BRUKINSA Delivers Landmark 74% 6-Year PFS in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia

Multiple long-term follow-up studies confirm BRUKINSA's superior efficacy and favorable tolerability versus ibrutinib in relapsed or refractory CLL

Additional ASH data from investigational BTK degrader, BGB-16673, highlight potential first- and best-in-class activity with durable responses in heavily pretreated patients with CLL

BeOne Medicines Ltd. (NASDAQ:ONC, HKEX: 06160, SSE: 688235)), a global oncology company, reaffirms its position as the leader in chronic lymphocytic leukemia (CLL) innovation by showcasing the depth, quality, and momentum of its hematology portfolio at the 67^th ASH Annual Meeting and Exposition in Orlando, Florida. The totality of BeOne's ASH data reinforce BRUKINSA^® (zanubrutinib) as the foundational Bruton's tyrosine kinase inhibitor (BTKi) of choice.

"At ASH 2025, we will present new data from across our CLL franchise, highlighting both the strength of BRUKINSA and the potential of BGB-16673," said Amit Agarwal, M.D., Ph.D., Chief Medical Officer, Hematology, BeOne. "Long-term data are the gold standard in CLL, and BRUKINSA continues to deliver the high levels of durable progression-free and overall survival that patients and physicians should demand from a BTK inhibitor. BGB-16673, the most advanced BTK degrader in the clinic with over 800 patients dosed to date, potentially represents the next wave of foundational innovation in oncology."

BRUKINSA continues to demonstrate unprecedented long-term efficacy with a favorable safety profile over more than six years of follow-up in treatment-naïve CLL/SLL.

In SEQUOIA (NCT03336333), a randomized, multicenter, global Phase 3 trial, BRUKINSA maintained progression-free survival (PFS) superiority versus bendamustine plus rituximab (BR) with an estimated 74% PFS at six years in treatment-naïve CLL or small lymphocytic lymphoma (SLL) compared with 32% PFS for BR. Highlights include:

• Arms A, B and C: BRUKINSA vs BR, as well as BRUKINSA in patients with del(17p) (Poster Presentation: 2129)
  • COVID-19 adjusted PFS rates were 77% (95% CI, 70.1-81.8) for BRUKINSA and 33% (95% CI, 25.5-40.4) for BR.
  • The overall survival (OS) at 72 months was 84% for BRUKINSA and 80% with BR. After adjusting for COVID-19, the OS rates were 88% and 82%, respectively.
  • In patients with del(17p), the six-year PFS was 64% (65% after COVID-19 adjustment) and the 72-month OS was 83%.
  • The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified.

"SEQUOIA's longer follow-up strengthens the evidence for continuous zanubrutinib use," said Constantine Tam, M.B.B.S., M.D., Head of Lymphoma Service at Alfred Health and Professor of Haematology at Monash University. "Patients continued to show durable disease control and consistent safety across study arms, meaningfully raising the bar for CLL patients, including those with harder-to-treat CLL."

• Arm D: BRUKINSA plus venetoclax in patients with or without del(17p) and/or TP53 mutations (Poster Presentation: 5669)
  • In the overall patient population, in which 58% of patients had del(17p) and/or TP53 mutation, the median PFS was not reached; the 36-month PFS rate was 87%.
  • The 36-month PFS rate for patients with del(17p) and/or TP53 mutation was 87% and for patients without del(17p) and TP53 mutation was 89%.
  • A total of 42 patients completed the BRUKINSA plus venetoclax combination and continued BRUKINSA monotherapy.
    • At 12 months following the combination period, peripheral blood undetectable minimal residual disease (uMRD) was maintained in 100% (18/18) of patients without del(17p) and TP53.
    • At 18 months following the combination period, uMRD was maintained in 92% (22/24) of patients with del(17p) and/or TP53 mutation.
  • The safety profile of BRUKINSA plus venetoclax was generally tolerable and no unexpected safety signals were identified.
  • The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) now recommend zanubrutinib plus venetoclax as a preferred first-line regimen for CLL/SLL.

New patient-reported outcomes data in R/R CLL suggest BRUKINSA may offer a more manageable side effect profile. Up to six-years of follow-up data support BRUKINSA's foundational role in CLL/SLL as the only BTK inhibitor with enduring PFS and long-term benefit over another BTK inhibitor.

ALPINE (NCT03734016) is a global, randomized, open-label, multicenter, Phase 3 study of BRUKINSA versus ibrutinib in patients with R/R CLL/SLL who received ≥1 prior systemic therapy. Highlights include:

• Symptom-based progression-free survival as a clinically relevant and patient-centric endpoint (Oral Presentation: 711)
  • This study is among the first analyses of patients with CLL/SLL to demonstrate a statistically and clinically meaningful association between longitudinal symptom deterioration and disease progression using joint modeling.
  • Deterioration in patient-reported fatigue, insomnia, and nausea/vomiting emerged as strong symptomatic indicators of disease progression.
  • Compared with ibrutinib, patients on BRUKINSA showed reduced risk of symptom deterioration associated with earlier disease progression.
  • The analysis showed that patients on BRUKINSA had lower odds of symptom worsening for nausea/vomiting, fatigue, pain, and insomnia.

• Up to six years of follow-up of patients from the BRUKINSA arm of ALPINE who continued in a long-term extension study (LTE-1; Poster Presentation: 2123)
  • With up to 73.5 months of follow-up, the median PFS for all patients was a striking 52.5 months; the 60-month PFS rate was 47.3% (50.4% adjusted for COVID-19). These results redefine what is expected for this patient population.
  • Among patients with del(17p), the median PFS was 49.9 months; the 60-month PFS rate was 38.2% (40.5% adjusted for COVID-19).
  • With longer follow-up, the prevalence of most adverse events of special interest remained stable year-over-year.

BGB-16673 (BTK degrader) clinical data demonstrates rapid, robust and deepening responses in patients with heavily pretreated R/R CLL/SLL, including those with prior BTKi treatment and mutations that confer resistance to BTK inhibitors. (Oral Presentation: 85)

Updated results from CaDAnCe-101 (NCT05006716), an ongoing open-label, Phase 1/2 study evaluating BGB-16673 monotherapy in patients with B-cell malignancies, showed responses across R/R CLL/SLL patient types, including those who had previously been treated with BTK inhibitors, BCL2 inhibitors, noncovalent BTK inhibitors, and those with BTK inhibitor resistance mutations. Highlights include:

• With a median follow-up of 19.8 months, 54.4% of patients remain on treatment. Across all doses, ORR was 85.3% and CR/CR with incomplete count recovery (CRi) rate was 2.9% with responses deepening over time.
  • In the group of patients dosed at the recommended phase 2 dose (RP2D; 200 mg QD), ORR was 94.4%.
  • In the patients with prior covalent BTK inhibitor, BCL2i, and noncovalent BTK inhibitor treatment, ORR was 75.0%.
• The 12- and 18-month PFS rates were 73.5% and 65.9% respectively.
• BGB-16673 was generally well tolerated in this heavily pretreated population with no treatment-related deaths and no new toxicities identified with a median treatment duration of 13.6 months.

For more information about our presence at the 2025 ASH Annual Meeting and Exposition, please visit our meeting hub: congress.beonemedicines.com.

About Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a life-threatening cancer of adults. It is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues.^1,2 CLL is the most common type of leukemia in adults, accounting for about one-third of new cases.^2,3

About BGB-16673

BGB-16673 is a potential first-in-class Bruton's tyrosine kinase (BTK) protein degrader and is the most advanced protein degrader in the clinic, with nearly 800 patients dosed to date in an extensive global clinical development program. This program includes three randomized Phase 3 trials in R/R CLL, including the head-to-head Phase 3 trial versus pirtobrutinib, which began enrolling in Q4 2025. Originating from BeOne's chimeric degradation activation compound (CDAC) platform, BGB-16673 is designed to promote the degradation, or breakdown, of both wildtype and mutant forms of BTK, including those that commonly result in resistance to BTK inhibitors in patients who experience progressive disease.

The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to BGB-16673 for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), and adult patients with R/R mantle cell lymphoma (MCL). Additionally, the European Medicines Agency (EMA) granted BGB-16673 PRIority MEdicines (PRIME) designation for the treatment of patients with Waldenstrom's macroglobulinemia (WM) previously treated with a BTK inhibitor.

About BRUKINSA^® (zanubrutinib)

BRUKINSA is an orally available, small molecule inhibitor of Bruton's tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

BRUKINSA has the broadest label globally of any BTK inhibitor and is the only BTK inhibitor to provide the flexibility of once or twice daily dosing. BRUKINSA is also the only BTK inhibitor to demonstrate superiority to another BTK inhibitor in a Phase 3 study.

The global BRUKINSA clinical development program includes about 7,100 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved in more than 75 markets, and more than 247,000 patients have been treated globally.

Select Important Safety Information

Serious adverse reactions, including fatal events, have occurred with BRUKINSA, including hemorrhage, infections, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity (including drug-induced liver injury).

In the pooled safety population (N=1729), the most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA were neutrophil count decreased (51%), platelet count decreased (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

Please see full U.S. Prescribing Information including U.S. Patient Information.

The information provided in this press release is intended for a global audience. Product indications vary by region.

About BeOne

BeOne Medicines is a global oncology company domiciled in Switzerland that is discovering and developing innovative treatments that are more accessible to cancer patients worldwide. With a portfolio spanning hematology and solid tumors, BeOne is expediting development of its diverse pipeline of novel therapeutics through its internal capabilities and collaborations. With a growing global team of nearly 12,000 colleagues spanning six continents, the Company is committed to radically improving access to medicines for far more patients who need them.

To learn more about BeOne, please visit www.beonemedicines.com and follow us on LinkedIn, X, Facebook and Instagram.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the potential benefits of BRUKINSA and BGB-16673; and BeOne's plans, commitments, aspirations and goals under the caption "About BeOne." Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeOne's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeOne's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeOne's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeOne's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeOne's limited experience in obtaining regulatory approvals and commercializing pharmaceutical products; BeOne's ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and those risks more fully discussed in the section entitled "Risk Factors" in BeOne's most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeOne's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeOne undertakes no duty to update such information unless required by law.

To access BeOne media resources, please visit our Newsroom.

¹ National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ)–Patient Version. Accessed November 2024. https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq.

² American Cancer Society. What is Chronic Lymphocytic Leukemia? Updated May 10, 2018. Accessed November 2024. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/what-is-cll.html.

³ American Cancer Society. Key Statistics for Chronic Lymphocytic Leukemia. Updated July 1, 2024. Accessed November 2024. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/key-statistics.html.

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