BRUKINSA^® (zanubrutinib) continues to show progression free survival (PFS) benefit compared with ibrutinib in extended follow-up of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) in the ALPINE trial

Results of several studies reinforce the favorable efficacy and safety profile for BRUKINSA, including in patients switching from other Bruton’s tyrosine kinase (BTK) inhibitors

Presentations highlight promising clinical activity of sonrotoclax, BeiGene’s investigational B-cell lymphoma 2 (BCL2) inhibitor, in three Phase 1/2 studies

First presentation of data from ongoing, first-in-human study of BeiGene’s novel BTK degrader, BGB‑16673, demonstrating a tolerable safety profile and notable clinical responses in heavily pre-treated patients

BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)--$BGNE #BeiGene--BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, today announced the presentation of new data across a range of assets and blood cancers at the upcoming 65^th American Society of Hematology (ASH) Annual Meeting and Exposition, taking place December 9-12 in San Diego, California. BeiGene has 24 abstracts accepted at ASH, with three abstracts scheduled for oral presentations.

“Our data at ASH showcase BeiGene’s leadership in the treatment of blood cancers, with promising clinical advances across our pipeline. Sonrotoclax, our BCL2 inhibitor, and BGB-16673, our BTK-degrader, both have very compelling results to date, and numerous presentations continue to underscore BRUKINSA as a potential best-in-class BTK inhibitor,” said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. “In addition to the sustained progression free survival benefit we see for BRUKINSA over ibrutinib with more than three years of follow-up for the ALPINE trial, we are sharing results of several studies that reinforce BRUKINSA’s safety and efficacy profile relative to other members of the class. At BeiGene, we are committed to advancing promising treatment options for patients living with blood cancers.”

Furthering Leadership in BTK Inhibition with BRUKINSA

BRUKINSA continues to show sustained PFS benefit versus ibrutinib in the global Phase 3 ALPINE trial of patients with R/R CLL/SLL with this longer follow up. Durable PFS was observed across major subgroups, including in the high-risk 17p deletion/TP53 mutated patient population. In addition, the overall safety and tolerability profile was consistent with previous ALPINE analyses, including persistently lower rates of cardiovascular events reported with BRUKINSA. Based on these results among patients receiving more than three years of treatment, BRUKINSA continues to be a more efficacious and better-tolerated treatment than ibrutinib for patients with R/R CLL/SLL. (Abstract #202, oral presentation)

Data from Waldenström Macroglobulinemia patients treated with and tolerating ibrutinib on the Phase 3 ASPEN trial who switched to receive BRUKINSA on a long-term extension study demonstrate generally improved safety and deepening of responses with the switch to BRUKINSA. (Abstract #3043)

In an ongoing Phase 2 study, patients with B-cell malignancies experiencing intolerance to acalabrutinib were transitioned to BRUKINSA, with favorable results. The data suggest that for patients intolerant of acalabrutinib, switching to BRUKINSA leads to better tolerance (rare recurrence of adverse events) while maintaining or deepening response. (Abstract #3279)

Advancing BeiGene’s Pipeline of Next-Generation Blood Cancer Treatments

In an ongoing Phase 1/2 study, patients with treatment-naïve (TN) CLL/SLL were treated with sonrotoclax in combination with BRUKINSA. The combination was observed to be well tolerated; no cases of tumor lysis syndrome (TLS) were observed. There was a 100% response rate, including deep responses, and at time of follow-up no patient experienced disease progression (100% PFS). (Abstract #327, oral presentation) Based on these results, a Phase 3 study assessing a fixed duration combination of sonrotoclax and BRUKINSA is planned.

Sonrotoclax has also been well tolerated with high response rates as monotherapy in a continuing Phase 1 study in patients with R/R marginal zone lymphoma (MZL). (Abstract #3032)

Sonrotoclax was also evaluated in combination with dexamethasone in patients with R/R multiple myeloma (MM) harboring t(11;14) at doses up to 640 mg. Promising initial data indicate the combination is safe and efficacious, with the majority of patients across all dose levels achieving clinical response, including deep responses. Further investigations in this setting are ongoing. The US Food and Drug Administration recently granted Orphan Drug Designation to sonrotoclax for treatment of multiple myeloma. (Abstract #1011, oral presentation)

The first presentation of data from an ongoing, first-in-human study of BeiGene’s novel, orally available BTK-targeted chimeric degradation activation compound (CDAC), BGB-16673, demonstrates a tolerable safety profile and notable clinical responses that are durable at this clinical cut off in heavily pretreated patients with B-cell malignancies, including those with BTKi-resistant disease. (Abstract #4401)

More details on BeiGene’s abstracts are available in the ASH program.

Raising Awareness Around the Importance of Mental Health and Cancer Care

BeiGene will host its second annual event at ASH focused on the mental health of people with cancer. The event is titled “Mental Health First Aid: Bridging Cancer Centers and Community Partners to Help Meet Acute Needs,” and it will take place on Friday, December 8 from 2:00 – 4:00 PM PT at the San Diego Wine and Culinary Center, Fallbrook Cellar, 200 Harbor Drive, San Diego, California. To learn more about this event and BeiGene’s “Talk About It" initiative, please visit https://www.cancerandmentalhealth.com/.

BeiGene Presentation and Panel Event for Investors and Analysts

BeiGene will host an event in San Diego on Sunday, December 10 at 8:00 pm PST for investors and analysts attending ASH. BeiGene senior management and invited speakers will review BeiGene’s pipeline and highlights of the presented data, followed by a Q&A panel. The event can be accessed live from the Investors section of BeiGene’s website at https://ir.beigene.com/, http://hkexir.beigene.com, or https://sseir.beigene.com. Archived replays will be posted for 90 days following the event.

For more information on the BeiGene abstracts, see below:

About BRUKINSA^® (zanubrutinib)

BRUKINSA is a 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.

About Sonrotoclax (BGB‑11417)

Sonrotoclax is an investigational small molecule B-cell lymphoma 2 (BCL2) inhibitor. It belongs to a class of BCL2 homology 3 (BH3) mimetics, and preclinical and IND-enabling studies have demonstrated potent activity and high selectivity of sonrotoclax against the antiapoptotic protein BCL2. Sonrotoclax is more potent and selective for BCL2 relative to BCLxL than venetoclax and shows the potential to overcome common BCL2 resistance mutations.

About BGB‑16673

BGB‑16673 is an orally available Bruton’s tyrosine kinase (BTK) targeting chimeric degradation activation compound (CDAC) designed to induce degradation of wildtype and multiple mutant forms of BTK, including those that commonly confer resistance to BTK inhibitors in patients who experience progressive disease.

About Tislelizumab

Tislelizumab is a humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD‑1) monoclonal antibody with high affinity and binding specificity against PD‑1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.

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

The MCL and MZL indications are approved under accelerated approval based on overall response rate. 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 monotherapy. Grade 3 or higher hemorrhage, including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.6% of patients treated with BRUKINSA monotherapy in clinical trials, with fatalities occurring in 0.3% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 30% 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 pre- and post-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 monotherapy. Grade 3 or higher infections occurred in 24% of patients, most commonly pneumonia (11%), with fatal infections occurring in 2.9% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci 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 (22%), thrombocytopenia (8%) and anemia (7%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 11% of patients, and Grade 4 thrombocytopenia occurred in 2.8% 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 13% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer reported in 7% of patients. Other second primary malignancies included malignant solid tumors (5%), melanoma (1.2%), and hematologic malignancies (0.5%). 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 3.7% of 1550 patients treated with BRUKINSA monotherapy, including Grade 3 or higher cases in 1.7% 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 0.2% 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.

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

In this pooled safety population, the most common adverse reactions, including laboratory abnormalities, in ≥30% of patients who received BRUKINSA (N=1550) included decreased neutrophil count (42%), upper respiratory tract infection (39%), decreased platelet count (34%), hemorrhage (30%), and musculoskeletal pain (30%).

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 is a global biotechnology company that is discovering and developing innovative oncology 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 more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn and X (formerly known as Twitter).

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 ability to advance promising treatment options for patients living with blood cancers; future planned studies that may be conducted by BeiGene; the future development, regulatory filing and approval and commercialization of BRUKINSA, sonrotoclax and BGB-16673; 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 and its 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.

Contacts

Investor Contact:
Liza Heapes

+1 857-302-5663

[email protected]

Media Contact:

Kyle Blankenship

+1 667-351-5176

[email protected]