BeOne Medicines AG (ONC) Earnings Call Transcript & Summary

Good day, everyone. Welcome to BeOne Medicines Q2 2026 Earnings Call Webcast. [Operator Instructions] At this time, I would like to turn the call over to the company.

Hello and welcome. Thank you 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, and 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 2026 financial guidance. And Lai Wang, President and Global Head of R&D, will discuss our R&D and pipeline progress. We will then open the call to questions. Joining the team for the Q&A portion of the call will be Dr. Wu, President and Chief Operating Officer; Matt Shaulis, 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?

Thank you, Dan, and welcome, everyone. Q2 was a very strong quarter across every dimension of our business. From a financial perspective, we achieved $1.7 billion in total revenues and $2.05 in GAAP earnings per ADS. This represents growth of 30% and 144% compared to the prior year, respectively. BRUKINSA, our foundational BTK inhibitor continues to exceed our high expectations in the marketplace. More than 6.5 years after its initial launch, BRUKINSA is seeing its highest level of sustained new patient starts showing favorable early trends in duration of therapy, and it's showing strong growth across all 5 approved indications. On the back of these strong results, we're raising our 2026 guidance ranges for revenue and GAAP operating income by $300 million and $250 million, respectively, and Aaron will detail this later. As impressive as our financial performance was in the quarter, our pipeline progress was equally significant. This is highlighted by the FDA approval of BEQALZI as the first and only BCL2 inhibitor in mantle cell lymphoma and the success of the Phase III MANGROVE study of BRUKINSA which is so exciting that it warrants the entire next slide. We also announced a $300 million expansion of our flagship U.S. manufacturing site in Hopewell, New Jersey. MANGROVE is yet another example of the growing body of evidence supporting BRUKINSA as the foundational BTK inhibitor. We're excited about MANGROVE for 2 key reasons: the first is because it represents the first chemo-free treatment option for patients with frontline mantle cell. And secondly, because when you see the data, we believe the efficacy will speak for itself. We're confident that this BRUKINSA-based chemo-free regimen has the potential to become the future standard of care for the roughly 21,000 new patients diagnosed with MCL each year in the major markets. Global submissions are planned for the second half of 2026, and we're looking forward to sharing the full data at an upcoming medical meeting. Let's now turn to BRUKINSA's commercial performance. In Q2, BRUKINSA's global revenues reached over $1.2 billion, representing growth of 31% year-over-year. BRUKINSA is the #1 BTK inhibitor both in the U.S. and globally, and it has the broadest label of any BTKi with approvals in 5 B-cell malignancies. We often talk about BRUKINSA in the context of CLL and with good reason. But it is important to remember that BRUKINSA is a very important option for patients with other B-cell malignancies, including MCL, Waldenstrom's, marginal zone and follicular lymphoma. BRUKINSA has now treated more than 300,000 patients across 80-plus markets, but market share alone doesn't tell the full story. The reason we're winning is scientific. And that story has 3 chapters: differentiated design, differentiated clinical outcomes and differentiated real-world evidence. At BeOne, we're committed to generating and sharing the evidence needed to fully characterize our medicines for the patients and physicians that we serve. On the left side of this slide, you can see the highlights of the breadth of Phase III data generated for BRUKINSA as a single agent. Here, you can see BRUKINSA has reported the most Phase III data of any single agent BTK. The right side illustrates the substantial body of data currently being generated in combination where you can see that BRUKINSA has the most reported and ongoing Phase III data of any BTKi agent. This slide demonstrates the scale of BRUKINSA's development plan compared to the more curated efforts of our peers. In addition to MANGROVE, BRUKINSA has 4 more potentially market-expanding Phase III readouts in the next 3 years. A major wave of data is coming that will extend BRUKINSA's evidence base and its label well into the future. One quick reminder of why BRUKINSA performs the way it does. From day 1, BRUKINSA was designed to deliver a complete and sustained BTK inhibition through its potency and its PK profile. Our hypothesis was simple. Continuous BTK coverage would translate into a superior, therapeutic profile. And over a decade of clinical and real-world evidence has really borne that out. And that's what the next few slides show. Let me remind you now that BRUKINSA is the only BTK inhibitor that has demonstrated PFS superiority versus ibrutinib in a head-to-head randomized trial. In Alpine, BRUKINSA delivered a hazard ratio of 0.69, and that separation has been sustained to a median follow-up of 42.5 months. In ELEVATE-RR, Acala showed early separation from ibrutinib, but that separation was not sustained. The curves crossed, and the final hazard ratio was one. And in Bruin314, Pirto reported a hazard ratio of 0.845. Put simply, there was very little differentiation between the 2 arms, with 48 PFS events reported for Pirto versus 50 for ibrutinib. And with respect to tolerability, Pirto showed numerically more discontinuations due to AEs zenibrutinib, whereas both BRUKINSA and Acala each showed markedly fewer discontinued zenibrutinib in their respective head-to-head trials. When comparing afibrates of next-generation BTK inhibitors across studies, it's important to understand the protocol differences that may affect patient selection and event reporting. As you can see on the left, both BRUKINSA and Acala studies in frontline CLL used highly similar eligibility criteria and AFib reported. In contrast, the Pirto studies utilized more restrictive eligibility criteria that may have resulted in a fitter study population, and they also incorporated sponsor adjudication of Afib events. As a reminder, Afib events and rates are known to rise substantially with age. In a large study of more than 17,000 adults in U.S. primary care clinics, the absolute prevalence of Afib was nearly 4% higher among those aged 70 to 74 as compared to 65 to 69. So factoring for this level of age difference in studies really matters. Despite the differences in inclusion criteria, which may have led to roughly half the percent of patients above the age of 75 in Bruin 313 and a 4-year lower median age in the Pirto studies and despite the differences in Afib reporting methods, Afib rates were generally similar in the active treatment arms across studies. Interestingly, if we apply the more restricted Bruin 313 and 314 eligibility criteria to the Sequoia population, 15 of the highest-risk patients would have been excluded from the BRUKINSA arm. And in fact, those 15 patients had roughly twice the rate of serious grade 3 or higher infections and more than twice the rate of deaths due to AEs compared to the overall study. This analysis underscores the extent to which differences in protocol inclusion criteria may play a key role in the clinical narrative. Although some have suggested that Pirto may be well suited for use in older patients due to lower Afib and improved tolerability, it is the least studied BTK inhibitor in that population. It lacks relevant long-term data with only 28 months of follow-up and the narrative about being more tolerable and having less Afib are not supported by the data. The totality of evidence continues to support BRUKINSA's best-in-class profile. One of the key lessons we've recently learned in CLL trials is that long-term follow-up matters. Many regimens can appear highly effective in the first 3 years, but that's not enough time to understand their true durability. This slide shows the reported landmark PFS at years 3 through 6 across the respective frontline CLL Phase III trials for the frontline treatment regimens. Recognizing the limitations of cross-trial comparisons, a few items jump out. One, the landmark PFS rates for BRUKINSA are higher and continue to diverge over time compared to the other 2 continuous BTKis. In fact, in year 6, the delta between the landmark PFS rates reaches 12%, which is equivalent of 1 in 8 patients not progressing. Two, there's an even more pronounced delta between BRUKINSA's landmark PFS and that of VO. In year 6, there's a delta of 21% or roughly 1 in 5 patients. While the all-comer story is compelling, the high-risk story is even more striking. It raises important questions about the use of the current fix duration regimens in high-risk patients, which I want to point out represent the majority of CLL patients. This is not a small patient subgroup. This slide shows how the current expiration treatments performed relative to the foundational BRUKINSA in unmutated IGHV patients. those with the highest unmet medical need. BRUKINSA remains durable, 84% landmark PFS at year 3 and 70% at year 6. In contrast, VO drops from 82% at year 3 to just 42% at year 6, a 40-point collapse. And AV amplify based on the limited data disclosed to date shows just 69% at year 3, which is, of course, lower than VO at a similar time point. There's a few important takeaways from this slide. First, while we're big believers in the promise of fixed duration, the existing Venn-based treatments are not compelling option for higher-risk patients, where foundational BRUKINSA has generated the best-in-class data. Second, long-term follow-up is critical in CLL. As you can see on this slide, many regimens look promising at 3 years, but by 6 years, the outcomes can diverge meaningfully, especially in high-risk patients. And that's why we've consistently prioritized long-term follow-up in our studies and why we believe 6-year data provide a more complete picture of treatment durability. It's also why we're concerned when reached on regimens based on only 3 years of data or less are made. We've been very surprised that some studies have not continued to report longer-term follow-up data because years 3 to 6 are critical to evaluate the true long-term benefit of any CLL therapy. Patient outcomes are at stake. The durability advantage that we're seeing in the clinical data for foundational BRUKINSA is increasingly being reinforced in the real world. And it's both consistent, and it's compelling. At ASCO 2026, we published an analysis of over 10,500 Medicare free service patients with previously untreated CLL. This is the largest real-world data set ever assembled in this setting. In this patient population, BRUKINSA reported statistically significant 24% and 36% reduction in the risk of death compared to those treated with Acala and ibrutinib, respectively, 24% and 36%. As you can imagine, this data set generated significant interest from physicians at ASCO, given both its size and the importance of these findings to the real-world U.S. Medicare population. The study has since been published in a peer-reviewed journal. And importantly, this is now one of several large real-world analysis, showing a consistent advantage for BRUKINSA, including a recent study of claims data from 17,000 frontline CLL patients, which also reported improved survival and treatment durability for BRUKINSA versus Acala. Stepping back, BeOne is the only company in the world with foundational medicines across the 3 mechanisms of action for B-cell malignancies. BRUKINSA, our foundational BTK inhibitor, BEQALZI, our recently approved next-generation, potentially best-in-class BCL2 inhibitor and Tacabrutideg, our potentially first and best-in-class BTK degrader. Only BeOne is equipped to provide the best-in-class therapies as monotherapy or in combination for every CLL patient and other lymphomas, regardless of their stage of disease, risk status or treatment preference. I've spoken about how 2026 is an inflection year for our solid tumor pipeline. And we presented data this quarter that supports our confidence in moving our CDK4 inhibitor, our B7-H4 ADC and our GPC3 4-1BB bispecific antibody into registrational trials. Looking forward to ESMO, we'll be sharing similar proof-of-concept data sets for 2 more potentially best-in-class medicines, our PRMT5 inhibitor and our CEA ADC. It's an incredibly exciting time for our company, for our portfolio and for our pipeline. And with that, I'll hand it over to Aaron for the financial results.

Thanks, John. Our second quarter financial results reflect strong execution and a durable and healthy underlying business as we invest with discipline to support growth over the long term. Starting with our commercial performance. we delivered another strong quarter across the portfolio with continued broad-based growth. Total revenue for the quarter was $1.7 billion, representing 30% growth compared to the prior year. U.S. BRUKINSA sales totaled $893 million, representing growth of 31%, which exceeded expectations due to several underlying factors. Despite the competitive environment, in Q2, we saw the highest level of sustained new patient starts since BRUKINSA's launch. Prescribers increasingly selected BRUKINSA for their patients given the totality of evidence for efficacy and durability and supported by the clinical data and their real-world experience. We also continue to see meaningful growth from indications beyond CLL, which speaks to the breadth of the BRUKINSA label and the diversification of the franchise. And while duration of therapy remains immature for BRUKINSA, the data suggests favorable duration relative to historical benchmarks. This makes sense given the unprecedented long-term data seen with Sequoia as well as recently published real-world studies that reinforce statistically significant advantages for BRUKINSA in time to discontinuation relative to both acalabrutinib and ibrutinib. And finally, patient adherence has also improved, potentially linked to the launch of the tablet formulation late last year, which reduced both pill size and burden. High adherence rates are important for patient outcomes, and we are pleased to see this progress. These factors are not unique to the U.S., and we expect they will support durable long-term global demand growth for BRUKINSA. Beyond BRUKINSA, TEVIMBRA generated $229 million in global sales, representing 18% growth versus the prior period. TEVIMBRA maintained its market leadership in China in the face of steep competition. Our global launches are also gaining traction and this is ahead of the potential catalysts associated with the approval of TEVIMBRA in combination with Xihura and chemotherapy for patients with first-line HER2-positive GEA. Our Amgen in-licensed portfolio also delivered $157 million in revenue, growing 25% year-over-year. Next, I'd like to highlight the broad-based nature of growth across geographies. The U.S. remained our largest market, contributing approximately $899 million in revenue during the quarter and growing 31% year-over-year. China contributed approximately $500 million in revenue and grew 17% year-over-year, demonstrated continued strength across our commercial portfolio while maintaining market leadership for both TEVIMBRA and BRUKINSA. Note that foreign exchange contributed 7% of reported growth given year-over-year renminbi strengthening. Europe continues to be an important growth driver for the company, generating approximately $208 million in revenue and growing 37% year-over-year. We also continue to see strong momentum across our rest of world markets, where revenue more than doubled to approximately $73 million. Key markets such as Japan and Brazil are making contributions that are increasingly meaningful at the enterprise level. Turning to the GAAP P&L. Gross profit was $1.5 billion with gross margin of just under 90%, benefiting from mix as well as productivity improvements for both BRUKINSA and TEVIMBRA. Operating expenses totaled $1.2 billion, representing 13% growth, reflecting advancement of key clinical programs and continued investment to support commercial growth. We continue to demonstrate the scalability of our model in the quarter with income from operations growing to $325 million. And finally, net income totaled $237 million. This includes the previously disclosed tax audit settlement, which had an approximate $60 million impact. GAAP diluted earnings per ADS were $2.05 compared with $0.84 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 $503 million representing growth of more than 80% year-over-year. Adjusted net income increased to $444 million, while adjusted diluted earnings per ADS increased to $3.84 and compared with $2.25 a year ago. Cash generation continues to build momentum with free cash flow doubling from the prior year period to $435 million. Turning to our updated full year outlook, which reflects the strong first half performance and confidence in the trajectory of our business. We are raising our revenue outlook by $300 million to a range of $6.6 billion to $6.8 billion. This increase reflects the continued strength we are seeing across the portfolio, led by BRUKINSA's performance in the U.S., ongoing global expansion and continued contributions from the broader commercial portfolio. We continue to expect gross margin to remain in the high 80% range. We are investing in both commercial execution and pipeline advancement with a modest increase in operating expenses to an updated range of $4.8 billion to $5 billion. Including those investments, the strength of the business translates to the bottom line, with the guidance raised in 2026 operating income by $250 million across the range. We now expect GAAP operating income of $1 billion to $1.1 billion and non-GAAP operating income of $1.7 billion to $1.8 billion. Other underlying assumptions remain unchanged. Overall, this updated outlook reflects the strong performance we've delivered year-to-date and our confidence in continued execution for the remainder of the year. As we have now rounded the first half of the year and while staying away from providing detailed guidance, I'd like to provide some perspectives as you update your models and begin thinking beyond this year. Our 2026 outlook provides confidence in the durability of our commercial business, including the prospects for continued BRUKINSA growth despite the competitive environment. And as you see in our implied operating expense guidance for the second half of the year, we are investing to realize the full potential of our pipeline that we believe will drive sustainable long-term value for shareholders and the potential to address multiple unmet need for patients. We remain committed to our dual objectives of growth with measured margin expansion in the near term. Operating expenses will continue to be prioritized against our high hurdle rates but can be expected to grow at a year-over-year rate in 2027, similar to what we've seen over the recent 2 years, given the positive progression of key pipeline assets. We look forward to providing our next financial update in November with Q3 results. And with that, I'll now pass the presentation over to Lai.

Thank you, Aaron. Hello, everyone. Thank you for joining us today. Across our portfolio, we'll continue to deliver meaningful progress. Starting with hematology, John already highlighted the positive readout from the MANGROVE study in treatment mantle cell lymphoma. BRUKINSA plus rituximab has the potential to redefine frontline treatment and become the first chemo-free regimen for these patients. For BEQALZI, we achieved our first FDA approval in relapsed refractory mantel cell lymphoma. Moving on to the CELESTIAL 301 study update. The regimen did not reach statistical superiority in the uMRD analysis versus the VO regimen. The IDMC recommended the study continue toward its primary regulatory endpoint of progression-free survival. While the uMRD comparison was an interesting scientific question, uMRD superiority represented a very high bar given the historical high uMRD rates associated with VO regimen. Importantly, uMRD rates do not consistently predict PFS outcomes when comparing different MOAs, such as BTK inhibitor versus anti-CD20 antibody. For example, in CR 17, despite 26% lower uMRD rates than VO, the ibrutinib venetoclax regimen demonstrated comparable PFS outcomes as VO. As a result, if a BTK inhibitor plus BCL2 inceptor combination achieved similar uMRD rates as VO, it should translate into better PFS than VO. Given the higher uMRD rates and exceptional durability observed with the regimen in Study 101, we remain highly confident in achieving the PFS end point. Next, our BTK degrader Tacabrutideg, continues to advance through potentially registrational Phase II studies, while our Phase III CaDAnCe-304 study against the Pirto remains on track. Together, this program support our ambition to lead the next generation of therapy in B-cell malignancies. In solid tumors, TEVIMBRA reached another important milestone with FDA acceptance and the party review of our HER2-positive GA application. We also made regulatory progress in China with the CDE accepting submissions for both TEVIMBRA and ZIIHERA. Beyond TEVIMBRA, we'll continue to advance a diversified and increasingly innovative pipeline. Our CDK4 inhibitor has begun Phase III development in breast cancer. Our GPC3 4-1BB bispecific recently completed enrollment in a potentially China registration-enabling HCC cohort. We also remain on track to initiate a Phase III study in second-line HCC before year-end. In addition, our PRMT5 inhibitor received FDA orphan drug designation for pancreatic cancer, and we initiated clinical development of our PD-1 VEGF CTLA-4 trispecific. The milestones from the last quarter are a reflection of more than strong execution. They demonstrated the power of focused on this strategy. We concentrate our investments in disease areas where we can establish leadership, building disease franchises rather than stand-alone products. Supporting that strategy is a growing technology from degraders and novel payloADCs to cell therapies and the T cell engagers. Because we're not tied to any single modality, we can pair the right biology with the right therapeutic approach. The result is a pipeline designed not just to be brought, but to be sustainable. As our innovation engine matures, we are creating gaps within disease area with multiple assets and mechanisms working together. That gaps opens the door to combinations from within our own portfolio, driving differentiation and maximizing the value of our innovation investments. As we discussed on the previous slide, our innovation engine is generating a growing number of high-quality opportunity across the portfolio. Historically, our solid tumor pipeline was heavily weighted toward immuno-oncology. The CDK4 inhibitor marked the beginning of a new chapter, one defined by more diversified mechanisms broader modalities and a sharper focus on specific tumor types. Today, that evolution is clearly visible. We now have 5 solid tumor programs that have achieved clinical proof of concept and are advancing towards pivotal development. Remarkably, each is on track to progress from first increment studies to pivotal stage in approximately 2.5 years. Our CDK4 inhibitor is already enrolled in Phase III. The B7-H4 ADC is expected to enter a pivotal study in ovarian cancer by year-end. For GPC3 4-1BB, we completed enrollment of the China registration intent expansion cohort with approximately 100 patients in just 2.5 months. You heard it right, it's only 2.5 months, underscoring our ability to execute at an exceptional speed. Based on this momentum, we also expect to initiate a Phase III study in second-line CC by year-end. In parallel, our CEA ADC and PRMT5 inhibitor have achieved a proof of concept and are advancing towards registration-enabling development. Taken together, these programs demonstrated a repeatable model built on differentiated science, disciplined portfolio strategy and a strong clinical execution. As multiple internal discovered assets advance into late-stage development, we are creating a growing number of value inflection points. Now let's take a closer look at some of the assets we highlighted at ASCO, starting with our CDK4 inhibitor. The data continue to be highly encouraging and are consistent with our scientific. At ASCO, we reported a potentially best-in-class profile, combining promising efficacy with differentiated hematological safety. That is the Phase III dose. BGB-43395 achieved an objective response rate of around 70% in combination with letrozole in first-line HER-positive, HER2-negative breast cancer. Safety remains a key point of differentiation. At the 400 milligram, the overall neutropenia rate was just 21% with no grade 3 or higher events. This compares favorably with both and approved CDK4/6 captures where severe neutropenia remains a meaningful clinical challenge. Together, these findings provide strong support for our ongoing Phase III program, which is enrolling rapidly. They also create opportunities for novel combinations across our portfolio, including with our CDK2 degrader BCL2 inhibitor and the KAT6 inhibitor. Turning to our GPC3 x 4-1BB program. BGB-B2033 continues to demonstrate what could be a breakthrough profile in HCC, combining strong monotherapy activity with a highly favorable safety profile. At ASCO, we reported objective response rate of over 30% in second line plus HCC comparable to current first-line combination regimens and well above what was reported with available TKIs in the post-IO setting. Safety remains a key differentiator, enabled by our unique BB approach. This profile supports development in earlier lines, where approximately 70 patients have already been enrolled in combination with TEVIMBRA and. Development momentum also remains strong. We completed enrollment in a potentially China registration enabling expansion cohort in post-IO, post-TKI HCC. In parallel, we are engaging with global regulatory authorities to explore accelerated approval pathways in second-line plus HCC based on the compelling efficacy and the safety profile observed to date. Turning to our B7-H4 ADC, BG-C9074. At ASCO, we presented data that supports its potential to become a leading program in ovarian cancer. The key differentiator is safety at 6 mg per kilo treatment-related grade 3 or higher adverse events were approximately 26%, less than half the rates reported for other ADCs in development for first-line ovarian cancer without biomarker selection. This profile is particularly attractive in the maintenance setting, where long-term tolerability is critical. We also reported encouraging efficacy including activity that appears independent of B7-H4 expression, supporting our all-comer development strategy. Based on this data, we plan to initiate a Phase III study in first-line maintenance ovarian cancer before the end of 2026, while continuing to expand the opportunity to endometrial cancer and TNBC. Taken together, C9074 combines competitive efficacy with potentially best-in-class tolerability, positioning it as a leading B7-H4 ADC. We're excited for ESMO where we have 12 abstracts accepted, including one rapid oral presentation and 9 posters. Highlights include our GPC3 x 4-1BB bispecific Phase I dose optimization data, the first exposure of Phase I proof of concept data for our PRMT5 inhibitor with a focus on non-small cell lung cancer and the initial evidence of clinical meaningful brain activity. An initial concept data for CEA ADC that underscore its compelling first-in-class potential in non-small cell lung cancer. Together, this presentation highlights the strength and the breadth of our innovation engine. We have covered most of the milestones already. I will just call out a few items on this slide. We remain on track for a potential accelerated approval submission of Taca in relapsed refractory CLL by the end of this year, further expanding our sales franchise in B-cell malignancies. In addition, we plan to start Tacasonro fixed-duration combination Phase III development in relapsed refractory CLL in 2027. In solid tumors, we expect to initiate pivotal studies for both our GPC3 x 4-1BB bispecific in second line plus HCC and our B7-H4 ADC in first-line maintenance ovarian cancer before year-end. Looking further ahead, both our PRMT5 inhibitor and the CEA ADC are positioned to enter Phase III development in 2027. I will now turn it back to John.

Thanks so much, Li, and we'll now open the call to Q&A. Please limit the number of questions to ensure we have time to hear from as many attendees as possible. Operator, please go ahead.

[Operator Instructions] Your first question comes from the line of Yanan Zhu with Wells Fargo.

Great. And congrats on the raise quarter. So could you provide more color on the growth of BRUKINSA sales. And specifically, I was wondering if you can quantify how much of the growth is coming from indications outside versus CRL itself. And within CLL, do you see any impact from the Acala launch? And how do you think the dynamics could evolve in the next couple of quarters from that perspective? And also very quickly on CELESTIAL-301, any color on the HR of the 2 arms. It sounds like it could be similar at this stage, but any color would be helpful.

Thanks. So I think we kind of got 3 sub questions in there. Maybe I will start and give a quick answer related to your question on Acala plus then, then we can jump to Aaron and he can answer your general BRUKINSA question, and we can come to CELESTIAL with Amit. So let me just start. I think right now, we're not seeing much impact from the AV AMPLIFY in the U.S. it's early. It's hard to say how it will evolve. And if Amit has extra detail on that, he can add it when he jumps to CELESTIAL. So with that, Aaron, do you want to talk more broadly about where growth is coming from?

Thank you. So we really saw BRUKINSA growth and really for the rest of our portfolio, driven by strong growth in demand across all of our regions. We spent some time talking about our U.S. business. And at the last quarter, we talked about the strength that we saw coming out of April and May. And obviously, that's continued into our second quarter performance. I highlighted in my prepared remarks, 3 core areas. The first, we are achieving our highest level of new patient starts since launch. So we're really pleased to see the uptake in the marketplace. This is driven by strength in CLL as well as our non-CLL indication. So we really do see that durable growth across all indications. You talked a bit about sort of context. I mean if you look at just prevalence across the 5 approved indications, there's about 1/3 of the total prevalence in those non-CLL indications. And we're punching a little bit above our weight in those areas because we actually have really strong share in those indications. The other piece that we had talked about was duration of therapy, and that continues to be highly constructive, yet immature. This is reinforced by real-world data, we talked about the study in 10,000 Medicare patients that were recently published. And this was really noteworthy, with BRUKINSA showing meaningful long-term benefits on discontinuation of therapy versus acalabrutinib and ibrutinib. In fact, BRUKINSA did not meet the median time to discontinuation in this data cut. And what we're really pleased about is how this relates directly to patient outcomes and experience. And this is what you see in our overall demand growth. As a result of data such as this, we have updated our internal planning assumptions to reflect longer duration of therapy. And overall, the business is just performing exceptionally well. So Amit, will you take the next question?

Yes. Thank you, Aaron. I think the question was about Amplify. And I think John mentioned this in his remarks, but long-term outcomes are very important in CLL. As we have seen, there is a huge difference between what happens with patients between years 3 and 6. And for AV, we only have the 3-year data. We don't have long-term data, and what we've seen from that data is the lowest rate of uMRD as well as landmark PFS even among the wind-based regimens. So while it is hard to say what will happen with this data set in 6 years, we do have other data sets that look better than AV at the 3-year mark with a longer follow-up, including Veno and Veni. And when we look at these data, they really highlight some of the challenges that are seen with the current venn-based fixed duration regimens. Now in particular, when we look at that unmutated IGHV, per patient population, which represents a majority of the frontline CLL patients, there's a clear distinction between the results from BRUKINSA and other ven-based combinations. For example, at 6 years, BRUKINSA has shows 70% PFS, whereas the fixed duration ven-based regimens show PFS in the low 40s. We're talking about a 30% difference in the PFS. This really matters. Now when we couple this with the fact that there are safety issues and some of the VEM-based regimens have serious infection rates of 20% to 30%, including fatal infections and the fact that almost half of the progression events our not even allowing patients an opportunity for retreatment, it is clear that these patients are really not being served well with -based regimens. And the fact that BRUKINSA is the treatment of choice makes a lot of sense. Now maybe I'll quickly address this. So that's your question around the hazard ratio. So as Lai mentioned in his prepared remarks, this was an IDMC event where the IDMC reviewed the data for the uMRD and BeOne remains unblinded to the data. So we do not have the details of the hazard ratio. But having said that, again, we remain very confident in the PFS endpoint and our ability to show superiority for ZS overview and for the primary regulatory endpoint, which is PFS. With that, I'll turn it back to John.

Yes. Thank you so much, Amit. And can we have another question, please, operator?

Your next question comes from the line of Reni Benjamin with Citizens.

Congratulations on an outstanding quarter. As my question mainly has to do with the MANGROVE study. Can you maybe provide some early physician feedback regarding the results you've disclosed? Any sort of thoughts on the study, not including rituximab maintenance arm and kind of how they're viewing the data? And how do the physicians kind of interpret this relative to the ECHO regimen, which has already been approved?

Thank you so much for the question. Again, we haven't disclosed that much data on this yet, but I think, Amit, this is back in your wheelhouse.

Yes. Thank you, John, and thank you for the question, Reni. So really, I think we're all very excited about the MANGROVE results. And really what MANGROVE has let us do is it's another great example of how BRUKINSA's differentiated profile leads to really meaningful advantage for patients. So from a design perspective, one of the important differences for MANGROVE compared to some of the other studies is that MANGROVE was designed to test a chemo-free regimen in that frontline MCL setting and show, for the first time, that it actually is better than the standard of care chemo-free -- chemotherapy regimens. The other BTK inhibitors, as you mentioned, ECHO being one example, have really added the BTK inhibitor to that chemotherapy regimen. And so they are more add-on rather than replacement designs. And MANGROVE for the first time, showed that a chemo-free regimen of ZR was superior to BR with a hazard ratio of 0.57 in favor of the ZR arm. And these results themselves are really unprecedented in terms of thinking about that chemo-free regimen. We've talked about the OS data being immature. But I think when you see that data, it will really sort of tell an important story there. And when we shared these results with physicians, KOLs, experts who treat MCL, they're really excited about this data. I think they really understand the impact that this can have. The fact that the chemo-free regimen really is going to allow for patients to avoid some of the toxicities that are seen with chemotherapy, avoid the rituximab infusion. Actually, there is a high level of interest in understanding what the rituximab maintenance-free regimen would also look like. And so overall, we've received very positive feedback from the community so far.

Yes. Thanks, Amit. I just want to reiterate that the response I've had is wonderful. So thank you so much, operator. Could we have the next question, please?

Your next question comes from the line of Michael Schmidt with Guggenheim.

I had one on the BTK degrader program, sticking with hematology. Maybe comment a bit about how you're tracking towards completing the first registration study in relapse refractory CLL? What is the efficacy buy in this setting, especially in the context of a single arm study? And longer term, how do you see the degrader program position relative to other programs, specifically the Norex Roche program?

Thanks, Michael. Nice to hear your voice. I think that Amit is very popular this morning. So please can you jump into that?

Yes. Thank you, John. So as Lai mentioned in his remarks, we remain on track and if the dealer support this, we're looking forward to that AA submission in Q4 of this year. Now I'll remind folks that the FDA has previously granted Fast track designation for tacabrutideg for adult patients with relapsed/refractory CLL, who received at least 2 prior lines of therapy, including a BTK and BCL2 inhibitor. And in the context of what we've seen so far from our Phase I data, across different patient populations, we've seen very encouraging, both response rates as well as the durability of those responses. And we think that this is a profile which is compelling. And when we think about previous accelerated approvals, we think that the profile really supports accelerated approval in that context. Now in addition to this, we also have important Phase III studies, which are executing very well. Particularly, I would call out a head-to-head comparison of tacabrutideg versus pirtobrutinib, the non-covalent BTK inhibitor. The study is enrolling very well, and we are very excited to share those results when they are available. And in addition to this, Lai mentioned the tacabrutideg + sonrotoclax relapsed/refractory study that we also plan to initiate early next year. So overall, I think this really reflects our growing confidence in the program and our ability to execute on a sort of profile, which is going to allow tacabrutideg to become a foundational asset in CLL along with the rest of our portfolio.

Thanks, Amit. And operator, we're ready for another question.

Your next question comes from the line of Etzer Darout with Barclays.

Great. Congrats on the updates, today. Maybe another one on MANGROVE, if you can maybe talk about when we could see an additional data cut here and any sort of potential presentations we may see around that? And then secondly, and maybe one for Lai around the pipeline. Just curious around the KAT6 design elements and the potential to combine maybe with the CDK4 selective program or other programs in our pipeline, just given sort of some of the other efficacies we've seen with that and the intriguing profile that, that could have. But again, does the safety being limited, just curious around sort of your design elements there to maybe overcome some of those limitations would be great.

Thanks so much for the question. Let's start with Amit and jump to Li.