BeiGene Advances Leadership in CLL at ASH 2024 with New Data From Its Hematology Franchise Including BRUKINSA® and Novel Pipeline Assets

5-year follow-up from SEQUOIA study demonstrated treatment with BRUKINSA reduced the risk of progression or death by 71% compared to bendamustine-rituximab in patients with treatment-naïve CLL, further solidifying its position as the leader in new patient starts in both frontline and relapsed/refractory (R/R) CLL with the broadest label of any BTK inhibitorAt a median follow-up of 1.5 years, promising data from the 320 mg expansion cohort of phase 1/1b study shows no progression in patients with treatment-naïve CLL treated with sonrotoclax, a next-generation BCL2 inhibitor, in combination with BRUKINSA highlighting the potential of this fixed-duration, oral-only combination as a best-in-disease optionData for BTK degrader BGB-16673 from phase 1/2 study highlight its potential in both treatment-resistant CLL and other B-cell malignancies representing high unmet needs

BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company that plans to change its name to BeOne Medicines Ltd., today announced the presentation of new clinical data at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, underscoring its leadership in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) through continued clinical success with BRUKINSA^® (zanubrutinib) and promising advancements in its pipeline assets.

“The breadth of data we’re presenting at ASH underscores BRUKINSA’s role as a best-in-class treatment for CLL and highlights BeiGene’s leadership in advancing the treatment landscape for B-cell malignancies,” said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. “BRUKINSA shows tremendous promise for patients as a monotherapy and as a backbone for best-in-class combinations. The combination of BRUKINSA and our investigational BCL2 inhibitor, sonrotoclax, demonstrated significant potential as a first-line therapy in CLL, with a 99% overall response rate, best uMRD rate of 92%, and was generally well-tolerated at a median follow-up of 19.4 months; this combination is expected to offer better efficacy than a fixed-dose V-O regimen. Additionally, our investigational BTK degrader could become a first-in-class treatment option for patients with CLL and other BTK-driven B-cell malignancies based on the results of data presented at ASH. BeiGene is primed to shape the future of CLL treatment and aims to meet the needs of CLL patients globally.”

Long-term follow-up results from the ongoing Phase 3 SEQUOIA study presented during ASH, which were simultaneously published in the Journal of Clinical Oncology, reaffirm BRUKINSA’s durable efficacy and differentiated safety profile across diverse CLL patient populations, including those with high-risk features. Additional findings spotlight the promising potential of BeiGene’s BTK-targeted chimeric degradation activation compound (CDAC), BGB-16673, which has shown rapid and deep responses in B-cell malignancies in phase 1/2 clinical trials. BeiGene is also developing a next-generation BCL2 inhibitor, sonrotoclax, aiming to improve the safety profile and feasibility of use for this class of drugs and deliver deeper and more durable responses. Together, these advancements reflect BeiGene’s comprehensive approach to addressing the complexities of CLL and its commitment to reshaping the treatment landscape for B-cell malignancies.

With a median follow-up of 61.2 months, data from the SEQUOIA study of patients with treatment-naïve CLL/SLL demonstrated that treatment with BRUKINSA reduced the risk of progression or death by 71% (HR, 0.29; 95% CI, 0.21-0.40; P<.0001*) compared to bendamustine-rituximab (BR). At 54 months, 80.1% of patients who received BRUKINSA remained progression-free (95% CI, 74.3, 84.7) while only 44.6% of patients who received BR remained progression-free (95% CI, 37.6, 51.3). At 60 months, PFS rates were 75.8% (95% CI, 69.0, 81.3) and 40.1% (95% CI, 32.7, 47.3) for BRUKINSA and BR, respectively. Notably, for patients in the study with unmutated IGHV, a prognostic biomarker that indicates a patient’s CLL may be more aggressive, treatment with BRUKINSA reduced the risk of progression or death by 79% compared to BR (HR, 0.21; 95% CI, 0.14-0.33; P<.0001*). The safety profile of BRUKINSA was consistent with the results of prior studies, and no new safety signals were identified. Grade ≥3 treatment-emergent adverse events of interest (AEIs) with BRUKINSA and BR included infection (30.0% and 22.5%, respectively), neutropenia (12.5%; 51.1%), bleeding (7.5%; 1.8%), thrombocytopenia (2.5%; 8.4%), and anemia (0.8%; 2.6%). Rates of atrial fibrillation were 7.1% with BRUKINSA and 3.5% with BR. The rate of discontinuation due to AEs was 20% in the BRUKINSA arm; 13% of patients discontinued BR early due AEs.(Abstract 3249)

“The long-term follow-up of SEQUOIA confirms the sustained efficacy of zanubrutinib over chemotherapy, regardless of IGHV status, in patients with treatment-naïve CLL,” said Mazyar Shadman, M.D. M.P.H., Associate Professor and Innovators Network Endowed Chair, Medical Director, Cellular Immunotherapy and the Bezos Family Immunotherapy Clinic at Fred Hutch Cancer Center. He also holds the Innovators Network Endowed Chair at Fred Hutch and is Associate Professor at Fred Hutch and University of Washington. “Notably, there is a deepening of responses, with a complete remission/complete remission with incomplete count recovery rate in the range of 20%, which, based on cross-trial comparison is higher than a typical BTK inhibitor used as monotherapy. Additionally, the incidence of adverse events of interest, such as atrial fibrillation and hypertension, appears comparable to the background risk of this patient population.”

In addition to BRUKINSA, BeiGene is advancing a robust pipeline to address the needs of CLL patients, including:

• Sonrotoclax (BCL2 Inhibitor): Presented data from the Phase 1/1b study (NCT04277637) demonstrated sonrotoclax, in combination with BRUKINSA, was generally well-tolerated and no cases of tumor lysis syndrome (TLS) were reported in patients with treatment-naïve CLL/SLL. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 49.6% of patients, with the most common (≥20%) being neutropenia (24% in 160mg cohort; 23% in 320mg cohort). With a median follow-up of 19.4 months (0.4–33.3 months), the combination achieved a 99% overall response rate (ORR), including in patients with high-risk features (51% had unmutated IGHV, 20% had TP53 mutation, and 9% had del(17p)). High and early rates of undetectable minimal residual disease (uMRD) were seen by week 24 of combination therapy, with responses continuing to deepen with time through week 48. Best uMRD rate was achieved in 92% of patients (n=112). At a median follow-up of over a year and a half, no progression has been observed in the 320 mg dose cohort. These data support continued evaluation of this combination in the ongoing registrational Phase 3 fixed-duration CELESTIAL-TNCLL study (NCT06073821) (Abstract 1012)
• BGB-16673 (BTK CDAC): Data from the Phase 1/2 CaDAnCe-101 CLL study (NCT05006716) demonstrated that treatment with BGB-16673 was generally well tolerated in this heavily pretreated population of patients. Promising antitumor activity was observed in patients with high-risk features, including in patients with BTK inhibitor-resistant mutations and those previously exposed to covalent BTK inhibitors, noncovalent BTK inhibitors, and BCL2 inhibitors. No atrial fibrillation was observed in either the CLL/SLL or WM cohorts.
  • From the cohort of CLL/SLL patients, BGB-16673 demonstrated an ORR of 94% at the 200mg dose. Furthermore, amongst all doses delivered, 2 patients achieved a complete remission/complete remission with incomplete count recovery (CR/CRi). Grade ≥3 TEAEs were reported in 57% of patients. The most common grade ≥3 TEAEs (≥10%) were neutropenia/neutrophil count decreased (20%) and pneumonia (10%). (Abstract 885)
  • From the cohort of Waldenström's macroglobulinemia patients, BGB-16673 demonstrated a 93% disease control rate (DCR) and 26% very good partial response (VGPR). Grade ≥3 TEAEs were reported in 45% of patients. The most common grade ≥3 TEAE (≥20%) was neutropenia/neutrophil count decreased. (Abstract 860)

For additional information about BeiGene’s presence at ASH 2024, please visit our meeting hub: congress.beigene.com.

The Company recently announced its intent to change its name to BeOne Medicines, reaffirming its commitment to develop innovative medicines to eliminate cancer by partnering with the global community to serve as many patients as possible.

*P-value was one-sided and descriptive.

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 Approximately 20,700 new cases of CLL will be diagnosed in the U.S. in 2024.³

About Sonrotoclax (BGB-11417)

Sonrotoclax is designed to block the B-cell lymphoma 2 (BCL2) protein, which helps cancer cells survive. It is part of a group of drugs called BH3 mimetics, which mimic natural cell death signals. Studies in the lab and during early drug development have shown that sonrotoclax is a potent and specific inhibitor of BCL2 with a short half-life and no accumulation. Sonrotoclax has shown promising clinical activity across a range of B-cell malignancies, and more than 1,300 patients have been enrolled to date across the global development program. The U.S. Food and Drug Administration (FDA) granted sonrotoclax Fast Track Designation for the treatment of patients with mantle cell lymphoma (MCL) and Waldenström macroglobulinemia (WM).

About BGB‑16673

BGB‑16673 is an orally available, brain-penetrating Bruton’s tyrosine kinase (BTK) targeting chimeric degradation activation compound (CDAC) 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. BGB-16673 is the most advanced BTK degrader in the clinic, with more than 350 patients treated to date across the global clinical development program. 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) who have been previously treated with at least two prior lines of therapy, including BTK inhibitor (BTKi) and B-cell lymphoma 2 (BCL2) inhibitor, and adult patients with R/R mantle cell lymphoma (MCL).

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. The global BRUKINSA clinical development program includes about 6,000 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved in more than 70 markets, and more than 100,000 patients have been treated globally.

U.S. Indications and Important Safety Information for BRUKINSA (zanubrutinib)

INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• Waldenström’s macroglobulinemia (WM).
• Mantle cell lymphoma (MCL) who have received at least one prior therapy.
• Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.
• Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy.

The MCL, MZL and FL indications are approved under accelerated approval based on overall response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients.

Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients.

Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.

Hepatotoxicity, Including Drug-Induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including BRUKINSA.

Evaluate bilirubin and transaminases at baseline and throughout treatment with BRUKINSA. For patients who develop abnormal liver tests after BRUKINSA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold BRUKINSA. Upon confirmation of DILI, discontinue BRUKINSA.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

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

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

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

About BeiGene

BeiGene, which plans to change its name to BeOne Medicines, is a global oncology company that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of nearly 11,000 colleagues spans five continents. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn, X (formerly known as Twitter), Facebook and Instagram.

Forward-Looking Statements

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 BeiGene’s leadership in advancing the treatment landscape for B-cell malignancies and ability to shape the future of CLL treatment; the success of BeiGene’s BTK degrader in treating patients; BeiGene’s ability to meet the global needs of CLL patients; and BeiGene’s plans, commitments, aspirations, and goals under the heading “About BeiGene.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene’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; BeiGene’s ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene’s ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene’s reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products; BeiGene’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 BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene’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 BeiGene undertakes no duty to update such information unless required by law.

To access BeiGene media resources, please visit ourNews & Mediasite.

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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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