Good day, everyone. Welcome to BeOne Q2 2025 Earnings Call Webcast. [Operator Instructions] 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 Miller, 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 an absolute increase of over [indiscernible] versus 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 3 takeaways with you. First, why 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 three, why you should pay close attention to our prolific and differentiated solid tumor pipeline. I want to come back now 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 9 years after ibrutinib. Here, we see the U.S. revenue performance of the 3 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 it's the fastest-growing brand, and it's the only BTK to be approved in 5 indications. Now 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, both for its strength as well as its 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…

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, and 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 having protected class status, the vast majority of patients have unfettered access to BRUKINSA and an even greater number achieve 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. And as mentioned last quarter, we also see some modest additional benefits on 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 and 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…

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 the portfolio update, we talked about how BeOne R&D is at a pivotal moment in its journey. Over the years, we have built a strong research, internalized global clinical development and manufacturing capabilities from 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 disease area of focus. And more importantly, 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, some highlights from our R&D progress in the second quarter. We have filed sonro's initial NDAs with the first 2 in China for relapsed/refractory CLL and the refractory/refractory mantle cell. The plan is to file mantle cell lymphoma globally later this year with a 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 that spans the full spectrum…

Thanks, Lai. We are now ready for Q&A. Joining us for the Q&A portion of the call is 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.

[Operator Instructions] Our first question comes from Jessica Fye with JPMorgan.

Congrats on a strong quarter. On BRUKINSA, I think in the beginning of the year, you mentioned you expect flat U.S. net price this year. Is that expectation evolved at all now that we're halfway through the year? And were there any inventory changes at the end of 2Q relative to the end of 1Q, you might be able to quantify? Second, 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? And then lastly, for the CDK4, I think at the R&D Day, you had talked about starting a second-line Phase III trial as soon as 4Q '25, and I see that's now in the press releases 2026. I guess recognizing that the, like as early as framing doesn't definitively mean you were going to start in late '25. What's the additional information you hope to gain prior to initiating that second-line Phase III trial and can you confirm what we should expect to see updated clinical data for that asset this year?

Thanks, Jess, for the question. So we have 3 parts to that question. I think the first on BRUKINSA and net pricing. Maybe, I'll ask Matt to comment on that.

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

The second part of that question was the BRUIN314 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 BRUIN314 study, [ OR superiority ] was not formally tested. Therefore, it is not statistically significant. Now I also want to point out, including the treatment-naive patients, it's likely to help the OR difference. Our ALPINE study of BRUKINSA versus ibrutinib in the relapsed/refractory CLL still remains the only head-to-head trial to demonstrate the superiority of one BTK inhibitor over another based on PFS endpoint. And the PFS endpoint is the golden standard in CLL. We believe in this setting, a positive readout of non-inferiority OR compared to ibrutinib is highly unlikely to be practice changing for the following reasons. Number one, there's no PFS data yet. Number two, it is compared to ibrutinib. Any new -- we believe any new continuous BTKi needs to demonstrate superiority over BRUKINSA, not ibrutinib. BRUKINSA should be the true standard now in treatment-naive settings. Number three, I think that it is still very early data. For BTK inhibitor, you really need a long follow-up to demonstrate your therapeutic benefit. We also expect pirto will primarily be sequenced after the covalent BTK inhibitor, particularly if we start thinking of the entire treatment journey for CLL patients, it is hard to imagine this data set will convince physicians that a better option is to go with pirto versus BRUKINSA given the results from BRUKINSA. Just a final note. I think the BRUIN314 alone is not sufficient for regulatory filing. As Lilly stated in their press release, it will be combined with 313 to form the basis for regulatory submission. BRUIN313 study is a pirto versus BR in treatment-naive CLL without 17p deletion. I think the key question here is whether BR is still a valid control and when it is filed for NDA in, let's say, 2026, if the trial reads positive. And also OS trend, I think, will be another important element to watch out. I'll probably pass this on to Mark to address the CDK4 question.

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. As the data are now coming in, we believe it would be prudent to let the data mature just a little bit more to inform our Phase III dose level selection. The magnitude of delay will be very modest, but it happens to move in from late '25 into early '26, which is why we're providing this updated guidance. I would also highlight for the first time we're disclosing our intent to start a frontline study with our CPK 4 inhibitor in 2026. So we remain very excited about that program. To your other question, we intend to share the data from dose optimization in combination with fulvestrant in 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. Ultimately, if you proved successful there, how do you think that the market plays out? Do you look at the V plus O combo was the initial target market? And how do you think about pricing if you're selling BRUKINSA and sonro into that market? And then do you -- what do you see or how should we think about the time-based therapy bleeding over into the normal course of operations or the rest of the market? That's my first one.

Sure. Happy to address that one, Sean. And I would say that we're very optimistic about the prospects for zani plus sonro. And you've heard from Lai some of the clinical underpinnings of that. Certainly, when it comes to our overall approach to driving adoption in CLL, we think that, that's going to be one of the primary drivers. And from a pricing standpoint, we're going to look at various different comparators for it. When it comes to fixed duration overall, I can say that so far, we haven't really seen much uptake of initial fixed dose utilization. Ven plus BTK isn't approved in the U.S. at the current time. So usage is off label. And we think that frankly, given what we've seen in the data so far, in comparison to continuous BTK, it would be inappropriate to see fixed duration use right now. As we've spoken many times, what we've seen of the current regimens that are available is that they're in very young and fit populations. And here I'm speaking about [ AV ] that also have limited risk factors. And we think that the benchmark really hasn't been met for deep and durable responses, strong PFS and safety and tolerability. However, to your point, with CELESTIAL, we believe that zani plus sonro is going to satisfy those benchmarks. So we don't see substantial fixed dose or fixed duration uptake in the near term, we see that BTK mono is going to continue to be strong. And then later, when we see the zani plus sonro data, we see that there will be bigger opportunities for fixed duration then.

Great. Great. And -- just on the pirto equation, many KOLs we speak to sort of reticence to see or reticent to say that they will see pirto moving to [ 1L ] even on good data because they're potentially losing that second-line option. But just to grab your latest thoughts on the resistance mechanisms associated with pirto versus BRUKINSA -- and what -- just frame the risk for us there, that would be very useful?

Yes, Lai, why don't you take that one?

Yes, I can probably take that question. In terms of the resistance mechanisms, it's still evolving. And clearly, pirto can work on covalent BTK inhibitor failed population, especially for the [ cysteine-481 ] mutations. And there are several other settlement mutations pirto can work on. So -- and unless there's a really strong data set demonstrating, I think a covalent BTK inhibitor works after pirto. I do believe a physician want to keep that option with the pirto to be treated, to be used after the covalent BTK inhibitors. And for the other things which I mentioned earlier on is about the data for 314 is still very, very early. And it's only OR non-inferiority. So we are also eagerly waiting for that data to be matured. And most importantly, I think if something want to go into the front line, it really need to compare to BRUKINSA, not ibrutinib any more.

In the interest of time. That's all I have for now.

Our next question comes from Ziyi Chen with Goldman Sachs.

Congratulations on a very strong quarter. Just 2 questions on financials and also the U.S. tariff. We actually see -- saw the gross margin has been improved notably in the second quarter compared to first quarter. So while the product revenue, we had seen 18% quarter-over-quarter growth, the absolute dollar amount for the cost of goods sold in second quarter was flattish versus the first quarter. So could you help us understand a bit more about how you have been controlling the manufacturing costs and optimizing that? And -- because this is really not being explained by product mix change. We guess definitely in terms of BRUKINSA, there has been some improvement. And another question is really on the U.S. tariff impact on the gross margin side. Just regarding the potential U.S. tariff on the pharmaceutical imports, which I think President Trump said that they will be put up initially a small tariff then eventually, it goes up to 150% in 18 months and getting up to 250%. So that's our guidance on the gross margin, which has been raised from mid-80s to mid- to high 80s reflect that potential tariff? And how should we look at the gross margin assumptions going forward?

Great. This is Aaron. Thank you so much for the question. So I'll take it in 2 parts. You're right. We've seen some improvement in gross margin on a quarter-over-quarter basis and certainly relative to last year. As I mentioned in my prepared remarks, that's really coming from improved production efficiencies, particularly for TEVIMBRA. We have a bit of price and also for mix. But we're certainly making efforts across our manufacturer and supply chain to continue to drive efficiency improvements. Largely in this quarter, it's TEVIMBRA. And then I also did mention as we think about the full year guide, the potential improvements for BRUKINSA. It's a great question relative to the U.S. tariffs. We've talked about in the past how our current guidance contemplates what we know today about tariffs. And that impact has largely been mitigated by how we globalize and regionalize our supply chain, and that includes our U.S. production for BRUKINSA and our investment in our Hopewell facility where I sit today, where we are qualifying this facility for TEVIMBRA production. As you mentioned, the big uncertainty remains around the current Section 232 investigation. We've all seen the headlines. We will monitor and obviously be very agile in our response to ensure both financial efficiency as well as, most importantly, operational efficiencies as we supply our life-saving medicines for patients. As I said, our '25 guide includes what we know today. Candidly, any announcements beyond that would likely not have a significant influence in our '25 results, just the way in which inventory is positioned and how that flows through the P&L. Future impacts while we believe would be manageable within the context of our P&L, it's just really too early to say to provide a forward outlook.

Just a quick one. Looking at the filing, you mentioned about second quarter, we saw benefit in net pricing for BRUKINSA in the U.S. Could you elaborate a bit more on that? What has been the benefit? And how should we look at the net pricing going forward?

Thank you, a great question. As we talked about historically, we do see relatively stable net pricing. That is what we are -- have seen in our current results. In my prepared remarks, we talked about mid-single-digit pricing in the U.S. This is largely the pull-through of our early year price increases, which is consistent with market practice and well within what the requirements under the IRA mandates. We do see some incremental benefit on a year-over-year basis relative to Part D reform. And I think we talked about at the last quarter, the prior year, including the manufacturing liability around the donut hole, which goes away and that's replaced this year by the manufacturer liability under the cost share. And in our case, we do benefit from the specified small manufacturer designation. So the combination of those 2 leads you to our mid-single-digit performance on a year-over-year basis for this year. I would say that modest benefit you see in the changes from Part D reform is something that you see more significantly in the front half of the year given the lapping of the donut hole, which largely occurs in the first half just based on that prior regime.

Our next question comes from Kelly Shi with Jefferies.

Congrats on another great quarter. First one, for the revenue guidance raised to $5 billion to $5.3 billion, what drove to this low-end bump? And specifically which product underpin that outlook? And second one, you point to 20-plus expected R&D milestones over the next 18 months. Could you provide more granularity on which ones might have been the most impactful events? And lastly, what are the newest learnings from adding translational studies regarding how BeOne's BTK degrader tackle resistance mutations acquired from the first-gen BTK inhibitors differently from pirto?

Great. Maybe -- this is Aaron. Maybe I'll start. Thanks for the question. So our update to our revenue guidance to $5 billion to $5.3 billion, really just reflects our confidence in execution in the first half of the year. We don't provide product revenue guidance. But I would just say, as you see in our current quarter performance as well as Q1, across the portfolio, both from a product perspective and a geographic perspective, we're pleased with our performance, and this update just signals our confidence in our execution. On that, maybe I'll hand it over to Lai on the R&D questions.

Yes. I'll probably address the -- the third question first about BTK degrader in terms of the resistance versus, let's say, pirto. There are 2 well-known resistant to pirto, which after the covalent BTK inhibitor, one of them is L528W, another one is T474 mutations. So far, BTK degrader can really work well with those mutations. And we're still at the early stage in terms of the experience of the BTK degrader in the clinic. So there hasn't been that many patients really progressed. We're actively following what kind of mutation were -- resistant mutation were emerging from the BTK degraders. But having said that, it doesn't look much more promising in terms of being able to overcome more broader spectrum of the BTK mutation for degrader versus the pirtobrutinib. Also, we have done some translational work using the cell line, using the animal model. It does seems like the degrader can probably have longer tumor suppression compared to, let's say, a pirtobrutinib or other covalent BTK inhibitors. Your other question is about the exciting milestones. Maybe I will talk about what's on the heme side of it. Then I will pass this over to Mark to comment on the solid tumor side of it. On the heme side of it, I think certainly be able to file sonrotoclax globally. This will mark the really important critical step for sonrotoclax. We are truly excited about this molecule for everything we have seen in the clinic. The combination of the sonrotoclax plus zanidatamab outstanding. Its own activity right now in the mantle cell lymphoma, which is the monotherapy study we did globally, and the data looks really interesting. This really formed the basis for the initial global filing and we're also now seeing activities for this one in the multiple myeloma, et cetera. It's not listed here, but certainly, we are moving very aggressively about that one into the potential pivotal stage as well. Then on the degrader side, we're very excited to get the pirto going, probably will be next couple of months. So we'll get pirto trials going and I think that one will potentially bring a better drug for patients in the relapsed/refractory settings. So Mark?

Thanks again, Lai. Again, for the solid tumor, the most important data disclosure that we're likely to have for the remainder of 2025 will be our CDK4 data at San Antonio Breast Cancer Symposium. Many of the new molecules that Lai highlighted in the solid tumor portfolio will have early data emerging. We're very pleased with the progress of the portfolio and we are hopeful that we'll be able to share data from multiple programs in the first half of 2026. And as Lai mentioned, at the R&D Day, we highlighted 4 programs, including CDK4, B7-H4, PRMT5 and FGFR2b that are showing very encouraging early data. And again, we look forward to disclosing more data from those programs, likely in the first half of next year.

Sorry, maybe just a I forgot to mention, which is that degrader will have the pivotal Phase II readout next year and hopefully that will lead into also a global filing for the degrader. That one is definitely very important in milestone as well.

Our next question comes from Yigal Nochomovitz from Citigroup.

Just a few questions, a couple on BRUKINSA and then one on the pipeline. Regarding BRUKINSA, you mentioned the majority of patients have unfettered access, and there's a step-up in access on appeal. I'm wondering if you could just provide a little more specifics in terms of the numbers associated with the access out of the gates and then what the access on an appeal? And then more generally, just in terms of the overall business globally, obviously, it shifted ex China. I'm just wondering if you've reached a point where it's essentially a steady state in terms of the product mix, revenue mix, China, Europe, United States and you're going to see steady growth across the board, or if there's still an expectation of movement of revenue more ex China. And then lastly, maybe for Lai. Could you comment more specifically on some of the powering assumptions on PFS -- PFS with respect to the CDAC versus [ pirto ] Phase III.

Super. Thanks for the question. And I'll start out and then hand things over to Aaron for revenue mix. Regarding your question around access out of the gate and then appeals, I think all of the access conversations start with our continued belief in BRUKINSA as a differentiated asset that's best-in-class amongst the BTKs and has this overwhelming body of evidence that John described, including thousands of patients in clinical trials, and we continue to evolve that with real-world evidence and other data. So we're seeing a preference for BRUKINSA with HCPs and with patients. And when it comes to the access component, oncology is a protected class and BRUKINSA continues to be listed on all Medicare Part D formularies. When it comes to that appeals process, it's important to remember that any preference or step edits don't impact existing patients at all. It's limited in new patient starts. And here, it's also important to remember that the majority of our claims are filled initially. And then if an appeals process is needed, we've been very successful in supporting accounts to work through that process. So going forward, we're really confident in continued access and growing demand and extending our value share ownership. Aaron, over to you for the next question.

Great. So I'll just really quickly and actually invite Xiaobin for his perspective. But certainly, Yigal, we're growing globally. And as we think about the mix of business, every region is growing at different paces. We're still quite early in many parts of the world in our launch trajectory. We've historically talked about Europe being earlier. Rest of World markets, including really important markets globally or even earlier in their launch cycle. So we would expect that our revenue mix to continue to diversify over time. But that's coming from a position of growth in all regions, including our China business. So Xiaobin, maybe I'll invite you for your perspectives.

Yes, sure. So as Aaron mentioned before, the biggest revenue driver today is U.S. and we achieved $685 million with growth rate of 43%. China is the second biggest contributor and grew also 23%. And we just got the publication of the IQVIA data and we moved up one position to be sixth biggest oncology company in China. And we grow very fast outside the U.S. and also China. In Europe, we grew close to 90%. In the rest of the world, means new markets and also [ JPAC ], we grew 170% and then you can say the dynamic. In China, we grew -- continues to be very strongly and far above the market. Outside China, we grew even much faster, including U.S., Europe and the rest of the world. That is a very healthy dynamic and we grow actually everywhere.

Yes. Maybe to the last question about the -- about our degrader PFS. I think on the Slide #28, if you take a look at, there was also a table under that PFS curve, was to point out the patient population we treated, our CADENCE 101 study had more [indiscernible] therapy, but more importantly, the double-exposed patient population was higher. And also, you may have some patients who are triple exposed. And with that kind of the worst prognostic patient population, we are seeing this nice PFS trend give us the confidence, but I don't have much more data than what you can see here because the data cut here was about March. So certainly, we have some -- a bit more data. But over speaking, I think that it's definitely trending towards the right direction. But again, I want to point out this is a cross-trial comparison.

Our next question comes from Reni Benjamin at Citizens JMP.

Congratulations on an amazing quarter. Maybe just to -- you're approved in 75 markets globally. Can you just remind us what's the total number of markets you'll be approved at in peak? And should this playbook be repeated for TEVIMBRA and sonrotoclax? Or are there other factors that may impact which markets you go into with either of those 2 drugs? And then just talking about the tablet formulation, which you've mentioned in the prepared remarks, is this something that could materially impact sales going forward? Or does it really just impact the cost of goods? And does this ultimately replace the current formulation?

Yes. For the first one, Dr. Wu, would you like to respond to total number of markets at peak and how it might differ from TEVIMBRA?

Sure. Our regulatory approval in so many countries, I can't remember anymore. We have a bunch of list, over 70 countries, including all the major markets for both products, TEVIMBRA and BRUKINSA, U.S., EU, U.K., Switzerland and many other major markets. In addition to those major market, we got also quite some approval -- regulatory approval in the emerging market like India and Indonesia, Thailand, so many other -- Brazil and Israel and many other countries. It's a bunch of list. If you want, we can send it to you the concrete list. In most of those countries, we launched product already, and we are also launching products in new markets.

And I'll gladly address the tablet question. This is primarily our commitment to patients. And ultimately, this tablet will be a more convenient and easier to use formulation. With regard to impacting sales in a material way, we think that this will continue to solidify our market leadership position on a commercial basis. And then I think you also asked a great question around will the formulation ultimately replace the capsule? In due course, we will move to simply having the tablet available for those patient-focused reasons.

Got it. And I'm sorry, just as a quick follow-up to Xiaobin's answer. Is the 75 markets that you're currently -- or greater than 70 markets that you're currently globally marketing in, is that -- is that it? Or does this -- is there even more to be expected, right? Or have we penetrated as many and now it's just growing in those markets, that's important?

Yes, great question. So we continue to expand our footprint. Just remember on our mission and BeiGene is set up also to -- our mission is to reach out to many more patients. So to provide innovative and affordable medicine. Therefore, our mission continues, and we definitely want to expand to more markets. In addition to that, we also get some new indications in this already registered market and expanded to new indications. We -- for the 70-plus registered countries, we do not have every indication yet in TEVIMBRA and also for -- even for BRUKINSA, we continue to register new indications. Yes, expanding continues.

Our final question comes from Michael Schmidt with Guggenheim.

Congrats on the great second quarter here. Bigger picture question on the covalent BTK inhibitor market in the U.S., which is still growing at 10% right now here in the first half of 2025. And so -- just curious if you could comment on what is driving overall market growth right now in the covalent BTK space? Is it duration of treatment versus additional patients coming on to therapy? And how should we think about the peak potential for the class, especially as we think about potential fixed duration combinations coming in into the future. And then how big of a near-term growth driver is the first-line MCL opportunity for BRUKINSA based on the mangrove data later this year. And then lastly, we're getting questions just on how you feel about expanding the BTK degrader development into autoimmune and inflammatory conditions. I know you mentioned you have a CSU study up and running now. But how should we think about the long-term potential of the degrader in autoimmune and inflammatory?

I'm happy to start out with the questions around covalent BTKs and the market as well as frontline mantle cell and MANGROVE and then maybe then pass it over to Lai. And I fully agree with your viewpoint that we see opportunities for longer DOT among the drivers. Certainly, if you look at ALPINE or other data sources, you'll see that BRUKINSA's duration of therapy is longer and of course, that goes hand-in-hand with better PFS. So we do see that there will be some growth potential within BTK for those reasons. And -- or some of what we described earlier, we think that the current fixed duration regimens, including AV, don't offer the deep and durable responses, the high PFS and the safety and tolerability that really is the benchmark for treatment. So we'll see what we believe will continue to be continued mono BTK growth in the market moving forward. Now for mantle cell and MANGROVE, we're certainly very encouraged. We think that will be a strong data set. Of course, mantle cell has limitations to the overall size of the patient prevalence and the opportunity for treatment. So we'll certainly see growth potential, but CLL will continue to be our main driver. With that, Lai over to you.

Thanks for the question about -- I think the question is related to how do we view about BTK degrader in non-oncology indication, especially for autoimmune. As you pointed out, we have started the study -- a Phase Ib study in the CSU. I want to point out 2 features about our BTK degrader. One of them is -- probably 3 features. Number one, it has really long half-life. This potentially can support different dosing frequency, which for certain disease, that might be very beneficial. Number two, it has been penetration. I think that will be also applicable for certain autoimmune disease. Number three, I think this one like the degrader mechanism, it can destroy a scalpel function. And for certain disease area, that's also very important. We're actively exploring different potentials for this molecule in the autoimmune disease. So stay tuned.

At this time, we've reached the end of the question and answer. 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 and the joint 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 already helped more than 1.8 million cancer patients, and I truly believe this is just the very beginning of what we will accomplish. I'm looking forward to sharing more updates and milestones with you as we progress through the year. And I would like to thank you all for joining us today and for your thoughtful questions. Thank you.