Thank you, and welcome back to the 2025 RBC Global Healthcare Conference. My name is Greg Renzo, one of the biotech equity research analysts, and we're pleased to be joined today by BeiGene . Representing the company, of course, we have the Chief Medical Officer, Dr. Mark Lanasa, the General Manager of North America, Matt Shaulis, and, of course, the Head of Investor Relations, Dan Maller. Gentlemen, thanks for joining. Great to have you today.
Thanks for having us.
Thanks for having us.
Guys, it's an eventful time at BeiGene , or of course, a transition to BeOne Medicines by name. Maybe we can just have you kick it off by providing us, and those who aren't quite familiar with BeOne, a brief overview of the company, the current state of affairs as it pertains to your business, and of course, the BRKINZA franchise.
Yeah, sure. I'm happy to start. Yeah, we'll transition to our new name, BeOne Medicines, by the end of the week, so we're really excited about that. Yeah, we were founded in 2010 with a vision to provide innovative medicines to millions of more patients worldwide. We've become, over the last 15 years, a fully vertically integrated global biopharma with over 11,000 employees now worldwide. We have deep capabilities in research, clinical operations, which I'm sure Mark will talk more about, and internal manufacturing, as well as commercial. You know, we're really focused on three key areas leaving 2024 and going into 2025, and that is solidifying our hematology leadership franchise, advancing our very deep pipeline, and then delivering financial performance.
If we start with the heme franchise leadership strategy, we're the only company out there right now with three wholly owned, potentially best-in-class medicines in CLL, and the key mechanisms of action that we believe will dominate the treatment paradigm for the next decade. That's obviously led with our BTK inhibitor, BRKINZA, which is the only BTK inhibitor to have complete and sustained BTK inhibition. It's the only BTK inhibitor to prove superiority to Imbruvica in a head-to-head trial. That has kind of parlayed into the commercial setting, right, where in the first quarter, we took the value share lead, revenue share lead for the first time. That's only two years from initial launch in CLL, so that's a huge accomplishment for the company.
The second asset in our heme franchise is Sonro, our second-generation BCL2 inhibitor, and we're focused on advancing that at full speed through late-stage development. We've fully enrolled our treatment-naive CLL phase three trial. We have two additional phase three trials that are initiating or have initiated in the last couple of months. Excitingly, with that program, we had our first registrational milestone in the first quarter where we filed for relapsed refractory MCL, sorry, CLL in China. We expect our first global registration in the second half of the year for that asset. The third asset in our heme franchise is our first-in-class BTK degrader. We've dosed over 600 patients on that program, and we're accelerating that at full speed. Excitingly, again, on that program, we initiated our first phase three trial last quarter.
We've had a head-to-head trial scheduled against pirtobrutinib in the second half of the year, and we remain on track to reach our milestone of a potentially phase two pivotal readout in 2026. Moving on from the heme franchise, we have a very deep pipeline, as Mark will tell folks about. We had 13 NMEs put into the clinic last year, and that was top in the industry. We're really excited about proof of concept data readouts coming this year. We've talked about 10 in 2025. Each of those have the potential to be really value-driving events for the company. In the financial performance area, you know, we've now reached the point, if you haven't looked at us in a couple of years, our P&L looks completely different than it did a few years ago.
You know, we did $1.1 billion in sales in the first quarter. That was up about 50% year over year, you know, maintaining a solid discipline on cost yielded our first-ever quarter of GAAP income in Q1. So really exciting for the company. I think the first quarter sets us up really well for 2025.
That's great. It's helpful to break down really the globalization of BeOne, those three pillars when you think about heme, the deep pipeline, and frankly, the financials, especially as you've given, as you and the company have given guidance for the first time for the year. Coming off of a very strong quarter, which really sets that base in leadership, and maybe, Mark, to you, I could just have you talk a little bit about some of those dynamics with BRKINZA. We have a handle on what seasonality looks like, about the strengths and the opportunity that's set forth in the BRKINZA leadership. Maybe just walk us through some of the insights that you took away from, as you had that momentum from 2024 into the first part of 2025, and what those drivers of performance look like.
Yeah, sure. Happy to talk a little bit about drivers of performance and that bridge from the fourth quarter into the first quarter. I think fundamentally, it all starts with the clinical differentiation of the product. You know, we really believe it's a best-in-class BTK and offers benefit to all patient groups that we've studied. And just to quickly recap, our ALPINE study in the relapse refractory setting showed head-to-head superiority versus Imbruvica and showed real consistency over time, both in an all-comers patient population as well as in those with molecular risk factors like DEL17P and TP53. Sequoia is our study in the treatment-naive setting where we showed superiority to BR, and that included, again, unmutated IgHV patient types. We continue to see CR rates look great and now have five-year follow-up. You know, we had that five-year follow-up data during the fourth quarter.
That was helpful. On to some of those drivers for, you know, really that bridge then into the first quarter, we built on this foundation of strong differentiation, you know, worked through the seasonality that's somewhat inherent in this market. We see in the first quarter that there's very often, you know, insurance renewals or changes in insurance, and at times that can prolong the time to a first fill or the time to existing fills. Certainly, in our case, with substantially more patients on therapy, you know, some of those prolongations of time to fill were more of an impact for us than they would have been in prior years. This is some of the typical seasonality. We also mentioned that there was some stocking that took place at the end of the fourth quarter.
Despite all of that, we continue to have growth in underlying demand. You know, BRKINZA is now the new patient start leader amongst all the BTKs across the B-cell malignancies. And as Dan mentioned, you know, a little bit earlier, you know, we're really pleased to be the value share leader amongst the BTKs now as well.
Yeah. You mentioned that market share of the new patient starts in first line. When you think about the competition and even the potential approval of Acala as a fixed duration just based on Amplify, how do you put that into context as we think about new patient starts and some of those patient dynamics?
Yeah. Look, we first and foremost really believe in the benefit of fixed duration therapy for patients. That's, I would say, probably more so in the long term. We believe that any therapy really needs to meet three goals: one, deep responses; two, strong PFS; and three, you know, really strong safety. As we've mentioned before, when we look at Amplify, we find those results to be somewhat underwhelming. For starters, if you look at the patient population, this was a very, very young patient population, limited comorbidities, lacking some of those molecular risk factors like DEL17P and TP53. Despite the advantages of being in that patient population, it had a really low undetectable MRD rate around 24%. We felt similarly that the PFS was a little bit underwhelming and could deteriorate in the future. We'll have to see.
Safety showed some infections, even to the level of some of those infections leading to hospitalization. We think that the opportunity for that fixed duration segment will be fairly limited given the patient population and those outcomes. We continue to believe that BRKINZA monotherapy will continue to have an opportunity for more new starts.
Got it. Got it. In the near term, how meaningful are the opportunities in first line MCL, the Mangrove, and then in follicular and marginal zone with the Mahogany? How do we think about sort of those incremental boosts?
Yeah, yeah, sure. Collectively, it's an attractive opportunity. Mantle cell, when we look at new cases each year, about 4,200; follicular, 15,000; and then marginal zone, about 6,500. As a group, you know, easily over 20,000 new cases a year. We again think that we're really well positioned clinically. I mentioned before the, you know, the overall differentiation that we have across our data sets, but this also extends across the B-cell malignancy. We think that this is a really great fit with our overall approach to the market. We think it bodes well for us, having recently become, you know, the value share leader amongst BTKs. We think these will be further opportunities to drive, you know, further expansion.
Yeah. Yeah. As Dan mentioned, if you haven't looked at BeOne Medicines in a few years, financially, the profile is just vastly different and really evolved quite nicely. We think about BRKINZA as being the leader today, but frankly, came in third to market. Maybe there was some degree of underestimation. With that, we've talked a little bit about some of the near term, some of the recent dynamics, which we all know, but you have your eye on the longer-term entrenchment. When it comes to the arms race of pricing pressure and pricing for value and jockeying with larger competitors, how do you put that into context for folks? It's certainly a question that comes up a great deal with our investors as well.
Yeah, sure. I would say overall, we're unique in that we're the company that has the opportunity for a CLL leadership strategy, right? We have BRKINZA, which we've spoken about. We have Sonro, which we'll be studying in the treatment-naive setting, the celestial study in combo with Xanu, and then we have a BTK degrader. Some of the risks that other companies might face for end-of-life cycle, you know, pricing pressures, we really take a portfolio approach to this, and we think that that portfolio will help us manage some things in the long haul and allow us to continue to be committed to this space and continue to do great, you know, discovery, research, and development.
Yeah. That's great. Maybe let's go there. Let's go to Sonro and maybe help us think about the profile relative to Venetoclax, obviously the currently only approved BCL2 inhibitor in the United States.
Sure. Thanks again for having us today. We do believe that Sonro is, again, has the potential to be a best-in-class medication because it was designed to have substantial preclinical differentiation from Venetoclax. Importantly, the PK, it starts with a PK, is fundamentally different. It's shorter, which may be a bit counterintuitive because for many mechanisms, we want to have continuous coverage and long PK. Here, actually, you don't need continuous coverage, and having shorter PK avoids drug accumulation, which mitigates the risk of tumor lysis syndrome, which is really a key early toxicity. That, in turn, provides an opportunity for a simplified ramp-up, less need for monitoring, less hospitalization. We think from both the provider and patient experience, it can be a much easier and much more straightforward process for the patient. That's also coupled with greater potency against the target.
We think that this has potential advantages not only in terms of safety and sort of the patient friendliness of the molecule, but also in terms of efficacy. We have recently had readouts that are quite favorable for the molecule. This has led to our first global filing for the molecule in China for conditional approval in mantle cell lymphoma. We have other data sets reading out, including in CLL, and we believe that we will have conditional approval opportunities for sonrotoclax in global markets, including here in the United States, as those data sets continue to mature. Again, I would highlight that we feel that we have a very, very unique opportunity with the combination of sonrotoclax and zanubrutinib to really change the paradigm for fixed duration therapy in the front line setting by having a best-in-class BTK and a best-in-class BCL2.
You mentioned the filings in China. Is there a potential to accelerate approval for sonrotoclax in the United States? How would the timing work out in the next inflection points and ultimately to get on market?
We do believe that there is an accelerated approval opportunity for mantle cell lymphoma in later line here in the United States. We do not believe that there is a later line accelerated approval opportunity for CLL. However, again, the Celestial study has completed enrollment. It will read out the key endpoint of the MRD rate 15 months after the last patient was enrolled in the study. While it is a regulatory upside, we certainly are continuing to engage with regulatory authorities, academic institutions, cooperative groups about the acceptability of undetectable MRD rates as a surrogate endpoint of clinical benefit that could align to Project Front Runner, be supportive of a conditional approval.
That's great. As you talk about, as the team talks about the franchise building, of course, the third leg here in CLL is the BTK CDAC, and certainly a great deal of excitement here seeing the head-to-head against Pirtobrutinib posting and our twice-a-year retreat to either ASH or to EHA, with EHA coming up. Maybe just highlight for us some of the EHA abstracts, what we should be expecting as far as looking at data maturity and how you are expanding on the profile there.
Yeah. I think for across the portfolio, both at ASCO and at EHA, we are sharing data with increased maturity across our portfolio. Certainly, we are going to share data for the BTK degrader. The key point that I would make is that we think that we have generated sufficient data to have strong proof of concept that supports the phase three study starts in the later line setting, both against standard of care, which happily has had its global first patient dose, as well as the study you just mentioned against Pirtobrutinib, which will get started in the second half of the year.
Just about the positioning of 16673 relative to BRKINZA, the franchise approach, but does the CDAC have a role in front line? How would the sequencing optimally occur down the road for patients?
It's a really important question, and we're open to the possibility that CDAC as a fundamentally different mechanism could be really impactful for patients. We have made the decision to begin with development in a later line setting, given that that's where the unmet medical need is. We think that we have compelling activity in those patients, which is why we started a phase three. We are beginning to look at combination studies with the CDAC, including with zanubrutinib, that we think ultimately would provide line of sight to earlier line settings, understanding that the bar in that setting is very high indeed, but we are absolutely open to exploring that and opening a development path to early line settings.
Great. Great. So much to talk about in the solid tumor franchise. Maybe the way we can dip our toe in is just highlighting the investor R&D day that's coming up in June 26th, I believe it is. Maybe just frame that up for us a little bit. I think there's interest in the CDK4 inhibitor, the breadth of your pipeline beyond this asset and what we've spoken about thus far. Maybe help us frame some expectations for that day.
Absolutely. I hope to see you all there. Again, it is June 24th, June 26th. We are very excited about the opportunity. I think broadly where we are, as you heard from Dan, we brought 13 molecules to the clinic last year. That is the most of any sponsor. We now believe that we are, shall we say, approaching a steady state. The thinking that you heard from Mark about the franchise approach to B-cell malignancies, we are looking to take that same approach, lung cancer, GI cancers, and myeloid malignancies, by bringing eight to ten new molecules a year across all these different therapeutic areas to enable in portfolio combinations. We are going to spend some time talking about that high-level R&D strategy of how do we accelerate building franchises in key disease areas that are common diseases with high unmet medical need.
Now, certainly, we want to highlight the early successes that we're having with the molecules that we brought into the clinic in late 2023 and into 2024. I'll spend some time talking about our breast cancer franchise. We'll share some new data for the CDK4 molecule, specifically highlighting what we believe is emerging differentiation in terms of safety. We're happy to share some of our data for efficacy, particularly in combination with fulvestrant, which we believe has the opportunity to be our first phase three study start. I will share updates for CDK2 and B7H4, both of which will be presented at ASCO, as well as disclose new targets that we have in the breast cancer space. I'll spend the majority of the balance of my time highlighting what we think is a really diverse and differentiated and potentially very impactful lung cancer franchise.
We're excited, very excited about our PRMT5 inhibitor. And then we have a portfolio of work ongoing in the EGFR space, including our EGFR degrader, multi-specific biologic targeting EGFR and CMET, and other emerging targets that we'll share at R&D day.
That's great. Maybe just a higher-level question, Mark. With so much going on in the pipeline, how is BeOne taking the evaluation approach to establish go-no-go decisions with many of these assets? What criteria set do you use? What is uniquely BeiGene's approach?
This is a super important question. In my role, it's also my great pleasure to be the Chair of our Development Review Committee. What I can say is that when a team brings a new molecule to the DRC for a first-in-human study, the expectation is that they're going to know what is their lead indication for development, what does standard of care look like. Fundamentally, what would constitute a differentiated medicine for the patients that we intend to develop that investigational medicine for? That sets very clear go-no-go criteria. Because we are a mid-sized organization with a large pipeline, we have to ask very focused questions related to, are we impacting the biology in the way that's expected? Is the PK meeting our expectations based on preclinical data? Is safety acceptable? Ultimately, is efficacy going to provide differentiation?
We have very, very clear go-no-go criteria. We have stopped some programs over the past 6-12 months that are not meeting those criteria. We will continue to focus on the investigational medicines that can be the most impactful future medicines.
Great. Maybe just circle back to ASCO. You touched on it a little bit, maybe with B7-H4, also the CDK2. Maybe set expectations. What are you excited about with some of the data sets that are coming ahead of the R&D day?
Certainly, we're very excited to share data with our B7-H4 targeting ADC. That molecule has been in the clinic for roughly 14 months. We have essentially completed dose escalation, not formally completed, but we're going to share safety and efficacy from dose escalation. We're seeing clinical responses and what we think is a very acceptable safety profile across a range of doses and a range of tumor types, which we believe opens a clear development path in both breast and gynecologic malignancies. For CDK2, that will focus on the monotherapy dose escalation experience. We do see that principally as a combination agent. Again, the focus will be on safety and PK. We will share efficacy data. We do think that our safety profile is consistent with being a very selective and potent CDK2 inhibitor.
We're happy with how those data sets are shaping up and look forward to combining our CDK2 with our CDK4 in the second half of the year.
Great. Great. Maybe we can just, in the last moment, just come back to the top line. As you've talked about the over $1 billion in revenues for the quarter, it's not just BRUKINSA, right? With Tevimbra, obviously the Amgen products that you're partnering with, maybe quickly just a commercial case for Tivimbra in the U.S. and in Europe. Just talk a little bit about there being room for another PD-1 in today's landscape and the potential arrival of biosimilars.
Yeah, sure. Yeah, on two counts there. One, we think it is a substantial market opportunity, although a very focused one for us. As I'm sure everyone's familiar with, Greg, the global PD-1 opportunity is about $50 billion. When we think specifically about upper GI, that becomes about $1 billion. Our expectations are shaped by our order of entry and that focused set of initial indications. There, we're quite pleased and confident, right? We recently got our front line esophageal label. We previously had a second line esophageal label. That was in addition to the front line gastric label. Here, we think there's real differentiation. Our median overall survival in that front line esophageal setting compares favorably to what we've seen in other studies with Pembro and Nivo.
In addition, we recently had an alternative dosing approval from the FDA that gives us Q2W and Q4W, which is really important for using the agent in combination with other therapeutics. We feel really good about our initial uptake, which is in line with expectations in the U.S. Certainly with regard to biosimilar entrants, we continue to be committed to accessibility and affordability. We price Tivimbra in the U.S. so that it would be the lowest cost of those PD-1 agents.
That's great. Maybe a quick closing question with a great deal of macro and geopolitical topics in the headlines and BeOne Medicines certainly being asked to respond and just remind us about your geographic contributions in the business, how this evolves in the near or long term. The question's always about exposure, but just remind us about how protected you are and how diverse you are as a company.
Yeah. You know, from a revenue diversity, certainly our mix has evolved, right? We have the look and feel of a global multinational pharma, and we will continue to expand revenue in Europe, revenue in rest of world markets where we're still in the really early days. We had a slide in our Q1 presentation which showed the contribution by region, by revenue, and the growth. You could really kind of see the high growth opportunity we have in some of those rest of world markets, including Europe.
That's great. That's great. Gentlemen, thanks for joining us. Great to have you. Look forward to ASCO as well as the R&D update in June.
Thanks again.
Thank you. Thanks everyone.
Thanks for having us.