BeOne Medicines (Nasdaq: ONC) Q2 2026 earnings call highlighted a rapidly expanding solid tumor pipeline, with five assets targeting pivotal-stage development within roughly 18 months, alongside important readouts across the company's hematology franchise. Management also disclosed new details on its emerging RAS and PRMT5 programs, including a previously undisclosed RAS-ON ADC concept and early evidence of central nervous system (CNS) activity with its PRMT5 inhibitor.
The hematology update was mixed. Positive Phase III data strengthened the case for zanubrutinib (Brukinsa) in frontline mantle cell lymphoma (MCL), while the CELESTIAL-301 combination study missed an undetectable minimal residual disease (uMRD) endpoint in chronic lymphocytic leukemia (CLL), increasing the importance of the study's primary progression-free survival (PFS) readout.
Total revenue for Q2 2026 was USD 1.7 billion, up 30% year-on-year, with Brukinsa contributing USD 1.2 billion. BeOne Medicines Ltd. (Nasdaq: ONC) raised its full-year 2026 revenue guidance to USD 6.6 billion–USD 6.8 billion.
CELESTIAL-301 misses uMRD endpoint as PFS readout remains pending
The Phase III CELESTIAL-301 study evaluating zanubrutinib plus sonrotoclax (Beqalzi) against venetoclax plus obinutuzumab in frontline CLL did not demonstrate statistical superiority on the uMRD endpoint.
An independent data monitoring committee (IDMC) recommended that the study continue toward its primary regulatory endpoint of PFS. BeOne remains blinded to the PFS data.
Wang Lai, President and Global Head of Research and Development, argued that uMRD rates do not consistently predict PFS across regimens with different mechanisms of action. He cited CLL17 data in which ibrutinib plus venetoclax produced lower uMRD rates than venetoclax plus obinutuzumab but delivered comparable PFS.
Chief Medical Officer for Hematology Amit Agarwal said management remains highly confident that CELESTIAL-301 will demonstrate PFS superiority. BeOne declined to disclose information from the IDMC review that could potentially unblind the company to the PFS result.
The uMRD miss removes a potential early point of differentiation for the zanubrutinib-sonrotoclax combination and increases the significance of the eventual PFS analysis in determining its potential role as a fixed-duration frontline CLL regimen.
MANGROVE backs chemo-free frontline approach in MCL
The Phase III MANGROVE study of zanubrutinib plus rituximab versus bendamustine plus rituximab in treatment-naive MCL reported a hazard ratio of 0.57 in favor of the zanubrutinib-rituximab arm.
Management described the study as the first to demonstrate superiority for a chemotherapy-free regimen over standard chemotherapy in frontline MCL, contrasting MANGROVE with previous BTK inhibitor trials such as ECHO, which added a BTK inhibitor to chemotherapy rather than replacing chemotherapy altogether.
Global regulatory submissions are planned for H2 2026, with full results expected at an upcoming medical meeting. Overall survival data remain immature.
The result potentially expands the role of zanubrutinib into a frontline chemotherapy-free treatment strategy for MCL.
Tacabrutideg accelerated approval submission targeted for Q4 2026
BeOne remains on track for a Q4 2026 accelerated approval submission for the BTK degrader tacabrutideg in relapsed/refractory CLL.
The US FDA granted Fast Track designation to tacabrutideg for patients who have received at least two previous lines of therapy, including a BTK inhibitor and BCL-2 inhibitor. Agarwal cited response rates and durability observed in Phase I development as supporting the planned submission.
The Phase III CaDAnCe-304 study is meanwhile comparing tacabrutideg directly against pirtobrutinib, the approved non-covalent BTK inhibitor developed by Eli Lilly.
BeOne also plans to initiate a Phase III study of a fixed-duration tacabrutideg-sonrotoclax combination in relapsed/refractory CLL in 2027.
Five solid tumor assets approach pivotal development
BeOne said five solid tumor programs have demonstrated clinical proof of concept and are advancing toward pivotal-stage development. Management expects each to progress from first-in-human testing to pivotal development in approximately 2.5 years.
The CDK4 inhibitor BGB-43395 is already enrolling patients in Phase III breast cancer studies. At ASCO 2026, BGB-43395 produced an objective response rate of approximately 70% in combination with letrozole in first-line hormone receptor-positive, HER2-negative metastatic breast cancer at the 400 mg Phase III dose.
Overall neutropenia occurred in 21% of patients, with no grade 3 or higher events. Management said the profile compares favorably with atirmociclib and approved CDK4/6 inhibitors, although cross-trial comparisons remain preliminary.
The B7-H4 antibody-drug conjugate (ADC) BG-C9074 is expected to enter a Phase III study in first-line maintenance ovarian cancer before year-end. BeOne reported treatment-related grade 3 or higher adverse events in approximately 26% of patients at the 6 mg/kg dose and said this was less than half the rates reported for some other ADCs under development in first-line ovarian cancer.
The GPC3×4-1BB bispecific BGB-B2033 completed enrollment of an approximately 100-patient cohort that could potentially support registration in China in 2.5 months. A Phase III study in second-line hepatocellular carcinoma (HCC) is expected to begin before year-end. Management said BGB-B2033 produced an objective response rate above 30% in second-line or later HCC at ASCO 2026.
A PRMT5 inhibitor and CEA-targeted ADC are expected to enter Phase III development in 2027, with initial clinical data from both programs due at ESMO 2026.
Q&A reveals CNS activity for PRMT5 inhibitor
During the analyst Q&A, Mark Lanasa, Chief Medical Officer for Solid Tumors, provided additional details on BeOne's PRMT5 inhibitor program.
The candidate entered clinical development in Q1 2025 and was designed to penetrate the CNS. Lanasa said the ESMO 2026 presentation will include both Phase Ia dose-escalation and expansion-cohort results, with enrollment particularly focused on patients with non-small cell lung cancer (NSCLC).
Importantly, Lanasa said BeOne is already seeing evidence of clinically meaningful CNS coverage. The observation could be relevant to the development of the PRMT5 inhibitor in MTAP-deleted cancers in which CNS metastases represent an important clinical challenge, including NSCLC.
Management said the eventual development program is expected to extend across multiple tumor types.
BeOne expands RAS strategy with degrader and RAS-ON ADC
The Q&A also provided new details on BeOne's emerging RAS pipeline.
Lanasa said a highly potent, CNS-penetrant RAS-ON inhibitor is expected to enter clinical development before the end of 2026.
BeOne is also developing a KRAS-targeting degrader and disclosed an additional RAS-ON ADC approach in which a RAS-ON inhibitor is used as the ADC payload. The concept extends the company's RAS strategy beyond conventional small-molecule inhibition into targeted protein degradation and targeted delivery.
The RAS-ON ADC disclosure is particularly notable as BeOne builds a broader platform around one of oncology's most intensely contested target families.
Forward-looking catalysts
- ESMO 2026 – first PRMT5 inhibitor and CEA ADC clinical data: BeOne plans initial clinical disclosures for both programs, with NSCLC a major focus. The results will provide the first clinical test of management's expectations for the programs ahead of potential Phase III development in 2027. The PRMT5 presentation should also provide greater clarity on the early CNS activity described during the earnings call.
- Tacabrutideg accelerated approval submission – Q4 2026: BeOne is targeting a US submission in relapsed/refractory CLL following previous treatment with both BTK and BCL-2 inhibitors. If successful, tacabrutideg could become the first BTK degrader to reach the US market.
- CELESTIAL-301 PFS readout – timing unspecified: Following the failure to demonstrate uMRD superiority, the primary PFS analysis has become an increasingly important test of zanubrutinib plus sonrotoclax as a fixed-duration frontline CLL regimen.
- Solid tumor Phase III expansion – H2 2026 to 2027: BG-C9074 and BGB-B2033 are expected to join BGB-43395 in Phase III development before year-end, followed by the PRMT5 inhibitor and CEA ADC in 2027.
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