BeOne Medicines (ONC) Investor Update summary

Strategic and portfolio evolution

• Emphasizes investment in early-stage discovery, rapid clinical proof of concept, and disciplined late-stage development to maximize ROI and competitive advantage, supported by 1,100 researchers and a CRO-free, tech-enabled model.

• Internalized, CRO-free clinical operations and technology platforms enable rapid, cost-effective global trial execution, with AI and automation poised to further improve efficiency.

• Pipeline has rapidly evolved, with significant expansion in both hematology and solid tumor assets, including 29 small molecule programs, 14 degraders, 19 preclinical ADCs, and 69 preclinical programs as of November 2024.

• Focus on early initiation of combination therapies and advancing only transformative medicines to late-stage development.

Solid tumor and breast cancer franchise update

• CDK4 selective inhibitor BGB-43395 shows rapid enrollment, favorable PK, low hematologic toxicity, and promising pharmacodynamic activity, with over 120 patients dosed in one year and strong, sustained TK1 inhibition.

• Phase 3 studies in first- and second-line hormone receptor-positive breast cancer are planned, with dose selection for expansion expected by year-end.

• The breast/gynecologic portfolio leverages CDK4i as a backbone for combination therapies across multiple lines and tumor types.

• Additional programs in CDK2, BCL2 inhibitors, and B7-H4 ADCs are advancing, with multiple data readouts anticipated in 2025.

Hematology and CLL leadership

• Three cornerstone assets—BTK inhibitor (zanubrutinib), BCL2 inhibitor (sonrotoclax), and BTK degrader—are positioned for multi-billion-dollar markets, with robust efficacy and safety data.

• Zanubrutinib demonstrates sustained PFS and superior safety versus competitors in both frontline and relapsed/refractory CLL, including high-risk subgroups, with broad global approvals and flexible dosing.

• Combination regimens such as BOVen (zanubrutinib, obinutuzumab, venetoclax) and sonrotoclax+zanubrutinib achieved high uMRD rates and deep, durable responses in TN CLL, with manageable safety profiles and no tumor lysis syndrome.

• Sonrotoclax, a next-generation BCL2 inhibitor, demonstrated best-in-class potential with high potency, improved safety, and broad development in CLL, WM, MCL, and MM, including a pivotal phase 3 trial (CELESTIAL-TNCLL) designed to show superiority over venetoclax+obinutuzumab.

• BTK degrader (BTK CDAC) exhibits high response rates, durable efficacy, and favorable safety in heavily pretreated B-cell malignancies, with pivotal trials and head-to-head studies against pirtobrutinib planned.