BeOne Medicines Ltd.

Good day, everyone. Welcome to B1 Medicine's Q1 2026 earnings call webcast. All lines have been placed on mute to prevent any background noise. After the speaker's 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 B1 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.b1medicines.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 IR website along with our earnings release. All information in this presentation is as of the date of this presentation, and we undertake no duty to update such information unless required by law. Now turning to today's call, as outlined on slide three. John Euler, our co-founder, chairman, and CEO, will provide a business update. Aaron Rosenberg, our CFO, will provide an update on our first quarter financial results and 2026 guidance. And Lai Wang, president and global head of R&D, will discuss our R&D and pipeline progress. We will then open the call to questions. And joining the team for the Q&A portion of the call will be Xiaobin Wu, President and Chief Operating Officer, Matt Shaulis, General Manager of North America, Mark Lanassa, Chief Medical Officer for Solid Tumors, and Amit Agarwal, Chief Medical Officer for Hematology. I'll now pass the call over to John. John?

Thank you, Dan, and welcome, everyone, and thank you for your time today. We entered 2026 with tremendous momentum. and our Q1 performance reflects strong execution across the business and a very solid start to the year. From a financial perspective, we achieved significant product revenue growth and gap earnings per ADS. These results underpin our confidence to raise our 2026 revenue guidance range by 100 million, as Aaron will discuss later. Our foundational hematology franchise consisting of Brukinza, Sonro, and our BTK CDAC is rapidly progressing, with approvals, launches, and key pivotal trial milestones expected in the near term. Both our heme franchise and our solid tumor pipeline will be on display at ASCO and EHA, where we have over 60 acceptances. At ASCO, we will present proof-of-concept data from three exciting solid tumor programs moving into late stage clinical trials, which Lai will tell you more about shortly. I'll begin today by highlighting the exceptional commercial and clinical progress of Brukinza, which has firmly established itself as the foundational BTK inhibitor. Brukinza continued its global leadership in the growing BTK market with first quarter sales of 1.1 billion, representing growth of 38%. We are seeing strong performance in all markets and all indications. Brukinza's large, consistent, and expanding body of clinical and real-world evidence has elevated the benchmark for what is possible in CLL. We believe that the data shows that only Brukinza provides the long-term outcomes that patients and physicians should expect and should demand. From its inception, Brukinza was designed to provide the best-in-class 24-7 BTK inhibition. Our hypothesis was that achieving complete and sustained BTK inhibition would result in a superior therapeutic profile, and that has been borne out in the almost seven years since, which I'll cover in the next few slides. At ASH 2025, Rukinza set a new standard in frontline CLL, with six-year progression-free survival reported at 74% and overall survival of 84%. Adjusting for COVID, those are 77% for PFS and 87% for OS at six years. CLL is an indolent disease, and admittedly, much of the data across the various medicines for the first three years looks similar, but outcomes beyond this are what truly matter to patients. So this slide builds on the scatter plot, but focuses on the landmark reported PFS at years three through six across phase three trials in frontline CLL. On the left, we see the data for Brukinza and the two continuous PTK inhibitors. Recognizing the limitations of cross-trial comparisons, the early landmark PFS rates for Brukinza are higher and continue to diverge over time. In year six, that reaches a delta of 12%, the equivalent of one in eight patients not progressing. On the right, we see an even more pronounced delta between Brukinza's landmark PFS and that of fixed duration regimens, such as VO. In year six, that's a delta of 21%, or roughly one in five patients. In the unmutated population, which is the majority of CLL patients, the difference between continuous Brukinza and VO is 27%, which is more than one in four patients who started the study. Now, AV has not reported the long-term landmark PFS data to be fully represented on this chart, but I will note that despite Amplify being studied in a young, fit population, which has a median age of 61 versus Sequoia's median age of 70, It has the lowest PFS of any regimen at three years. The last amplified data cut was April 30th, 2024, over two years ago. An additional follow-up data has not been provided, though. Of course, it exists. Brukinza is the only BTK inhibitor that has demonstrated superiority on efficacy versus ibrutinib in a head-to-head trial. Here, we can see the Kaplan-Meier curves from Brukinza and the other BTK inhibitors in their respective head-to-head trials versus ibrutinib in relapsed refractory BTK-naive CLL patients. Brukinza demonstrated superiority with a hazard ratio of 0.69 and a p-value of 0.001. When we presented the initial early cut of these data to the CLL community, the universal feedback was, this is great, but in an indolent disease, we need to see longer follow-up. And there was an important scientific reason for that. Ibrutinib has a known tolerability issues that could potentially influence a patient's ability to stay on the therapy during early treatment. In the ElevateRR study at Calibrutinib, had previously showed early PFS separation from ibrutinib, but that early separation was not sustained. As you can see in the middle panel, acalabrutinib actually crossed over and became numerically worse than ibrutinib at roughly 33 months and reported a hazard ratio of one. And again, while early separation was an encouraging signal, CLL prescribers wanted to see, with Brukinza, sustained separation with longer follow-up to be convinced. You can see that in Alpine, Brukinza showed exactly that. After these data were presented, the adoption of Brukinza began in earnest. Perto, with a very short follow-up period of only 18 months, shows the weakest early separation versus Ibrutinib. with a hazard ratio of 0.845 and a p-value of 0.4102. The CLL community needs to see much longer follow-up data from PERTO, but given this curve, PERTO may face challenges demonstrating statistical superiority on PFS. So what about tolerability? PERTO is self-described as a third-generation BTK inhibitor. with the hope that it would be more tolerable than the second generation covalent BTK inhibitors. In reality, the Bruin 314 study, HERTO demonstrated numerically more adverse events leading to discontinuation than ibrutinib. This is important because it has potential ramifications for use in specific subgroups, such as older patients. Notably, in the BRUIN 313 trial in first-line CLL, the average age of patients randomized to PERTO was 65 years old, roughly five years younger than the respective first-line trials for both of the second-generation covalent BTKIs. But taken together, PERTO's limited follow-up, lack of differentiation on efficacy and tolerability over abrutinib, and its mechanistic rationale designed for covalent BTKI resistance do not support moving it from the relapse setting where it currently plays a much needed role. Brukinza's comprehensive body of evidence continues to expand. It consistently is supporting it as the foundational best-in-class BTK inhibitor. Last quarter, we highlighted three published studies that illustrate Brukinza's efficacy and safety benefits over the existing fixed duration regimens, VO, IV, and AV. And at ASCO, we'll present new evidence from over 58,000 real-world patient data sets, each of which demonstrate the significant real-world benefits of Brukinza. While Brukinza's momentum as the foundational BTK continues, we're aggressively moving to redefine the fixed duration treatment landscape with our next-generation foundational BCL2 inhibitor, Sonro. We intentionally designed Sonro to be 14 times more potent and 6 times more selective than Venetoclax, and with a much shorter half-life to minimize drug accumulation. This differentiated profile may enable a simpler ramp-up compared to the burdensome monitoring that is required by the first-generation agent. The trial studying this optimized ramp-up schedule is progressing well. Sonro's first approvals are as monotherapy, but its true transformative potential lies in combination with Brukinza. The clinical data that we're generating with the combination of Brukinza and Sonro is truly exciting. In the 101 trial shown here, ZS demonstrated a UMRD rate of above 90%. a remarkably flat PFS curve, and a favorable safety profile. This compares very favorably with AV on the right, where in a much healthier, younger population, they saw a UMRD of only 34%. We look forward to sharing updated data from this trial at ASCO. With three phase studies underway, The ZS combination has the potential to change the first-line CLL treatment paradigm and enable B1 to participate in half of the market where today we have no presence. Finally, I want to highlight the progress of our BTK-CDAC, a novel potential therapy for patients who have progressed on other treatments. Our BTK-CDAC is first in class. It shows complete BTK degradation, and it holds a clear mechanistic advantage in terms of BTK mutation coverage. Data presented at ASH 2025 showcased its profound efficacy in heavily pretreated patients, including those with mutations conferring resistance to both covalent and non-covalent BTK inhibitors. In our Phase I-II study, the patients receiving the recommended 200 mg dose achieved an outstanding 94.4% overall response rate, with responses deepening consistently over time. Based on the strong efficacy and favorable safety profile of the molecule, we're advancing highly ambitious clinical development plan, including several phase three trials that are well underway. We've guided to a potential accelerated approval submission in the U.S., relapsed refractory CLL in the second half of this year. In summary, our foundational hematology franchise has never been stronger. Brukinza's driving continued global revenue growth, Sonro is poised to disrupt the fixed duration market, and our BTK-CDAC is leading the next wave of innovation in CLL. Only B1 is uniquely equipped to provide the best-in-class therapies every CLL patient, regardless of their stage of disease. We're looking forward to ASCO and EHA this year, where we will have a large leadership presence, highlighting our foundational medicines and our three rising stars from the solid tumor portfolio, which Lai will tell us more about shortly. With that, I'll pass it over to Erin to provide our financial update.

Thanks, John. In Q1, we sustained strong business momentum across our product portfolio. Product revenue reached $1.5 billion in the quarter, representing 34% year-over-year growth. Brukinza global revenues totaled $1.1 billion, with strong growth and performance across all approved markets and indications. In the U.S., Brookings' Q1 sales were 761 million, principally driven by volume growth of approximately 28% versus Q1 2025. The U.S. saw a mid-single-digit pricing benefit on a year-over-year basis with non-recurring gross-to-net favorability of approximately 20 million in the period. Excluding these items, we continue to expect relatively stable pricing in 2026, consistent with prior commentary. Q1 results reflect the typical seasonality patterns seen across the BTKI class, including inventory dynamics and one fewer shipping week in the first quarter. The business performed nicely relative to our range of expectations for the quarter, with increasingly positive demand signals in March, which have carried through to April. We are confident around performance in the U.S. for the year, and this is reflected in our guidance update. Meanwhile, Tevimbra reported a 20% increase with sustained market leadership in China despite the competitive environment. We are pleased with contributions from launch markets with approximately half of the growth for Tevimbra coming from markets outside of China. InLicense and other products also showed continued strength, growing 27% year over year, including robust performance from our Amgen InLicense portfolio. XGiva continued to perform very well in the quarter with $90 million of revenue. Of note, we did see several biosimilar entrants file for approval in April, which could lead to enhanced competition for XGiva. We are pleased with the early market reception for Sunratoclax, our foundational next-generation BCL-2 inhibitor approved in China for post-BTKI CLL-SLL and relapsed refractory MCL. We continue our solid execution across all geographies. The U.S. remains our largest market, generating 766 million with year-over-year growth of 36%. China revenue totaled $465 million, a 17% increase compared to the first quarter of 2025, of which 5% was driven by foreign exchange. We continue to see good performance and sustained leadership from Tavimbra and Brukinza. Europe contributed $191 million, representing growth of 64%. Foreign exchange contributed approximately 11% of this growth, given euro strengthening on a year-over-year basis. We continue to drive demand growth for Brukinza in Europe in all major markets, and there remains plenty of opportunity to increase brand share given Brukinza's differentiated long-term data across all patient types. While the AV combination has yet to achieve broad market reimbursement, we have observed BCL2-BTKI fixed-dose treatments gaining traction in some early markets. As we've discussed, Europe is a more mature market for these fixed-dose treatments given the legacy availability of venetoclax plus ibrutinib. The long-term data is clear on the efficacy and durability of Burkinza across all patient risk factors, particularly for the large unmutated population, which we expect will continue to support growth moving forward. Rest of world markets grew 104%, driven by market expansions and new launches in key markets such as Japan and Brazil. Now turning to the other components of our GAP P&L. Gross margin improved to 89% from approximately 85% in the prior year. This improvement primarily reflects the benefits from favorable product mix, price, and cost efficiencies. Operating expenses grew by 16%, totaling $1.1 billion as we are investing to support our commercial growth and rapidly advance our innovative pipeline. The weighting of growth between SG&A and R&D is expected to normalize over the course of the year, with both converging toward rates consistent with the overall OPEX growth implied by our full year guidance. Income from operations totaled $250 million. an increase from $11 million in the prior period. Income tax expense totaled $32 million for the first quarter, primarily reflecting cash tax expenses in certain geographies. Altogether, net income totaled $227 million, with gap-diluted earnings per ADS of $1.96. Our non-GAAP P&L includes adjustments for typical items with a full reconciliation provided in the appendix. Non-GAAP income from operations totaled $414 million in the first quarter, up from $139 million in the prior period. And non-GAAP net income came in at $375 million for the first quarter, which translates to diluted non-GAAP earnings per ADS of $3.24. We generated free cash flow of 161 million in the first quarter, an increase of 173 million over the prior period. Note that operating and free cash flow is typically lower in the first quarter due to working capital seasonality. Now, turning to our 2026 financial guidance update. We like what we see so far in the U.S. with strong demand growth and with relatively stable net pricing. Growth is anticipated in all markets and will benefit from continued global expansion. And we anticipate modest full-year initial contributions from our launches of Zanadatamab and Sonro. And our guide incorporates all current and anticipated competitive market dynamics. Given our Q1 performance and assessment of recent trends, we now project 2026 revenue to be between 6.3 billion to 6.5 billion, an increase of 100 million across the range. Our estimate of GAAP gross margin remains in the high 80% range with continued benefit from mix and a full year of productivity from improvements implemented last year. GAAP operating expense expectations are unchanged between $4.7 billion and $4.9 billion. Given our top line improvement, GAAP operating income estimates are updated to be between $750 and $850 million with a corresponding change in non-GAAP operating income. In summary, we are pleased with our start to the year and are confident with how 2026 is shaping up. And with that, I'd like to pass the call over to Lai.

Thank you, Aaron. Hello, everyone. Thank you for joining us today. This slide highlights recent progress across B1's pipeline. In hematology, Bokinsa's mangrove phase III study in tumor-naive mental cell lymphoma remains on track, with interim PFS readouts expected next month, supporting a potential first chemo-free regimen in this setting. So long is approaching a key inflection, with U.S. PDUFA decision expected soon, alongside EU submission and ESMO guideline inclusion. Our BTK-CDAC continues to advance, with potentially pivotal Phase II programs in relapse, refractory CRL, and waterstorm, and the Phase III head-to-head study versus PDO is on track to complete enrollment in early 2027. In solid tumors, Devambra received a U.S. priority review in HER2-positive gastric cancer. In parallel, the CDK4 inhibitor has activated its first phase III site, and the GPC341BB bispecific is enrolled in a potentially pivotal HCC study. In addition, we acquired an exclusive option to license a novel PD-1 VGF CTLA-4 trispecific, which is expected to enter the clinic in June. In immunology, we made a data-driven decision not to pursue IRAC-4 in rheumatoid arthritis, while the BTK-CDAC CSU Phase II study is on track to initiate by year-end. The progress you just saw reflects the very deliberate way we are building our pipeline. Our strategy starts with focus, selecting a small number of disease areas where we believe we can lead, and then building depths, not just the single assets. What enables this approach is our in-house technology stack. Spanning CDACs, novel payload ADCs, CellSLP, and emerging platforms like T-Cell Engagers. We're not bound to a specific target or platform alone. We systematically match the right biology with the right modality to build a pipeline that is deep and sustainable. That engine has clearly accelerated. From 2011 to 2020, we delivered 11 new market entities, building the foundation with assets like ZANU and Tesla. Between 2021 and 2023, we added another 10 AMEs, demonstrating consistent productivity and execution. The momentum stepped up again in the last two years, with 18 AMEs across small molecules, CDAC, ADC, and the trispace fan bodies, reflecting the maturation of our in-house platforms. Looking ahead, we expect to sustain a cadence of roughly 8 to 10 MEs per year from 2026 and beyond. Innovation at B1 is accelerating, systematic, and built to scale. As our innovation engine accelerates, It is producing a broad but intentionally focused pipeline across our key disease areas. We have built the depths with multiple mechanisms and modalities coexisting within the same indications. This is important because it creates unique opportunities for proprietary combinations developed entirely within our own portfolio, which drives higher return on investment rather than relying on external assets. 2026 marks a true inflection year for our solar tumor portfolio. After several years of disciplined build-out, we now have a new wave of programs advancing toward registration. In breast cancer, our CDK4 inhibitor is moving to late-stage development in a large, well-established setting, while the B7H4 ADC continues to advance with encouraging signals in gynecological and breast cancers. In liver cancer, the GPC-341BB bispecific represents a focused, first-in-class approach designed specifically for HCC with a potentially pivotal study actively enrolling. We're also advancing our PMT-5 inhibitor, which is already being evaluated in first-line settings, underscoring its potential relevance in earlier lines of therapy. Finally, based on the exciting early data, we are planning pivotal trials for our CADC, further strengthening the solar tumor portfolio. Taken together, our solar tumor pipeline is clearly shifting from early promise to late-stage execution, with multiple programs advancing toward meaningful late-stage milestones. While several of these programs we highlight are in large, well-understood cancers, such as CDK4 in breast cancer, there remains less appreciation for the opportunity in hepatocellular carcinoma HCC. As we said at JPM, there is much work left to do in cancer, and HCC is a clear example. As the sixth most common cancer worldwide, it is the third leading cause of cancer deaths, reflecting decimal five-year survival rates that are well below many other major cancers. A truly differentiated, potentially game-changing approach in this setting can meaningfully improve patient outcomes and expand what is already a multi-billion dollar market. The unmet medical need you just saw in HCC demands not only innovation, but the ability to execute with sense of urgency. Our first-in-class program, GPC34MBV, is a clear demonstration of our unprecedented clinical execution capability. We moved from first-in-human dosing to enrolling the first patient in a potentially registrational study in just 19 months. This is exceptionally fast for a novel bispecific insular tumor. This escalation was completed in under six weeks per cohort. We have enrolled over 200 patients in 20 months, including over 45 first-line HCC patients treated in combination with TSLA and BEV, giving us early experience across clinical meaningful settings. Along the way, the program has received a fast track and orphan drug designation by FDA. At the bottom of this slide is the simple view of the potential pivotal study design with OR by IRC as the primary endpoint. Our school 2026 will be an important moment for B1. We have 24 abstracts accepted, including three oral presentations, underscoring both the breadth and the momentum of our pipeline. You will see the clinical updates across key programs, including our CDK4 inhibitor, B7H4ADC, and the GPC341BB. Please join us at our OSCO Investor Relations event on June 1st to learn more about our clinical data and why we are so excited about these assets. LB1, we'll move quickly to clinical proof concept and advance only programs with the strongest data into late-stage development. You can see how that discipline is being applied across the portfolio in the actions we are taking this year. We will have additional data disclosure this year for programs such as PMT-5 and the CEADC, while new assets like ADAM-9 ADC and the KRG-1 have recently entered the clinic. At the same time, we have made data-driven departization decisions in programs such as CDK2 inhibitor, EGFR-CDEC, MAT2A inhibitor, and PEN-KVS inhibitor, allowing us to reallocate resources toward the potentially highest impact opportunities. This is exactly how our strategy is intended to work. Move fast to prove concepts. identify the most promising candidates, and invest aggressively to maximize patient impact. In addition to our focus on our internal breakthroughs, we are further strengthening our pipeline through selective external innovation. BON110 is a good example of that approach and it represents a potential IO backbone for our solar tumor portfolio. What differentiates the trispecific from PD-1 VGA bispecific is the addition of a CTLA4R, which gives the potential for deeper and more durable immune activation. Importantly, this creates broad opportunity for proprietary combinations across our pipeline, including ADCs and the 4-1BB-based programs. This program is on track to enter clinic next month. We have covered most of the milestones already, so I will just call out three remaining 2026 catalysts. First, we expect to initiate a solo phase three study in second-line plus multiple myeloma later this year, extending our BCR2 strategy into a new important patient population. Second, in the second half of this year, assuming the data is supportive, we expect an accelerated approval submission for our BTK-CDAC in a relaxed refractory CLL. And finally, We anticipate a U.S. approval for Tevembra in first-line HER2-positive gastric cancer, marking a meaningful regulatory milestone in solid tumors. I will now turn it back to John.

Thanks, Lai. We'll now open the call to Q&A. Can you please limit the number of questions to ensure that we have time to hear from as many attendees as possible? Operator, can you please go ahead?

Thank you. If you would like to ask a question, please use the raise hand icon, which can be found at the bottom of your webinar application. When you're called on, please unmute your line and ask your question. We'll now take a moment for the queue to assemble. Our first question is from Miguel Nachovenbevich from Citigroup. Please unmute your line.

Hi, great. Thank you very much for taking the questions. John, you've consistently highlighted Brukinza as the only BTK to demonstrate superiority versus ibrutinib in alpine, as you just noted on slide 10. I'm just curious, because one of your competitors, Lilly, has also been highlighting Pyrido's performance versus ibrutinib. as recently as some of their materials in the recent earnings call stating 76% risk reduction versus ibrutinib in treatment naive and 27% PFS risk reduction in a relapsed refractory BTK naive. So I'm just wondering if you could help contextualize that and sort of sort out the apparent disconnect there. Thank you.

Here you go. Thanks for the question. Appreciate it. And I think that's probably best handled by Amit.

Yeah, happy to take that, John. Thank you for that question. So, unequivocally, what we're saying is correct. Brookins has the only BTKI to demonstrate superiority to Ibrutinib in a head-to-head study. So, before I talk about some of the specific problems with the PERTO claims, let me just talk about a couple of important study conduct principles. So in an open label study, when you have two arms being compared, the standard industry practice based on regulatory guidance is to actually look at the data assessed by an independent review committee or an IRC, rather than relying on investigator assessments. This is for the obvious reason that investigator assessments can favor the experimental arm over the control arm. Also, it is important to ensure that there is no discordance in the investigator and IRC results. And I'll come back to that in a minute. A second important aspect is that there should be predefined alpha allocation for the subgroups being tested and the order of testing itself. So all of the claims have to be based on alpha allocated predefined subgroups rather than exploratory subgroups. So with that, to talk a little bit more specifically about the Bruin 314-based claims. Now, what you may have seen in some of the presentations is a claim on risk reduction compared to Ibrutinib in the relapse setting of about 26%. But if you actually look at the IRC data, and John had this in his presentation, what you see is that there are only two events that separate the two arms. So the PERTO arm has reported 48 events, and the IBRUTNEB arm has noted 50 events. So if you compare this to the investigator curves, you can see that there is a significant discordance, and this really highlights the importance of the IRC curves. Now, with a two-event difference here, the likelihood of this comparison showing statistical significance, even with longer follow-up, seems to be very low. And John made the important point that with ibrutinib in particular, as patients are able to tolerate it, we've seen what happened with the Elevate RR study as well. Now, moving on to the treatment-naive group, the claims are even more questionable because this is a very small subgroup of the overall trial population, and according to the JCO paper, is not even listed in the hierarchy of testing. So this is not a predefined group. And moreover, even in this group, when you look at the IRCSS difference, that is not statistically significant. And finally, for the treatment-naive group, given the extremely short follow-up of the Bruin study, questions around long-term safety, treatment sequencing, as well as overall benefits over other BTK inhibitors remains quite questionable. So I think really to conclude, what I can say is based on all of this data, Brookinsa remains the only BTK inhibitor to have shown clear superiority.

Thank you. Thanks a bit. And I don't think that's a like technical statistical answer. I think this is the governing chart. IRC that the industry recognizes. And as Amit shared, the data is what the data is. So anyway, we're very comfortable with that statement. Okay, thank you. Operator, could we have the next question, please?

Thank you. Our next question is from Kalpit Patel from Wolf Research. Please unmute your line and ask your question.

Good morning, and thanks for taking the questions. One on Brukinza's Celestial TN-CLL trial. We were expecting UMRD results, but we didn't see that on the slide deck, so curious on the update there. And then second, for the D-greater, the CDAC, what hurdle are you targeting? What efficacy hurdle for filing for accelerator approval? Thank you.

Thanks so much. Those are great questions, but I think we're back to you.

Yeah, happy to take those as well. Thank you, John. So for the celestial UMRD question, let me start by talking a little bit about how that study is set up. So just as a quick reminder, the celestial 301 study effectively has dual primary endpoints. One is the UMRD at the end of the treatment in the two arms, and the other is PFS or progression-free survival. So in our case, progression-free survival is a traditional regulatory endpoint and is the base case for our filing. So we expect PFS to be the endpoint that will support regulatory approval for that regimen. UMRD is not currently accepted as a regulatory endpoint, but obviously it remains scientifically very interesting, as well as there's efforts ongoing from a regulatory perspective as well. So in Q3 of this year, our IDMC will review the UMRD data across the arms and tell us whether statistical significance has been met or not. Irrespective of the outcomes for UMRD, we will disclose that externally at the next proximate opportunity, and the study will continue to the PFS readout, essentially unchanged with no change in the study conduct. Now, it is worth noting that demonstrating statistical significance versus VO is an extremely high bar. And if positive, the Celestial 301 study would be the first study to show UMRD superiority for a BTK and BCL2 combination over VO. In prior large studies, VO has shown the highest benchmark UMRD rates. So just as an example, if you look at the recently reported CLL17 trial, The UMRD rates for VO are 73.3%, and for VI, they are 47.2%. Even with the UMRD rate difference of 25% in the two arms, the PFS for VO and VI are essentially superimposable. So you can imagine that even if the ZS-UMRD rates are on par with the VO rates, we will actually feel quite good about the likelihood of demonstrating PFS benefit. Based on this data and the data that we've seen to date with the Sondra 101 study, we remain very confident in achieving the PFS endpoint, even if UMRD is not statistically significant. Also, we have a separate ongoing phase three head-to-head versus AV, which we feel based on the data presented so far represents a meaningfully lower bar for UMRD than VO in terms of the MRD rates. And either trial can enable global registration in that frontline setting. So we look forward to bringing ZS to patients based on these two trials. Now, quickly, just on the degrader, we've been enrolling patients in the relapse refractory patients in a phase two study. And as far as benchmarks are concerned, I think this is an evolving area depending on what are considered available and approved therapies in the U.S. But certainly, you know, based on that study and as well as the studies run with pertobrutinib as monotherapy, we're sort of looking at a benchmark of somewhere between 50 to 70 percent depending on the population. Thank you, John.

Thanks so much for the answer. And could we have the next question, please?

Thank you. Yes. Our next question is from Jessica Five from JP Morgan. Please unmute your line and ask your question.

Hey, guys. Good morning. Thanks for taking my questions. I was just hoping you could give us a status update of what inning you think we're in of Brookings' launch in Europe. And then for the BDK-CDAC, which I believe you suggested could be launching next year in relapse refractory CLL, following potential filing later this year. Can you talk about how we should think about the initial launch ramp for that one? Thank you.

Perhaps I can kind of answer the first question. I'm not very good at innings because I'm from Pittsburgh and our baseball team is not so great. But, you know, I think as we all know, Europe takes a while to launch and to work your way on to reimbursement. And, you know, I think we've always been behind there versus the U.S. We're very encouraged by what we see, but I think that it's still pretty early in those days and we see the opportunity for substantial growth for Grukenza as a single agent. Of course, with the combination when Sonro comes into play, You know, we think this is, you know, game changing. And, you know, the opportunity for that is just tremendous in every country across the world. That's the first question. The second question is the CDAC launch ramp.

On the CDAC launch ramp, I think that's a question that we could refer to that. Hi. Glad to take that question around CDAC launch ramp. I think you've already heard from Amit and also from John about aspects of the CDAC clinical profile, which we anticipate will be very strong and particularly note the head-to-head trial design versus Peerdo and those later lines of therapy. So in terms of overall launch ramp, we think that It should be relatively robust, would anticipate a typical S-shaped uptake curve. But again, we think it's a well-prepared market and we're confident about its prospects.

And I think one of the nice things about that program and Sonaro is both of these largely leverage the existing infrastructure that we have in place. you know, which is, you know, great for us and makes it much easier effort, but it's also, you know, economically highly favorable.

So that's a great thing about having several programs that overlap on the, you know, clinicians that are using those medicines.

Okay. Thank you so much. Can we have the next question, please?

Our next question is from Leonid Timoshev from RBC. Please unmute your line and ask your question.

Hey, guys. Thanks for taking my question. Just wanted to ask on the immunology programs. Looks like CSU is moving ahead potentially to a phase two, I guess. Is that suggesting that you're encouraged by what you're seeing out of the phase 1B? And related to that, could you maybe provide some color on why the IRAC4 and RA was discontinued? Thanks.

Sure. probably lie your best to answer that question, please?

Yeah. We are planning to initiate the phase two for our BDK CDAP program in the CSU by the end of the year, based on the current data we have seen from the phase one study. In terms of the IRAC4 in the rheumatoid arthritis, we decide to not further pursue the RE trial based on emerging new data. We're in the process of analyzing the data and decide the next steps for this program.

All right, operator, can we have the next question, please?

Thank you. Our next question is from Zee Chen from Goldman Sachs. Please unmute your line and ask your question.

uh thank you for taking my questions and uh congrats at a very strong first quarter uh just one question regarding the recent deal on the church 160 uh the pd1 veg fcta for tri-specific uh could you share a bit more about your view on ascent and particularly amid the competition of emerging pd1 budget by specific and also different strategy for tri-specific and also talking about The FC silence strategy is definitely going to be reduced toxicity of DCTLA-4, but also it's going to lose potentially Treg depletion. So what is your view on that? Thank you.

Sure. Thank you so much for the question. Again, I think we'll go right back to live.

Yeah, this molecule, we call it BON110, previously called HH160, was engineered to simultaneously block the three well-established pathways, and there certainly has been bispecific between the PD-1 VGF and the PD-1 CTL4, demonstrating clinical activity. We believe by adding the CTLA4 arm will present potential differentiation from the current existing bispecifics. As for the tuning out to the FC function is to exactly to the point you raised is to try to mitigate the tox concern. We do believe from pre-con data, this kind of engineering will be able to still retain largely the efficacy by removing some of the safety liabilities.

Thank you. All right. We have another question, please.

Our next question comes from Gregory Renza from Truist Securities. Please unmute your line and ask your question.

Great, thanks. Good morning, John and team. Congrats on the quarter. Thanks for taking my question. Maybe I'll weave in Aaron here for a bit and just ask a bit on the guidance. Aaron, you acknowledge that you like what you see with the growth in the markets, but also some assessment of recent trends. Perhaps you could just elaborate further on the pieces that enabled you to feel confident about revenue performance for the rest of the year. And if you could, if I may, just ask a bit about some of the factors to consider when it comes to the net pricing. I think we heard you mention consistency, but just wanted to give you an opportunity to elaborate further on maybe some of those headwinds, but also pressures if they are by and large passed and into guidance at this point. Thanks so much.

Great. Thanks for the question, Greg. So as I said in the prepared remarks, we really do like what we see in the setup for the year. Q1 came in on expectations, but particularly we were encouraged by performance in the United States, both in March and into April. You mentioned price. When we issued our original guidance, we talked about relatively stable net pricing. We feel very confident in that as we enter the year, given where we are with our various contracting opportunities. So we feel really good about that moving forward for the balance of 2026. I did touch on in Q1, we had 20 million or so of non-recurring gross to net. So that obviously occurred in Q1, and we anticipate that will pass through for the year. So overall, we really like where the business is sitting, strength in the United States, but really strong performance across all of our geographies. I think you see really strong growth with our European business. Our China business continues to perform and demonstrate leadership. And we're still in very, using Jessica's analogy, very early innings. in rest of world where the business doubled again in the first quarter. So we really like the setup. That's what gives us confidence for the guidance update with the $100 million improvement across the range. Thanks for the question.

All right. Thank you, Aaron. Could we move to another question, please?

Thank you. Our next question is from Michael Schmidt from Guggenheim. Please unmute your line and ask your question.

Oh, hey, guys. Congrats on the great first quarter here. Perhaps switching back to the pipeline, a question about the GPC 341BB by Specific, where it sounds like there's, you know, things are starting to emerge that are quite interesting. And perhaps could you just comment a bit more about the pivotal study in second line HCC? How should we think about the efficacy bar in this setting? It seems like there's an ORR readout planned. And then longer term, how do you think about the overall opportunity for this asset, perhaps in frontline HCC and other opportunities? Thanks so much.

Thanks for the question. Good to hear your voice. And perhaps we can have Mark answer that.

And Mark, you may be muted. And if Mark doesn't jump in, we'll have Lai answer that. Maybe he's been disconnected.

Happy to address this question. In terms of the, we're in the process of having the discussion with the health authorities to discuss about, you know, the ball. You will see our The phase 1 data at this year's OSCO. The abstract should be released soon, but we will have further data updates at the OSCO oral presentation as well as at our investor relationship relation events. We're quite confident about the early data we have seen with this asset. And certainly, we have already enrolled over 40 patients in the frontline HCC in combination with tesolizumab as well as bevacuzumab. The early data is quite encouraging. We're looking forward to bringing this effective medicine to patients around the globe with HCC.

Thanks so much, Lai. Could we jump to the next question?

Thank you. Our next question is from Rennie Benjamin from Citizens. Please unmute your line and ask your question.

Great, thanks very much for taking the questions and congratulations on a great quarter. My question is regarding Sonoranoclax and the launch in China. Can you talk a little bit about how that's going? Is it tracking like Rukinza did, or is it tracking according to internal expectations? And maybe related to that, you know, what do you think might be the competitive dynamics once Enriotoclax is approved here in the U.S., even though it'll be for MCL, you know, any sort of on-label or potential off-label use that might impact Brukinza or, you know, the CLL market as a whole? Thank you.

Hey, thanks for the question. Xiaobeng, do you want to start? Maybe I can finish.

Yeah, so the launch is very encouraging. In China, we got approval in January, and eight days later, we launched the product. So far, YTD, we have over 300 hospitals across the country starting to treat patients in China. And also, Soronto is also included. in China in the Cisco guideline for first-line CAA, second-line CAA, and also second-line mental CAA, and also for the IML. So second-line IML is also listed in the guideline. And we are very, very happy. The initial feedback from the hospital are very encouraging. So this is China's situation.

Thanks so much, Xiaobing. I think that with the launch in the U.S., you know, we're very encouraged by everything we see with Sunro. As we've described, you know, it's a more potent, more selective, specifically designed, you know, PK parameters to try to make this a very differentiated and more effective medicine. We believe that will be the case in the initial indication where it's approved as a single agent. And the combination data, it's just in our minds game changing. Now, you have to work your way to approvals before you're an official commercial product. And we are working our way through that process. At the same time, you know, we will take the data that we have and we'll share it with the guideline committees all across the world and see if they are willing to have those join the guidelines. And, you know, it's great data. So, you know, hopefully there's some chance that that can occur. But we're very, very excited about this as game changing medicine and many indications based on the data we see today. Okay, thank you so much. Could we take another question or two and then we probably have to wrap up.

Thank you. Our next question is from Yaron Werber from TKD Cowan. Please unmute your line and ask your question.

Great. Thanks so much. Maybe a couple of questions. The first one, you mentioned a little bit that AV, Aaron, is gaining some traction in some markets. I wasn't sure if those were sort of ex-US, and I don't know if you can expand on that. And then secondly, on the CDK4 inhibitor at ASCO, in any sense, sort of what can we expect? How mature would the durability data be at that point on efficacy? Thank you.

Uh, thanks Sharon. Uh, nice to hear your voice too. You stuck in two questions there, I think on the AV question. Um, you know, I think that what Aaron was referring to probably is the statements that they've made, that they're having some international, you know, success in some perspective. I think from our point of view, it's not something that we've seen widely in the U S and it's hard for us to track exactly. From the CDK4 perspective at ASCO, I do believe that we have Mark back connected. So let's see if he can handle that question and we can hear him.

Thank you, John, and I hope you could hear me okay. Thank you, Yaron, for the question. We're very excited to share our updated data at ASCO for our CDK4 program. We encourage everyone listening to the call to visit our poster, which will be on Monday morning of ASCO. We'll be sharing data from approximately 60 patients who are frontline for stage four disease treated in combination with letrozole. What we will show is a strong response rate across a range of doses tested that informed our phase three dose selection. We'll also be showing early but encouraging data about the beneficial effect of food and improving the GI tolerability profile. Because the anticipated progression-free survival for frontline breast cancer is over two years, the maturity still remains quite low at this time. But again, we're very excited to share the early efficacy and safety data.

Okay. Next question, please. Thank you, Mark.

Thank you. Our final question is from Sean Laman from Morgan Stanley. Please unmute your line and ask your question.

Good morning, John and team. Hope everyone's well. John, in the business, you're showing some really strong operating leverage and you've now got meaningfully positive operating income and net income. Maybe it's a question for Aaron, but looking out, how would you characterize sort of growth in OPEX versus the top line and just the efficiencies that you're really showing in your R&D engine? Thanks. Please, Aaron.

Great. Thanks for the question, Sean. This happens to be amongst my favorite questions because that means our pipeline has so much opportunity. It's going to make such a difference for patients. And ultimately, as you know, that's what creates value in this industry. You know, we don't provide long-term guidance, but I've shared a number of times, you know, we really have two objectives as we think about managing the business financially. The first is that we are undoubtedly a growth company. You see that in our performance and our guidance. And the second, to do that in a sustainable way, which means driving continuous operating leverage. Now, we've talked about moving toward margin expansion continuously, but in a measured way that matches the opportunity in front of us. So we really like the setup to be able to hit on both of those objectives and look forward to running the business and making a difference relative to our purpose for the long term.

Thank you. Thanks a lot, Aaron. And I do want to thank everyone for participating in the call. I think, again, in summary, we delivered a very strong first quarter and a solid start to 2026. We executed against our priorities, we drove revenue growth, and we're raising our full year outlook. At the same time, as you can see, the pipeline's entering a really critical phase of execution with foundational strength in hematology and a clear inflection point in solid tumors as our programs are advancing into later stage development. We have demonstrated, again, the power of the B1 superhighway and our strategic competitive advantage that we have in executing, which helped make investment in R&D more attractive in our organization than other places in the industry. And again, the aspiration and vision of our company, which we feel closer to than we ever have, is to be the company that is creating the most impact for cancer patients globally. That means lots of medicines and lots of indications that are truly game changing for patients. And I feel more confident today than I ever have that we're on a path to being that company, not in decades, but in years. I really want to thank the patients and the families that we serve our physicians and our partners, and our more than 12,000 colleagues and their families who focus and urgency make our progress possible. We're really encouraged by the momentum. We're confident where we're headed and we're focused on developing medicines that are great for patients. So thank you all so much for joining us today and have a wonderful week.