Good day, everyone. Welcome to BeOne Medicine's Q3 2025 Earnings Call Webcast. [Operator Instructions] After the speakers' remarks, there will be a question-and-answer session. At this time, I would like to turn the call over to the company.

Hello and welcome. Thanks for joining us today. I'm Dan Maller, Head of Investor Relations at 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 the 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, CFO, will provide an update on our third 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. And joining the team for the Q&A portion of the call will be Xiaobin Wu, President and Chief Operating Officer; Matt Shaulis, our General Manager of North America; and Mark Lanasa, our Chief Medical Officer for solid tumors. I'll now pass the call over to John. John?

Thanks, Dan, and thank you, everyone, for joining us today. The third quarter marked another strong quarter of execution. From a financial perspective, revenue reached $1.4 billion, which represents 41% year-on-year growth. GAAP earnings per ADS were $1.09, which represents growth of more than $2 over Q3 of last year. And we generated over $350 million of free cash flow during the quarter. As Aaron will touch on, we strengthened our balance sheet and ended the quarter with over $4 billion in cash. BRUKINSA has continued its momentum with sustained U.S. leadership, and it's now the #1 BTK inhibitor globally. Sonro, our next-generation BCL2 inhibitor recently received FDA breakthrough designation in relapsed/refractory mantle cell lymphoma. And we're really excited about the totality of data emerging from that molecule, some of which we're going to highlight today. BRUKINSA, Sonro and our BTK CDAC are the core elements of our leadership in B-cell malignancies, and they'll be on display next month at ASH where we'll present 47 abstracts from across our heme portfolio. The quarter also yielded multiple developments across our growing solid tumor pipeline, including clinical proof-of-concept for multiple early-stage assets, which Lai's going to discuss in more detail later. So let me start with BRUKINSA, the backbone of our heme franchise. BRUKINSA continued to perform exceptionally well in the third quarter, growing 51% and exceeding $1 billion in quarterly global revenue for the first time. As a result and also for the first time, BRUKINSA is now the global value share leader amongst the growing BTK market. This, of course, is a major milestone for BRUKINSA and for our company. As I discussed in detail on our Q2 earnings call, the commercial success of BRUKINSA is not by chance. It's the direct result of an overwhelming body of evidence that…

Thanks, John. In the third quarter, we sustained business momentum across our product portfolio with another quarter of solid execution by our global commercial teams. Product revenue reached $1.4 billion in the second quarter, representing 40% year-over-year growth. BRUKINSA global revenues eclipsed $1 billion for the first time in a quarter growing 51% driven by strong performance across all geographies. As John mentioned, BRUKINSA is now the leading BTK globally. In the U.S., we grew BRUKINSA volume by approximately 40% versus Q3 2024, driven by the quality and differentiation of our long-term clinical data across all patient types. The pricing dynamics in the United States were consistent with commentary provided last quarter with a mid-single-digit pricing benefit on a year-over-year basis. Meanwhile, TEVIMBRA reported a 17% increase reflecting continued market leadership in China, albeit in an increasingly competitive market environment. This growth was supplemented by early contributions from launch markets. Our in-licensed products also showed continued strength, growing 17% year-over-year, driven by growth of 31% from the Amgen in-licensed asset portfolio. We continue to see solid execution as we look at revenue from a geographic dimension. The U.S. remains our largest market, generating $743 million with year-over-year growth of 47%. China revenue totaled $435 million, a 17% increase supported by TEVIMBRA and BRUKINSA market leadership and growth from our in-license assets. Europe contributed $167 million, with 71% year-over growth as we continue our launch trajectory of BRUKINSA with increased share across all major markets. And rest of world markets grew 133% and driven by market expansions and new launches. Now turning to the other components of our GAAP P&L. Gross margin improved to 86% from approximately 83% in the prior year. This improvement reflects the benefit from favorable product mix, price and product cost efficiencies, offset by period costs related…

Thank you, Aaron. Hi, everyone. Thanks for joining us today. Let me start with hematology. We have 50 abstracts, including 6 orals from our hematology portfolio have been accepted for presentation at ASH this year. This is a tremendous validation of the strength and the depth of our signs. I will highlight some of those key data later in my presentation. Importantly, sonro has now received FDA breakthrough therapy designation for mental cell lymphoma. We're actively working on its first filing around the globe and our BTK integrated program has just started the Phase III head-to-head trial versus pirtobrutinib in the last refractory cell patients, a major step towards transforming the space. On the solid tumor side, our momentum continues to build. We have achieved proof-of-concept for several innovative programs, including our CDK4 inhibitor, B7-H4 ADC, PRMT5 inhibitor under GPC3x41BB bispecifics. To be noted, most of these assets have been in the clinic for less than 18 months and some less than 1 year, this is the level of efficiency and the focus we aim to deliver across the portfolio. For CDK4 we aim to initiate a Phase III trial in first-line BC in the first half of 2026. On the non- oncology side, our IRAK4 CDAC program achieved over 95%, IRAK4 [ protein ] degradation in healthy volunteers skin tissue, a clear PD proof-of-concept. We have already initiated a Phase II trial in rheumatoid arthritis. Over the past few years, especially in the last 24 months, we have dramatically increased our output from the discovery engine. In that time, we have advanced 16 new molecule entities into the clinic, including 13 from our internal research team. Among them, all molecules have already achieved clinical proof-of-concept, supporting pivotal study plan. This does not count our 4 degrade program, achieving tissue…

Thanks, Lai. We'll now open the call to Q&A. [Operator Instructions] Operator, please go ahead.

[Operator Instructions] Our first question will come from Yaron Werber with Cowen and Company.

Hopefully, you can hear me.

Yes.

Congrats, really nice quarter. I'm going to violate the rule right away. Just 2 quick questions. Number one, BRUKINSA's the global leader. You're obviously a little bit behind in Europe in terms of when you launched any sense and when new territories are coming in to accelerate that? And then secondly, Life for the CDAC data in the first half next year in CLL for the potentially support accelerated approval, can you give us a sense of what to expect there? And sort of how mature is the PFS is going to be?

Right. So Xiaobin, do you want to start?

Yes. In Europe, we grow for BRUKINSA are tremendously, so close to 70%. And we notified in Europe in some country like Germany, Austria, AMPLIFY launched. And we don't see much excitement among the [indiscernible] and the company may actively switch the mono acala to AMPLIFY. But so far, we have not -- we see some prescription, but not extremely a lot prescription. Therefore, the total acala in Europe, if you see the number, is flattening.

So regarding to the CDAC data, and this is a single-arm study, so likely to be based on the ORR as well as the DOL. So depending on the first discussion with the agency, as usually, it will be probably about 12 months after the last patient.

Our next question comes from Reni Benjamin with Citizens Bank.

Congratulations on another amazing quarter. Would love to just focus on the earlier stage pipeline a little bit. You had mentioned proof-of-concept data. Can you maybe provide a little bit more color as to what you're seeing with some of these other assets? And should we be thinking that all these would likely progress to Phase III trials moving forward? And if I can sneak one in, is there a teaser you could provide regarding the 10 new molecular entities that you're filing next year? Is there a novel target that you're most excited about?

We wish that science worked in a way where everything worked. But Lai, why don't you answer that question?

I'll probably refer to Mark because he is in the frontline for all this data, Mark?

Thank you, Lai. Thank you, [ Reni ] what I would say is that for all of our early programs, we established very clear criteria of what success looks like based upon the preclinical data what are we looking for in terms of PK, PD, safety and ultimately, efficacy? If you think back to the slide that Lai showed where he talked about where the different programs stand. I think you can think about that as some of those programs are meeting all of those criteria, the 4 of CDK4, PRMT5, B7-H4, GPC3, and therefore, we're actively planning acceleration to Phase III studies and program growth. Others, we continue to wait for data. And we believe that we'll have the data to make the final determination for both of the programs in the first half of '26.

Yes. Then in terms of the new [ molecular ] entities we are going to bring to clinic next year. I'm going to use the GPC3 4-1BB as an example. To be honest, among the program we took into the clinic last year, that certainly was not the most exciting one for us based on the preclinical data. But certainly, we are very pleased with what we have seen in the clinic today. So I'm not going to say which one is the most exciting one for us in the next year, but we're certainly looking forward to bring more. Just want to emphasize one more thing. What you have seen from BeOne is really just the beginning, what you can see from our really prolific discovery engine.

Next question comes from Andrew Berens with Leerink Partners.

Let me give my congratulations on the progress and execution for the quarter. I think with Aaron's question, you answered one of the ones I had because Astra in their earnings release today did highlight the fixed duration AMPLIFY regimen getting traction in Europe, but it sounds like you guys have not seen a lot of that yet. So I just wanted to confirm that that's what you said. And then a question on the PRMT5 program. It's still expected by year-end. Just wondering, I know you mentioned the first-line PDAC and non-small cell lung cancer opportunity. Just wondering how you think of combination partners for those settings?

Yes. I confirm and the -- so Ocala market share and also the revenue in the last 3 months are pretty stable in Germany and not increasing -- of course, with AMPLIFY approval and the fixed duration of AMPLIFY will be added to the respective guideline. This may give some plus for [ Ocala ]. But overall, in Europe and also in Germany, the [ Ocala ] total data flattening.

Mark, do you want to take the second part?

So we, as you heard, are very excited about our PRMT5 molecule. That's only been in the clinic since January of this year. But given its high potency and CNS penetration, we're now seeing objective responses across multiple tumor types, including both lung and pancreatic cancer as well as additional tumor types. And critically, given its high selectivity, we're also seeing a very favorable safety profile that we think will enable combinations, which will be key to unlocking the potential of this mechanism. And therefore, we're advancing into frontline to combine with current standards of care. We do not yet have the data, but it is our expectation that we'll be able to combine with chemotherapy and PD-1 in non-small cell lung cancer and standard of care chemotherapy in frontline pancreatic cancer, and we'll look for similar development opportunities in early lines of other tumor types with frequent MTAP deletion.

Okay. Any belief that maybe combining with some of the selective agents might work in certain mutations like RAS mutations.

So we are very interested in RAS biology. Our pan-KRAS molecule is advancing through Phase I. We discussed at R&D Day a commitment to bring multiple additional RAS targeting molecules into the clinic. So certainly, in pancreatic cancer, for example, we will ultimately look to combine PRMT5 with KRAS. So again, the aspiration given potency and selectivity is that we should be able to combine with whatever is the appropriate additional therapies for that patient given the disease state and any other concurrent mutations.

Our next question comes from Yigal Nochomovitz with Citigroup.

Okay. Great. This one is for Lai or Mark. Maybe. Could you give a little more detail on the design of the CDK4, Phase III in terms of what you can say at this point about the control arm, the size of the study, anything on the powering? And also what are the doses that are the final contenders for that study?

Please go ahead, Mark.

So at R&D Day, we talked about the 3 dose levels that are being explored in our expansion phase, 240, 400 and 600. We've completed enrollment of our frontline cohorts. And we're very excited with the data as they're coming in. We are seeing a high response rate that we think will justify as initiation of a Phase III study the core hypothesis with the molecule is that having a more selective CDK4 inhibitor will be superior to currently available CDK4/6 inhibitors. And therefore, we're intending a head-to-head study we're still waiting for data to make final decisions around study size and powering, but we certainly should be able to share those details in the near future as we move towards a Phase III study start by the end of the first half of next year.

Okay. And then I think Lai mentioned the new Phase III ZS versus AV. I was just wondering regarding the rationale around that. I was under the impression you kind of already knew the conclusion there that ZS was better? So I'm just curious as to the rationale for that additional investment to further prove that point.

Please go ahead.

Yes. Thank you for the question, and we agree with your comments. But we felt this is important to establish ZS as really the best oral fixed duration regimen. So we picked the one which likely will be approved soon by FDA, the AV regimen. We do have a lot of confidence in term for this particular study.

Yes. I think if I just elaborate a little bit on that, we encourage everyone to look frequently at the CLL data, especially the long-term data that we've presented but still people will say, well, there's no head-to-head study against [ Ocala ] versus [indiscernible]. And still, people will discount the body and wealth of information that's there. And I think when you look at the data and you talk to the top KOLs, I think at this point, with this long-term data, it's very clear. But nonetheless, there's always someone who says there's not direct head-to-head. And I think this commercially is helpful, and it's helpful to bridge that information gap help educate people more quickly. I mean just when we're looking at that space, the long-term data, it's meaningfully different with all the cross trial comparison. As we said, it's double-digit different. look at the PFS, look at the OS data. It's impressive, but we still get that comment in a small portion of the population around the globe. So we just think, it's important to do this so we can ensure that everyone is getting the best medicine and the best regimen. So we're committed to doing it.

Our next question comes from Leonid Timashev with RBC.

I just want to ask maybe on some of the commercial dynamics you're seeing outside of the early line setting in CLL and maybe more in the relapsed/refractory setting is how is BRUKINSA share holding up or growing there? And then ultimately, how do you expect the mix of a degrader BRUKINSA and covalent inhibitors to play in the future there?

Sure. Matt, please.

Sure, happy to address that. Yes, we continue to see strong new patient start share across the lines of therapy, including in that relapse setting. And then as we've discussed in the past, we're really confident in our overall CLL franchise leadership strategy. You made reference to the multiple mechanisms that are in our portfolio. And as you've heard from John, we continue to have confidence in our BTK mono due to our head-to-head superiority with another BTK and our best-in-class profile. Including PFS, safety and tolerability in the long-term setting that John mentioned. We also see an opportunity for therapy that will include zanu plus sonro. We've spoken before about the requirements for therapy there. And we're confident in a really strong MRD PFS safety and tolerability profile, but also in the convenience that sonro can bring to that regimen. So of course, we see the future opportunity for fixed duration with zanu plus sonro. But right now, we're confident in monotherapy. Of course, when it comes to the degrader we see a clear opportunity there in later lines of therapy. I'm sure you're familiar with resistance mutations that can happen in those earlier lines, and we have the confidence to do a head-to-head superiority study for the degrader versus pure dose. So we see a strong opportunity across patient types in the cross lines of therapy in CLL.

Our next question comes from Sean Laaman with Morgan Stanley.

Just to go back on the CDK4 inhibitor, just to maybe throw some meat on the bones around the decision not to pursue later lines and to go for first line. And then also just to confirm, are we still going to see some data at San Antonio and what do you hope to present at that forum?

Thank you very much, Sean. Yes. So again, what we're seeing in our expansion cohorts is a very strong emerging response rate. We are waiting for data maturity. Now in the context of the strength of that data and also importantly, the context of emerging data externally, so there are a number of new agents that are leading to both fragmentation in the second-line as well as an increasing bar for success in second-line. We always view the second-line opportunity as a transitional opportunity for this molecule and the key study as the frontline study. So given this external dynamic and our strong internal data, we made the decision to deprioritize second-line and to accelerate frontline. And again, we're very much looking forward to that study. Currently, we then subsequently made the decision that we would not share the second-line data this year San Antonio. We think those data are relevant to our dose level selection for Phase III in frontline and we, therefore, will not have data for this molecule at the San Antonio, but look forward to sharing data at a future venue that will -- should we say substantiate our plans for the Phase III study in frontline.

Great. And one quick follow-up just on zani plus sonro versus [V plus O]. So Phase IIIs are recruited earlier this year. What's sort of the signpost pathway or the map going forward in terms of future announcements around that trial?

Lai, do you want to answer that, please?

Yes. So to me, in that particular study is a PFS events-driven studies, as you can imagine, with the control arm using the vial, it's really good therapy as well. So it would take a little bit of time to get into the PFS readout at the same time, we are also monitoring the uMRD rate, this will be something we can probably take an earlier look at.

Our next question comes from Jess Fye with JPMorgan.

I have one on the EGFR targeted assets. I guess what in particular makes you say that the EGFR cMET product goes in the promising bucket, whereas the EGFR CDAC is in the still exploring bucket. Is that based on clinical data? Or if not, can you just elaborate on kind of how you segment of those.

Sure, Mark. Please go ahead.

Sure. Thank you, Jess. So we have a number of different EGFR targeted therapies that are moving forward. And as I mentioned earlier, for each program based upon the preclinical evidence, we have expectations of what we would like to see for the molecule initially in terms of PK and safety, but ultimately in terms of efficacy. So what we're seeing from the EGFR MET-MET Trispecific, though it's very early days in dose escalation is that we are seeing clinically meaningful responses with that agent. With the EGFR degrader, we continue through dose escalation. We've had some tumor regressions. We're happy with the PK and the safety profile. We simply need more data maturity. It's important to highlight that these are 2 totally different mechanisms of action, and therefore, our expectations for what we would expect from each molecule are somewhat different.

Our next question comes from Clara Dong with Jefferies.

Can you hear me?

Yes.

Congrats on the quarter. So you talked about the seasonality for the entire BTKi class. So just wonder how the seasonality dynamics differ across key regions in the U.S., Europe and the rest of the world as well. And then just looking at the time line for sonro and the BTK CDAC entering the market, sonro expected to file for MCL in the U.S. this year and BTK CDAC could have a pivotal readout next year in CRL. So is this the right understanding that potentially BTK CDAC that can be approved first in CLL in the U.S.? And how do you anticipate this influencing physician sequencing strategy across B-cell malignancies special in CLL?

So Aaron, going to lock.

Great. Thanks for the questions, Clara. So as I said in my prepared remarks, I just wanted to reinforce as you think about your models, the seasonality patterns, this is really a focus in the U.S. where we typically do see inventory builds across the sector in the fourth quarter and then that unwinds to a degree in the first quarter. And then we did reference back to the same calendar issues that we experienced in '25 also in '26. Globally, you see that to a lesser effect in our business in China, Q4 is typically a relatively lighter quarter by comparison. But given the magnitude and import in terms of percentage of revenue, for BRUKINSA in the U.S., we thought it was really important to highlight as you think about rolling over your models from '25 to '26. So I can hand it over to Lai.

Aaron, you're correct. In terms of in the U.S. as well as probably use out of that -- CDAC is likely to get the CLL approval probably ahead of the sonro, but that's not the case in China. In China, we already filed the [ someone ] for the CLL, which we're also anticipating approval early next year. In terms of sequence of the therapy, we view that CDAC can provide a really broad coverage in terms of patients who had BTK inhibitor. As shown actually in one of the slide in today's presentation, this really covers pretty much everything except maybe one mutation. So we do believe this is probably at this moment based the level evidence is positioned very well in the later line therapies after the COVID and BTK inhibitor.

Our next question comes from Michael Schmidt with Guggenheim Partners.

I just had another bigger picture question around the CLL market. As you noted in the slides, I mean it sounds like the AMPLIFY regimen has moderate uptake. But fixed duration treatment will clearly be part of the CLL treatment landscape longer term, including your own combination. And so I was just wondering how you think about how that might impact the overall size of the CLL market, the BTK inhibitor market longer term? And then just a clarification on seasonality, Aaron. I know you made some comments around inventory in stocking at the end of the year. But then when I look at guidance, it seems like the top line the higher end, the top end of the range for revenue could be achieved with almost only flat Q-on-Q growth. And so was just wondering if there's anything else going on in 4Q that we should be aware of?

So maybe I'll start with a quick answer around that. As I laid out earlier in this long-term PFS really matters. You have 6 years of follow-up for data matters. These are cancer patients and you don't want progression there's no area outside of CLL I've seen where people talk about, let's take a regimen where you give up years of milestone PFS. You just don't see that. Whether it's van-based fixturation treatments or other BTKs or [Porto], really all options beside chemo, they look pretty decent at 2 to 3 years. And there just isn't enough time to understand the durability and the outcome for patients. BRUKINSA consistently shows best long-term patient outcomes in CLL. It's why it's the standard of care, and it's why it's the global leader. The more follow-up we show as we're doing at ASH, the more differentiated it looks. The 6-year data in CLL in first-line and second-line and in all high-risk subgroups, the story is the same, the best long-term outcomes for patients. It's 6 years follow-up, 74% PFS rate for BRUKINSA in first-line CLL. When you COVID-adjust this at 77%, our OS is 84%, 88% COVID-adjusted. In ELEVATE TN, Acalus PFS is 62%, and their OS is 76% at the same time period. In second-line and deletion 17p, it's the same story. Unparalleled median PFS from Alpine and our SEQUOIA Deletion 17P data shows that BRUKINSA works very well in high-risk patients. It's just not the case with the other options. And we're still reporting our follow-up data because it tells the story. Where is the other data? Where is the long-term data from ELEVATE? Where is it from CAPTIVATE. Where is it from AMPLIFY. It's very noticeable, it's not being reported. And with respect to [Porto] it's 18 months of follow-up in second-line CLL it's not even close to being long enough. And as we've mentioned, 2 to 3 years, you just can't differentiate yet. And I think from that perspective, we're extremely confident in both the short term. And when we talk about long term, the really exciting thing is this desire to have fixed duration treatments. It's a great thing if you can get there. And so far, it does look like SC is going to be unlike anything we've seen yet. It's too early to be sure. There's not enough long-term follow-up data for that either, but the early data looks noticeably different than anything we've seen before. So we're really, really excited about that. Now maybe I'll jump to Aaron to answer some of the other parts of that question.

Yes, thanks. Obviously, there's tremendous opportunity across the franchise as we think about where we're participating today in a $12 billion in growing market, whether you look at it from either a BTK space or an overall CLL space. To your question on the guidance, we did reinforce the seasonality really to make sure we support dialing in your modeling in that regard, given the history. We feel really confident on our execution over the course of the year. As you referenced, we've taken up the bottom of our range from where we started we started the year at 4.9% to 5.3%, and now we're at 5.1% to 5.3%, showing increased confidence and really the great execution from our global teams. As you said, if you annualize the current quarter run rate and you think about the next quarter, we feel that the range that we provided is certainly within our expectations. The import of the seasonality common is really specific to the United States, and we want to make sure that, that perspective is really incorporate. Thank you.

There are no further questions at this time. I will turn the call over to John Oyler for closing remarks.

All right. Thank you all. I would like to point out that a few weeks ago, BeOne celebrated our 15th anniversary as a company. It's very hard to believe that in this relatively short period of time we've been able to become one of the leading oncology companies in the world. I'd really like to think that this is because, as you heard today, were driven by scientific excellence, exceptional speed, and a relentless drive to provide the best long-term outcomes for patients. And on behalf of everyone here at BeOne, I'd really like to thank the broader oncology community including the patients, their families, the clinicians, our employees and all of you who have been with us for the journey. We truly believe that together, we are how the world stops cancer, and we're just getting started. So thank you again for your time today and your thoughtful questions. Have a great day.