Marginal zone lymphoma refractory

BEIJING--(BUSINESS WIRE)-- InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on cancer and autoimmune diseases, today announced the 2023 annual results as of 31 December 2023. Financial Highlights Revenue increased by 18.1% to RMB738.5 million in 2023, including RMB670.7 million from orelabrutinib, an increase of 18.5%, mainly due to the continuous and rapid ramp-up of orelabrutinib sales. Gross Profit increased by 26.6% to RMB610.1 million in 2023, with a gross profit margin of 82.6%, representing an increase of 5.5%, mainly due to the increase of orelabrutinib sales and the reduction in the unit cost of sales. Research and Development Expenses increased by 17.5% to 751.2 million in 2023, primarily due to heightened spending on global clinical trials that have made significant progress and strategic investments in early-stage candidates poised to become key future assets. The Loss decreased by 27.8% to RMB645.6 million. Cash and Bank Balance stood at approximately RMB8.2 billion. With this robust cash position, the Company is well-positioned to expedite the clinical development of key projects and invest in a competitive pipeline. Accelerating Pipeline Development for the Benefit of Patients In 2023, InnoCare has continued to advance its robust pipeline across various clinical stages, continuously unleashing the power of innovation to meet unmet medical needs. Orelabrutinib has become the first and only BTK inhibitor approved for the treatment of relapsed or refractory Marginal Zone Lymphoma (r/r MZL) in China, an indication which has been included in the updated 2023 National Reimbursement Drug List (NRDL) without a price cut. The Company has continuously forged ahead on the road to improving public health. Additionally, the Phase II study results of our novel TYK2 inhibitor, ICP-332, met the primary endpoints in patients with moderate-to-severe atomic dermatitis. From research, clinical development, manufacturing, commercialization, to global collaboration, InnoCare not only established an integrated platform, but also formulated a clear growth strategy aimed at benefiting patients worldwide as we embark on the Company 2.0 phase. Building A Leading Franchise in Hemato-Oncology With orelabrutinib (BTK inhibitor) serving as the backbone therapy and a key component of InnoCare’s extensive pipeline in hemato-oncology – including tafasitamab (anti-CD19 antibody), ICP-248 (BCL2 inhibitor), ICP-B02 (CD20xCD3 bispecific antibody), ICP-490 (CRBN E3 Ligase modulator), and potential future developments from internal and external sources - InnoCare strives to become a leading player in hemato-oncology both in China and worldwide. Orelabrutinib's exceptional safety and efficacy profiles promise synergistic benefits when combined with other pipeline drugs, such as ICP-248 (BCL2 inhibitor). InnoCare intends to address various segments, such as non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and leukemia, utilizing both single and combination therapies. Orelabrutinib Orelabrutinib was approved for the treatment of relapsed/refractory marginal zone lymphoma (r/r MZL) in April 2023 and included in the NRDL. Orelabrutinib has thus become the first and only BTK inhibitor for r/r MZL in China, which also marks orelabrutinib’s third indication approved in China. Patient enrollment of the Phase III registrational trial of orelabrutinib for the first-line treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was completed in China in the first half of 2023. The Company expects to submit the NDA in the third quarter of 2024. In the U.S., patient enrollment of the Phase II registrational trial for relapsed/refractory mantle cell lymphoma (r/r MCL) was completed. The Company expects to submit the NDA to the U.S. Food and Drug Administration (US FDA) in the third quarter of 2024. The Company is initiating a global Phase III study of orelabrutinib for the first-line treatment of MCL. Orelabrutinib was approved by the Health Sciences Authority (HSA) of Singapore for the treatment of adult patients with r/r MCL, which marks InnoCare’s entrance onto international commercial markets. The Company expects to submit r/r MZL NDA in Singapore in 2024. The Company is initiating a Phase III MZL confirmatory study with orelabrutinib. The strategic combination of orelabrutinib with BCL2 inhibitor, ICP-248, for the first line treatment of CLL/SLL. A Phase III registrational study of orelabrutinib for the first-line treatment of MCD subtype diffuse large B-cell lymphoma (DLBCL) is ongoing in 45 sites in China. Tafasitamab Patient enrollment of the registrational trial of tafasitamab in combination with lenalidomide for the treatment of r/r DLBCL was completed in China. The Company expects to submit the biologics license application (BLA) in the second quarter of 2024 and anticipates BLA approval in the first half of 2025. Tafasitamab in combination with lenalidomide was approved by the Department of Health, the Hong Kong Special Administrative Region, China, and approved for use in Bo’ao and Greater Bay Area with first prescription issued respectively. ICP-248 The preliminary results demonstrated good safety pro achieved favorable pharmacokinetic (PK), demonstrating differentiation from other BCL2 inhibitors. So far, seventeen patients were dosed, and among six evaluated patients, the ORR was 100%, with three complete responses (CR) in which two achieved undetectable minimal residual disease (uMRD). The clinical trial approval of ICP-248 in combination with orelabrutinib as a first-line therapy for CLL/SLL in March 2024. In the U.S., the IND was cleared in January 2024. ICP-248 will become an important asset for the Company’s globalization. ICP-248 is a novel, orally bioavailable BCL2 selective inhibitor, developed as monotherapy or in combination with orelabrutinib for the treatment of CLL/SLL, MCL, AML, and other NHLs. ICP-B02 (CM355) The preliminary data of both the intravenous infusion (IV) and the subcutaneous (SC) formulations have shown good efficacy of ICP-B02 in patients with follicular lymphoma (FL) and DLBCL. All 13 patients who were treated with ICP-B02 at doses ≥6mg achieved response, resulting in an ORR of 100%. Among the nine patients who were evaluable in the SC group, seven achieved a complete response (CR), including two with DLBCL. Based on the encouraging results of ICP-B02 single agent, the Company is planning for dose expansion study of ICP-B02 in combination with other immunochemotherapies for earlier lines of treatment in NHL patients. An IND for the combination therapies has been submitted. ICP-B02 is a CD20xCD3 bispecific antibody co-developed with Keymed. ICP-490 The Phase I dose escalation study is ongoing in China with multiple myeloma (MM) patients, demonstrating a good tolerability and safety profile. Pharmacodynamic (PD) analysis showed deeper degradation of primary pharmacological targets Aiolos (IKZF3) and Ikaro (IKZF1). In September 2023, the IND was approved to conduct a clinical trial of ICP-490 in combination with dexamethasone. ICP-490 shows strong potential in hemato-oncology therapeutics as a monotherapy or in combination with others. ICP-490 was developed from InnoCare’s molecular glue platform for the treatment of MM and other hematological malignancies. ICP-B05 (CM369) The Phase I trial is ongoing, showing good tolerability with no DLT observed. The preliminary results demonstrate favorable PK pro PD biomarker, Treg depletion, was observed. Dose escalation in solid tumors has been escalated up to 150 mg, which is also the initial dose designated for NHL. Preliminary efficacy was observed in NHL. ICP-B05 is an anti-CC chemokine receptor 8 (CCR8) monoclonal antibody, a potential first-in-class drug co-developed with KeyMed as a monotherapy or in combination with other therapies for the treatment of various cancers. Developing B-cell and T-cell Pathways in Autoimmune Diseases Autoimmune diseases can affect almost every organ in the body and can occur at any age. The global market for autoimmune disease therapeutics anticipated to reach $185 billion by 20291. The Company has fortified its powerful discovery engine focusing on global frontier targets for the development of differentiated autoimmune therapeutics through B-cell and T-cell pathways, aiming to offer first-in-class or best-in-class treatments to the massive unmet medical needs with promising market potential worldwide and/or regionally. Orelabrutinib ITP: The Company has achieved proof of concept (PoC) of orelabrutinib for the treatment of primary immune thrombocytopenia purpura (ITP), with a Phase III registrational trial underway in China. The last patient is expected to be enrolled by the end of 2024. In June 2023, the ITP Phase II result was orally presented at the European Hematology Association (EHA) 2023 Hybrid Congress. The results showed that 40% of patients met primary endpoint at 50mg. 83.3% achieved durable response among patients met the primary endpoint. A subgroup analysis of patients who previously responded to glucocorticoids (GC) or intravenous immunoglobulin (IVIG) showed that 75.0% of patients at the 50mg dose achieved the primary endpoint. SLE: The Phase IIa trial for systemic lupus erythematosus (SLE) demonstrated positive results, with remarkable SLE Responder Index (SRI)-4 response rates observed in a dose dependent manner, along with trends indicating a reduction in proteinuria levels. A Phase IIb trial is ongoing, and the Company expects to complete patient enrollment by mid-2024. MS: The 24-week data of orelabrutinib from the multiple sclerosis (MS) global Phase II trial is consistent with the previous reported 12-week data in terms of both efficacy and safety. The primary endpoint was achieved dose-dependently (Cmax driven) in all three active orelabrutinib treatment groups. Notably, a 92.3% relative reduction was achieved in cumulative number of new gadolinium (Gd) + T1 lesions at week 24 at 80mg QD compared to placebo arm (which switched to orelabrutinib 50mg QD after Week 12). This reduction stands out as a leading indicator of efficacy when compared to other MS therapies that are approved or in developmental stages. All orelabrutinib groups achieved T1 new lesion control after 4 weeks of treatment, with effects sustained through 24 weeks. The 80 mg QD cohort showed the highest reduction rate of cumulative number of new lesions Gd+T1 lesions and the best for lesion control throughout 24 weeks, with the best safety profile, indicating orelabrutinib’s potential as a leading MS treatment. NMOSD: The Phase II clinical trial for the treatment of neuromyelitis optica spectrum disorder (NMOSD) is ongoing in China. ICP-332 The latest data of ICP-332 for the treatment of patients with moderate-to-severe atopic dermatitis (AD) has been released at the 2024 American Academy of Dermatology (AAD) Annual Meeting as a late-breaking oral presentation. ICP-332 demonstrated an outstanding efficacy and safety profile. ICP-332 achieved multiple efficacy endpoints in the 80 mg QD and 120 mg QD dosing groups respectively, including the percentage change in Eczema Area and Severity Index (EASI) score from baseline, EASI 50, EASI 75, EASI 90 (improvement of at least 50%, 75% and 90% in EASI score from baseline), Investigator’s Global Assessment (IGA) 0/1 (score of 0 ‘clear’ or 1 ‘almost clear’) with >= 2 points improvement, and Pruritus Numerical Rating Scale (NRS) score from baseline, etc. The mean percentage change from baseline of the EASI score reached 78.2% and 72.5% at the 80 mg QD and 120 mg QD groups respectively, both with a highly significant P value (p<0.0001), compared to 16.7% for the patients receiving placebo. The percentages of patients achieving at least 75% improvement in EASI 75 were significantly higher in the ICP-332 80 mg QD (64.0%, p<0.0001) and 120 mg QD (64.0%, p<0.0001) groups than that of placebo (8.0%), which are better than the reported efficacies of multiple approved innovative drugs treated for 12 weeks or 16 weeks (not a head-to-head comparison). In the ICP-332 80 mg QD group, the response rates of EASI 90 and IGA 0/1 with >=2 points from baseline demonstrated a 40.0% (P=0.0009) and 32.0% (P=0.0047) improvement respectively compared with the placebo group. ICP-332 was safe and well tolerated in AD patients. The overall incidence rates of adverse events (AEs) and AEs related to infections and infestations in the two treatment groups were comparable to that of the placebo group. The Company expects to start the patient enrollment of the Phase III trial for AD in China, initiate US trials, and initiate a Phase II trial for a second indication of vitiligo in 2024. ICP-332 is a novel tyrosine kinase 2 (TYK2) inhibitor that is being developed for the treatment of various T-cell related autoimmune disorders. ICP-488 The Phase I trial has been completed, with preliminary efficacy assessed in psoriasis patients. The least-squares mean percentage change from baseline in the Psoriasis Area and Severity Index (PASI) score indicated preliminary significantly difference between the ICP-488 6 mg once-daily dosing group and placebo group at week 4 (38% vs 14%, p=0.0870). PASI 50 assessments demonstrated a 42% improvement with treatment of ICP-488 at 6 mg QD. Following single ascending doses (1mg to 36mg) and multiple ascending doses (3mg -12mg) once daily, ICP-488 plasma exposures were dose proportional. No significant food effect was observed following co-administration with standard high-fat, high-calorie meals. ICP-488 demonstrated good tolerability and safety. The TRAE rate was the same between the ICP-488 arm and placebo arm. The Phase II study of psoriasis is ongoing, InnoCare targets to finish the patient enrollment in the first half of 2024. ICP-488 is a potent and selective TYK2 allosteric inhibitor that binds to the pseudo kinase JH2 domain of TYK2 and blocks IL-23, IL12, type 1 IFN, and other cytokine receptors. ICP-B02 (CM355) ICP-B02 (SC & IV) induced a profound and sustained depletion of peripheral B- cells after first infusion in Phase I/II clinical trial in r/r NHL patients. Given the critical role of B-cells in a variety of severe autoimmune diseases, ICP-B02 may have wider applications in severe autoimmune diseases. ICP-923 (New Target) IL-17 is a pro-inflammatory cytokine that plays an important role in immune functional responses. Orally administered small molecules targeting IL-17 may represent a convenient alternative to IL-17-targeting monoclonal antibodies for patients. This novel orally available small molecule can potently block the binding of both IL-17AA and IL-17AF to IL-17R. Building Innovative Solid Tumor Assets InnoCare strives to expand the breadth of its pipeline to cover solid tumor diseases areas through a combination of targeted therapy and immune-oncology approaches. The Company believes that potential best-in-class molecule, zurletrectinib (ICP-723), will enable InnoCare to establish a solid footprint in the field of solid tumor treatment. To benefit a broader range of patients, InnoCare’s rapidly maturing early-stage pipeline, including the cornerstone therapy ICP-192, ICP-189 and ICP-B05 immune-oncology treatment, aims to offer competitive treatment solutions for a large array of solid tumors, both in China and worldwide. Zurletrectinib (ICP-723) InnoCare is accelerating the registrational trial of zurletrectinib in China. The NDA is expected to be submitted by the end of 2024. An outstanding efficacy of 80-90% ORR was observed in adult patients with various cancers carrying NTRK gene fusion who received ≥8 mg dosages. Zurletrectinib was shown to overcome acquired resistance to the first generation TRK inhibitors, bringing hope for patients who failed prior TRKi therapy. The Company is conducting a clinical trial of zurletrectinib for pediatric (2 to 12 years old) and adolescent patients (12 to 18 years old). Patient enrollment of pediatric patients is ongoing, with PR observed. ICP-189 InnoCare and ArriVent reached a clinical development collaboration to evaluate the anti-tumor activity and safety of the combination of InnoCare’s novel SHP2 allosteric inhibitor, ICP-189, with ArriVent’s third generation EGFR inhibitor furmonertinib in patients with advanced non-small cell lung cancer (NSCLC). Currently, the combo study is underway. NSCLC is the predominant subtype of lung cancer, accounting for approximately 85% of all cases2. The novel SHP2 allosteric inhibitor, ICP-189, is being developed for the treatment of solid tumors as a single agent and/or in combination with other antitumor agents. Preliminary efficacy was observed in ICP-189 monotherapy. As of this announcement, the dosage has been escalated up to 120 mg with no DLT observed, and it has shown a favorable PK pro a long half-life. The patient enrollment at 160mg QD is ongoing. As a potential first-in-class SHP2 inhibitor, ICP-189 is an ideal partner for combination with multiple targeted and immune-oncology therapies in solid tumors. ICP-189 has demonstrated significant anti-tumor effect in tumor models driven by KRASG12C mutation and EGFR over-expression. Gunagratinib (ICP-192) The latest data of gunagratinib in patients with cholangiocarcinoma (CCA) was presented at 2023 ASCO-GI3. Gunagratinib showed good efficacy and safety in previously treated patients with locally advanced or metastatic CCA harboring FGR2 gene fusions or rearrangements. Other Corporate Development InnoCare appointed Xin Fu and Jeff Chen as Chief Financial Officer and Chief Commercial Officer respectively. InnoCare was approved by the Hong Kong Stock Exchange to remove "B" from the stock code from May 12, 2023. This is another important milestone in the Company's development. Following the approval for commercial production, InnoCare Guangzhou quickly launched the manufacturing of orelabrutinib, which is now available to patients in China. This achievement allows InnoCare to cover the entire industry chain from in-house research and development to production. Dr. Jasmine Cui, the Co-founder, Chairwoman and CEO of InnoCare, said, "We must maintain the entrepreneurial spirit and persist in continuous innovation, focusing on key objectives with high quality growth, so as to make our contributions to patients, partners, and the broader biopharmaceutical industry. We’re committed to deepening our focus on original innovation, pushing forward multiple innovative molecules to further strengthen our pipeline; we will accelerate the registrational trials both in China and worldwide, aiming to submit multiple NDAs; we will increase market penetration to achieve our long-term strategy and realize significant sales increases; we will amplify our global presence and push more projects to reach international markets.” To know more about the detailed financial data and business updates of InnoCare 2023 annual results, please log in to . Conference Call Information InnoCare will host a conference call at 8:30 p.m. Beijing time on March 28 in English and at 9:30 p.m. Beijing time in Chinese on March 29, 2024. Participants must register in advance of the conference call. Details are as follows: For English conference call, please register through the below link: For Chinese conference call, please register through the below link: Forward-looking Statement This report contains the disclosure of some forward-looking statements. Except for statements of facts, all other statements can be regarded as forward-looking statements, that is, about our or our management's intentions, plans, beliefs, or expectations that will or may occur in the future. Such statements are assumptions and estimates made by our management based on its experience and knowledge of historical trends, current conditions, expected future development and other related factors. This forward-looking statement does not guarantee future performance, and actual results, development and business decisions may not match the expectations of the forward-looking statement. Our forward-looking statements are also subject to a large number of risks and uncertainties, which may affect our short-term and long-term performance. About InnoCare InnoCare (HKEX: 09969; SSE: 688428) is a commercial stage biopharmaceutical company committed to discovering, developing, and commercializing first-in-class and/or best-in-class drugs for the treatment of cancer and autoimmune diseases with unmet medical needs in China and worldwide. InnoCare has branches in Beijing, Nanjing, Shanghai, Guangzhou, Hong Kong, and United States. ___________________________________ 1 iHealthcareAnalyst, Inc., Oct. 3, 2023 2 Cancer-free 3 2023 ASCO GI Abstract

BRUKINSA is the first and only BTK inhibitor approved across five oncology indications and the first and only approved in follicular lymphoma Approval based on positive results from ROSEWOOD trial showing BRUKINSA plus obinutuzumab achieved higher overall response rate versus obinutuzumab alone BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- BeiGene Ltd. (Nasdaq: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to BRUKINSA® (zanubrutinib) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL), in combination with the anti-CD20 monoclonal antibody obinutuzumab, after two or more lines of systemic therapy. The indication is approved under accelerated approval based on response rate and durability of response, marking BRUKINSA’s fifth indication in B-cell malignancies in the U.S. “This accelerated approval of BRUKINSA represents an important advancement, offering the first and only BTK inhibitor treatment for follicular lymphoma patients in the U.S. who have either not responded to initial therapies or have experienced relapse,” said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. “BRUKINSA is the only BTK inhibitor to date that shows efficacy with this type of malignancy and now has the broadest label, including five oncology indications, of any medication in its class globally. This is a testament to BRUKINSA’s differentiated clinical pro our continued commitment to bringing this much-needed treatment option to patients around the world.” BRUKINSA was approved for the treatment of R/R FL under the FDA’s accelerated approval program based on the overall response rate (ORR) from the ROSEWOOD trial (NCT03332017), as assessed by an independent review committee (IRC). Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory MAHOGANY (NCT05100862) trial, which is underway. The application for R/R FL was also granted Fast Track Designation and Orphan Drug Designation by the FDA. The ROSEWOOD trial is a global, randomized, open-label Phase 2 study of BRUKINSA plus obinutuzumab compared with obinutuzumab alone in 217 patients with R/R FL who received at least two prior lines of systemic therapy. In the study, the ORR by IRC was 69% in the BRUKINSA plus obinutuzumab arm versus 46% in the obinutuzumab arm (P=0.0012), with a median follow-up of approximately 20 months. Responses were durable, with an 18-month landmark duration of response (DOR) of 69% in the BRUKINSA combination arm.i BRUKINSA plus obinutuzumab was generally well-tolerated, with safety results consistent with previous studies of both medicines.i Serious adverse reactions occurred in 35% of patients who received BRUKINSA in combination with obinutuzumab. Adverse reactions led to permanent discontinuation of BRUKINSA in 17% of patients. Christopher Flowers, M.D., Division Head of Cancer Medicine and Chair of the Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center commented, “Patients living with follicular lymphoma often experience relapse or do not respond to treatment and need options for treatment during the course of their illness. The findings from the ROSEWOOD trial highlight the significant clinical advantage of treating patients who experience relapse or have refractory follicular lymphoma with zanubrutinib plus obinutuzumab.” “Follicular lymphoma can significantly impact patients' lives and prove to be challenging, especially for those whose condition has advanced despite undergoing prior treatment or experienced relapse,” said the Follicular Lymphoma Foundation. “However, the emergence of new treatment options which have been shown to be effective and well-tolerated, including second generation BTK inhibitors such as zanubrutinib in combination with existing therapies, brings hope to those dealing with advanced follicular lymphoma.” In addition to R/R FL, BRUKINSA is also approved in the U.S. as a treatment for adult patients with Waldenström’s macroglobulinemia; mantle cell lymphoma, who have received at least one prior therapy, R/R marginal zone lymphoma, who have received at least one anti-CD20-based regimen; and most recently chronic lymphocytic leukemia or small lymphocytic lymphoma. BRUKINSA is the first and only BTK inhibitor to demonstrate PFS superiority in a head-to-head clinical trial versus ibrutinib in patients with R/R CLL in the global Phase 3 ALPINE trial. In a recent presentation, BRUKINSA showed sustained PFS benefit versus ibrutinib in a longer term follow up. Durable PFS was observed across major subgroups, including in the high-risk 17p deletion/TP53 mutated patient population. BRUKINSA is approved in 70 markets, including the U.S., EU, Great Britain, Canada, Australia, China, South Korea and Switzerland in selected indications, and it is under development for additional indications globally. The global BRUKINSA development program includes more than 5,000 subjects enrolled to date in 29 countries and regions. About Follicular Lymphoma Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL), accounting for 22% of all NHL cases.ii Approximately 15,000 cases are diagnosed in the U.S. each year.iii While FL remains incurable, people with the condition can live a long time. The five-year survival rate is about 90%, and approximately half of people diagnosed with FL can live with the disease for nearly 20 years.iv 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 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. 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 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, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit 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 and commitment to bring BRUKINSA to patients around the world; the significance of the clinical advantages of treating R/R FL patients with BRUKINSA plus obinutuzumab; BeiGene’s advancement, anticipated clinical development, regulatory submissions and commercialization of zanubrutinib, particularly as a treatment for R/R FL; 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 annual report on Form 10-K, 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. References i Zinsani PL, et al. ROSEWOOD: A Phase II Randomized Study of Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Patients With Relapsed or Refractory Follicular Lymphoma. J Clin Oncol. 2023;41(33):5107-5117. iiLeukemia & Lymphoma Society. Treatment for Indolent NHL Subtypes. Accessed February 16, 2024. Available at: . iii Leukemia & Lymphoma Society. Follicular Lymphoma (FL). Accessed February 16, 2024. Available at: . iV Cleveland Clinic. Follicular Lymphoma. March 25, 2022. Accessed February 16, 2024. Available at: . To access BeiGene media resources, please visit our News & Media site.

Matching adjusted indirect comparison addresses key questions and limitations associated with previously presented analysis and suggests efficacy advantage of BRUKINSA vs acalabrutinib BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- BeiGene, Ltd. (Nasdaq: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced a new matching adjusted indirect comparison (MAIC) of the efficacy of BRUKINSA® (zanubrutinib) versus acalabrutinib in relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) based on data from the Phase 3 ALPINE and Phase 3 ASCEND trials. The analysis suggests a progression-free survival and complete response advantage for BRUKINSA versus acalabrutinib, as well as potentially improved overall survival. These data will be presented during the 28th Annual International Congress on Hematologic Malignancies® in Miami from February 29 - March 3. “The CLL landscape is evolving rapidly, and this MAIC provides timely comparative effectiveness data for physicians, and reinforces zanubrutinib role as a foundational CLL treatment via a robust evaluation of the efficacy in the ASCEND and ALPINE studies; the presented analysis not only accounts for differences in key patient characteristics, but also clarifies the impact COVID-19 may have had on study outcomes,” said Mazyar Shadman, M.D. M.P.H, Study Author and Innovators Network Endowed Chair, Associate Professor of Hematology and Oncology, Lymphoid Malignancies and Immunotherapy, Fred Hutch Cancer Center and University of Washington. “Head-to-head randomized clinical trials are the gold standard when it comes to evaluating the potential impact of individual treatments for patients. MAICs are intended to be hypothesis-generating, provided they are conducted with appropriate rigor to minimize potential biases.” In this MAIC, individual patient-level data from ALPINE was matched against the aggregate data from ASCEND. An unanchored MAIC was used due to the lack of a common comparator arm between the ALPINE and ASCEND trials. Given the differences in the timing of the studies, with respect to the onset of the COVID-19 pandemic, the analysis adjusted for the impact of COVID-19 in the ALPINE study. In a previously published MAIC of BRUKINSA versus acalabrutinib,1 there were significant limitations that precluded a robust efficacy comparison, including the exclusion of data from the final analysis of ALPINE, lack of adjustment for the impact of COVID-19 on the outcomes, lack of adjustment for key differences in patient characteristics, the effective sample size, and the exclusion of complete response rate and overall survival from the analysis. “BeiGene is committed to continuing to further our understanding of the efficacy and safety of our therapies and their potential to help patients among other options,” said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. “This MAIC addresses key questions raised in a previously published analysis, presenting a more holistic representation of the efficacy associated with BRUKINSA versus acalabrutinib in relapsed or refractory chronic lymphocytic leukemia setting.” BRUKINSA is the only Bruton’s tyrosine kinase (BTK) inhibitor to demonstrate progression-free survival superiority vs ibrutinib in R/R CLL, as observed in the ALPINE trial.2 Acalabrutinib has demonstrated improvement in progression-free survival vs rituximab plus idelalisib/bendamustine in R/R CLL in the ASCEND trial and has also demonstrated progression-free survival noninferiority vs ibrutinib R/R CLL patients with chromosome 17p or 11q deletions in the ELEVATE-RR trial.3,4 The MAIC suggests that investigator-assessed progression-free survival was improved for BRUKINSA versus acalabrutinib in both the unadjusted population (HR=0.77 [95%CI: 0.55-1.07]), as well as the base case adjusted population (HR=0.68 [95%CI: 0.46-0.99]). Additionally, the odds ratio (OR) for complete response favored BRUKINSA over acalabrutinib in the unadjusted (OR=2.88 [95%CI: 1.18-7.02]) and base case adjusted populations (OR=2.90; [95%CI: 1.13-7.43]). Results for the sensitivity analysis were consistent with the base case. The overall survival trend remained consistently in favor of BRUKINSA. For additional details of the analysis, please refer to the full poster presentation. While MAIC analyses can be hypotheses-generating, in the absence of head-to-head data, the safety of a drug may be best evaluated using all available evidence across indications. A recent independent Mayo Clinic meta-analysis of 61 trials involving 6,959 patients who received ibrutinib plus an anti-CD20 antibody, acalabrutinib, and BRUKINSA extensively analyzed the adverse event profiles of the two therapies across several indications and reported key differences in the safety profiles of the two treatments.5 BRUKINSA is approved in 70 markets, including the U.S., China, EU, Great Britain, Canada, Australia, South Korea and Switzerland in selected indications, and it is under development for additional indications globally. The global BRUKINSA development program includes more than 5,000 subjects enrolled to date in 29 countries and regions. About MAICs Match adjusted indirect comparisons are intended to be hypothesis generating, and do not establish superior efficacy or safety of one drug over another. Results should be viewed in the context of study limitations and available clinical data. About ALPINE ALPINE is a randomized, global, Phase 3 trial (NCT03734016) comparing BRUKINSA with ibrutinib in previously treated patients with R/R CLL or small lymphocytic lymphoma (SLL). In the trial, a total of 652 patients across Europe (60%), the United States (17%), China (14%), and New Zealand and Australia (9%) were randomized to receive BRUKINSA (160 mg orally twice daily) or ibrutinib (420 mg orally once daily) until disease progression, death, or unacceptable toxicity. The primary endpoint of overall response rate (ORR) was assessed by both investigator and independent review committee (IRC) using the modified 2008 iwCLL guidelines, with modification for treatment-related lymphocytosis for patients with CLL, and as per Lugano Classification for non-Hodgkin’s lymphoma for patients with SLL. Key secondary endpoints included PFS and the rate of atrial fibrillation or flutter; other secondary endpoints included duration of response, overall survival, and incidence of adverse events. There was a pre-specified hierarchical testing of non-inferiority followed by superiority for ORR as assessed by investigator and IRC. As ORR superiority was demonstrated, progression-free survival was tested for noninferiority and superiority under hierarchical testing. In an extended follow-up of the ALPINE study at a median follow-up of 39 months, BRUKINSA showed sustained PFS improvement versus ibrutinib (HR: 0.68 [95% CI, 0.53-0.86] P=0.0011) among R/R CLL/SLL patients, with durable PFS benefit observed across key subgroups, including patients with 17p deletion or TP53 mutation (HR: 0.52 [95% CI, 0.33-0.83] P=0.0047). PFS benefit was consistent across multiple sensitivity analyses, demonstrating that PFS advantage with BRUKINSA was primarily driven by efficacy, and not better tolerability. The overall safety and tolerability pro consistent with previous ALPINE analyses, including persistently lower rates of cardiovascular events reported with BRUKINSA. The most commonly reported treatment emergent adverse events (≥20%) with BRUKINSA were COVID-19-related infection, neutropenia, hypertension, and upper respiratory tract infection.6 About BRUKINSA® (zanubrutinib) BRUKINSA is a small molecule inhibitor of 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 or small lymphocytic lymphoma Waldenström’s macroglobulinemia 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 and U.S. Patient Information. 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, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit 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 the potential of BeiGene’s therapies to help patients; the efficacy and safety of BRUKINSA versus acalabrutinib in patients with R/R CLL; BeiGene’s advancement, anticipated clinical development, regulatory submissions and commercialization of zanubrutinib, particularly as a treatment for R/R FL; 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 annual report on Form 10-K, 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 our News & Media site. 1 Kittai AS, et al. A matching-adjusted indirect comparison of acalabrutinib versus zanubrutinib in relapsed or refractory chronic lymphocytic leukemia. Am J Hematol. 2023 Dec;98(12):E387-E390. doi: 10.1002/ajh.27110. Epub 2023 Oct 9. PMID: 37811799. 2 Brown JR, et al. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2023 Jan 26;388(4):319-332. doi: 10.1056/NEJMoa2211582. Epub 2022 Dec 13. PMID: 36511784. 3 Ghia P, et al. ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. J Clin Oncol. 2020 Sep 1;38(25):2849-2861. doi: 10.1200/JCO.19.03355. Epub 2020 May 27. PMID: 32459600. 4 Sharman JP, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020 Apr 18;395(10232):1278-1291. doi: 10.1016/S0140-6736(20)30262-2. Erratum in: Lancet. 2020 May 30;395(10238):1694. PMID: 32305093; PMCID: PMC8151619. 5 Hwang S, et al. P632: COMPARISON OF TREATMENT-EMERGENT ADVERSE EVENTS OF ACALABRUTINIB AND ZANUBRUTINIB IN CLINICAL TRIALS IN B-CELL MALIGNANCIES: A SYSTEMATIC REVIEW AND META-ANALYSIS. Hemasphere. 2023 Aug 8;7(Suppl ):e47546cf. doi: 10.1097/01.HS9.0000969432.47546.cf. PMCID: PMC10428881. 6 J. R. Brown, et. Al. Extended Follow-up of ALPINE Randomized Phase 3 Study Confirms Sustained Superior Progression-Free Survival of Zanubrutinib Versus Ibrutinib for Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (R/R CLL/SLL). Blood 2023; 142 (Supplement 1): 202. doi: .