BeOne Medicines Ltd. Q2 FY2025 Earnings Call

Good day, everyone. Welcome to BeOne Q2 2025 Earnings Call Webcast. At this time, I would like to turn the call over to the company.

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

Thank you, Dan, and welcome, everyone, to our Q2 earnings call. We had a spectacular second quarter. Our revenue reached $1.3 billion, which represents 42% year-on-year growth. GAAP earnings per ADS grew $2 from Q2 of last year, and we generated $220 million of free cash flow in Q2. This is a significant increase compared to last year. From a commercial perspective, BRUKINSA has cemented itself as the #1 BTK inhibitor in the U.S. market. This quarter, we also hosted an R&D Day where we shared three key takeaways. First, we believe our internal capabilities and our sense of urgency will drive superior returns on R&D. Second, how our hematology franchise is poised for sustained leadership into the next decade. And third, why you should pay close attention to our prolific and differentiated solid tumor pipeline. I want to return to BRUKINSA, the cornerstone of our CLL franchise. BRUKINSA's best-in-class profile has resulted in rapid adoption by patients and physicians across the U.S., despite launching in CLL nine years after ibrutinib. Here, we see the U.S. revenue performance of the three approved covalent BTK inhibitors since BRUKINSA's CLL approval. The chart speaks for itself. The gap between us and the competition continues to widen. BRUKINSA is both the market share leader and the fastest-growing brand, and it's the only BTK to be approved in five indications. The success of BRUKINSA is not an accident; it's the direct result of an overwhelming body of evidence accumulated over more than a decade. This evidence is remarkable for both its strength and consistency. When we designed BRUKINSA, our preclinical hypothesis was that sustained inhibition of BTK in the disease compartment and improved selectivity for BTK over off-target kinases would translate to a differentiated medicine for patients. Since then, BRUKINSA has treated thousands of patients in clinical trials and over 200,000 patients commercially. BRUKINSA has differentiated itself every step of the way, from human PK to clinical response, to PFS, and now in the market where it continues to generate compelling real-world data. As you know, the goal in oncology drug development is to hit the target hard and then never let up, never give the cancer an opportunity to grow. As seen on our slides, the prior generation BTK inhibitors only hit the target for a fraction of the day. However, BRUKINSA is different. It was designed to inhibit BTK 24 hours a day, seven days a week. We hypothesized that BRUKINSA's superior target coverage would translate to superior clinical benefits for patients. In the ALPINE trial, BRUKINSA drove higher responses compared to ibrutinib. This result was clear at the earliest data cut and more importantly, was maintained with longer follow-up. Our goal is to see whether the collective and consistent results across preclinical human PK and tumor shrinkage would be associated with improved and sustained PFS. Clearly, it was. BRUKINSA is the only BTK to demonstrate superior PFS and favorable safety in a head-to-head trial against ibrutinib. In the ALPINE trial, BRUKINSA exhibited a 34% reduced risk of progression or death and lower cardiac toxicity versus ibrutinib. There were zero cardiac deaths in the BRUKINSA arm versus six in the ibrutinib arm. In the Deletion 17P and TP53 subpopulations, which are the toughest patients to treat, BRUKINSA's treatment effect was even more pronounced, showing a 52% reduced risk of progression or death versus ibrutinib. The ALPINE data showed that BRUKINSA is the best-in-class option for all types of patients regardless of mutation or risk status. Fast forward to today, patient and physician adoption has driven BRUKINSA to be the top BTK inhibitor in the U.S. This slide shows two examples of recent presentations and publications supporting BRUKINSA's differentiation versus both acalabrutinib and ibrutinib. On the left is a real-world study demonstrating that patients treated with BRUKINSA had longer time to discontinuation, lower discontinuation rates, and less healthcare resource utilization than those treated with acalabrutinib and ibrutinib across all patients, notably more pronounced in older patients over 65. On the right is another recent publication by a leading CLL KOL recognizing BRUKINSA's differentiated data and how BRUKINSA can provide the best outcomes for their patients. Looking beyond BRUKINSA, BeOne stands out as the only company with fully owned, differentiated, and potentially best-in-class assets across all three foundational MOAs in CLL. We're already combining these assets in multiple Phase III trials to improve outcomes for CLL patients even further. We believe our relentless focus on serial innovation and CLL positions us as the only company that can address the full scope of unmet patient needs across all lines of therapy and subpopulations. That said, we're far more than a CLL company; we're a global oncology company, with a wealth of upcoming milestones on the horizon. By the end of 2026, we expect the initial global approval of sonro and potentially pivotal data for our BTK CDAC. Our internal clinical team will be running more than 20 Phase III trials, anticipating more than 10 proof-of-concept data readouts, and our research organization will again advance more than 10 NMEs into the clinic. With that, I'll pass it over to Aaron for the financial update.

Thanks, John. Product revenue reached $1.3 billion in the second quarter, representing 41% year-over-year growth. BRUKINSA's global revenues were $950 million, growing 49% year-over-year, driven by strong performance across all geographies. As John mentioned, BRUKINSA is now the clear value share leader in the growing U.S. BTK market. We continue to grow volume at a robust rate across all approved indications. This was seen again in Q2 with demand growth of 35% year-over-year and 10% sequentially, driven by the quality and differentiation of our long-term clinical data across all patient types. With our strengthening market position, we have seen competition aggressively discounting. Despite this, given our broad access strategy and protected class status, the vast majority of patients have unfettered access to BRUKINSA, with an even greater number achieving access upon appeal. We strongly believe in open access policy, which is clearly in the best interest for patients and preferred by doctors. Moving forward, we will continue to pursue contracting strategies that seek to achieve this goal while preserving the value of our clinically differentiated innovative medicines for the long term. From a pricing perspective, Q2 performance includes a mid-single-digit benefit largely associated with the annual increase taken at the beginning of the year. As mentioned last quarter, we also see some modest additional benefits in net pricing from Medicare Part D reform given our designation as a specified small manufacturer. We are confident in our long-term market leadership position for BRUKINSA as our revenue guidance fully factors in current market conditions. Meanwhile, TEVIMBRA reported a 22% increase, reflecting continued market leadership in China, supplemented by early contributions from launch markets. Our in-licensed products also showed continued strength, growing 27% year-over-year. Our China team launched zanidatamab in the quarter, providing an important new treatment option for patients with HER2 high-expression biliary tract cancer, historically an underserved patient population. Our geographically diverse product revenue mix continues to fuel strong growth across all key regions. The U.S. remains our largest market, generating $685 million with year-over-year growth of 43%. China revenue totaled $429 million, a 23% increase supported by TEVIMBRA and BRUKINSA's market leadership and growth from our in-licensed assets. Europe contributed $152 million, with 87% year-over-year growth as we continue our launch trajectory with BRUKINSA, increasing share across all major markets. The rest of world markets grew by 168% driven by market expansions and new launches. BRUKINSA was launched in Japan in March and had the largest uptake in the class in the three months since. TEVIMBRA is also launching in key markets, including Japan, South Korea, and Brazil, and we are encouraged by the early market responses. Turning to our Q2 2025 GAAP P&L, which illustrates our focus on top-line growth with meaningful margin expansion. Total revenue for the quarter was $1.3 billion, driven by the factors I previously highlighted. Gross margin improved to approximately 87% from 85% in the prior quarter, reflecting benefits from favorable product mix, price and production cost efficiencies. Operating expenses grew by 18%, totaling $1.1 billion as we are investing smartly to support our commercial growth and rapidly advance our innovative pipeline. Income tax expense of $5 million for the quarter includes discrete adjustments of approximately $14 million, primarily related to updated provision estimates for R&D tax credits. Our continued focus on margin expansion has translated to net income reaching $94 million in the quarter, representing diluted earnings per ADS of $0.84, a significant improvement compared to the same quarter last year. Our non-GAAP P&L includes adjustments for typical items with a full reconciliation provided in the appendix. Non-GAAP net income reached $253 million, reflecting an increase of $230 million compared to the previous year. This performance translated to diluted non-GAAP earnings per ADS of $2.25 for the second quarter. Given our execution, we are updating our full year 2025 guidance with total revenue expectations now ranging between $5 billion and $5.3 billion. The mid- to high 80% range for GAAP gross margin reflects favorable mix dynamics and the earlier realization of cost of goods efficiencies for TEVIMBRA. It also accounts for the recent anticipated approval for BRUKINSA's tablet formulation. The tablet achieves a lower cost of goods in addition to many patient benefits that this new formulation affords, including reduced pill burden and size with improved support for dosing flexibility. Operating expense guidance is unchanged. We project operating expenses between $4.1 billion and $4.4 billion. We remain committed to achieving positive GAAP operating income, and we expect to generate positive free cash flow for the year. Free cash flow is a broader measure of cash generation, accounting for both operational activities as well as capital expenditures. We are pleased with our execution in the first half of 2025 and remain focused on full-year delivery across all financial performance measures. With that, I'd like to pass it over to Lai.

Thank you, Aaron. Hello, everyone. Thanks for joining us today. As John mentioned, we recently hosted an Investor R&D Day. In addition to a data and portfolio update, we talked about how BeOne R&D is at a pivotal moment in its journey. Over the years, we have built strong research, internalized global clinical development, and manufacturing capabilities from the ground up, allowing us to discover, develop and deliver novel oncology medicines faster and more cost-effectively than industry standards. Our strategically advantaged capabilities are now at a scale and fully functional across R&D. You all know we have built a strong CLL franchise, but it took us a long time. Now with all these newly built capabilities, we believe we can reproduce our success in CLL across our other disease areas of focus and do it much faster. This is very exciting. Our goal is to build a deep pipeline in each of these disease areas to create strong in-portfolio synergy. Next, I’ll highlight our R&D progress in the second quarter. We have filed sonro's initial NDAs with the first two in China for relapsed/refractory CLL and refractory mantle cell lymphoma. The plan is to file mantle cell lymphoma globally later this year with longer follow-up. We presented over 60 abstracts from our heme portfolio at ASCO, EHA, and ICML and initiated new Phase III studies for sonro and our BTK CDAC in relapsed/refractory CLL. In addition, we provided updates from our solid tumor portfolio at ASCO and R&D Day. For the CDK4 program, we’re actively planning Phase III trials for both first-line and second-line hormone receptor-positive breast cancers. In the next few slides, I will walk you through our progress in CLL. We have built a comprehensive registration program spanning the full spectrum of CLL from treatment-naive to the relapsed/refractory settings. In the frontline setting, BRUKINSA has already established itself as a leading BTK inhibitor. With the combination of BRUKINSA plus sonrotoclax, we are advancing what we believe will be the best-in-class fixed duration regimen. For relapsed/refractory patients, our BTK degrader should become a cornerstone of continuous therapy. We are also advancing fixed duration regimens, including sonro plus CD20 antibodies. Additionally, we are evaluating sonro plus BTK CDAC, which can potentially be used for all patients in the second line regardless of what frontline treatment was used. We are determined to offer CLL patients important options throughout their treatment journey. Sonro, our next-generation B-cell inhibitor, has key characteristics that position this product to be potentially best-in-class. Sonro is 14 times more potent than venetoclax, which may translate into superior efficacy in the clinic. In addition, improved selectivity, shorter half-life, and lack of drug accumulation could offer a more favorable overall safety profile. Furthermore, sonro offers a more patient-friendly ramp-up with potentially only one clinical visit required during ramp-up compared to up to eight visits for venetoclax. Sonro has a broader development program with three Phase IIs for accelerated approvals and three ongoing Phase IIIs. Diving into the combination data, the zanidatamab plus venetoclax-ZS regimen achieved very high rates of undetectable uMRD at 10 minus 4, 92% in the 320-milligram cohort regardless of the risk status. With a median follow-up of 25.5 months, no PFS events have occurred in the 320-milligram cohort and only one event occurred in the 160-milligram cohort. A total of 137 patients treated in these two cohorts combined is no small data set. Thirty-five patients have elected to stop therapy after week 96, and all remain in remission, with some beyond 12 months without treatment. I would like to draw your attention to the table shown on this slide. With the normal caveats of a cross-trial comparison, ZS has demonstrated the highest uMRD rate and unmatched PFS for the respective follow-up when compared to other venetoclax-based fixed duration therapies. There are important deficiencies with other fixed duration therapies, like the low 34% uMRD rate and underwhelming three-year PFS rate of 77% observed with AV despite the ultra-fit population starting in the AMPLIFY trial. In terms of the new treatment paradigm in frontline CLL, safety and convenience are as important as efficacy. ZS showed a favorable safety profile with fewer high-grade adverse events and no deaths associated with the intravenous use of obinutuzumab, as well as cardiac toxicity and death linked to ibrutinib. We did not observe clinical or laboratory TRS, and we are optimistic that for the vast majority of patients, only one clinical visit will be required during ramp-up. In conclusion, we believe that the ZS combination has the potential to be a game changer for our fixed duration option for CLL patients. Moving to the third asset in our heme franchise, our BTK CDAC is the most advanced BTK degrader in the clinic with best-in-class features. The degradation mechanism can overcome and prevent emerging resistance mutations while disrupting the scaffolding function of BTK proteins. Long half-life in the clinic has resulted in sustained BTK degradation with daily dosing. We have a broader development program ongoing, including two pivotal Phase IIs for accelerated approval, two ongoing Phase IIIs, and one more in start-up. We provided an update on BTK CDAC Phase I results at EHA. In the graph on the left, you can see our BTK CDAC trending towards almost two years of median PFS in heavily pretreated CLL patients, which looks favorable compared to the recently published pirtobrutinib data from the BRUIN321 study shown on the right, with the usual caveats of cross-trial comparisons. The head-to-head trial versus pirto will start soon. Going beyond CLL, here we present an overview of the broad clinical development plan and clinical study across our heme franchise in non-CLL indications. This is designed to maximize the clinical and commercial value of BRUKINSA, sonrotoclax, and the BTK CDAC as part of our strategy for our B-cell malignancy franchise and beyond. Moving on to solid tumors, our solid tumor pipeline includes diverse modalities and mechanisms across three disease franchises: breast and gynecological cancers, lung cancers, and GI cancers. We revamped our entire solid tumor pipeline over the last two years, with every single asset either having entered the clinic in the past two years or expected to be in the clinic by the end of this year. This showcases our ability to quickly establish a deep and highly competitive pipeline in our areas of focus. Finally, I'd like to highlight a few key milestones within our pipeline. We have achieved critical goals for the year, with some completed ahead of schedule, such as the CLL and mantle cell filings for sonro in China. In the latter half of the year, we anticipate several significant milestones, including the global filing of sonro in relapsed/refractory mantle cell lymphoma. Additionally, we expect potentially pivotal data from our BTK CDAC in relapsed/refractory CLL and initiated global filings in 2026. Turning to our early-stage pipeline, we are actively moving some of these assets into late-stage development, including our CDK4 inhibitor and B7-H4 ADC. We look forward to sharing more data in future updates. With that, I will turn the call back to Dan.

Thanks, Lai. We are now ready for Q&A. Joining us for the Q&A portion of the call are Xiaobin Wu, President and Chief Operating Officer; Matt Shaulis, our General Manager of North America; and Mark Lanasa, Chief Medical Officer for solid tumors. I kindly ask participants to limit the number of questions to ensure we have time to hear from as many attendees today as possible. Operator, we are ready for the first question.

Our first question comes from Jessica Fye with JPMorgan.

Congrats on a strong quarter. On BRUKINSA, I think at the beginning of the year, you mentioned you expect flat U.S. net price this year. Has that expectation evolved now that we're halfway through the year? Were there any inventory changes at the end of Q2 relative to the end of Q1 that you might be able to quantify? Secondly, what was your reaction to the BRUIN-CLL-314 data for pirto versus IMBRUVICA in that mixed frontline and relapsed population? And what are you going to be watching for when those details are eventually presented? Lastly, regarding the CDK4, I think at the R&D Day, you mentioned starting a second-line Phase III trial as soon as Q4 '25, but I see that's now in the press releases for 2026. I recognize that the “as early as” framing doesn't definitively mean you were going to start in late '25. What additional information do you hope to gain prior to initiating that second-line Phase III trial, and can you confirm when we should expect to see updated clinical data for that asset this year?

Thanks, Jess, for the question. That's a three-part question, so maybe I'll ask Matt to comment on the first part regarding BRUKINSA and net pricing.

Sure. Thanks for the question, Jessica. We anticipate stable pricing through the remainder of the year and have no significant inventory levels to comment on.

The second part of that question was the BRUIN-314 reaction. Lai, I think I'd point that one to you.

Yes, thank you for that question. It is important to note that in the BRUIN-314 study, OR superiority was not formally tested, and therefore, it is not statistically significant. I also want to point out that including treatment-naive patients likely contributes to the OR difference. Our ALPINE study of BRUKINSA versus ibrutinib in the relapsed/refractory CLL remains the only head-to-head trial to show the superiority of one BTK inhibitor over another based on the PFS endpoint, which is the gold standard in CLL. We believe that in this setting, a positive readout of non-inferiority OR compared to ibrutinib is unlikely to be practice-changing for several reasons: number one, there’s no PFS data yet; number two, it is compared to ibrutinib; and any new continuous BTK inhibitor needs to demonstrate superiority over BRUKINSA, not ibrutinib. BRUKINSA should now be the true standard in treatment-naive settings. Moreover, I think it is still very early data. For BTK inhibitors, long follow-up is needed to show therapeutic benefit. We also expect pirto to primarily be sequenced after covalent BTK inhibitors. Therefore, it is hard to imagine this dataset will convince physicians that the better option is to use pirto instead of BRUKINSA based on BRUKINSA's results. Lastly, I think the BRUIN-314 alone is not sufficient for regulatory filing. As Lilly stated in their press release, it will be combined with BRUIN-313 to form the basis for regulatory submission. The key question will be whether BR is still a valid control. When filed for NDA in 2026, if the trial reads positive, the OS trend will be another important element to watch.

Thank you, Lai, and thank you, Jess. Good morning. We set an ambitious target for our first Phase III start by the end of 2025. However, as the data come in now, we believe it would be prudent to let the data mature a bit more to inform our Phase III dose level selection. The magnitude of the delay will be modest, pushing the timing from late '25 to early '26, which is why we're updating our guidance. Also, for the first time, we disclose our intent to start a frontline study with our CDK4 inhibitor in 2026. We're very excited about that program. To your other question, we intend to share the data from dose optimization in combination with fulvestrant at this year's San Antonio Breast Cancer Symposium.

Our next question comes from Sean Laaman at Morgan Stanley.

On the CELESTIAL-TNCLL trial, and I think it's 303. If successful there, how do you envision the market will play out? Do you consider the V plus O combination the initial target market? How should we think about pricing if you're selling BRUKINSA and sonro into that market? Additionally, how should we view the time-based therapy bleeding into normal operations or the rest of the market?

Happy to address that one, Sean. We are very optimistic about the prospects for zanidatamab plus sonro. You've heard from Lai on the clinical underpinnings of that. Certainly, regarding our overall approach to driving adoption in CLL, we think this will be one of the primary drivers. From a pricing standpoint, we will consider various comparators. As for fixed duration overall, we haven't seen much uptake of initial fixed-dose utilization; ven plus BTK isn't currently approved in the U.S., so usage is off-label. Given our observations from the data, we believe it would be inappropriate to see fixed duration use right now. As we've discussed before, the current regimens available tend to be used in very young, fit populations with limited risk factors, and we think the benchmark for deep and durable responses, strong PFS, and safety and tolerability hasn't yet been met. However, to your point, with CELESTIAL, we believe that zanidatamab plus sonro will satisfy the benchmarks, hence BTK monotherapy will remain strong until we see the zanidatamab plus sonro data, where bigger opportunities for fixed duration may arise.

Great. On the pirto equation, many KOLs we speak with express hesitance around the idea of pirto moving to frontline even with good data, as they may lose access to that second-line option. Can you share your thoughts on the resistance mechanisms associated with pirto versus BRUKINSA and frame the risk for us?

Lai, would you take that one?

Yes, I can address that question. In terms of resistance mechanisms, it's still evolving. Clearly, pirto can work on covalent BTK inhibitor failure populations, especially for cysteine-481 mutations. There are several other mutations pirto can work on as well. It is important to highlight that unless there is strong data showing that the covalent BTK inhibitor can work after pirto, physicians will likely wish to keep pirto as an option after covalent BTK inhibitors are utilized. I also want to reiterate that the BRUIN-314 data is still very early. It’s only showing OR non-inferiority. Most critically, if something is to enter frontline treatment, it needs to demonstrate superiority over BRUKINSA, not just ibrutinib.

Our next question comes from Ziyi Chen with Goldman Sachs.

Congratulations on a very strong quarter. I have two questions on financials and regarding the U.S. tariff. We've seen the gross margin improve notably in Q2 compared to Q1. While product revenue showed 18% quarter-over-quarter growth, the cost of goods sold in Q2 was flat versus Q1. Can you help us understand how you've been controlling manufacturing costs and optimizing that? Because this cannot solely be explained by product mix change. Additionally, regarding the potential U.S. tariff on pharmaceutical imports, which I understand President Trump stated would start small and potentially rise to 150% in 18 months, could you clarify if this guidance on gross margin reflects that potential tariff, and how we should view gross margin assumptions going forward?

Great. This is Aaron. Thank you for the question. I'll take it in two parts. You're right, we've seen improvement in gross margin quarter-over-quarter and relative to last year. As I mentioned in my prepared remarks, this is coming from improved production efficiencies, particularly for TEVIMBRA, alongside some price improvements and product mix. We are making significant efforts across manufacturing and supply chain to drive efficiency improvements. Largely, in this quarter, that’s TEVIMBRA. Regarding the U.S. tariffs, we've mentioned in the past how our current guidance takes into account what we know today about tariffs. This impact has been largely mitigated by our global and regional supply chain, including our U.S. production for BRUKINSA and our investments in our Hopewell facility, where we are qualifying this facility for TEVIMBRA production. As you noted, the uncertainty remains concerning the current Section 232 investigation. We’ll monitor the situation and remain agile in our response to ensure both financial efficiency and operational efficiencies as we supply our life-saving medicines to patients. As I mentioned, our 2025 guidance reflects our current knowledge. Any announcements beyond that are less likely to significantly influence our 2025 results due to how inventory is positioned and how that flows through the P&L. Future impacts could be manageable within the context of our P&L, but it’s too early to provide a forward outlook.

Just a quick one. Regarding the filing, could you elaborate more on the net pricing for BRUKINSA in the U.S. as mentioned in Q2? What was the benefit, and how should we consider net pricing going forward?

This is Aaron again. Great question. We do traditionally see relatively stable net pricing, which is exactly what we have seen in our current results. In my prepared remarks, we discussed mid-single-digit pricing impacts in the U.S., largely resulting from early year price increases, which is consistent with market practice. Additionally, we see some incremental benefit on a year-over-year basis related to Part D reform. As mentioned last quarter, the prior year included the manufacturing liability around the donut hole, which is no longer a factor, as that has been replaced by manufacturer liability under the cost share this year. Given the specified small manufacturer designation, this combination leads to our mid-single-digit performance year-over-year.

Our next question comes from Kelly Shi with Jefferies.

Congrats on another great quarter. For the revenue guidance raised to $5 billion to $5.3 billion, what drove this low-end bump? Specifically, which products underpin that outlook? Additionally, you mentioned 20-plus expected R&D milestones over the next 18 months. Could you provide more detail on which ones might have the most significant impact? Lastly, what have you learned from adding translational studies regarding how BeOne's BTK degrader tackles resistance mutations acquired from first-gen BTK inhibitors compared to pirto?

Thanks for your question. Our update to revenue guidance to $5 billion to $5.3 billion reflects our confidence in execution in the first half of the year. We do not provide specific product revenue guidance, but as seen in our current quarter performance as well as Q1, we’re pleased with our performance, and this update signals our confidence. On that note, Lai, do you want to tackle the R&D questions?

Sure, I’ll address the third question first regarding the BTK degrader's response to resistance compared to pirto. There are two well-known resistant mutations to pirto, L528W and T474 mutations, but so far, the BTK degrader works well with those mutations. We are still in the early stages regarding experience with the BTK degrader in the clinic, and there haven’t been many patients who progressed. We're actively following the types of resistance mutations emerging from the BTK degraders. However, the data does appear more promising in terms of longer tumor suppression when compared to pirto or other covalent BTK inhibitors. Regarding R&D milestones, for our heme side, we certainly aim to file sonrotoclax globally, which is a critical step for the molecule given everything we have seen in the clinic. The combination of sonrotoclax and zanidatamab shows outstanding activity in the mantle cell lymphoma monotherapy study globally, which will form the basis for the initial global filing. We’re also observing activity from this combination in multiple myeloma. On the degrader side, we’re excited to get pirto going in the coming months. We see that potentially providing a better drug for patients in the relapsed/refractory settings. Mark, do you want to take the solid tumor side?

Thank you, Lai. For the solid tumor, we’ll likely share the most important data disclosures for the remainder of 2025 at the San Antonio Breast Cancer Symposium. Many of the new molecules Lai highlighted in the solid tumor portfolio will have early data emerging. We’re pleased with the progress of the portfolio and look forward to sharing data from multiple programs in the first half of 2026. As Lai mentioned at the R&D Day, we're particularly excited about the four programs including CDK4, B7-H4, PRMT5, and FGFR2b that are showing very encouraging early data. We expect to disclose more data from those programs likely within the first half of next year.

Additionally, our degrader will have pivotal Phase II readouts next year, which could lead to a global filing. That’s also a significant milestone.

Our next question comes from Yigal Nochomovitz from Citigroup.

I have a few questions, a couple regarding BRUKINSA and then one on the pipeline. For BRUKINSA, you mentioned that the majority of patients have unfettered access and that there’s a step-up in access on appeal. Can you provide more specifics regarding the numbers associated with access for new patients and appeals? More generally, in terms of global business, considering the shift ex-China, have you reached a steady state concerning product mix and revenue across China, Europe, and the U.S., or do you still expect revenue to continue shifting more outside China? Lastly, could you comment more on the powering assumptions on PFS with respect to the CDAC versus pirto Phase III?

Thank you for the question. To address the access component, all access discussions begin with our belief in BRUKINSA as a differentiated asset that's best-in-class among the BTKs with a strong body of evidence that John described, comprising thousands of patients in clinical trials, and we’re continuing to evolve that with real-world evidence and additional data. We’re observing a preference for BRUKINSA from both healthcare providers and patients. As for the access component, oncology is a protected class, and BRUKINSA remains listed on all Medicare Part D formularies. Regarding the appeals process, it is essential to recognize that any preferences or step edits do not impact existing patients but apply to new patient starts. The majority of our claims are filled initially, and if an appeal is necessary, we have been successful in assisting accounts to navigate that process. We remain confident about ongoing access and increasing demand for BRUKINSA's ownership in value share. Aaron, over to you for the next question.

Certainly, Yigal. We’re growing globally, and each region is progressing at different rates. We’re still in early stages of our launch trajectories in many parts of the world. Historically, Europe has been earlier with regions in the rest of the world, including critical markets, being even earlier in their launch phases. So we expect our revenue mix to continue diversifying over time, with growth across all regions, including China. Xiaobin, do you have any added insights?

Certainly. As Aaron mentioned, the U.S. is our biggest revenue driver, achieving $685 million with a growth rate of 43%. China is the second biggest contributor, growing 23%. We recently published IQVIA data showing our position climbed to the sixth biggest oncology company in China. We are rapidly growing outside both U.S. and China as well. In Europe, we saw close to 90% growth. The rest of the world, comprising newer markets and JPAC, achieved 170% growth, showcasing a healthy dynamic across our regions. While we continue to experience strong growth in China, our expansion outside of China is even more accelerated.

To address your final question concerning empowering assumptions for PFS regarding CDAC versus pirto, as shown on Slide 28, there is a table below the PFS curve. Our CADENCE 101 study notably involved more heavily pre-treated patient populations. Importantly, a higher portion of patients had double or triple exposures, which reflects a worse prognostic pool. We see an encouraging PFS trend that gives us confidence, but I don't have more data than what you see here, given the data cut was around March. While we see positive trends, I must underscore that this is a cross-trial comparison.

Our next question comes from Reni Benjamin at Citizens JMP.

Congratulations on an excellent quarter. You're currently approved in 75 markets globally. Can you remind us how many markets you expect to be approved in at peak? Should this playbook be replicated for TEVIMBRA and sonrotoclax, or are there different factors influencing which markets you pursue for these two drugs? Additionally, regarding the tablet formulation mentioned in your prepared remarks, could this materially affect sales going forward, or does it primarily impact cost of goods? Will this eventually replace the current formulation?

Dr. Wu, could you respond to the total number of peak markets and how it might differ for TEVIMBRA?

Sure. We are currently approved in over 70 countries, including all major markets for both TEVIMBRA and BRUKINSA: U.S., EU, U.K., Switzerland, along with approvals in emerging markets like India, Indonesia, and Brazil. We continue to launch products in new markets and seek additional regulatory approvals across markets. Our mission remains focused on reaching as many patients as possible. With TEVIMBRA and BRUKINSA, we look to our major markets first but also tap into emerging markets wherever possible.

Regarding the tablet, our commitment to patients drives this. The tablet will be a more convenient formulation for patients. While the sales impact is difficult to quantify, we believe this will solidify our market leadership. Regarding if the formulation will replace the capsule, over time, the goal is to transition fully to the tablet due to patient preference.

Got it. As a quick follow-up to Xiaobin's answer: is the 75 markets where you are currently globally marketing it, is that it? Or is there potential for even more markets, or have we reached peak penetration and now it's just about growth in those markets?

Great question. We are continually expanding our footprint. BeiGene's mission is to reach as many patients as possible by providing innovative and affordable medicine. Therefore, our mission continues, and we aim to expand into more markets. We also aim to get new indications in the already registered markets while simultaneously focusing on launching in new markets.

Our final question comes from Michael Schmidt with Guggenheim.

Congrats on the great second quarter here. A bigger picture question on the covalent BTK inhibitor market in the U.S. is still growing at 10% right now here in the first half of 2025. Can you comment on what drives this overall market growth right now in the covalent BTK space? Is it due to duration of treatment or additional patients coming on to therapy? How should we think about the peak potential for the class, especially with potential fixed duration combinations coming in the future? How significant of a near-term growth driver is the first-line MCL opportunity for BRUKINSA based on the mangrove data later this year? Lastly, how do you feel about expanding BTK degrader development into autoimmune and inflammatory conditions? I know you mentioned that you have a CSU study currently up and running. Could you provide insights on the long-term potential of the degrader in autoimmune and inflammatory?

I'm happy to start with the covalent BTK market insights. We see that growth is driven predominantly by longer durations of therapy and higher treatment adherence. Analyzing data from ALPINE and additional sources indicates that BRUKINSA's duration of therapy is longer, correlating with better PFS. We believe substantial growth potential exists within the BTK space for those reasons. As for the mantle cell and MANGROVE data, we’re encouraged and believe that will provide a valuable data set. Given the prevalence of mantle cell, however, it will have limitations regarding overall patient size, but CLL continues to be our primary driver. Lai, over to you.

Regarding the BTK degrader's development into autoimmune and inflammatory conditions, we initiated a Phase Ib study in CSU. I want to point out three key features of our BTK degrader: one, long half-life, which allows for flexible dosing, potentially beneficial for certain diseases; two, its tissue penetration which could also apply to autoimmune diseases; and three, the degradation mechanism capable of overcoming resistance, which is important for specific disease areas. We are actively exploring various potentials for this molecule in autoimmune diseases, and we are excited about its prospects.

At this time, we have reached the end of the question and answer session. I will turn the call over to John Oyler for closing remarks.

Thank you. In closing, our second quarter results demonstrate exceptional execution across our key priorities. Our success is due to the sense of urgency and dedication of our more than 11,000 colleagues across the globe, as well as the collaborative efforts of the patients, clinicians, advocacy groups, regulators, and investors who have united with us in a joint effort and shared commitment to fight cancer globally. BeOne has helped over 1.8 million cancer patients, and I believe this is just the very beginning of our accomplishments. I'm looking forward to sharing more updates and milestones with you as we progress through the year. Thank you all for joining us today and for your thoughtful questions. Thank you.