolio and the continued strength of the underlying commercial business. Let's turn to the geographic composition of our business. Growth remains broad-based across every region. The U.S. generated approximately $1 billion in product revenue and remains our largest market. BEQALZI launched in the U.S. in the relapse refractory MCL, and we're excited for this innovative medicine to be available for patients in this setting.

[Aaron Rosenberg, CFO at BeOne Medicines]

Given the size of the approved indication and the timing of launch, we do not expect BEQALZI to be a meaningful revenue driver this year. China contributed approximately $527 million, growing 21% in its seasonally high third quarter. Growth was seen across our commercial portfolio, with continued market leadership for both TEVIMBRA and BRUKINSA, and launch contributions from BEQALZI and ZIIHERA. Note that foreign exchange contributed 7% of reported growth, given year-over-year renminbi strengthening. While our Amgen portfolio delivered 26% growth in Q3, we are beginning to see some impact from biosimilars for XGEVA that was highlighted earlier in the year. This competition, along with potential VBP inclusion risks for XGEVA and KYPROLIS, will likely lead to revenue pressure for these brands beyond 2026. Europe generated approximately $234 million, growing 41%, driven by demand growth for BRUKINSA and launch uptake for TEVIMBRA.

[Aaron Rosenberg, CFO at BeOne Medicines]

Our rest of world markets contributed approximately $80 million, representing 58% growth. Key markets such as Japan and Brazil are making contributions that are increasingly meaningful at the enterprise level. Turning to the GAAP P&L. Total revenue was $1.9 billion, compared with $1.4 billion in the prior year. Gross margin was approximately 88%. This includes a non-cash intangible asset impairment charge of $22 million associated with the company's decision to revert promotional rights for PHESGO. Operating expenses totaled approximately $1.25 billion, representing 19% growth as we continue to invest behind the advancement of our pipeline and commercial growth. Moving down the P&L, we continue to demonstrate substantial scalability in the model, with income from operations growing 157% to $419 million, even as we continue an increased investment behind the tremendous opportunity of our late-stage pipeline. Finally, net income totaled $385 million.

[Aaron Rosenberg, CFO at BeOne Medicines]

GAAP diluted earnings per ADS were $3.28, compared with $1.09 in the prior period. Now turning to our adjusted results, with a full reconciliation provided in the appendix of our results presentation. Adjusted income from operations increased to $612 million, representing growth of more than 79%. Adjusted net income increased to $539 million, while adjusted diluted earnings per ADS increased to $4.59, compared with $2.65 a year ago. Cash generation continues to build momentum, with free cash flow up 34% from the prior year to $474 million. Turning to our updated full-year outlook. Given our performance through the third quarter and our expectations for the remainder of the year, we are raising and narrowing our 2026 guidance.

[Aaron Rosenberg, CFO at BeOne Medicines]

We now expect total revenue of $6.9 billion-$7 billion, compared with our prior range of $6.6 billion-$6.8 billion. We continue to see a modest net pricing benefit in the U.S. for BRUKINSA for the balance of the year. Looking ahead to 2027, we expect relatively stable net pricing. Note that the increase in our Medicare Part D manufacturer liability will likely pivot the modest tailwind we've seen in 2026 to a flat to modest headwind next year. This is a statutory increase associated with our specified small manufacturer designation for BRUKINSA. Our gross margin outlook remains unchanged in the high 80% range. We now expect operating expenses of $4.9 billion-$5 billion, a narrowing of the prior range of $4.8 billion-$5 billion. We expect GAAP operating income of $1.2 billion-$1.3 billion, an increase of $200 million across the range.

[Aaron Rosenberg, CFO at BeOne Medicines]

Finally, we expect non-GAAP operating income of $1.9 billion-$2 billion, also an increase of $200 million across the range. Moving to income taxes, I would like to provide an update on the income tax valuation allowance that I spoke about earlier this year. As background, we have historically been in a valuation allowance whereby the accumulated deferred tax assets we have, or have a reserve against them. Given our recent history of earnings, we believe there will be sufficient positive evidence to recognize a portion of these assets. We continue to evaluate and assess the magnitude, but the current expectation is that the reversal will occur in the fourth quarter, and that it will result in a material tax benefit to the income tax provision, and correspondingly, to our full-year GAAP net income.

[Aaron Rosenberg, CFO at BeOne Medicines]

In reporting periods after the reversal occurs, we will reflect deferred tax assets in our financial statements, and our effective tax rate will become a more meaningful and predictable metric, although it might take several years to normalize. We plan on providing additional commentary for this in our fourth quarter call. As we look beyond 2026, I would like to make one broader point on the trajectory of operating margins. The business is performing really well, and our underlying earnings power has continued to increase, as you see in our guidance updates over the course of the year. This profitability has translated into free cash flow and an increasingly strong balance sheet, which provides us with increased financial and strategic flexibility. Moving forward, we now have multiple differentiated assets advancing into pivotal development across some of oncology's largest indications.

[Aaron Rosenberg, CFO at BeOne Medicines]

Given the quality of these opportunities, and those that will come from the next wave of our model, as well as potential business development, we intend to continue investing with discipline to maximize our impact for patients and value for shareholders. As I said last quarter, we anticipate 2027 operating expenses growth to be at least consistent with where we have been over the past several years, given the size of our pipeline opportunity. As a result, while we expect operating income to continue to grow meaningfully, the pace of margin expansion is likely to be modest as compared to 2025 and 2026, as we balance near-term margin percentage gains with investment in future growth. With that, I will turn the presentation over to Lai.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

Thank you, Aaron. We continue to make strong progress across our pipeline this quarter in both hematology and solid tumors. Today, I will highlight several important clinical and development updates, including the new solid tumor data we recently presented at ESMO. Let me start with a few highlights across the portfolio. For BRUKINSA, in treatment-naive mantle cell lymphoma, we have completed submissions in the U.S., Europe, and China, and the FDA has granted priority review. The MANGROVE results will also be featured in a plenary presentation at ASH. For BEQALZI, CELESTIAL-304 remains on track to complete enrollment before year-end. For tacabrutideg, the phase II portion of CaDAnCe-101 met its primary endpoint, and following discussion with the FDA, we are planning for a potential submission in mid-2027. I will come back to tacabrutideg in more details shortly. In solid tumors, we continue to accelerate our late-stage programs.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

For our CDK4 inhibitor, we are increasing the sample size of the phase III KANDELA-302 study. Importantly, we are doing this to bring the study readout earlier. We have achieved first subject enrolled for our B7-H4 ADC, Starstone-301 phase III study. This marks the second start of a phase III study in our solid tumor franchise this year. We are also advancing our GPC3 x 4-1BB bispecific into pivotal development, while development of our PRMT5 inhibitor and CEA ADC continues to advance following the data presented at ESMO. Stepping back, this progress reflects our deliberate R&D strategy. We are building depth in disease areas where we believe we can establish leadership rather than developing individual assets in isolation. We do this across small molecules, degraders, ADCs, and multispecifics, matching modality to biology, and increasingly building combinations from within our portfolio. Our goal is not simply to generate more molecules.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

It is to create the next treatment paradigm that can meaningfully improve outcomes for patients. Now let me come back to tacabrutideg. The phase II study in relapsed/refractory CLL achieved its primary ORR endpoint, with encouraging duration of response, PFS, and safety. We are targeting a potential FDA submission in mid-2027. Our growing confidence in CaDAnCe-304 is also allowing us to optimize the broader development program. We are increasing enrollment number in 304 study from 500 to 600 patients to accelerate the readout, while remaining on track to complete enrollment in early 2027. Given our increased confidence in 304 outcome, we are converting CaDAnCe-302 to a phase II study. Importantly, we will continue to expand the program. Our phase III study of tacabrutideg plus sonrotoclax in relapsed/refractory CLL is on track to begin enrollment in the first half of 2027.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

The right-hand panel highlights what we believe differentiates tacabrutideg, excellent selectivity in kinome and the protein degradation assays. Primarily a BTK degrader, tacabrutideg also provides a distinct secondary BTK inhibitory function that may increase the barrier to resistance and potentially extend the response duration. We will share additional data at ASH. Turning to solid tumors, I will start with our GPC3 x 4-1BB bispecific. HCC remains an area of significant unmet medical need. In the U.S., liver cancer ranks sixth in cancer mortality. Its incidence is similar to that of multiple myeloma and the triple-negative breast cancer, and higher than that of the small cell lung cancer and the EGFR mutant non-small cell lung cancer. Despite this burden, there have been only two global phase III HCC studies since 2021, far fewer than any of the other tumor types shown on this slide.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

At ESMO, BGB-B2033 monotherapy demonstrated a 36% confirmed response rate in heavily pretreated second-line plus HCC, with strong durability and a favorable safety profile without CRS. This compares favorably with historical TKI response rate of approximately 5%-10% in this setting. We are moving quickly into registration and development. The potential pivotal third-line plus cohort for China and Korea is fully enrolled. Before year-end, we expect to initiate both a second-line plus single-arm study, supporting a potential U.S. accelerated approval pathway, and a second-line plus phase III confirmatory trial. We are also very encouraged by the progress of our first-line combination with TEVIMBRA and Avastin, supporting our plan to initiate a global phase III study in first-line HCC in the first half of 2027. Let me first highlight the differentiated safety profile.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

The treatment-related adverse events shown here are predominantly low-grade, with very few grade 3 or higher events among the most frequently reported adverse events. Importantly, we have not observed CRS. Now turning to efficacy. In addition to the high response rate, I really want to emphasize the durability of the responses. Among the 27 confirmed responders, the six-month duration of response rate was approximately 79%. The long-lasting responses we are seeing are reminiscent of the durability that has been a hallmark of immune therapies. Our second major ESMO dataset was BGB-58067, our brain-penetrant PRMT5 inhibitor. We have observed objective responses across multiple MTAP-deficient tumor types. In previously treated MTAP-deficient EGFR wild-type non-small cell lung cancer, the confirmed response rate was 38.5%, with median PFS of 8.1 months. We also observed intracranial responses in patients with brain metastasis. The potential opportunity extends beyond non-small cell lung cancer.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

MTAP deletion occurs across a number of tumor types. Our development strategy includes pancreatic cancer, GBM, and potentially other tumors. In non-small cell lung cancer, we are already evaluating combination with PD-1 and chemotherapy in first-line setting. In pancreatic cancer, we plan to begin evaluating combinations with the RAS inhibitors from our Revolution Medicines collaboration before year-end. Here again, our strategy is to take an encouraging early signal and rapidly build a broader development program around the differentiated properties of the molecule. Looking more closely at the efficacy, I first want to highlight the durability we're seeing. Responses have been durable, and we are also seeing patients with prolonged stable disease. This is encouraging because the benefit appears to extend beyond patients who achieve an objective response. Another important feature of BGB-58067 is brain penetrance.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

Among non-small cell lung cancer patients with active brain metastasis, the confirmed intracranial response rate was 30.8%. What I found particularly interesting is the low intracranial progression rate of 16%. This is substantially lower than what has been reported for Dato-DXd and docetaxel, and it is more in the range of what we see with CNS-penetrant targeted therapies such as osimertinib. Let me turn next to BG-C477, our CEA ADC. At ESMO, we presented initial proof-of-concept data in heavily pretreated CEA non-small cell lung cancer. The confirmed response rate was 60%, with a six-month DOR rate of 73% in phase I-A dataset. We also observed a favorable safety profile, including no grade 3 or higher ILD or ocular events in the dataset presented. Approximately one-third non-small cell lung cancer tumors are estimated to have high CEA expression.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

Based on these early results, we're developing BG-C477 across the non-small cell lung cancer treatment spectrum. A global phase III study in second-line non-small cell lung cancer is in planning. A first-line combination cohort with PD-1 is ongoing. We're also evaluating opportunity in earlier stage disease. Looking more closely at the efficacy, we're seeing broad activity across both squamous and non-squamous non-small cell lung cancer and across EGFR status. Within the non-squamous disease, the response rate was numerically higher in EGFR wild type than in EGFR mutant patients. We're also encouraged by the durability. The six-month PFS rate was 76.2%, and the median PFS has not been reached at the data cutoff. Let's turn to ASH. We have 45 accepted abstracts and five oral presentations across BRUKINSA, BEQALZI, and tacabrutideg, including MANGROVE in treatment-naive mantle cell lymphoma at the ASH plenary.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

We believe MANGROVE supports the potential for BRUKINSA to establish new chemo-free standard of care in treatment-naive mantle cell lymphoma. In CLL, our seven-year overall survival data show life expectancy matching the general population, moving us closer to our cure zone ambition. As John discussed, real-world evidence continues to report a survival advantage for BRUKINSA. For BEQALZI, the frontline combination with BRUKINSA showed 100% three-year PFS rate, while the ramp-up data highlight convenience advantages over venetoclax. For tacabrutideg, longer clinical follow-up and the differentiated mechanistic data continue to support its potential as the first and best-in-class BTK degrader, including a distinct design that may address resistance mechanisms and the high selectivity among BTK degraders in the clinical relevant whole blood assays. We'll have much more to discuss at our ASH investor event on December 14. Let me close with this overview of our upcoming milestones.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

As you can see, we have already addressed the vast majority of this today, reflecting the significant momentum across both hematology and the solid tumor portfolios. We will provide additional updates on our 2027 milestones at J.P. Morgan. And with that, I will turn it back to John.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thanks, Lai. We will now open the call to Q&A. Please limit the number of questions that you have so we can ensure that we have time to hear from as many attendees as possible. Operator, please go ahead.

[Operator]

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. Okay, we have our first question from Jessica Fye from J.P. Morgan. If you would like to unmute yourself, please, Jessica.

[Jessica Fye, Analyst at J.P. Morgan]

Hey, good morning, guys. Thanks for taking my question. Couple on the pipeline. Can you just expand a little bit on what is behind the timing shift on the filing for tacabrutideg for relapsed/refractory CLL? For the GPC3 x 4-1BB bispecific, I guess for Mark or Lai, I think BioNTech had some interesting liver cancer data for their PD-1/VEGF bispecific combined with the B7-H3 ADC in liver cancer. Can you talk about where you think your GPC3 x 4-1BB bispecific might have advantages over that regimen? Thank you.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thanks, Jessica. Hope you are well. I guess we can start with Amit and then move to Mark.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

Thank you, John. Let me provide a little bit of color on the tacabrutideg update. First off, we are pleased to report the positive readout of the phase II trial. As Lai mentioned in his prepared remarks, the study met its primary endpoint of ORR. In terms of other endpoints like duration of response, progression-free survival, and safety, the data is very strong and reinforces our confidence in the program. We did recently have discussions with the FDA on our potential accelerated approval submission. Based on those discussions, the FDA requested some additional follow-up. As a result of this, we are now planning to file for accelerated approval in mid-2027. What I will say is this is not an unusual request from the FDA, especially for a first approval of a new molecular entity. Again, overall, we remain confident in the program.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

As Lai also provided an update, what we are doing for this CaDAnCe-304 trial, which is our head-to-head trial versus pirtobrutinib, we are increasing the size of that trial. We think this will accelerate the timing of that interim readout and allow us to keep the enrollment timelines manageable. Really looking forward to all of these updates in 2027. With that, I will turn it over to Mark.

[Mark Lanasa, SVP and Chief Medical Officer for Solid Tumors at BeOne Medicines]

Thank you, Amit, and thanks, Jess, for the question. We are very excited about the potential of our GPC3 x 4-1BB targeting bispecific and have increasing confidence that this will be a transformative molecule for patients with hepatocellular carcinoma. As you heard from Lai, at ESMO, we recently reported a monotherapy response rate in later line, extensively pre-treated patients of 36%. These responses were durable with a six-month duration of response rate of 79%. Critically, we are delivering that efficacy with a highly favorable safety profile. Hepatocellular carcinoma is somewhat unique among solid tumors in that cytotoxic chemotherapy is really not a part of the standard of care. That is because these patients have compromised liver function and associated comorbidities. Therefore, while ADCs do have a meaningful response rate in this patient population, tolerability is a major challenge, and therefore durability becomes difficult.

[Mark Lanasa, SVP and Chief Medical Officer for Solid Tumors at BeOne Medicines]

With our favorable safety profile and very favorable efficacy profile, we have already been combining, as you heard from Lai Wang, with TEVIMBRA plus bevacizumab in a frontline patient population. We have enrolled over 70 patients, so we think that we have clear line of sight, not only in the later line patient segment where we have shared compelling data, but also in earlier lines of therapy where our favorable safety profile will enable higher order combinations to maximize patient benefit.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thank you, Mark.

[Operator]

Thank you.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Next question, please.

[Operator]

Okay, we have our next question from Yigal Nochomovitz, and they're from Citigroup. You can ask your question, please.

[Yigal Nochomovitz, Director at Citigroup]

Hi, hope you can hear me. Thanks for taking the questions and for the strong quarter. I just had three quick ones. John, you mentioned, of course, the fast and furious data coming for the next three years for the CLL franchise. I'm wondering if at this point, you're able to provide a little bit more granular timing with respect to the first PFS readouts for the fixed duration studies, the two that you're running, AV versus AV and versus VO. Second, maybe for Lai or Mark, with regard to the PRMT5 and the RevMed combination, do you expect or not expect to see a DDI with RASONQUE as, of course, we've seen with some competing PRMT5s? Third, on the CEA, anything to read into with respect to the differential efficacy on the mutants versus the wild types? Thank you.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Yeah. I think maybe we can start with Lai, and Lai, if you want to pass off to your team, please go ahead.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

Happy to. I will just comment on the DDI question related to PRMT5 with the RevMed assets. We have done preclinical modeling, and so far data suggests there's no significant concern around the potential DDI. Certainly, this need to be validated in the clinical setting. Maybe I'll pass this on to Mark to comment on the CEA ADC.

[Mark Lanasa, SVP and Chief Medical Officer for Solid Tumors at BeOne Medicines]

Thank you, Lai. Thank you, Yigal. This is something that we noted in the early emerging data. However, I would caution that the number of patients included, particularly in the EGFR mutant analysis, is relatively small. We are very excited about what we are seeing in terms of the response rate across all patients with non-small cell lung cancer, and importantly, durability is strong across these patients as well. We are currently in our dose optimization and expansion phase, and we will be able to share larger data sets in the near future.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

Amit, same comment. Yeah.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

Yeah. Thank you for the question, Yigal. On the two phase III studies, the CELESTIAL-301 study where we are comparing ZS to VO, and the CELESTIAL-304 study where we are comparing ZS to AV, again, as you know, both of those are event-based endpoints, and so we have not shared yet the approximate timelines, but we are hoping to do that in 2027. Overall, I would say, things are going really well with the ZS program. We will have updates at ASH from the 101 study, so we will share some updates in 2027.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thank you so much.

[Yigal Nochomovitz, Director at Citigroup]

Thank you very much.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Next question, please.

[Operator]

Our next question comes from Sean Laaman from Morgan Stanley.

[Sean Laaman, Analyst at Morgan Stanley]

Good morning, John and team. Congratulations on the results and hope everyone's well. I have two questions. The first one relates to the RevMed collaboration. You are funding and conducting the phase III RASonate 312 CRC study. What does that responsibility indicate about your long-term ambitions in precision oncology, is the first question. The second one, maybe one for Aaron, is just the commentary on margins. I think you said expect a more moderate pace in margin expansion versus this year and last year, but are you expecting margin to keep increasing from here, given the significant R&D investment BeOne has going on? Thank you.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Sure. I think we'll start with Lai and then move over to Aaron. Thank you.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

Yeah. Thank you so much for the question. This is the major reason I think that RevMed want to do this collaboration with BeOne, because they believe in our development superhighway. So we're conducting the 312 study, which is the frontline study in the CRC, which is testing the RASONQUE in combination with the standard care. We're very excited about this opportunity, and hopefully this will help RevMed to really fulfill their ambition about be the leader in the RAS space. Then certainly, this will also give us opportunity to potentially combining our pipeline assets with their molecules even further, as I think we mentioned in the press release. In addition to combining the PRMT5 with the RevMed assets, we're also combining our EGFR×MET×MET trispecific antibody with RevMed asset.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

As you can imagine, a combination with zoldonrasib in the CRC will be one of the leading indications for us to explore.

[Aaron Rosenberg, CFO at BeOne Medicines]

Thanks for the question, Sean. First, let me just start by saying, we are in an incredibly strong position financially, and we're really proud of what we've accomplished in our profile. The business is performing really well, and the setup continues to support growth, albeit at a larger base of business as we look forward. Since 2024, we've shifted, as you know, to a profit-making business, with operating margins that are set to expand by more than 10% in 2026 alone, based on the midpoint of our current guidance. That's something we're really proud of, and candidly, as you see in our guidance updates this year, it's at a pace ahead of where we thought we'd be at this time. Moving forward, our key message is that we're building a company to last, and it's supported by increasing financial flexibility.

[Aaron Rosenberg, CFO at BeOne Medicines]

We have tremendous opportunity with our pipeline and our repeatable innovation model, and we are going to invest to realize that full potential. As a result, we anticipate operating expenses to grow at a similar rate, as I said last quarter, to what we have seen over the last couple of years. Taken together, we do expect we will be able to fund our future ambitions while driving meaningful growth in profits, although the pace of growth in profit margin percentage will be modest as compared to what you have seen in recent years. Thanks for the question. Really appreciate it.

[Sean Laaman, Analyst at Morgan Stanley]

Thank you.

[Operator]

Our next question comes from Andrew Berens from Leerink. If you would like to ask your question, please.

[Andrew Berens, Analyst at Leerink]

Hi. Thanks, and congrats on all the progress, guys. Definitely the pipeline is expanding very rapidly. I guess two for me. One, as we go into ASH, how you are seeing the CDAC BTK agents fitting into the evolving treatment paradigms, especially with pirto seemingly moving more forward. Then, another one on the PRMT5 program that we saw at ESMO. How do you think your collaboration with RevMed positions this program relative to companies that have a head start in combos, like Pango and PDAC and then breast and lung?

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Yeah, thanks for the question. Why don't we start with Amit and then move to Mark?

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

Yeah, thank you for that question. In terms of the tacabrutideg program, I think again, we're very excited about the program as a whole and what we're presenting at ASH. Lai alluded to this a little bit. I think one of the interesting preclinical presentations that we will have at ASH is really this idea of having a secondary inhibitor function, and really what we think this is going to, or how we think this is going to translate into the clinic is particularly on the durability side of things. Beyond this, I think we're very well positioned to execute on that broad development plan for tacabrutideg. You heard a little bit of an update on our head-to-head study versus pirto, which is designed to show that tacabrutideg is clearly superior to pirto.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

As pirto moves in earlier lines, I think having this particular data set is going to be particularly important. But beyond this, we're also initiating a study of tacabrutideg plus sonro in the relapse CLL space, which we believe will be the fixed duration or best fixed duration treatment for that patient group, regardless of what type of treatments that they've received in the frontline treatment paradigm. Beyond this, we also see major challenges with the triplet regimen that pirto has just released on with the pirto and rituximab dataset, because the CD20 antibody really might be adding more toxicity there than providing clinical benefit. Overall, we're very confident in the program and really looking forward to some of these new studies with tacabrutideg.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thank you. Now maybe we take over to Mark.

[Mark Lanasa, SVP and Chief Medical Officer for Solid Tumors at BeOne Medicines]

Thank you, Amit, and thank you, Andy, for the question. We are very excited about the opportunity to combine our CNS penetrant PRMT5 inhibitor with the RevMed RAS(ON) molecules. In addition to the clinical data that has been disclosed for that combination, we also have strongly supportive preclinical evidence that we have generated in-house for that combination. I would highlight that in the recent disclosure that we had at ESMO, there were really a large number of patients treated across a broad number of solid tumors. So, we have a substantial global footprint in our phase I study. The amendment for the RevMed molecules has already gone through. It is posted on clinicaltrials.gov. We anticipate that enrollment will begin imminently. There is very high investigator enthusiasm. Therefore, we believe that our development superhighway, again, can close any time gap. As you heard from Lai, we are also not expecting a drug-drug interaction.

[Mark Lanasa, SVP and Chief Medical Officer for Solid Tumors at BeOne Medicines]

Therefore, we think that we have all the ingredients in place with a best-in-class PRMT5 inhibitor plus the development superhighway that we can meaningfully close the gap and ultimately be leaders in this space.

[Andrew Berens, Analyst at Leerink]

Thank you.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Let's next question, please.

[Operator]

Okay. Our next question comes from Gregory Renza from Truist Securities. Gregory, just checking if you can hear us. If not, we will move on to the next question.

[Gregory Renza, Analyst at Truist Securities]

Yes, I can. Thank you. Good morning, John and team. Let me add my congratulations on the progress and the results. Maybe just a question to follow up on the tacabrutideg updates. Good to see your increased confidence. Maybe just talk a little bit about just confirming your confidence about accelerated approval filing once you've implemented the changes that you're highlighting today. Maybe just talk a little bit about how you see that peak opportunity perhaps evolving. Do the updates in that confidence perhaps help to alter or maybe inform the longer-term positioning? Lastly, if I may, I'm just seeing the mention of the CSU trial and just broadening in the I&I. Maybe talk a little bit about that potential expansion and how intact that is. Thanks so much.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Great. Thanks for the question. It's always hard to answer regulatory questions, but Amit, please share what you can.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

Yeah. Thank you, John, and thank you for that question, Greg. What I would say is, again, I think right now we're very happy with the results we've seen from the phase II trial. Particularly when it comes to accelerated approvals, we certainly want to make sure that we respect that regulatory process. Without getting too ahead of ourselves, we remain confident in what the dataset shows and the unmet need in that particular population, and look forward to continuing the engagement with the FDA. Ultimately, I think the accelerated approval opportunity is still a smaller opportunity in the broader context of the program, and particularly the trials that we're outlining now, whether it's the head-to-head versus pirtobrutinib, or even the combination trials and future development that we have planned for tacabrutideg as a whole, we think that those are more meaningful opportunities.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

And certainly, as that head-to-head study reads out, it will open up the possibilities for a broader group of CLL patients to benefit from tacabrutideg. So we certainly think that the opportunity is much more beyond the accelerated approval opportunity. Perhaps I will ask Lai to comment on the CSU part of things.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

Yeah, we took a little bit of time to really contemplating our strategy for our BTK CDAC. We do believe with this extremely long half-life, we have a potential advantage for this molecule. We are on pace to initiate the CSU trial early 2027.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

All right. Thanks. Next question, please.

[Operator]

Our next question comes from Kalpit Patel from Wolfe Research.

[Analyst at Wolfe Research]

Hi, this is Mitchell on for Kalpit. Thank you for taking our question, and congrats on the result. We wanted to ask on the 1L breast cancer study. We noticed that the trial increased in size. Given that this is an event-driven study, can you help us understand how adding more patients gets you to the readout sooner, or keeping the required number of events changed, or have some of the same statistical assumptions? Thank you.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thanks. I'll pass that to Mark.

[Mark Lanasa, SVP and Chief Medical Officer for Solid Tumors at BeOne Medicines]

Great. Thank you for the question. The KANDELA-302 study is progressing very well. We're actually recruiting slightly ahead of our internal projections, and we've had very strong investigator feedback to date on the study design and their early experiences in the trial. In that context, upsizing the study has a number of statistical benefits that are conveyed by increasing the power of the study, and it is our belief that we will be able to enroll this somewhat larger study, approximately 10% larger study, in the same period of time we were originally projecting for the originally sized study of a little over 1,000 patients, now 1,200 patients. Without changing the assumptions in terms of the overall event rates, that actually pulls in our timeline somewhat because we have increased our statistical power.

[Mark Lanasa, SVP and Chief Medical Officer for Solid Tumors at BeOne Medicines]

Again, if the period of enrollment is fixed, then we will get to that readout earlier.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thanks, Mark. Next question.

[Operator]

We have our next question from Yaron Werber, who is from TD Cowen.

[Yaron Werber, Analyst at TD Cowen]

Great. Thanks so much. Congrats on all the progress. So maybe just two quick questions. First of all, on tacabrutideg, the pushout sort of to mid-next year, is that had to do with looking at more durability data? Are you thinking about filing for a broad label, essentially including both BTK inhibitors, covalent, non-covalent, and a BCL2? Then secondly, for the RASONQUE frontline CRC study, I just wanted to catch, in combination with chemo, is that phase III starting by year-end this year, or is it early next year? Thank you.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thanks so much. Hope you're well. I guess we're going back to Amit and Mark.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

Yeah. Thank you, John, and thank you for that question. In terms of the population for the phase II study, certainly this was a mix of patients who had covalent BTK inhibitor and a BCL2 inhibitor, as well as patients who had a covalent, non-covalent, and BCL2 inhibitor. We have seen encouraging results across those populations. To your question about the sort of shift there, it is related to the follow-up that we see, and certainly, this is something that we can expect given that new molecular entity, typically the FDA can ask for more data in terms of both the safety as well as the durability data. That is where we are with that one. Then I think the other question was for Mark.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

For Mark, yeah.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

I can take the other question, which is related to the 312 study for RevMed. We are initiating the study. We are working very closely with RevMed. At this moment, we will not be able to comment on exactly the time of the first patient to be dosed.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thanks so much. Next question, please.

[Operator]

Okay, we have our next question from Ziyi Chen, who is from Goldman Sachs.

[Ziyi Chen, Analyst at Goldman Sachs]

Good morning. Thank you for taking my questions. Congrats on another beat and raise. First is going to be on BRUKINSA. BRUKINSA has been the BTK leader for years now, and we have not seen a slowing down in the market share gain trend. What has been the drivers in the past few quarters behind the acceleration? Also, under this context, how do you see the impact of the new pirto's updated data for the BRUIN CLL-313 trial in the first line with a much longer median follow-up period? That is my first question. Second, we are really a big fan of GPC3 x 4-1BB, excited about the data as well. Given the safety profile now looks very good, we are kind of curious about the plan for 4-1BB-based pipeline expansion.

[Ziyi Chen, Analyst at Goldman Sachs]

What will be the next big thing, coming from 4-1BB-based bispecifics that we could be seeing and also prove the 4-1BB-based bispecific design is expandable to broader pipeline? Thank you.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Sure. I think that we will start with Matt, jump to Amit, and then go back to Lai, because Mark may be getting tired today.

[Matt Shaulis, General Manager of North America at BeOne Medicines]

Thanks, John. We are very pleased with the momentum in BRUKINSA. In terms of drivers, we continue to be a new patient start share leader across our indication settings. This is driven by very strong long-term data across CLL patient types and physician experience that is leading to preference. We have also, as you heard Aaron comment, been very pleased to see our duration of therapy and a more mature view on that with claims and real-world evidence that is more mature and allowed us to get a good read on what we believe is a pretty substantial duration of therapy. We have also seen growth come from indications beyond CLL in our other B-cell malignancies, particularly with some strength in Waldenstrom's. With regard to pirto, happy to comment on that as well.

[Matt Shaulis, General Manager of North America at BeOne Medicines]

We, of course, note that this was studied in a limited patient population, has limited data in elderly patients, no long-term data, and really limited differentiation on safety, like infections, cytopenias, and discontinuation rates. I think the most important factor is that these resistance mechanisms to pirto confer resistance to covalent BTK inhibitors. As a result, physicians do not want to burn a line of therapy, and thus far, we have really seen uptake contained to the later lines of therapy. I will hand it over to Amit to make some further commentary on that.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

Yeah, thank you, Matt. I think in terms of really the frontline setting, we continue to believe BRUKINSA is the gold standard when it comes to the data that has been presented so far. When you look at especially the long-term outcomes with a six-year PFS of 74%, with a COVID adjustment of 77%, and an overall survival of 84%, really, I do not think the data stacks up for pirto just yet. Obviously, the approval for pirto in the frontline was based on the BRUIN CLL-313 study, where pirto was being compared to BR, which really in the U.S. is an obsolete control arm. The initial results were presented with a very short follow-up. The biggest problem with this study, besides the control arm, is really the demographic skew of that study.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

The study enrolled really young patients, and when you look at the safety data there, it really needs to be evaluated in the light of that patient demographics. As Matt alluded to this, when you look at the BRUIN CLL-314 data, there is very little differentiation between pirto and ibrutinib. On efficacy, there are two events that separate pirto and ibrutinib the last time this data was presented. So basically, we are talking about 48 versus 50 PFS events. On the safety side, pirto just did not show any significant difference versus ibrutinib in terms of infection, cytopenias, and discontinuation rates. Even the AFib rate, when you age match it really is very comparable to what we have seen in SEQUOIA.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

In addition to this, as Matt highlighted, when we talk with thought leaders in CLL, the idea of effectively giving pirto ahead of a covalent BTK inhibitor and potentially burning a line of treatment, if you would, really is not appealing. We're not surprised that there is very limited uptake for pirto in the frontline. With that, I'll hand it to Mark.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

Maybe I can jump to take this question. Thank you, Ziyi Chen. This is a really very good question. I love to answer it. I want to mention beside the greater safety profile, what we have observed with GPC3x4-1BB, this immune kind of immediate MOA is really validated by the clinical data. If you look at the spider plot, we actually have a patient who, not only the response is durable, we actually have some patient begin to show up the response very late. There was one patient become a responder at week 36. 4-1BB is not the strongest kind of the T-cell activator. When you combine this potentially in the first line with some other agent which can help to control disease, which we believe this drug perhaps will perform even better.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

Over the years, we have built this really strong feedback loop between the preclinical to the clinical. Once we, in our preclinical hypothesis of GPC3x4-1BB was validated in the clinic setting, we began to really think about how can we maximize the value of our proprietary 4-1BB platform. We're working on two things. One is really leveraging this unique binder as well as the testing system to set up a whole set of the TA 4-1BB pipelines. I can assure you there are many programs we're working on at this moment. In addition to that, we're also work on next generation. We believe there are further room to improve on the current 4-1BB T-cell activator. That is also coming. Starting from next year, you'll begin to see new molecules coming from our 4-1BB platform.

[Lai Wang, President and Global Head of Research and Development at BeOne Medicines]

This will be one of the important technology platform we will leverage to build our pipeline.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Next slide. Can we get another question, please?

[Operator]

Our next question comes from Michael Schmidt from Guggenheim. If you'd like to unmute yourself and ask your question, please.

[Michael Schmidt, Analyst at Guggenheim]

Hey, guys. Thanks for taking my questions. I just had a housekeeping question on guidance. It looks like the updated guidance suggests flat to down revenue in the fourth quarter sequentially. Just wondering if that is just seasonality, conservatism, or if there's anything else going on towards the end of the year. Then just regarding the MANGROVE plenary at ASH, just remind us of the opportunity in that particular setting for the BRUKINSA franchise. Thanks so much.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Sure. Thanks, Michael, for the question. We'll start with Aaron and then move on to Amit.

[Aaron Rosenberg, CFO at BeOne Medicines]

Great. So thanks for the question. We are doing $5.1 billion of revenue, 33% growth. I mentioned when you account for the $50 million in timing that I noted, sequential and year-over-year growth are largely consistent where we tracked through the first three quarters of the year. Similarly, expenses reflect typical seasonality that you see in the industry as well as the increasing investments from our late-stage R&D programs. The guide therefore reflects a fairly consistent investment growth whether you have seen over the past two years and that will continue into 2027, as I said before. Thank you.

[Amit Agarwal, Chief Medical Officer for Hematology at BeOne Medicines]

Yeah. Thank you, Aaron. So in terms of MANGROVE, again, I think this is really exciting in terms of just what this means for frontline MCL patients. As we have indicated before, MANGROVE is the first and only chemo-free regimen for these patients that has shown superiority over a chemo regimen. The data and the fact that this is being accepted as a plenary presentation really speaks to the broader excitement that the oncology and hematology community are seeing with this particular regimen. Similarly, I think the priority review, we are hoping that this will come to the patients very soon. I will turn it over to Matt to talk a little bit about the commercial opportunity here.

[Matt Shaulis, General Manager of North America at BeOne Medicines]

Thanks, Amit. Just to put it into context, mantle cell is about 4,000 U.S. patients a year as compared to right around 20,000 CLL patients a year. So that gives you a sense of the size. As you heard from Amit, there is a really important unmet need for effective treatment options in frontline mantle cell that are supported by robust clinical evidence particularly in the setting where MANGROVE was studied. So this opportunity with a chemo-free option in previously untreated mantle cell with the strong efficacy and safety data that we will be bringing to the market, we think when approved will lead to extending the overall BTK class share within the space. Then, of course, we believe that we will take brand share within that class and really drive some growth here.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

All right. Thank you.

[Xiaobin Wu, President and COO at BeOne Medicines]

We also submitted the application in Europe and China. This also first line mantle cell patient in China and Europe, so 3,000 and 4,000 each. That provide additional opportunity for us.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Terrific. All right. If there's no-

[Operator]

Okay, then-

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

further questions. Are there further questions?

[Operator]

There are no further questions. I will now turn the call over to John Oyler for closing remarks. Thank you.

[John Oyler, Co-Founder, Chairman, and CEO at BeOne Medicines]

Thanks so much. In closing, we have never been better positioned. Our commercial business is delivering, our pipeline is deeper than ever, and our model is proving repeatable. The work ahead is significant, but so is the opportunity. I really want to thank the patients and the families that we serve, our physicians, our partners, and our more than 12,000 colleagues around the world whose focus and urgency make our progress possible. Thank you all so much for joining us today, and have a wonderful week.

Participants

Executives

• Dan Maller, Vice President of Investor Relations
• John Oyler, Co-Founder, Chairman, and CEO
• Aaron Rosenberg, CFO
• Lai Wang, President and Global Head of Research and Development
• Amit Agarwal, Chief Medical Officer for Hematology
• Mark Lanasa, SVP and Chief Medical Officer for Solid Tumors
• Matt Shaulis, General Manager of North America
• Xiaobin Wu, President and COO

Analysts

• Jessica Fye, Analyst at J.P. Morgan
• Yigal Nochomovitz, Director at Citigroup
• Sean Laaman, Analyst at Morgan Stanley
• Andrew Berens, Analyst at Leerink
• Gregory Renza, Analyst at Truist Securities
• Analyst at Wolfe Research
• Yaron Werber, Analyst at TD Cowen
• Ziyi Chen, Analyst at Goldman Sachs
• Michael Schmidt, Analyst at Guggenheim