BeiGene Highlights Waldenström’s Macroglobulinemia Innovation at IWWM 2024

BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced it will share research from studies evaluating BRUKINSA^® (zanubrutinib), Bruton tyrosine kinase (BTK) chimeric degradation activation compound (CDAC) degrader BGB-16673 and B-cell lymphoma 2 (BCL2) inhibitor sonrotoclax in patients with Waldenström’s macroglobulinemia at the 12th International Workshop on Waldenström's Macroglobulinemia (IWWM) Oct. 17-19 in Prague, Czech Republic.

BeiGene has seven presentations at IWWM 2024, and Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene, will give the opening ceremony keynote, “Innovating for Impact: How BeiGene is Advancing Products and Pipeline to Address Waldenstrom’s Macroglobulinemia and Beyond.”

“Waldenström’s macroglobulinemia is a rare and incurable cancer, and many patients face treatment failure after initial lines of therapy,” Dr. Mobasher said. “Our BTK inhibitor BRUKINSA has become a standard of care for these patients and as shown through our long-term follow-up data at IWWM, continues to demonstrate deep and durable responses with favorable safety. Additional presentations demonstrate our continued commitment to developing and evaluating new treatment options for Waldenström’s macroglobulinemia patients and include results from Phase 1 studies of our BTK CDAC degrader BGB-16673 and BCL2 inhibitor sonrotoclax. We are encouraged by these results and look forward to advancing these assets to help more patients with WM.”

During IWWM, BeiGene research will be shared in two invited talks, three oral presentations and two posters. Key presentations are outlined below.

IWWM Session Title & Timing (CEST)	Session Type	Asset	Key Findings
BTK-Inhibitors in WM I (Oct. 18, 11:30 a.m.-12:30 p.m.)	Oral presentation	BRUKINSA	Long-term safety and efficacy data from ASPEN LTE1, a long-term extension study evaluating ibrutinib-treated patients from ASPEN who switched to BRUKINSA, show that worsening of ibrutinib treatment-emergent AEs following transition to BRUKINSA was rare, as was the emergence of new events. The study also finds that efficacy is also maintained or improved in these patients.
BTK-I Intolerant and Resistant Disease (Oct. 18, 2:30-3:30 p.m.)	Invited talk	BGB-16673	Preliminary safety and efficacy data from the phase 1 CaDAnCe-101 study demonstrates that BGB-16673 has a tolerable safety profile and shows promising antitumor activity in heavily pretreated patients with BTK inhibitor-exposed relapsed/refractory (R/R) WM, including those with BTK and CXCR4 mutations. BGB-16673 was recently granted Fast Track Designation by the U.S. Food and Drug Administration for R/R chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).
	Invited talk	BRUKINSA	Updated results from a Phase 2 study of WM patients who switched to BRUKINSA after becoming intolerant to other BTK inhibitors, including ibrutinib and acalabrutinib, show that most adverse events (AEs) that led to intolerance did not recur after treatment with BRUKINSA. Additionally, efficacy was maintained or improved in these patients.
WM Poster Presentations & Reception (Oct. 18, 4:30-6:30 p.m.)	Poster	BRUKINSA	An analysis of the Phase 3 ASPEN study demonstrates that peripheral neuropathy (PN) symptom resolution with BTK inhibitors correlates with depth of disease response, with faster symptom resolution with BRUKINSA than ibrutinib in patients achieving PN resolution.
	Poster	N/A	Results of a UK-wide patient-centered experience survey demonstrate that active monitoring for asymptomatic patients with WM is highly variable, with more than half of participants stating their experience could be improved.
Plenary Session II (Oct. 19, 9-10 a.m.)	Oral Presentation	Sonrotoclax	Results from the Phase 1 study show that sonrotoclax was generally well tolerated and the preliminary antitumor activity is encouraging in patients with heavily pretreated R/R WM.
Clinical Trials in Progress for WM II (Oct. 19, 4-5 p.m.)	Oral presentation	Sonrotoclax	Trial-in-progress presentation provides an overview of a Phase 2 study of sonrotoclax in patients with R/R WM, who have been previously treated with a BTK inhibitor therapy or anti-CD20–based systemic therapy.

About Waldenström’s Macroglobulinemia (WM)

Waldenström’s macroglobulinemia (WM) is a rare B-cell lymphoma that occurs in less than 2% of patients with non-Hodgkin lymphomas.¹ The disease usually affects older adults and is primarily found in bone marrow, although lymph nodes and the spleen may be involved.² Typically, patients present between the ages of 60 and 70 years. For reasons that are unclear, WM is almost twice as common in men as in women and is more common in Caucasians than other ethnic groups.³ WM is a rare cancer seen only in approximately three to five per million people per year.²

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.

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 othersolid 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.

This information is intended for a global audience. Product indications vary by region.

About BeiGene

BeiGene 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 more than 10,000 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 BRUKINSA’s ability to provide deep and durable responses with favorable safety for WM patients; BeiGene’s ability to further advance its BTK CDAC degrader BGB-16673 and BCL2 inhibitor sonrotoclax; 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.

1 Buske, C, et al. Treatment and outcome patterns in European patients with Waldenström’s macroglobulinaemia: a large, observational, retrospective chart review. The Lancet Haematology 2018; 5: e0299-309.

2 Lymphoma Research Foundation. Getting the Facts: Waldenström Macroglobulinemia. Accessed March 2022. Available at https://lymphoma.org/wp-content/uploads/2021/12/LRF-Waldenstrom-Macroglobulinemia_Factsheet.pdf

3 IWMF. Frequently Asked Questions – Waldenstrom’s Macroglobulinemia. https://iwmf.com/frequently-asked-questions-waldenstrom-macroglobulinemia/

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