All right. Well, welcome everybody to the 46th annual healthcare conference from TD Cowen here at Boston. I'm Yaron Werber, biotech analyst, along with my colleague, Jaena Han. It's a great pleasure to kick off the conference on our end with a fireside chat with BeOne Medicines. With us today, to my left, is Aaron Rosenberg, Chief Financial Officer, to his left, Mark Lanasa, Chief Medical Officer of solid tumors. Gentlemen, thanks for joining us. We appreciate it.
Thank you.
Thanks very much.
lots to talk about. Aaron, maybe let me start with you because we're sort of fresh, off the guidance.
Yes.
The guidance was $6.2 million-$6.4 million in revs on the heels of another nice BRUKINSA beat in Q4. You know, as everybody remembers, Q1, there's usually a little bit of seasonality, so it's important to keep in mind. When you think about the guidance, what sort of went into it? I think some people were kinda hoping for a little bit better. Consensus was $6.4, you bracketed it. It sounded like the guidance might be a little conservative, but maybe give us a little bit of a sense what went into it and also from a competitive standpoint, what are you assuming?
Sure. Again, it's a privilege to be with you all today. Thanks for the question. 2025, as you said, we exited the year really strongly. You know, I think if we reflect back to the beginning of 2025, we established guidance. It was our first year of doing so. I think over the course of 2025, we demonstrated our credibility and ability to deliver on that range, continuously increasing the bottom end of the range, and ultimately finishing 2025 modestly above that initial guide. As we think about 2026, you know, we're building on the momentum coming with the business and with our Q4 exit. It demonstrates significant growth consistent with that demand creation across all of our geographies. We're really pleased with the setup for the year.
Obviously, our guide includes all the competitive dynamics that you might consider. We talked about driving growth in the U.S. market. We talked about relatively stable net pricing in the U.S. market. We really feel confident about the setup for 2026. You know, as you think about the range of $6.2 billion-$6.4 billion.
Mm-hmm
... you're talking about $1 billion of growth on a year-over-year basis. We feel really confident as we enter the year.
In terms of competition from AVO and potentially Jaypirca, although Jaypirca looks like if it gets approved for frontline, it's gonna be literally toward the end of the year, probably Q4, what did you assume for that?
We certainly considered the approval for AVO. I think as you all know, AVO was not approved. We've talked at length about our view of the data, whether it be the 34% uMRD, the 76% 3-year PFS for the AVO regimen. Obviously, in comparison to the benchmark SEQUOIA data that we talked about at ASH for BRUKINSA.
Mm-hmm
... of 77% on a COVID-adjusted basis for six years. We feel really confident about the durability and growth of our BRUKINSA business. Certainly we accounted for competitive dynamics and the entries in the market in that guide.
Of the billion, I know you don't guide globally. Can you give us a little bit of a sense? Obviously, the global expansion, I mean, China, you're the number one brand. In Europe, you're still very much growing, and Europe in general is growing, or ex-U.S., I should say. How much of that is U.S. versus ex-U.S. growth?
We haven't provided forward looking in our guide on a regional split, but what I would say is if you look at our 2025 exit, we are growing globally. You know, each of our regions has a different level of maturity in its launch life cycle. You're seeing, you know, very strong growth in our China and U.S. businesses, and really continuing to drive demand for BRUKINSA in those markets and showing leadership. You know, BRUKINSA established itself as the number one BTK globally in 2025, and that span widened in Q4. You see that both globally and in the United States, where BRUKINSA grew 14% sequentially Q4 versus Q3, and with the competition growing 4% in that same period.
Outside of those markets, our European business was a bit earlier in the launch life cycle. In 2024, the business nearly tripled. In 2025, the business grew more than 70%. We're still continuing to drive increasing share in all of our core markets in Europe. Rest of world markets, you know, growing more than 100% in 2025 is even earlier in the launch life cycle. We have important markets that are first coming online and we're really enthused about the setup there.
What about, just remind us seasonality, Q1 usually is a little bit of a weaker quarter because of insurance resets. Just remind us the cadence. Q3 sometimes is a little bit weaker, but then Q2 and Q4 are strong. Maybe just remind us cadence, how that works.
Yeah. I think that's fair. Q2 and Q4 are typically, as we focus on the United States, the strongest quarters. Other regions have different dynamics. As an example, in our China business, Q4 actually is typically not the strongest quarter. As we look at the setup between Q4 and Q1, I think it's quite similar to what you would have seen in 2025, the exit of 2024 into 2025, and this is really driven by typical inventory movement that happens in the United States in Q4. As you said, insurance resets also play a dynamic in Q1. What we've talked about is if you're thinking about the profile in Q1 of 2026, might be easier just to think about it from a year-over-year perspective as opposed to a sequential.
But those dynamics are the same, including what we thought, you know, what is an unusual event, you know, having one fewer shipment week in Q1 of 2025. That actually repeats itself from a calendar perspective in Q1 2026. So that's happened two years in a row.
Okay. It's one less week in Q1. Can we talk a little bit about R&D expenses are ramping nicely, but again, revenues are growing faster than OpEx, and we'll ask Mark a lot of questions shortly on solid tumors.
Yes.
You are continuing to expand your pipeline. Now, your pipeline has... there's a lot going on in phase III with BCL-2, with BTK degrader. Those will eventually kinda roll off. CDK4 is about to start, and you're beginning to move things into phase II. phase I is obviously cheaper than phase III. At some point, you're gonna start having a lot more phase III programs over the next year or two. At what point would you... Will you wanna partner a few of the assets? How much can you handle yourself? Any thoughts, and does it make sense to partner the CDK4?
Sure. Maybe I could touch on your first part of the question, then maybe hand it over to Mark to talk about our CDK4 program.
Mm-hmm. Mm-hmm.
We're really fortunate. You know, having the amount of innovation and the quality assets that we have is the most valuable, the most valuable asset in our industry. Having the ability to discover assets with high throughput and then leverage our core competitive advantage of taking those inventions and moving them through our early clinical development organization and our CRO-free model, which we call our global clinical development superhighway, you know, to get to proof of concept in time and cost advantage way, that is a competitive advantage for the company. You know, as you talk about the overall investment, from a financial profile perspective, we've demonstrated our commitment to both growth and margin expansion.
You saw those kinetics in 2025, where we grew the business very strongly, and obviously we shifted toward profitability, and we generated more than $940 million in free cash in 2025. We're committed to both of those things, growing and doing so, while driving margin expansion. What we've talked about is doing that in a measured way because what we don't wanna do is shortchange all the opportunity that we have in the pipeline. Our R&D portfolio, as you said, you know, every portfolio has its own evolution.
As you mentioned, the hematology investments, obviously those are coming online, for our sonrotoclax and our BTK CDAC, you know, and those investments and to some degree, you know, replaced earlier stage investments with BRUKINSA's core development and TEVIMBRA's core development, and we'll have that same kind of cycle as we move our earlier stage assets to late development. We will continue to invest, and you saw in our guide that we have a an expense range that's kind of similar growth to where we were in 2025. In terms of partnership.
Mm
... you know, I think what we've said is, first, we're in a very fortunate position, where we've a wealth of assets. They're largely wholly developed and owned. And we have a financial profile and a balance sheet that allows us to prosecute those. We don't have to do anything. We will look at every asset and decide what is the most value-creating approach for a given asset. We will.
Mm-hmm
... commercialize, we have the capability, and take those many, if not all those programs to the clinic, to the completion. Certainly we have the ability to think about what's the best way to maximize value from a shareholder perspective and for the assets themselves, because ultimately these are medicines that we wanna make sure get to patients.
Yeah. all right.
Please.
Perfect segue.
Thank you very much, many thanks as well for having us here this morning. I guess just to build a little bit on what Aaron was saying, and perhaps one of my favorite numbers that we provided in earnings was that in 2024 and 2025, we progressed over 200 dose escalation or cohorts in early phase studies at a median time of six to seven weeks. This is absolutely unprecedented across oncology development. The important point is that, we also are stopping programs that are not meeting our internal criteria for what does a clinically impactful medicine look like. Eagle-eyed listeners can go back and look at our pipeline last year compared to this year. You'll see there's probably been six or seven programs that we've stopped for not meeting those targets.
The great news is we just highlighted five programs at earnings that we think have a clear path to registrational study starts. There's other programs that are also looking good, for example, our BG-T187, the EGFR MET trispecific, our FGFR2b ADC. We think that we will continue to have a very high success rate of molecules emerging from early into late and hopefully ultimately becoming.
Mm-hmm
... differentiated medicines for patients, and happy to talk about CDK4 or any of the other programs we highlighted.
On the CDK4, on BGB-43395, you've now given us sort of what the trial design's gonna look like. It's very similar to the atirmociclib study, both about 1,060 patients, head to head against CDK4/6, looking at superiority, primary is PFS. I think Pfizer's looking for data in 2028. Is there any way to expedite it, or on your side, or is it you have to do superiority and PFS?
Yeah
there's no short-changing that?
Right. I think there's two factors that we've been thinking about. One is, again, operational excellence. We have demonstrated not only can we deliver early phase studies really quickly and with quality, but also late phase studies. We enrolled our CELESTIAL-TNCLL treatment naive study of zanubrutinib and sonrotoclax in only 13 or 14 months, greater than 20 countries, over 600 patients. We will definitely look to progress that study as quickly as possible. The second point is that there can be, shall we say, nuances in the analysis plan around studies that can lead to differences in the timing of specific readouts.
Yeah
... and we're considering those options as well in terms of how the data will be sequenced through readouts, that we don't disclose the timings of our. We don't disclose the details of our analysis plan nor the timings of the readout beyond the primary analysis.
Does it make sense in parallel to run another phase III maybe with a triple, either with a SERD or maybe with a PI3K alpha mutant selective?
We recognize that this is really a quickly evolving field. We look forward to data later this year for the SERDs in the frontline setting. We'll see what those show. Reasonably likely that there will be a clinically meaningful benefit in a frontline setting, though not a foregone conclusion. That likely would be a different phase III study, and then as you correctly highlight, there is strong emerging data that the PIK3CA segment, which is relatively stable through lines of therapy, is likely to be an actionable patient population for the frontline. We believe that the study that we have designed is the right study to show head-to-head superiority of more selective CDK4 inhibitor over a CDK4/6.
Certainly we want to have a relevant combination strategy and whether that means oral SERDs, it'll be gated based upon data disclosures to come this year. PIK3CA inhibitors are an area of interest, then internally, we're also developing KAT6, CDK2 degrader. We've got a novel BCL-2 inhibitor in combination as well. We're thinking about multiple novel combinations both for later line and potentially early line, depending upon data.
Okay. When you're thinking about the 393 and comparing it to Afinitor, and we haven't seen obviously the full phase I data yet, you gave us the dose, escalation. We haven't seen the dose expansion yet. How do you think the two will differentiate?
We will, again, it is our intent to share those data at a major medical congress in the upcoming second quarter. We have enrolled over 60 patients in the frontline CDK4/6/9/8 patient population across different dose levels using FDA's nomenclature. This is our dose optimization experiment that helps us to decide that phase III dose. We intend to disclose those data for both efficacy and safety. We're really happy with how those efficacy data have matured, and we look forward to sharing those, not only to convince you all, but to importantly convince investigators that they should enroll patients on our study, that we're presenting a good option for their patient. I think as it relates to safety, the data that we've shared previously, the data continues to emerge in a similar way.
We're extremely happy with the hem tox profile we're seeing with our molecule. We think it speaks to being the most four versus six selective molecule, very low rates of liver function test abnormalities. We continue to have predominantly low-grade diarrhea, which we have worked to optimize the medical management of in the ongoing phase I study. Our investigators are extremely supportive of moving to this frontline phase III study, and we're excited to get started.
Okay. I mean, you have a lot of other assets, as you noticed. You mentioned there's five assets that you're moving forward. There's the B7H4, there's the MTA cooperative brain penetrant, there's the GPC3-41BB bispecific, there's the IRAK CDAC, and I am missing one more.
CEA-ADC.
The CEA ADC as well. Can you give us maybe a little bit of a sense, how much data are we gonna get from these assets this year?
We intend to have data disclosures at a major medical congress in the second quarter, not only for CDK4, but also for B7H4 and GPC3 by 41BB. If time allows, I'd love to say a little bit more about GPC3 by 41BB at some point this morning as a potential first-in-class molecule. We intend to have our data disclosures for PRMT5 and CEA-ADC in the second half of the year. Abstracts being written at this time. We will have additional data flow for the IRAK4 CDAC in rheumatoid arthritis in the second half of the year.
Okay. This is a, is a great time to why not talk about the CEA ADC and the GPC3. The GPC3, you've said, already met your pre-specified threshold with responses.
Yes.
This is the first time anybody's had a GPC3 that worked. This is presumably in HCC.
Yes.
Zymeworks has one that's an ADC-
Yes
... that's behind in phase I. Can you comment about that target? Is it mostly HCC relevant? Are there other tumors that you might want to expand into?
Yeah.
The therapeutic window maybe?
We're, I think, both Ly and I are presenting that molecule as the pleasant surprise of 2025 because it is a potential first-in-class molecule. GPC3 is expressed in over 80% of cases of hepatocellular carcinoma. It turns out that the typical patient with liver cancer does not have a great performance status. Those patients have a lot of comorbidities, including liver failure of various degrees in most patients. Therefore, we wanted to choose a immunoconjugate that would potentially have a favorable safety profile, which is why we selected 41BB. There are several other GPC3 targeting molecules that are ADCs or cellular therapies.
They do have a meaningful response rate, but they also have substantial associated toxicity. We're really gratified to see with our molecule that we have multiple responding patients with PD-1 pre-treated HCC in a very, very favorable safety profile that we think will not only enable later line development as monotherapy, but also enable earlier line combinations that will maximize benefit for patients. We've already been in conversations with regulatory authorities about this data set. FDA has already granted this molecule fast track designation , so we're working to move this molecule into registrational studies as quickly as possible, likely starting later this year. Again, we look forward to disclosing data, and we can talk in more detail about data later this in the second quarter.
The, the registrational strategy is probably single agent in experienced patients as you do in combination moving it up?
Exactly. We are planning for single agent in later line patients. We are already combining with bevacizumab and tislelizumab, our PD-1, to give line of sight to a frontline opportunity. I forgot to address the component of your question that it turns out that in addition to HCC, about 50% of squamous histology non-small cell lung cancers also express GPC3. There are other tumor types that express GPC3, and we'll be looking in due course to generate evidence in these tumor types as well.
Okay. Great. You mentioned the CEA ADC as well.
Yes
a few words about that.
That molecule was an internally discovered molecule using our linker payload technology, which is a topoisomerase 1 cytotoxic payload. Given the expression of CEA in colorectal cancer, this was brought forward as to first ask questions in colorectal cancer, but also in other CEA-expressing tumors, which relatively frequently includes gastric cancer, but also a reasonable proportion of non-small cell lung cancers with adenocarcinoma histology. We're seeing responses across all of those different histologies, and we look forward to sharing those data across different histologies, and sharing plans for potential fast-to-market and registrational opportunities given the strength of data in the second half of this year.
Okay. Jaena, over to you. Okay, maybe I'll throw in another one, in the meantime. On the B7H4 ADC, what should we expect there, and is the goal to... What would be the front tumor you'd wanna go into?
B7H4 is a competitive target. There are competitor molecules. We are very excited about the data that's emerging, again, both in terms of safety and efficacy. We think that numerically we have favorable differentiation for our molecule in that space. We will share those data in the second quarter as well. We are working towards our initial phase III study start in breast or gynecologic cancers. We're being coy about the first indication given the high competitive intensity. I would highlight that not only is there competition within B7H4 as a target, but more broadly across the landscape of topoisomerase conjugated ADCs because there's an emerging body of evidence, and what KOLs are also telling us is that TOP1 after TOP1 is generally not effective, even if you've switched the target.
We're incorporating that type of thinking into our design strategy as well, or development strategy as well.
What I know you probably can't say too much, in terms of when you think about which tumors which would be free or following a previous TOP1, which ones would those be? You, you mentioned gyn and breast obviously.
Yeah. Well, I think, our point is we don't want to follow a prior TOP1.
Yep.
We want to develop an either a TOP1 naive patient population or have willingness to go head-to-head against a TOP1 where we think that, either with strength of data or biomarker selection, we would have an opportunity to go head-to-head. We'll be sharing data across our key indications of breast, ovarian, and endometrial cancers, at the upcoming medical congress. I almost slipped that time.
Yeah.
Again, we're very excited about the potential of that molecule and think it has a clear path to a phase III study start this year.
Maybe I'll ask one more on PRMT5.
Yeah
Jaena, maybe BCL-2 and BTK next. On PRMT5, that's a hot target-
Yeah
that is took a while.
Yes.
It's beginning to finally show its merits. You have a brain-penetrant molecule as well. How deep are the responses you're seeing and how durable?
So, uh-
Maybe is that. It sounds like it's gonna end up going into a combo regimen and not so much mono.
Yeah.
Is that right, or do you have a better molecule that you could do as mono?
Our molecule is the most potent PRMT5. It also has the greatest selectivity for PRMT5, but as you mentioned, critically, it is also brain-penetrant. Some of the other competitor molecules are fairly potent, so we're happy with the data that is emerging in terms of efficacy, both in terms of response rate and durability. The things that we think will be important differentiators for us are our wide therapeutic index and favorable safety profile, and again, particularly in non-small cell lung cancer, the criticality of having CNS penetrance to prevent CNS progression or relapse. We are working hard to develop clinical data sets to support that has clinically meaningful CNS penetration, not only in lung cancer, but also intend to study this molecule in aggressive gliomas, which we think is another important differentiation.
We're also planning to develop in pancreatic cancer, given the favorable safety and efficacy that we are seeing. Those are our three key indications, and we're working as swiftly as we can. We do think that this is a really important target, and there's increasing belief among prescribers, investigators, that this ultimately is going to be a clinical target.
Great. I do wanna touch a little bit on your heme pipeline. For the BCL-2, venetoclax is doing very well, $2.8 billion in sales in 2025, with 70% coming from CLL. In your view, what kind of market potential do you see for the BCL-2 class in CLL, and how is sonrotoclax going to take share?
Sure. Thanks for the question. venetoclax is a very good medicine. It has significant impact, and it's, as you said, it's on a $3 billion run rate. I think, you know, the issue with the BCL-2 class is really its usability, which has really hampered its uptake, both, you know, in the United States and globally, given the challenges of administration and monitoring and the associated patient experience. You know, with sonrotoclax, you know, talking about a medicine that is 14x more potent, 6x more selective, and importantly has 1/5 the half-life at about five hours relative to 26, that really addresses the accumulation of the BCL-2. Which therefore we hope will lead to a ramp regimen and monitoring that will be far superior to what venetoclax has.
Ultimately we believe that unlocks the full potential of this, of this mechanism, particularly in the community setting, where, you know, there's many more CLL patients treated in the community than there are in academic centers. This is really an opportunity to unlock this potential therapy in those settings to a greater degree, and ultimately the data, which it's early with the phase I data we've disclosed, but the relative effect of our zanubrutinib and sonrotoclax treatment relative to other fixed dose regimens are really non-comparable. You know, talking about MRDs above 90%, 100% three-year PFS, no AEs leading to death. I mean, the data is early and maturing.
We're looking forward to the full clinical readouts, but we really believe the combination of the effect of the medicine, its safety profile, and ultimately its usability, will lead to a much greater market for this class.
My only add is we have also disclosed intent to start a phase III study in multiple myeloma this year, which is a white space opportunity, patients with a t(11;14) translocation, which we think ultimately can be market expanding and bring the benefit of BCL-2 to a broader group of population patients.
Right. Yeah, the CLL, obviously the combo data is very exciting. Multiple myeloma, new opportunity. Near term, I think the first approval is going to be in MCL in the first half of this year. How should we think about revenue specifically in MCL and these kind of smaller indications?
We've talked in our prepared remarks with the quarter, you know, the initial indications in the U.S. in the relapsed refractory MCL setting, and we already have achieved our approvals and our, and patients are getting the benefit from this medicine in China in both the relapsed refractory MCL as well as the post-BTK, CLL, and SLL population. Initially, these are important opportunities for patient experience, to fulfill a very important unmet medical need for patients. These are smaller opportunities relative to the larger scale opportunity, obviously with the combination trial with Sonro. We look forward to initial experience, and then we'll monitor the uptake over time. Obviously, we don't yet have a U.S. approval.
That will be in the first half of this year, we hope, and then we'll look forward to providing more updates on the launch trajectory.
Makes sense. Then on the de-
No.
On the degrader, you're running the head-to-head trial versus Jaypirca. Based on the data so far, what gives you confidence to run this kind of head-to-head study in the post-BTKI setting?
Yeah. We've shared some of that data at earnings, that if you look at the BRUIN CLL study and the later line patient population versus the data that we've shared at ASH and other hematologic congresses, that we think the depth and durability of responses that we've seen in a more heavily pre-treated population really gives us a high degree of confidence in superiority. The other thing that's always nice is the qualitative feedback from the investigators who are using both molecules, and they have also been stating that we should run this study, that they believe that we would likely have a positive head-to-head study. Which we believe makes sense. You wanna fundamentally change the mechanism in a post-BTK by treated patient population.
Do you have any plans to move it earlier line as well in combination, or will it be reserved for post-BTKI?
The hematology team is having that strategic conversation now. I think that the peak behind the curtain is that, again, our view is that BRUKINSA is really an optimized medicine, that it has around the clock coverage, its PK characteristics and whatnot. We don't think that there's room to improve upon that molecule as an inhibitor. We also think that the degrader, given its broad coverage of BTKI emergent resistance mutations, that it makes sense to have that be positioned in later line, but we're open to the possibility that it's such an efficacious molecule that there could be a path to earlier line usage. We're looking at combinations with BCL-2 that would be a very potent later line combination that could be considered as well.
We're leaving the door open, though we remain strongly committed to the utility of frontline BRUKINSA, either as continuous therapy or in fixed duration with some sonrotoclax.
Great. Lastly, any commentary on how the profile for your degrader stacks up against Nurix's degrader, which I know is far behind?
Yes. We estimate that we're probably a year and a half ahead of the Nurix molecule, both in terms of our single arm study that's enrolling, two and three line pre-treated patient population, as well as in execution of our two phase III studies against either investigator choice or Jaypirca. Again, we think we're ahead. We believe that we have operational advantages given our global network in CLL. Importantly, we also believe that we have a better molecule. It's not just about timing and positioning, but we think that we have not only a first-in-class, but a best-in-class degrader.
Thanks.
Maybe just the last question, 'cause I know we're at time. It took you, as you mentioned, 14 months to enroll the CELESTIAL-TNCLL frontline study, right?
Yes, sir.
The head-to-head against Jaypirca, you started in Q3, so that was about six months ago or so. Is there a chance to finish enrollment this year?
I don't know. I'm sorry. Sorry, Aaron, I'm not sure.
Okay. Well, terrific. Team, thanks so much for joining. We appreciate it.
It's great to see you.
Thank you so much.
Thank you.