Form 8-K BeiGene, Ltd. For: Jun 07

June 11, 2021 4:23 PM EDT

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Exhibit 99.1

BeiGene Announces Acceptance of a Supplemental Biologics License Application in China for Tislelizumab in Microsatellite Instability-High (MSI-H) or Mismatch Repair-Deficient (dMMR) Solid Tumors

BEIJING, China and CAMBRIDGE, Mass. – June 7, 2021 -- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, today announced that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted a supplemental Biologics License Application (sBLA) for anti-PD-1 antibody tislelizumab for the treatment of patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors.

“We are excited by the acceptance of our filing for tislelizumab in patients with MSI-H or dMMR solid tumors, which underscores our ongoing commitment to pursuing the full potential of tislelizumab, a potentially differentiated checkpoint inhibitor, and expanding its access where there is unmet medical need. This submission also marks the seventh indication submitted to health authorities, including three approvals for our tislelizumab program,” commented Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. “Results from our Phase 2 trial demonstrated that tislelizumab’s treatment effect was consistent and durable across tumor types and endpoints. We are encouraged by the data and plan to continue our communications with the CDE, hoping to bring this medicine to more patients.”

The sBLA is supported by clinical results from a single-arm, multi-center, open-label, pivotal Phase 2 clinical trial (NCT03736889) to evaluate efficacy and safety of tislelizumab as monotherapy in patients with previously treated locally advanced unresectable or metastatic MSI-H or dMMR solid tumors, with an enrollment of 80 patients in China. Patients received tislelizumab 200 mg intravenously every three weeks until disease progression, unacceptable toxicity, or withdrawal. Radiological imaging was performed at nine weeks and then every six weeks for the first year of therapy and every 12 weeks thereafter. The primary efficacy analysis set included patients who received any dose of tislelizumab with measurable disease per independent review committee (IRC) at baseline. The primary endpoint of this trial is objective response rate (ORR) as assessed by IRC per RECIST v1.1; secondary endpoints include time to response (TTR), duration of response (DoR), disease control rate (DCR), and progression-free survival (PFS) as assessed by investigator and IRC, overall survival (OS), and safety and tolerability. Results of this study were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

About Microsatellite Instability-High or Mismatch Repair Deficient Solid Tumors

Microsatellite instability-high (MSI-H) cancer cells have a greater than normal number of genetic markers called microsatellites, which are short, repeated sequences of DNA. Cancer cells that have large numbers of microsatellites may have defects in the ability to correct mistakes (also known as mismatch repair deficiency, or dMMR) that occur when DNA is copied in the cell. MSI-H and dMMR tumors are found most often in colorectal cancer and other types of gastrointestinal cancer and endometrial cancer, although they may also be found in cancers of the breast, prostate, bladder and thyroid.

About Tislelizumab

Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.





The China National Medical Products Administration (NMPA) has granted tislelizumab approval in three indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy; and conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies and for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

In addition, four supplemental Biologics License Applications for tislelizumab have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are under review for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy, for patients with previously treated with at least one systemic therapy hepatocellular carcinoma and for patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors.

BeiGene has initiated or completed 17 potentially registration-enabling clinical trials in China and globally, including 13 Phase 3 trials and four pivotal Phase 2 trials.

In January 2021, BeiGene and Novartis entered into a collaboration and license agreement granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

Tislelizumab is not approved for use outside of China.

About the Tislelizumab Clinical Program

Clinical trials of tislelizumab include:

Phase 3 trial comparing tislelizumab with docetaxel in the second- or third-line setting in patients with NSCLC (NCT03358875);

Phase 3 trial comparing tislelizumab to salvage chemotherapy in patients with relapsed or refractory classical Hodgkin Lymphoma (cHL; NCT04486391);

Phase 3 trial in patients with locally advanced or metastatic urothelial carcinoma (NCT03967977);

Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced squamous NSCLC (NCT03594747);

Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced non-squamous NSCLC (NCT03663205);

Phase 3 trial of tislelizumab in combination with platinum-based doublet chemotherapy as neoadjuvant treatment for patients with NSCLC (NCT04379635);

Phase 3 trial of tislelizumab combined with platinum and etoposide versus placebo combined with platinum and etoposide in patients with extensive-stage small cell lung cancer (NCT04005716);

Phase 3 trial comparing tislelizumab with sorafenib as first-line treatment for patients with hepatocellular carcinoma (HCC; NCT03412773);

Phase 2 trial in patients with previously treated unresectable HCC (NCT03419897);




Phase 2 trial in patients with locally advanced or metastatic urothelial bladder cancer (NCT04004221);

Phase 3 trial comparing tislelizumab with chemotherapy as second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC; NCT03430843);

Phase 3 trial of tislelizumab in combination with chemotherapy as first-line treatment for patients with ESCC (NCT03783442);

Phase 3 trial of tislelizumab versus placebo in combination with chemoradiotherapy in patients with localized ESCC (NCT03957590);

Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment for patients with gastric cancer (NCT03777657);

Phase 2 trial of tislelizumab in patients with relapsed or refractory cHL (NCT03209973);

Phase 2 trial in patients with MSI-H/dMMR solid tumors (NCT03736889); and

Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment in patients with nasopharyngeal cancer (NCT03924986).

BeiGene Oncology

BeiGene is committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines to patients across the globe. We have a growing R&D team of approximately 2,300 colleagues dedicated to advancing more than 90 clinical trials involving more than 13,000 patients and healthy volunteers. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 40 countries. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. The Company currently markets three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis Pharma AG granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

About BeiGene

BeiGene is a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide. With a broad portfolio of more than 40 clinical candidates, we are committed to expediting the development of our diverse pipeline of novel therapeutics through collaborations or our own internal capabilities, with the aspirational goal of radically improving access to medicines for two billion more people by 2030. BeiGene is a headquarter-less company by design, with a growing global team of approximately 6,000 colleagues across five continents. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.




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 data from the Phase 2 trial of tislelizumab in patients with previously treated locally advanced unresectable or metastatic MSI-H or dMMR solid tumors, the filing and potential approval of a sBLA in China based on this data, BeiGene's advancement, anticipated clinical development, regulatory milestones and commercialization of tislelizumab, and BeiGene’s plans, commitments, aspirations and goals under the headings “BeiGene Oncology” and “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 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 and commercialization of its drug candidates and achieve and maintain profitability; the impact of the COVID-19 pandemic on the BeiGene’s clinical development, regulatory, commercial, and other operations, as well as 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 National Cancer Institute. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mismatch-repair-deficiency. Accessed June 2021.

Investor ContactMedia Contact
Craig WestLiza Heapes or Vivian Ni
+1 857-302-5189+1 857-302-5663 or + 1 857-302-7596
ir@beigene.commedia@beigene.com







Exhibit 99.2

Shoreline Biosciences and BeiGene Announce Strategic Worldwide Collaboration to Develop and Commercialize Genetically Modified Natural Killer (NK) Cell Therapies

BeiGene has worldwide development and commercialization rights, with Shoreline having an option to retain U.S. and Canadian rights on up to two of four targets

SAN DIEGO, CA, CAMBRIDGE, MA & BEIJING, China – June 9, 2021 — Shoreline Biosciences, Inc., a biotechnology company developing intelligently designed allogeneic off-the-shelf, standardized and targeted natural killer (NK) and macrophage cellular immunotherapies derived from induced pluripotent stem cells (iPSC) for cancer and other serious diseases, and BeiGene, Ltd. (Nasdaq: BGNE; HKEX: 06160), a global biotechnology company, today announced an exclusive worldwide strategic collaboration to develop and commercialize a portfolio of NK-based cell therapeutics with Shoreline’s iPSC NK cell technology and BeiGene’s research and clinical development capabilities for different malignancies.

“BeiGene is a globally recognized biotechnology leader, and we are thrilled to announce our collaboration today,” said Kleanthis G. Xanthopoulos, Ph.D., Shoreline Chairman & CEO. “We look forward to combining our iPSC NK cells with BeiGene’s discovery and clinical development expertise as the parties work to accelerate the development of the next generation of cell therapies for patients around the world.”

Under the terms of the agreement, Shoreline will receive an upfront cash payment of $45 million from BeiGene and will be eligible to receive additional R&D funding, milestone payments and royalties based upon the achievement of certain development, regulatory, and commercial milestones. In the multi-target collaboration, the companies have agreed to work jointly to develop cell therapies for four designated therapeutic targets, with an option to expand the collaboration at a future date. Clinical development will be led by BeiGene globally, with Shoreline responsible for clinical manufacturing. BeiGene will have commercial rights globally, with Shoreline having an option to retain U.S. and Canadian commercialization rights for two targets. In connection with the agreement, BeiGene has an option to acquire an equity stake in Shoreline in its next round of equity financing, subject to specified conditions.

“We are excited to collaborate with Shoreline as BeiGene looks to expand our pipeline of transformative medicines from small molecule and antibody therapeutics to off-the-shelf cell therapies, a compelling area of research that has been primarily out of reach for many of the world’s patients,” said John V. Oyler, Co-Founder, Chairman, and Chief Executive Officer of BeiGene. “We look forward to collaborating with Shoreline, a leading company in developing iPSC-derived allogeneic cell therapies, as we combine our protein engineering technologies with Shoreline’s standardized NK cell therapy technology. We are hopeful that this combination, along with our clinical development expertise for solid tumor and hematologic malignancies, will bring cell therapies to more patients who need them.”

About Shoreline’s iPSC NK cell technology

Shoreline has developed a proprietary platform focused on iPSC-derived natural killer (NK) cells and macrophages that are optimized with precise and rational genetic reprogramming. The Shoreline NK cell and macrophage-based cell therapies are designed to provide an effective and efficient means for targeting and killing tumors as well as repairing tissue homeostasis. Shoreline’s approach, based on the advantage of its iPSC cell engineering and expansion, is being used to create a streamlined, affordable, and scalable manufacturing process that can deliver cell therapy treatments to patients in a more cost-effective, time-saving manner. Shoreline’s technology is at the forefront of regenerative medicine and is being used to develop potential therapies to treat a wide range of diseases including cancer, inflammatory and genetic diseases.





About Shoreline Biosciences

Shoreline is a biotechnology company dedicated to advancing the development of intelligently designed allogeneic off-the-shelf, targeted, and standardized cellular immunotherapies for cancer and other serious diseases. Shoreline is building a pipeline of natural killer (NK) cell and macrophage-cell therapy candidates derived from its deep expertise in iPSC differentiation methods and genetic reprogramming of disease relevant pathways. Shoreline has a strategic manufacturing relationship with the Advanced Cell Therapy Laboratory and is supported by high-quality institutional investors including Boxer Capital, BVF, Commodore, Cormorant, Janus Henderson Investors, Logos, Kite, a Gilead company, Wedbush Healthcare Partners, Stork Capital, and others. Shoreline Biosciences is headquartered in San Diego, CA.

For more information, please visit https://shorelinebio.com/ and engage with us on LinkedIn.

About BeiGene

BeiGene is a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide. With a broad portfolio of more than 40 clinical candidates, we are committed to expediting the development of our diverse pipeline of novel therapeutics through collaborations or our own internal capabilities, with the aspirational goal of radically improving access to medicines for two billion more people by 2030. BeiGene is a headquarter-less company by design, with a growing global team of approximately 6,000 colleagues across five continents. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.

BeiGene’s 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 future development and potential commercialization of therapeutic candidates using the licensed technology; potential payments to Shoreline Biosciences; the potential of the licensed technology; and the parties’ commitments and the potential benefits of the collaboration. 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 products and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its technology and drugs; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGene’s limited operating history and BeiGene's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; the impact of the COVID-19 pandemic on the Company’s clinical development, commercial and other operations, as well as 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.

Shoreline Biosciences Investor and Media Contact:
Amy Conrad
Juniper Point
(858) 366-3243
amy@juniper-point.com

BeiGene Investor Contact:
Craig West
(857) 302-5189

ir@beigene.com




BeiGene Media Contact:
Liza Heapes or Vivian Ni
(857) 302-5663 or (857) 302-7596

media@beigene.com


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Exhibit 99.3

BeiGene Presents Long-Term Efficacy and Safety Results from Three Pivotal Trials of BRUKINSA® (Zanubrutinib) and Tislelizumab at EHA2021

BRUKINSA demonstrated long-term clinical benefits and tolerability in patients with mantle cell lymphoma and chronic lymphocytic leukemia at extended follow-up of nearly three years

Tislelizumab achieved deep and durable responses in classical Hodgkin’s lymphoma with a median progression-free survival of 32 months and no new safety signals at 34-month follow-up

Company to host investor call and webcast today at noon ET (18:00 CEST)

CAMBRIDGE, Mass. & BEIJING, China – June 11, 2021 – BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, today announced long-term follow-up results from three pivotal trials in its hematology program at the 26th European Hematology Association 2021 (EHA2021) Virtual Congress, including a pivotal Phase 2 trial of its anti-PD-1 antibody tislelizumab in relapsed or refractory (R/R) classical Hodgkin’s lymphoma (cHL) in an oral presentation, and two pivotal Phase 2 trials of its BTK inhibitor BRUKINSA® (zanubrutinib) in R/R mantle cell lymphoma (MCL) and in R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in poster presentations.

“We are excited to see the long-term clinical benefits tislelizumab and BRUKINSA provided for patients in these pivotal trials, which supported the approvals in the relapsed or refractory setting of cHL and CLL or SLL in China, and MCL in both the U.S. and China,” said Jane Huang, M.D., Chief Medical Officer, Hematology at BeiGene. “With additional treatment exposure, tislelizumab achieved a higher complete response rate with no new safety signals identified, and the deep responses translated to impressive progression-free survival outcomes. And in the two BRUKINSA trials, our selective next-generation BTK inhibitor showed sustained deep responses and remained well-tolerated in these patients. As BeiGene continues to expand our global footprint, we plan to work to bring these important therapies to more patients in need.”

Long-Term Follow-up Results of Tislelizumab in R/R cHL

Oral presentation; Abstract code: S207

The 34-month follow-up results from the single-arm, multicenter, pivotal Phase 2 trial (NCT03209973) demonstrated that tislelizumab was active and generally well-tolerated as a treatment for patients with R/R cHL. Results from this pivotal Phase 2 trial supported the conditional approval of tislelizumab for the treatment of patients with cHL who received at least two prior therapies in China in December 2019.

“Despite the progress made by previous checkpoint inhibitors in R/R cHL treatment, only a minority of patients can achieve a CR,” said Yuqin Song, M.D., Ph.D., chief physician and deputy director of the Lymphoma Department at Beijing Cancer Hospital and a principal investigator of the trial. “As demonstrated in the 34-month follow-up results, tislelizumab achieved deep, durable, and consistent responses in these patients regardless of subgroup characteristics, and nearly 70% of patients reached complete remission. We are hopeful that this NMPA-approved immunotherapy can bring continued clinical benefits to patients with R/R cHL in China.”

With a median follow-up time of 34 months, tislelizumab demonstrated deep and durable responses in patients with R/R cHL across all patient subgroups. The IRC-assessed overall response rate (ORR) was 87.1% (95% CI: 77.0, 93.9) and the complete response (CR) rate was 67.1% (95% CI: 54.9, 77.9). The median progression-free survival (PFS) was 31.5 months (95% CI: 16.53, not estimable [NE]), and the PFS rate at 24 months and 36 months was 55.4% (95% CI: 42.2, 66.8) and 40.8% (95% CI: 25.2, 55.8), respectively. The median overall survival (OS) was not reached, and the OS rate at 24 months and 36 months was 93.9% (95% CI: 84.5, 97.7) and 84.8% (95% CI: 70.5, 92.6), respectively.



Tislelizumab remained generally well-tolerated with long-term exposure. Most adverse events were Grade 1-2 and no new safety signals were identified. Treatment-emergent adverse events (TEAEs) of any grade were reported in 97.1% of patients, and Grade ≥3 TEAEs occurred in 41.4% of patients. Treatment discontinuation due to TEAEs occurred in 8.6% of patients.

Long-Term Follow-up Results of BRUKINSA in R/R MCL

Poster; Abstract code: EP789

The 35-month follow-up results from the single-arm, open-label, multicenter pivotal Phase 2 trial (NCT03206970) demonstrated BRUKINSA’s long-term benefit and tolerability for patients with R/R MCL. Results from this pivotal Phase 2 trial were part of the data package that supported the accelerated approval of BRUKINSA in this indication in the U.S. in November 2019 and the conditional approval in China in June 2020.

“With nearly three years of patient follow-up, BRUKINSA sustained a high response rate in patients with R/R MCL, and the safety profile remained largely unchanged with longer treatment exposure,” said Yuqin Song, M.D., Ph.D., chief physician and deputy director of the Lymphoma Department at Beijing Cancer Hospital and a principal investigator of the trial. “We hope these encouraging results will further establish this highly selective BTK inhibitor as a preferred treatment for patients with R/R MCL in the approved geographies.”

With a median follow-up time of 35.3 months and a median duration of exposure of 27.6 months, BRUKINSA demonstrated high, deep, and sustained efficacy in patients with R/R MCL, and responses were generally consistent across patient subgroups. The investigator-assessed ORR was 83.7% (95% CI: 74.2, 90.8), including 67 patients who achieved a CR (77.9%). The median PFS was 33.0 months (95% CI: 19.4, NE) and the estimated 36-month PFS rate was 47.6% (95% CI: 36.2, 58.1).

In long-term follow-up, the safety profile of BRUKINSA largely remained the same. Most adverse events occurred during the early stage of BRUKINSA treatment, with no additional dose reduction, treatment discontinuation, or death due to TEAEs. Grade ≥3 TEAEs occurred in 50.0% of patients.

Long-Term Follow-up Results of BRUKINSA in R/R CLL or SLL

Poster; Abstract code: EP639

Based on the 34-month follow-up results from the single-arm, open-label, multicenter pivotal Phase 2 trial (NCT03206918), BRUKINSA continued to demonstrate deep and durable responses in patients with R/R CLL, regardless of subgroup characteristics, and was well-tolerated with no new safety signals identified. Results from this pivotal Phase 2 trial supported the conditional approval of BRUKINSA in China in June 2020 for the treatment of adult patients with CLL or SLL who have received at least one prior therapy.

“With an additional 19-month follow-up time, BRUKINSA continued to demonstrate promising efficacy and tolerability, as deeper responses were observed in more patients and no new safety signals were identified,” Wei Xu, M.D., Ph.D., professor at the First Affiliated Hospital of Nanjing Medical University and a principal investigator of the trial. “High-risk patients with del (11q), del (17p), and/or TP53 mutation were also able to achieve deep and durable responses, and PFS among patients with a prolonged PR-L was on par with patients who achieved a CR or PR.”

After a median follow-up time of 34 months, responses to BRUKINSA increased and deepened over time and were consistent across all subgroups. The IRC-assessed ORR was 87.9%, including six patients who achieved a CR (6.6%), 63 patients who achieved a PR (69.2%), and 11 patients who achieved a PR with lymphocytosis (PR-L; 12.1%).



With a longer follow-up, BRUKINSA continued to be generally well-tolerated in patients with R/R CLL, similar to the previously reported data, with no new safety signals identified. TEAEs of any grade were reported in all patients (100%), and Grade ≥3 TEAEs occurred in 83.5% of patients. Treatment discontinuation due to TEAEs occurred in 15.4% of patients and fatal TEAEs occurred in 6.6% of patients.

To learn more about BeiGene’s research and development and activities around EHA2021, please visit https://beigenemedical.eu.

BeiGene EHA2021 Investor Conference Call and Webcast Information

BeiGene will host an investor and analyst conference call and webcast to discuss results from the interim analysis of the ALPINE trial, other data presented at EHA2021, and the BRUKINSA clinical program, today Friday, June 11, at 12:00 p.m. (noon) ET (18:00 CEST).

A live webcast of the conference call can be accessed from the investors section of BeiGene’s website at http://ir.beigene.com or http://hkexir.beigene.com. An archived replay will be available two hours after the event for 90 days.

About Tislelizumab

Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

The China National Medical Products Administration (NMPA) has granted tislelizumab approval in three indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy; and conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies and for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

In addition, four supplemental Biologics License Applications for tislelizumab have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are under review for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy, for patients with previously treated unresectable hepatocellular carcinoma, and for the treatment of patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors.

BeiGene has initiated or completed 17 potentially registration-enabling clinical trials in China and globally, including 13 Phase 3 trials and four pivotal Phase 2 trials.

In January 2021, BeiGene and Novartis entered into a collaboration and license agreement granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

Tislelizumab is not approved for use outside of China.




About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is approved in the following indications and regions:

For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;

For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;

For the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;

For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021); and

For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021).

To-date, more than 30 marketing authorization applications in multiple indications have been submitted outside of the United States and China, covering countries in the European Union and more than 20 other countries.

* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

** This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher bleeding events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 2% of patients treated with BRUKINSA monotherapy. Bleeding events of any grade, including purpura and petechiae, occurred in 50% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration 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) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 23% of patients treated with BRUKINSA monotherapy. The most common Grade 3 or higher infection was pneumonia. 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 (27%), thrombocytopenia (10%), and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy.

Monitor complete blood counts during treatment and treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 9% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin), reported in 6% of patients. Advise patients to use sun protection.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter have occurred in 2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 0.6% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

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 at least 1 week after the last dose. Advise men to avoid fathering a child during treatment and for at least 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 in > 10% of patients who received BRUKINSA were neutrophil count decreased (53%), platelet count decreased (39%), upper respiratory tract infection (38%), white blood cell count decreased (30%), hemoglobin decreased (29%), rash (25%), bruising (23%), diarrhea (20%), cough (20%), musculoskeletal pain (19%), pneumonia (18%), urinary tract infection (13%), hematuria (12%), fatigue (11%), constipation (11%), and hemorrhage (10%). The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).

Of the 118 patients with MCL treated with BRUKINSA, 8 (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).



Drug Interactions

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

CYP3A Inducers: Avoid co-administration with moderate or strong CYP3A inducers.

Specific Populations

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

INDICATION

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Please see full U.S. Prescribing Information at www.beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at www.beigene.com/PDF/BRUKINSAUSPPI.pdf.

BeiGene Oncology

BeiGene is committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D team of approximately 2,300 colleagues dedicated to advancing more than 90 clinical trials involving more than 13,000 patients and healthy volunteers. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 40 countries. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. The Company currently markets three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

About BeiGene

BeiGene is a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide. With a broad portfolio of more than 40 clinical candidates, we are committed to expediting the development of our diverse pipeline of novel therapeutics through collaborations or our own internal capabilities, with the aspirational goal of radically improving access to medicines for two billion more people by 2030. BeiGene is a headquarter-less company by design, with a growing global team of approximately 6,000 colleagues across five continents. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.



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 clinical benefits of tislelizumab and BRUKINSA, BeiGene's plan for the advancement, and anticipated clinical development, regulatory milestones and commercialization of tislelizumab and BRUKINSA, and BeiGene’s plans, commitments, aspirations, and goals under the headings “BeiGene Oncology” and “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 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 and commercialization of its drug candidates and achieve and maintain profitability; the impact of the COVID-19 pandemic on the BeiGene’s clinical development, regulatory, commercial, and other operations, as well as 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.

Investor ContactMedia Contact
Craig WestLiza Heapes or Vivian Ni
+1 857-302-5189+1 857-302-5663 or + 1 857-302-7596
ir@beigene.commedia@beigene.com


Exhibit 99.4

BeiGene Presents ALPINE Results at EHA2021 Demonstrating Both Efficacy and Safety Advantages of BRUKINSA® (Zanubrutinib) in Head-to-Head Comparison to Ibrutinib in Chronic Lymphocytic Leukemia

The Phase 3 ALPINE trial met the primary endpoint at interim analysis, with BRUKINSA showing superiority in investigator-assessed overall response rate versus ibrutinib

Early progression-free survival and overall survival data are supportive of findings in response rate

BRUKINSA demonstrated superiority in key secondary endpoint of atrial fibrillation or flutter and advantages in overall cardiac safety

Company to host investor call and webcast today at noon ET (18:00 CEST)

CAMBRIDGE, Mass. & BEIJING, China – June 11, 2021 – BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, today presented results from the interim analysis of the Phase 3 ALPINE trial comparing its BTK inhibitor BRUKINSA® (zanubrutinib) to ibrutinib in adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), including superiority in the primary endpoint of investigator-assessed overall response rate (ORR) and superiority in a key secondary endpoint of atrial fibrillation or flutter.

These results were reported in an oral presentation as part of the Presidential Symposium and featured during the congress press briefing at the 26th European Hematology Association 2021 (EHA2021) Virtual Congress, taking place virtually on June 9-17, 2021.

“While ibrutinib has transformed the outlook for patients with chronic lymphocytic leukemia, or CLL, not all patients respond to treatment and toxicities associated with prolonged exposure remain an issue,” commented Peter Hillmen, MBChB, Ph.D., Professor of Experimental Haematology at University of Leeds and principal investigator of the ALPINE trial. “The ALPINE trial is the only head-to-head study in CLL to demonstrate an efficacy advantage for a more selective BTK inhibitor over ibrutinib. Compared to ibrutinib, BRUKINSA demonstrated superiority in investigator-assessed overall response rate in patients with relapsed or refractory CLL. Additionally, the event rate of atrial fibrillation or flutter, an important indicator of cardiac toxicity, was also significantly lower with BRUKINSA.”

“The positive data from the interim analysis of the ALPINE trial, including a superior overall response rate by investigator assessment, supportive initial data in progression-free survival and overall survival, and a significantly lower rate of atrial fibrillation of any grade, reinforce our belief that the differentiated profile of BRUKINSA can provide clinical benefits for patients with CLL,” said Jane Huang, M.D., Chief Medical Officer, Hematology at BeiGene. “As evidenced in ALPINE and ASPEN, our head-to-head trials of BRUKINSA against the first-generation BTK inhibitor ibrutinib, this potentially best-in-class molecule can provide meaningful responses and consistent safety advantages for these patients. In addition to ALPINE, we are evaluating BRUKINSA in the Phase 3 SEQUOIA trial in treatment-naïve CLL, and expect to share topline results as early as later this year.”




Interim Analysis of the ALPINE Trial Comparing BRUKINSA to Ibrutinib in R/R CLL

Oral presentation; Abstract code: LB1900

Results from the planned interim analysis presented at EHA were based on the first 415 patients enrolled in the ALPINE trial, including 207 on BRUKINSA treatment and 208 on ibrutinib treatment.

In the interim analysis, with a median follow-up time of 15.3 months, the trial met the primary endpoint with BRUKINSA demonstrating superiority in ORR, defined as the combined rate of complete responses (CRs) and partial responses (PRs), per investigator assessment. In the ORR analysis conducted by independent review committee (IRC), BRUKINSA demonstrated non-inferiority in the interim analysis. Efficacy results included:

As assessed by investigator, BRUKINSA achieved an ORR of 78.3% (95% CI: 72.0, 83.7), a statistically significant improvement compared to 62.5% (95% CI: 55.5, 69.1) with ibrutinib (p=0.0006);

As assessed by IRC, BRUKINSA achieved an ORR of 76.3%, numerically higher but not statistically significant compared to 64.4% with ibrutinib (p=0.0121 compared to the pre-specified stringent statistical boundary of p<0.0099 set for the interim analysis);

In patients whose tumor exhibited chromosome 17p deletion (del[17p]), the ORR was 83.3% in the BRUKINSA arm, compared to 53.8% in the ibrutinib arm, as assessed by investigator;

PFS data were early at the time of interim analysis and formal analysis will be performed when the target number of events is reached. The PFS rate at 12 months was 94.9% in the BRUKINSA arm, compared to 84.0% in the ibrutinib arm (descriptive p=0.0007; descriptive hazard ratio [HR]=0.40 [95% CI: 0.23, 0.69]), as assessed by investigator; and

OS data were early at the time of interim analysis. The OS rate at 12 months was 97.0% in the BRUKINSA arm, compared to 92.7% in the ibrutinib arm (descriptive p=0.1081; descriptive HR=0.54 [95% CI: 0.25, 1.16]).
In the interim analysis, the ALPINE trial also met a pre-specified key secondary endpoint related to safety, with BRUKINSA demonstrating a statistically significant lower risk of atrial fibrillation or flutter and advantages in the overall cardiac safety profile, compared to ibrutinib. Treatment discontinuation was more common in the ibrutinib arm. Safety results included:

195 patients (95.6%) in the BRUKINSA arm experienced at least one adverse event (AE) of any grade, compared to 205 patients (99.0%) in the ibrutinib arm, and the most common (≥10%) AEs included anemia (BRUKINSA vs. ibrutinib: 13.2% vs. 15.0%), arthralgia (9.3% vs. 14.0%), contusion (10.3% vs. 8.7%), cough (12.7% vs. 6.3%), diarrhea (16.7% vs. 19.3%), hypertension (15.7% vs. 13.0%), muscle spasm (2.9% vs. 11.1%), neutropenia (19.6% vs. 15.5%), upper respiratory tract infection (21.6% vs. 14.0%), and urinary tract infection (10.8% vs. 8.2%);

114 patients (55.9%) in the BRUKINSA arm experienced Grade ≥3 AEs, compared to 106 patients (51.2%) in the ibrutinib arm;

56 patients (27.5%) in the BRUKINSA arm experienced serious AEs, compared to 67 patients (32.4%) in the ibrutinib arm;

Dose reduction and interruption due to AEs occurred in 23 patients (11.3%) and 81 patients (39.7%) in the BRUKINSA arm, respectively, compared to 25 patients (12.1%) and 84 patients (40.6%) in the ibrutinib arm;




16 patients (7.8%) discontinued BRUKINSA treatment due to AEs, with none caused by cardiac disorders; in comparison, 27 patients (13.0%) discontinued ibrutinib treatment due to AEs, with seven caused by cardiac disorders, including two of atrial fibrillation, and one each of cardiac arrest, cardiac failure, myocardial infarction, palpitations, and ventricular fibrillation;

Fatal AEs were reported in eight patients (3.9%) in the BRUKINSA arm, compared to 12 patients (5.8%) in the ibrutinib arm;

A key secondary endpoint of atrial fibrillation or flutter of any grade occurred in five patients (2.5%) in the BRUKINSA arm, significantly lower than the 21 patients (10.1%) in the ibrutinib arm (p=0.0014);

Grade ≥3 atrial fibrillation or flutter occurred in two patients (1.0%) in the BRUKINSA arm, compared to four patients (1.9%) in the ibrutinib arm;

Additional AEs of special interest of any grade included cardiac disorders (BRUKINSA vs. ibrutinib: 13.7% vs. 25.1%), hemorrhage (35.8% vs. 36.2%), major hemorrhage (2.9% vs. 3.9%), hypertension (16.7% vs. 16.4%), infections (59.8% vs. 63.3%), neutropenia (28.4% vs. 21.7%), secondary primary malignancies (8.3% vs. 6.3%), skin cancers (3.4% vs. 4.8%), and thrombocytopenia (9.3% vs. 12.6%); and

Grade ≥3 AEs of special interest included cardiac disorders (BRUKINSA vs. ibrutinib: 2.5% vs. 6.8%), hemorrhage (2.9% vs. 2.9%), major hemorrhage (2.9% vs. 2.9%), hypertension (10.8% vs. 10.6%), infections (12.7% vs. 17.9%), neutropenia (18.6% vs. 15.0%), secondary primary malignancies (4.9% vs. 1.9%), skin cancers (1.5% vs. 1.0%), and thrombocytopenia (3.4% vs. 3.4%).





Summary of ALPINE Interim Results

ALPINE
Summary
BRUKINSA
(n=207)
Ibrutinib
(n=208)
Efficacy Results
Investigator-Assessed ORR (Primary Endpoint)78.3%
(95% CI: 72.0, 83.7)
62.5%
(95% CI: 55.5, 69.1)
p=0.0006
IRC-Assessed ORR76.3%64.4%
p=0.0121 compared to the pre-specified stringent statistical boundary of p<0.0099
ORR in del(17p)83.3%53.8%
12-Month PFS Rate*94.9%84.0%
descriptive p=0.0007; descriptive HR=0.40 (95% CI: 0.23, 0.69)
* PFS data were early at the time of interim analysis and formal analysis will be performed when the target number of events is reached.
Overall Safety Results
AEs of any grade95.6%99.0%
Grade ≥3 AEs55.9%51.2%
Serious AEs27.5%32.4%
AEs leading to treatment discontinuation7.8%13.0%
Fatal AEs3.9%5.8%
Adverse Events of Special Interest (Any Grade)
Atrial Fibrillation
or Flutter
(Key Secondary Endpoint)
2.5%10.1%
p=0.0014
Cardiac Disorders13.7%25.1%
Hemorrhage35.8%36.2%
Major Hemorrhage2.9%3.9%
Hypertension16.7%16.4%
Infections59.8%63.3%
Neutropenia28.4%21.7%
Secondary Primary Malignancies8.3%6.3%
Skin Cancers3.4%4.8%
Thrombocytopenia9.3%12.6%

To learn more about BeiGene’s research and development and activities around EHA2021, please visit https://beigenemedical.eu.




BeiGene EHA2021 Investor Conference Call and Webcast Information

BeiGene will host an investor and analyst conference call and webcast to discuss results from the interim analysis of the ALPINE trial, other data presented at EHA2021, and the BRUKINSA clinical program, today Friday, June 11, at 12:00 p.m. (noon) ET (18:00 CEST).

A live webcast of the conference call can be accessed from the investors section of BeiGene’s website at http://ir.beigene.com or http://hkexir.beigene.com. An archived replay will be available two hours after the event for 90 days.

About Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, with a global incidence of approximately 114,000 new cases in 2017.1,2 CLL affects white blood cells or lymphocytes in the bone marrow.1 Proliferation of cancer cells (leukemia) in the marrow result in reduced ability to fight infection and spread into the blood, which affects other parts of the body including the lymph nodes, liver and spleen.1,3 The BTK pathway is a known route that signals malignant B cells and contributes to the onset of CLL.4 Small lymphocytic lymphoma (SLL) is a non-Hodgkin’s lymphoma affecting the B-lymphocytes of the immune system, which shares many similarities to CLL but with cancer cells found mostly in lymph nodes.5

About ALPINE

ALPINE is a randomized, global Phase 3 trial (NCT03734016) comparing BRUKINSA against ibrutinib in previously treated patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

In the trial, a total of 652 patients were randomized into two arms, with the first receiving BRUKINSA (160 mg orally twice daily) and the second receiving ibrutinib (420 mg orally once daily) until disease progression or unacceptable toxicity. The primary analysis of overall response rate (ORR), defined by pre-specified non-inferiority of BRUKINSA versus ibrutinib, was assessed by investigator and independent review committee (IRC) using the modified 2008 iwCLL guidelines, with modification for treatment-related lymphocytosis for patients with CLL, and per Lugano Classification for non-Hodgkin’s lymphoma for patients with SLL. There was hierarchical testing of non-inferiority followed by superiority in ORR as assessed by investigator and IRC. Key secondary endpoints include progression-free survival (PFS) and event rate of atrial fibrillation or flutter; other secondary endpoints include duration of response, overall survival, and incidence of adverse events. The study is ongoing, with pre-specified final analysis of ORR superiority by IRC assessment and formal analysis of PFS when the target number of events is reached. Results are expected in 2022.

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is approved in the following indications and regions:

For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;



For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;

For the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;

For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021); and

For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021).

To-date, more than 30 marketing authorization applications in multiple indications have been submitted outside of the United States and China, covering countries in the European Union and more than 20 other countries.

* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

** This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher bleeding events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 2% of patients treated with BRUKINSA monotherapy. Bleeding events of any grade, including purpura and petechiae, occurred in 50% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration 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) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 23% of patients treated with BRUKINSA monotherapy. The most common Grade 3 or higher infection was pneumonia. 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 (27%), thrombocytopenia (10%), and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy.


Monitor complete blood counts during treatment and treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 9% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin), reported in 6% of patients. Advise patients to use sun protection.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter have occurred in 2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 0.6% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

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 at least 1 week after the last dose. Advise men to avoid fathering a child during treatment and for at least 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 in > 10% of patients who received BRUKINSA were neutrophil count decreased (53%), platelet count decreased (39%), upper respiratory tract infection (38%), white blood cell count decreased (30%), hemoglobin decreased (29%), rash (25%), bruising (23%), diarrhea (20%), cough (20%), musculoskeletal pain (19%), pneumonia (18%), urinary tract infection (13%), hematuria (12%), fatigue (11%), constipation (11%), and hemorrhage (10%). The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).

Of the 118 patients with MCL treated with BRUKINSA, 8 (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).

Drug Interactions

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

CYP3A Inducers: Avoid co-administration with moderate or strong CYP3A inducers.

Specific Populations

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

INDICATION



BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Please see full U.S. Prescribing Information at www.beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at www.beigene.com/PDF/BRUKINSAUSPPI.pdf.

BeiGene Oncology

BeiGene is committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D team of approximately 2,300 colleagues dedicated to advancing more than 90 clinical trials involving more than 13,000 patients and healthy volunteers. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 40 countries. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. The Company currently markets three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis Pharma AG granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

About BeiGene

BeiGene is a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide. With a broad portfolio of more than 40 clinical candidates, we are committed to expediting the development of our diverse pipeline of novel therapeutics through collaborations or our own internal capabilities, with the aspirational goal of radically improving access to medicines for two billion more people by 2030. BeiGene is a headquarter-less company by design, with a growing global team of approximately 6,000 colleagues across five continents. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.

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 results from the interim analysis of the Phase 3 ALPINE trial, the potential clinical benefits and advantages of BRUKINSA compared to other BTK inhibitors, expected timelines for the final analysis of the ALPINE trial and topline results from the Phase 3 SEQUOIA trial, BeiGene's plan for the advancement, and anticipated clinical development, regulatory milestones and commercialization of BRUKINSA, and BeiGene’s plans, commitments, aspirations, and goals under the headings “BeiGene Oncology” and “About BeiGene”. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including the risk that preliminary data from the interim analysis of the Phase 3 ALPINE trial may differ at the final analysis; the risk that interim and/or final results of the ALPINE trial will not support filings for regulatory approvals of BRUKINSA for the treatment of patients with CLL, and the timing of any such filings and potential approvals; clinical data continue to support a risk-benefit profile for BRUKINSA; 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 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 and commercialization of its drug candidates and achieve and maintain profitability; the impact of the COVID-19 pandemic on the BeiGene’s clinical development, regulatory, commercial, and other operations, as well as 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.

Investor ContactMedia Contact
Craig WestLiza Heapes or Vivian Ni
+1 857-302-5189+1 857-302-5663 or + 1 857-302-7596
ir@beigene.commedia@beigene.com

References

1.American Cancer Society. Cancer Facts & Figures 2021. Atlanta; American Cancer Society; 2021. Available here: Cancer Facts and Figures 2021

2.Global Burden of Disease Cancer Collaboration. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017. JAMA Oncol. 2019;5(12):1749-1768.

3.National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version. Available here: Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version

4.Haselager MV et al. Proliferative Signals in Chronic Lymphocytic Leukemia; What Are We Missing? Front Oncol. 2020; 10: 592205.

5.Cancer Support Community. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Available here: https://www.cancersupportcommunity.org/chronic-lymphocytic-leukemiasmall-lymphocytic-lymphoma.



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