What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2022-02-28 compared with 2021-02-25 · 614 added, 722 removed, 976 unchanged (58% of the section changed)

We are a global, commercial-stage biotechnology company focused on discovering, developing, manufacturing, and commercializing innovative medicines to improve treatment outcomes and expand access for patients worldwide.

Our research organization has delivered ten molecules into the clinic in our first ten years, including our two lead commercial medicines, BRUKINSA ® , a small molecule inhibitor of Bruton’s Tyrosine Kinase (“BTK”) for the treatment of various blood cancers, and tislelizumab, an anti-PD-1 antibody immunotherapy for the treatment of various solid tumor and blood cancers.

We are marketing BRUKINSA ® in the world’s two largest pharmaceutical markets, the United States and China, and tislelizumab in China, with an established, science-based commercial organization.

We have built state-of-the-art biologic and small molecule manufacturing facilities in China to support the potential future demand of our products, and we also work with high quality contract manufacturing organizations (“CMOs”) to manufacture our internally developed clinical and commercial products.

We are a leader in China-inclusive global clinical development, which we believe can facilitate faster and more cost-effective development of innovative medicines.

Our internal clinical development capabilities are deep, including a more than 1,600-person global clinical development team that is running more than 60 ongoing or planned clinical trials.

This includes more than 25 pivotal or registration-enabling trials for three product candidates that have enrolled more than 12,000 patients and healthy volunteers, of which approximately one-half have been outside of China, as of January 2021.

We have over 45 products and product candidates in commercial stage or clinical development, including 7 approved medicines, 5 pending approval, and over 30 in clinical development.

Supported by our development and commercial capabilities, we have entered into collaborations with world-leading biopharmaceutical companies such as Amgen and Novartis to develop and commercialize innovative medicines globally.

Since our inception in 2010 in Beijing, we have become a fully integrated global organization of over 5,300 employees in 14 countries and regions, including China, the United States, Europe and Australia.

Our mission is to provide access to high-quality, innovative, impactful, and affordable medicines to billions more people globally.

We believe that we have built competitive advantages in research, clinical development, manufacturing and commercialization that will drive our business into the future.

We intend to continue to develop and expand our competitive advantages and become a global leader by focusing on the following key strategic imperatives:

We currently have three approved medicines that were discovered and developed in our own labs, including BRUKINSA ® , a small molecule inhibitor of Bruton’s Tyrosine Kinase (BTK) for the treatment of various blood cancers;

tislelizumab, an anti-PD-1 antibody immunotherapy for the treatment of various solid tumor and blood cancers;

and pamiparib, a selective small molecule inhibitor of PARP1 and PARP2.

We have obtained approvals to market BRUKINSA ® in the United States, the People's Republic of China (China or the PRC), the European Union (EU), the United Kingdom (U.K.), Canada, Australia and additional international markets, and tislelizumab and pamiparib in China.

By leveraging our China commercial capabilities, we have in-licensed the rights to distribute 13 approved medicines for the China market.

Supported by our global clinical development and commercial capabilities, we have entered into collaborations with world-leading biopharmaceutical companies such as Amgen and Novartis Pharma AG (Novartis) to develop and commercialize innovative medicines.

We are 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.

Our internal clinical development capabilities are deep, including a more than 2,200-person global clinical development team that is running more than 90 ongoing or planned clinical trials in over 30 medicines and drug candidates.

This includes more than 30 pivotal or potentially registration-enabling trials across our portfolio, including our three internally discovered, approved medicines.

We have enrolled in our clinical trials more than 14,500 subjects, of which approximately one-half have been outside of China.

We have built, and are expanding, our internal manufacturing capabilities through our state-of-the-art biologic and small molecule manufacturing facilities in China to support current and potential future demand of our medicines, and plan to build a commercial-stage biologics manufacturing and clinical R&D center in New Jersey.

We also work with high quality contract manufacturing organizations (CMOs) to manufacture our internally developed clinical and commercial products.

Since our inception in 2010, we have become a fully integrated global organization of over 8,000 employees in 23 countries and regions, including the United States, China, Europe, and Australia.

We were founded to fight cancer with a belief that millions of people around the world still have limited or no access to high-quality, innovative, and affordable medicines.

We also believe that the industry is in a time of fundamental change driven by regulatory policy updates, scientific progress, and globalization.

To seize this opportunity, we have built key competitive advantages in research, clinical development, commercialization, and manufacturing that are designed to drive our business into the future.

We intend to continue to expand our competitive advantages and become a global leader by focusing on the following key strategic imperatives:

Research and innovation focus .

We have built one of the largest research teams in China with more than 450 people and a robust suite of capabilities that fuel our innovation pipeline.

To date, our research organization has advanced more than 10 internally discovered molecules into the clinic and, of those programs, two medicines have been approved for commercial use in multiple indications.

Our team has discovered promising new drug candidates, including our investigational TIGIT antibody and BCL-2 inhibitor currently in development.

We plan to continue to invest in research and innovation with the aim of discovering additional innovative product candidates for patients.

We have built significant oncology research capabilities with a team of more than 700 scientists with a proven track record of discovering innovative medicines.

Our approach is to leverage our deep internal capabilities and technology platforms to develop medicines that are expected to be highly impactful and have a clear differentiation hypothesis.

The strength of our research has been validated by our global clinical trial results, regulatory approvals, and collaborations.

From our internal discovery engine, we have successfully developed three approved medicines:

BRUKINSA ® , tislelizumab, and pamiparib.

We are also developing ociperlimab (TIGIT antibody), which is in pivotal stage trials and was recently entered into an option, collaboration and license agreement with Novartis for North America, Europe and Japan;

BGB-11417 (BCL2 inhibitor), which is expected to start pivotal trials in 2022;

multiple early-stage clinical assets, including OX40, TIM3, and PI3K delta, HPK-1, that are expected to have initial clinical data readouts in 2022 and 2023;

and have over 50 additional pre-clinical programs, approximately one-half of which may potentially be first-in-class or best-in-class.

Going forward, we plan to continue to invest in research and innovation with the aim of discovering additional first-in-class or best-in-class innovative medicines for patients.

World-class clinical development .

We believe that leveraging our leadership position in China-inclusive clinical development will enable us to develop products with advantages in speed and cost efficiency, while maintaining quality.

We plan to continue to invest to in-source our clinical capabilities to mitigate the challenges associated with relying on third-party contract research organizations ("CROs"), with the intention of becoming one of the best clinical development organizations in the world.

We believe that global clinical development capabilities are essential to succeed in the current and future environment.

We have built an internal clinical development and medical affairs team of over

2,200 people worldwide that develops our product candidates largely without the assistance of third-party contract research organizations (CROs).

We believe this approach has several benefits:

first, we can be more inclusive in the location and number of clinical sites to help improve enrollment speed and the diversity of patients in our trials;

second, we have control over our own technology systems and can focus on improved operational excellence;

and third, we believe there are cost advantages through large scale and China-inclusive multi-regional clinical trials that have a broad patient population.

We aim to improve the speed and cost-efficiency of clinical development while maintaining the highest global quality standards.

We believe that our demonstrated ability to successfully complete large-scale, multi-regional clinical trials is one of our most important strategic competitive advantages and addresses a large challenge in the pharmaceutical industry – clinical development, which accounts for the majority of time and cost required to bring most oncology medicines to patients.

China commercial leadership .

We have built a large commercial team in China, with over 2,200 colleagues spread across the country and organized under experienced executive leadership.

We believe that we have established BeiGene as a high-quality, science-driven, leading provider of innovative and affordable medicines in China.

We aspire to grow our commercial portfolio through both internal discovery efforts and through in-licensing additional products and product candidates, striving to be a partner of choice and creating mutual benefits with our partners wherever possible.

We believe that our commercial capabilities in China, coupled with our China-inclusive clinical development capabilities conducted at global-quality standards, enable us to attract favorable in-licensing

opportunities.

We plan to further invest in our China commercial organization and create advantages in scale, speed, and quality to establish our commercial leadership in China.

We have built a strong, science-based commercial team in China, with over 3,100 colleagues spread across the country for broad and deep coverage and organized under experienced executive leadership.

We have built a commercial portfolio of oncology medicines through our internal discovery and in-licensing efforts, striving to be a partner of choice and creating mutual benefits with our partners wherever possible.

We plan to further leverage our China commercial organization and create advantages in scale, speed, and quality to continue to establish ourselves as a commercial leader in China.

Global leadership, access, and reputation .

We have launched BRUKINSA ® in the United States and built a targeted commercial team focused on medical thought leaders in blood cancer treatments.

This competitive foothold is based on the clinical differentiation of our approved products and product candidates and our deep relationships.

We aspire to establish our reputation globally as a leading biotechnology company by delivering highly effective and differentiated medicines in the United States, China, Europe and new markets.

In the United States, we market BRUKINSA ® and have a targeted commercial team focused on medical thought leaders in blood cancer treatments.

This competitive foothold is based on the differentiated clinical profile of BRUKINSA ® .

BRUKINSA ® sales have continued to grow in the U.S.

as we expand our label in multiple new indications.

Our strategy is to commercialize our medicines broadly throughout the world.

In Europe, we recently received approval for BRUKINSA ® in Waldenström’s macroglobulinemia (WM), and we are launching the product across European countries.

Our commercial capabilities have also expanded into Canada through our own affiliate and into Latin America through a distribution partner.

In the Asia Pacific region, we have launched, or are planning to launch our products, including in China, Australia and other key countries.

All together, BRUKINSA ® has been approved in 45 countries, with additional filings pending or planned.

We aspire to establish our reputation globally as a leading biotechnology company by continuing to deliver highly effective and differentiated medicines in the United States, China, Europe, and other international markets.

Broad accessibility.

We believe that our commercial scale in China, potentially lower upfront development costs through China-inclusive clinical development, sizeable portfolio of innovative therapies, and overall commercial expertise in serving large, underserved populations give us a unique advantage and create an opportunity for us to be an early mover in providing innovative medicines at affordable prices to many geographies that are not traditionally the focus for pharmaceutical or biotechnology companies.

We believe that our commercial scale in China, potentially lower costs and faster speed in clinical development, sizeable portfolio of innovative product candidates, and overall commercial expertise in serving large, underserved populations give us a unique competitive advantage and create an opportunity for us to be an early mover in providing innovative medicines at more affordable prices to many geographies that are not traditionally the focus for international pharmaceutical or biotechnology companies.

We plan to focus our long-term strategy on seeking approvals of our portfolio compounds globally and building clinical development and commercial capabilities in these markets, either alone or through our collaborators.

2 unchanged sentences

PRODUCT LEAD INDICATIONS MECHANISM OF ACTION REGULATORY STATUS BEIGENE COMMERCIAL RIGHTS PARTNER

R/R MCL (U.S.) 1 / R/R MCL 2 and R/R CLL/SLL 2 (China)

BTK inhibitor Approved in the U.S.

and China Global N/A

tislelizumab 4

1L Squamous NSCLC/ R/R classical Hodgkin’s lymphoma 2 / R/R PD-L1+ urothelial carcinoma 2

Anti-PD-1 antibody Approved in China Outside North America, Japan, EU and six other European countries 4

pamiparib 2L+ BRCA-mutated ovarian cancer PARP inhibitor NDA accepted in China Global N/A

R/R MCL 1 , WM & R/R MZL 1 ;

R/R MCL 2 , R/R CLL/SLL 2 & R/R WM 2 ;

BTK inhibitor Approved in the U.S., China, EU and other markets Global N/A

tislelizumab 1L Squamous and Non-Squamous NSCLC/ 2/3 L NSCLC/ R/R classical Hodgkin’s lymphoma 2 / 2/3 L HCC 2 / R/R PD-L1+ UC 2

Anti-PD-1 antibody Approved in China;

BLA accepted in U.S.

Outside North America, Japan, EU and six other European countries

pamiparib 3L BRCA-mutated ovarian cancer 2

PARP inhibitor Approved in China Global N/A

Giant cell tumor of bone 2 / Skeletal Related Events (SREs) 2

Anti-RANK ligand antibody Approved in China Mainland China

Acute lymphocytic leukemia Anti-CD19 x anti-CD3 bispecific T-cell engager (BiTE) Approved in China Mainland China

Multiple myeloma Proteasome inhibitor NDA accepted in China Mainland China

Breast cancer Microtubule inhibitor Approved in China 3

Mainland China

R/R Acute lymphocytic leukemia 2

Anti-CD19 x anti-CD3 bispecific T-cell engager (BiTE) Approved in China Mainland China

R/R Multiple myeloma 2

Proteasome inhibitor Approved in China Mainland China

R/R adult multiple myeloma, newly diagnosed multiple myeloma, previously treated follicular lymphoma Anti-angiogenesis, immuno-modulation Approved in China Mainland China

Myelodysplastic syndromes, acute myeloid leukemia, chronic myelomonocytic leukemia DNA hypomethylation Approved in China Mainland China

Idiopathic multicentric Castleman disease IL-6 antagonist BLA accepted in China Greater China

High-risk neuroblastoma Anti-GD2 antibody BLA accepted in China Mainland China

BAT1706 (Avastin biosimilar) Colorectal, lung, liver cancers Anti-VEGF antibody BLA accepted in China Greater China

Idiopathic multicentric Castleman disease IL-6 antagonist Approved in China Greater China

High-risk neuroblastoma 2

Anti-GD2 antibody Approved in China Mainland China

POBEVCY ® (Avastin biosimilar)

Colorectal and lung cancers Anti-VEGF antibody Approved in China Greater China

TAFINLAR ® (dabrafenib)

BRAF inhibitor Approved in China China Broad Markets 7

MEKINIST ® (trametinib)

MEK inhibitor Approved in China China Broad Markets 7

VOTRIENT ® (pazopanib)

Advance renal cell carcinoma VEGFR inhibitor Approved in China China Broad Markets 7

AFINITOR ® (everolimus)

Advanced renal cell carcinoma 6

mTOR inhibitor Approved in China China Broad Markets 7

ZYKADIA ® (ceritinib)

ALK + NSCLC ALK inhibitor Approved in China China Broad Markets 7

Approved under accelerated approval.

2 unchanged sentences

Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

As announced previously, the NMPA suspended the importation, sales and use of ABRAXANE ® (nanoparticle albumin-bound paclitaxel) in China supplied to BeiGene by Celgene Logistics Sàrl, a Bristol Myers Squibb (BMS) company.

Tislelizumab collaboration with Novartis announced January 2021.

The transaction is expected to close in the first quarter of 2021, subject to expiration or early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

The approval is applicable to all 27 EU member states, plus Iceland, Lichtenstein and Norway.

For patients with unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic therapy.

TAFINLAR and MEKINIST are being investigated in combination by Novartis for NSCLC indications.

Following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy.

Rights to promote and market in China's broad markets pursuant to a Market Development Agreement with an affiliate of Novartis Pharma AG dated December 19, 2021, subject to transfer of responsibilities pursuant to the terms of the agreement.

Abbreviations:

ALK = anaplastic lymphoma kinase;

BLA = Biologics License Application;

BRAF = B-rapidly accelerated fibrosarcoma;

CLL = chronic lymphocytic leukemia;

HCC = hepatocellular carcinoma;

MCL = mantle cell lymphoma;

MEK = mitogen-activated protein kinase (MAPK) / Extracellular-signal regulated kinase (ERK);

mTOR = Mammalian target of rapamycin;

MZL = marginal zone lymphoma;

NSCLC = non-small cell lung cancer;

R/R = relapsed / refractory;

RT = radiotherapy;

SLL = small lymphocytic lymphoma;

UC = urothelial carcinoma;

VEGFR = vascular endothelial growth factor receptor;

WM = Waldenström’s macroglobulinemia

We commercialize the following internally developed cancer medicines:

BRUKINSA ® is a second-generation small molecule BTK inhibitor designed to maximize BTK occupancy and minimize off-target binding effects.

We are marketing BRUKINSA ® in the U.S.

BRUKINSA ® received accelerated approval in the United States as a treatment for MCL in adult patients who have received at least one prior therapy (November 2019), as well as conditional approval in China for adult patients with MCL who have received at least one prior therapy and adult patients with CLL or SLL who have received at least one prior therapy (June 2020).

In China, we have filed a supplemental new drug application ("sNDA") for BRUKINSA ® for the treatment of patients with relapsed/refractory ("R/R") Waldenström’s macroglobulinemia ("WM"), and that application is pending under priority review.

We have also filed additional applications for approval in the European Union ("EU"), Australia and Canada, for R/R WM and Australia, Canada and Israel for R/R mantle cell lymphoma ("MCL").

In December 2020, we announced inclusion of BRUKINSA ® in the updated National Reimbursement Drug List ("NRDL") by the China National Healthcare Security Administration ("NHSA") for BRUKINSA ® ’s approved indications.

Market Opportunity and Competition

BRUKINSA ® is a second-generation small molecule inhibitor of Bruton’s Tyrosine Kinase (BTK) designed to maximize BTK occupancy and minimize off-target binding effects.

BTK is a key component of the B-cell receptor (BCR) signaling pathway and is an important regulator of cell proliferation and cell survival in various lymphomas.

BTK inhibitors block BCR-induced BTK activation and its downstream signaling, leading to growth inhibition and cell death in certain malignant white blood cells called B-cells.

Zanubrutinib is an orally active inhibitor that covalently binds to BTK, resulting in irreversible inactivation of the enzyme.

We are marketing BRUKINSA ® in the United States, China, Europe, the United Kingdom, Canada, Australia and other markets.

In the United States, BRUKINSA ® received accelerated approval as a treatment for mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (November 2019), and has since also been approved for patients with Waldenström’s macroglobulinemia (WM) and relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.

The MCL and MZL indications were 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 a confirmatory trial.

In addition, a supplemental new drug application (sNDA) has been accepted for review by the U.S.

Food and Drug Administration (FDA) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with a PDUFA date of October 22, 2022.

In Europe, BRUKINSA ® received approval from the European Commission (EC) for the treatment of adult patients with WM who have received at least one prior therapy or for the first-line treatment of patients unsuitable for chemo-immunotherapy.

The approval is applicable to all 27 European Union (EU) member states, plus Iceland, Liechtenstein and Norway.

BRUKINSA ® has also been approved in the U.K.

and Switzerland.

In addition, two marketing authorization applications have been accepted for review by the European Medicines Agency (EMA) for the treatment of patients with MZL and for the treatment of patients with CLL.

In China, BRUKINSA has received conditional approval for adult patients with MCL who have received at least one prior therapy and adult patients with CLL or SLL who have received at least one prior therapy and for the treatment of patients with R/R WM.

In addition, an sNDA has been accepted for review by the China National Medical Products Administration (NMPA) for the treatment of adult patients with treatment-naïve CLL or SLL.

In December 2021, we announced the inclusion of BRUKINSA ® for WM in the updated National Reimbursement Drug List (NRDL) by the China National Healthcare Security Administration (NHSA).

Currently, all three approved indications for BRUKINSA ® are included in the NRDL.

BRUKINSA® is also approved in Australia for WM and MCL, in Canada for WM, MCL and R/R MZL, and in South Korea for R/R MCL and R/R WM and numerous other markets (a total of 45 countries as of February 28, 2022).

Market Opportunity

Lymphomas are blood-borne cancers involving lymphatic cells of the immune system.

2 unchanged sentences

B-cell lymphomas make up approximately 85% of NHLs and comprise a variety of specific diseases involving B-cells at differing stages of maturation or differentiation.

According to statistics from the Surveillance, Epidemiology and End Results (SEER) program of the U.S.

National Cancer Institute, there were 77,240 new NHL cases and 19,940 deaths in 2020 in the United States, and of these NHL cases the incidence of CLL was 21,040 cases and there were 4,060 deaths from CLL.

Similar SEER analyses calculated U.S.

incidence rates of 3,000 for MCL and 1,350 for WM.

According to the China National Central Cancer Registry ("NCCR"), International Agency for Research on Cancer ("IARC"), and Frost and Sullivan ("F&S") research, in China, the number of new cases of NHL reached 90,000 in 2019.

The compound annual growth rate from 2015 to 2019 was 2.6%, and the number of new cases of NHL is expected to reach 102,000 and 116,000 in 2024 and 2030, respectively.

In China, diffuse large B-cell lymphoma ("DLBCL") is the most common NHL subtype, accounting for 41.0%, while follicular lymphoma and MCL are the other two largest subtypes of lymphoma, accounting for 6.1% and 3.4%, respectively.

Conventional methods of treating lymphomas vary according to the specific disease or histology, but generally include chemotherapy, antibodies directed at CD20, a molecular marker found on the surface of B-cells, and, less frequently, radiation.

Recently, significant progress has been made in the development of new therapies for lymphomas, including BTK inhibitors, the phosphoinositide 3-kinase ("PI3K") inhibitors, idelalisib, copanlisib and duvelisib, and the Bcl-2 inhibitor, venetoclax.

The BTK inhibitor IMBRUVICA ® (ibrutinib) was first approved by the U.S.

Food and Drug Administration ("FDA") in 2013 for the treatment of patients with MCL who have received at least one prior therapy.

Since that time, ibrutinib has received supplemental FDA approvals for the treatment of patients with CLL/SLL, CLL/SLL patients with 17p deletion, patients with WM, patients with marginal zone lymphoma ("MZL") who have received at least one prior anti-CD20-based therapy, patients with chronic graft versus host disease after failure of one or more lines of systemic therapy, in combination with rituximab in WM, and in combination with obinutuzumab in CLL/SLL.

Ibrutinib is also approved by the European Medicines Agency ("EMA") for the treatment of patients with MCL, CLL and WM.

Ibrutinib has been approved in over 90 countries and regions, and it was approved and launched in China at the end of 2017 for the treatment of patients with R/R CLL/SLL and R/R MCL.

Subsequently, in July 2018, ibrutinib was also approved for first-line CLL/SLL.

Another BTK inhibitor, CALQUENCE ® (acalabrutinib), was approved by the FDA in 2017 under accelerated approval for the treatment of patients with MCL who have received at least one prior therapy, and in November 2019 for use in adults with CLL/SLL as a single agent or in combination with obinutuzumab.

In 2020, global revenues for BTK inhibitors were approximately $7.1 billion according to published reports.

In 2021, global revenues for BTK inhibitors were approximately $8 billion according to published reports, including approximately $5.5 billion in the United States.

Global revenues are projected to be more than $15 billion in 2026 according to published reports.

Tislelizumab is a humanized IgG4 monoclonal antibody against the immune checkpoint receptor programmed cell death protein 1 (PD-1) that we specifically designed to minimize binding to Fc receptor gamma (FcγR), which is believed to play an essential role in activating phagocytosis in macrophages, to minimize its negative impact on T effector cells.

Tislelizumab is approved in China in six indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy, for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, and for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy.

The China National Medical Products Administration (NMPA) also granted conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies, 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, and for the treatment of patients with hepatocellular carcinoma (HCC) who have received at least one systemic therapy.

Full approval for these indications is contingent upon results from ongoing randomized, controlled, confirmatory clinical trials.

Tislelizumab was included in the NRDL in 2020 for cHL and UC and in 2021 for non-squamous NSCLC, squamous NSCLC and HCC, covering all of its five eligible approved indications.

In addition, we have submitted three supplemental Biologics License Applications (BLAs) for tislelizumab that are under review by the Center for Drug Evaluation (CDE) of the NMPA, including for patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors, for the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have disease progression following or are intolerant to first-line standard chemotherapy, and for first-line treatment of patients with recurrent or metastatic nasopharyngeal cancer (NPC).

We are evaluating tislelizumab in a broad pivotal clinical program for both solid tumor and hematological indications, both globally and in China.

Tislelizumab is approved in China for the treatment of patients with classical Hodgkin’s Lymphoma ("cHL") who have received at least two prior therapies (December 2019);

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 (April 2020);

and the first-line treatment of patients with advanced squamous non-small cell lung cancer ("NSCLC") in combination with chemotherapy (January 2021).

In addition, we have filed sNDAs in China for tislelizumab for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy and for previously treated patients with unresectable hepatocellular carcinoma ("HCC").

In December 2020, we announced the inclusion of tislelizumab in the updated NRDL by the China NHSA in tislelizumab’s approved cHL and UC indications.

In January 2021, we announced a collaboration and license agreement with Novartis Pharma AG to develop, manufacture and commercialize tislelizumab in the United States, Canada, Mexico, the EU, UK, Norway, Switzerland, Iceland, Liechtenstein, Russia and Japan (the "Novartis Territory").

The transaction is expected to close in the first quarter of 2021, subject to expiration or early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

Upon closing of the collaboration, we will receive an upfront payment of $650 million and are eligible to receive up to $1.3 billion in regulatory milestones, $250 million in potential sales milestones and royalties on future sales of tislelizumab in the Novartis Territory.

We retained worldwide rights to commercialize our proprietary products in combination with tislelizumab.

Market Opportunity and Competition

A number of PD-1 or PD-L1 antibody medicines have been approved by the FDA.

These include Merck’s KEYTRUDA ® (pembrolizumab), BMS’s OPDIVO ® (nivolumab), Roche’s TECENTRIQ ® (atezolizumab), AstraZeneca’s IMFINZI ® (durvalumab), Pfizer and Merck Sereno’s BAVENCIO ® (avelumab), and Regeneron and Sanofi’s LIBTAYO ® (cemiplimab).

In the global setting, several PD-1 or PD-L1 antibody agents are in late-stage clinical development in addition to tislelizumab, such as GlaxoSmithKline’s dostarlimab and Pfizer’s sasanlimab.

In China, as of February 1, 2021, there are five other approved PD-1 antibodies, OPDIVO ® (nivolumab) and KEYTRUDA ® (pembrolizumab), as well as Junshi’s TUOYI (toripalimab), Innovent’s TYVYT (sintilimab), and Hengrui’s AIRUIKA ® (camrelizumab), and there are two approved PD-L1 antibody agents AstraZeneca's IMFINZI ® (durvalumab) and Roche's TECENTRIQ ® (atezolizomab).

There are approximately 40 more PD-1 and PD-L1 agents in clinical development in China.

Globally, the top four PD-1/PD-L1 antibody medicines had sales of approximately $26.5 billion in 2020 based on public reports.

We believe that there is a large commercial opportunity in China for PD-1 and PD-L1 antibody medicines.

Currently available clinical data suggest that some of the most prevalent cancers in China, such as lung, gastric, liver and esophageal cancer, are responsive to this class of agents.

According to the World Health Organization's GLOBOCAN online database, in 2018 China suffered 39%, 50%, 47%, and 56% of all deaths from lung, gastric, liver, and esophageal cancers, respectively, in the world.

Collectively, these four tumor types comprised over 2.3 million new cases in 2016 in China alone, according to Chen et al.

In addition, China has a higher proportion of PD-1 responsive tumors in its total annual cancer incidence in comparison to other geographies like the United States or Europe.

According to Chen et al.

2016, the annual incidence of the top ten PD-1 responsive tumors in China is estimated to be 3.0 million out of 4.3 million in total annual cancer incidence.

In comparison, the estimated annual incidence of the top ten PD-1 responsive tumors is 0.9 million out of 1.7 million in total annual cancer incidence in the United States, and 0.9 million out of the 1.8 million total in the EU5 countries (United Kingdom, France, Germany, Spain and Italy) according to the SEER program of the U.S.

National Cancer Institute and the World Health Organization.

Pamiparib is an investigational, selective small molecule inhibitor of poly ADP-ribose polymerase 1 ("PARP1") and PARP2 enzymes.

We have 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, we announced a collaboration and license agreement with Novartis to develop, manufacture and commercialize tislelizumab in the United States, Canada, Mexico, the EU, UK, Norway, Switzerland, Iceland, Liechtenstein, Russia and Japan (the "Novartis Territory").

We retained worldwide rights to commercialize outside of the Novartis Territory and with our proprietary products in combination with tislelizumab.

In the United States, we have filed a BLA with the FDA for tislelizumab as a treatment for patients with unresectable recurrent locally advanced or metastatic ESCC after prior systemic therapy.

This BLA has a PDUFA target action date of July 12, 2022.

In addition, Novartis has disclosed plans to submit additional marketing applications in its territory.

Market Opportunity

Globally, the top four PD-1/PD-L1 antibody medicines had revenues of approximately $30.5 billion in 2021 based on public reports.

We estimate 2022 China PD1/L1 market (net revenue) will amount to approximately $2.4 billion.

Global revenues are projected to be more than $50 billion by 2025 according to published reports, driven by multiple factors including indication expansion, approvals and adoptions in earlier lines of therapies, further market penetration, and extension of duration of therapy.

Pamiparib is a, selective small molecule inhibitor of poly ADP-ribose polymerase 1 (PARP1) and PARP2 enzymes.

Pamiparib has demonstrated pharmacological properties such as brain penetration and PARP-DNA complex trapping in preclinical models.

We are evaluating pamiparib as a potential monotherapy and in combinations for the treatment of various solid tumors.

A new drug application ("NDA") for pamiparib for patients with ovarian cancer ("OC") has been accepted and granted priority review in China by the Center for Drug Evaluation ("CDE") of the NMPA, and is currently pending approval.

Market Opportunity and Competition

Many tumor types have been shown to be responsive to PARP inhibitors, including OC, breast cancer, prostate cancer, and gastric cancer ("GC").

Pamiparib is currently in global clinical development as a monotherapy or in combination with other agents for a variety of solid tumor malignancies.

To date, more than 1,300 patients have been enrolled in clinical trials of pamiparib.

In China, pamiparib received conditional approval for treatment of patients with germline BRCA (gBRCA) mutation-associated recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy in May 2021.

Full approval for this indication is contingent upon results from ongoing corroborative trials confirming the clinical benefit of pamiparib in this population.

Pamiparib was included in the 2021 NRDL in its approved indication.

Market Opportunity

Many tumor types have been shown to be responsive to PARP inhibitors, including ovarian cancer (OC), breast cancer, prostate cancer, and gastric cancer (GC).

PARP inhibitors have demonstrated encouraging activity both in R/R patients as well as in the maintenance setting.

In the United States, in 2020 there were approximately 21,750 new cases of OC, 276,480 new cases of breast cancer, and 27,600 new cases of GC, according to the U.S.

National Cancer Institute's SEER online database.

In China, there were approximately 52,000 new cases of OC, 326,000 new cases of breast cancer, and 456,000 new cases of GC in 2019, according to NCCR, IARC and F&S research.

A number of PARP inhibitors have been approved by the FDA.

These include AstraZeneca’s LYNPARZA ® (olaparib), Clovis Oncology’s RUBRACA ® (rucaparib), GlaxoSmithKline’s ZEJULA ® (niraparib), and Pfizer’s TALZENNA ®

(talazoparib).

AbbVie’s veliparib is in late-stage development.

In 2020, global sales of the PARP class were approximately $2.4 billion according to company reports.

In China, AstraZeneca received approval for olaparib in August 2018.

Zai Labs obtained development and commercial rights for niraparib in China, and its NDA was approved by the NMPA in December 2019.

Fluzoparib from Hengrui/Hansoh was approved in December 2020.

We are currently commercializing, or plan to commercialize, the following cancer medicines in China under an exclusive license from Amgen:

6 unchanged sentences

The patients experience pain, swelling, and limitation of joint movement at the primary site.

In China, there were 2,086 new cases of GCTB in 2019, according to the China NCCR, IARC, and F&S research.

In China, there were 2,086 new cases of GCTB in 2019, according to the China NCCR, IARC, and Frost & Sullivan research.

To date, XGEVA ® is the only approved therapy for the treatment of GCTB.

2 unchanged sentences

Bone metastases cause pain, compromised quality of life, and SREs, which include pathologic fracture, the need for radiation or surgery to bone, hypercalcemia of malignancy, and spinal cord compression.

Both XGEVA ® and bisphosphonates reduce the morbidity of metastatic bone disease, mainly by decreasing SREs.

XGEVA ® and bisphosphonates, two different classes of anti-resorptive, can reduce the morbidity of metastatic bone disease, mainly by decreasing SREs through different mechanisms of actions.

Similar to bone metastases in patients with solid tumors, multiple myeloma has a major feature of osteolytic bone disease that can lead to severe disability and morbidity, including SREs.

XGEVA ® is also indicated for the prevention of SREs in patients with multiple myeloma.

In China, there are a number of biosimilars for denosumab in clinical development, including from Shandong Boan Biotechnology Co., Qilu Pharmaceutical Co., and Shanghai Henlius Biotech Co.

BLINCYTO ® (blinatumomab), a bispecific CD-19 directed CD3 T-cell engager, is the first and only approved bi-specific T-cell engager (BiTE) immunotherapy.

1 unchanged sentence

In China, BLINCYTO ® received conditional approval as a treatment for adult patients with R/R ALL in December 2020.

We expect to begin commercializing BLINCYTO ® in the first half of 2021.

We began commercializing BLINCYTO ® in the August 2021.

ALL is the most common childhood malignancy and accounts for approximately one-quarter of all childhood malignancies.

5 unchanged sentences

KYPROLIS ® (carfilzomib), a proteasome inhibitor, has been approved in over 60 countries for use in patients with R/R multiple myeloma (MM).

It has been filed in China as a treatment for patients with MM, and the NDA has been accepted by the NMPA and is pending approval.

It was approved in China as a treatment for patients with R/R MM in July 2021 and we began commercializing KYPROLIS ® in January 2022.

In the class of proteasome inhibitors, VELCADE ® has been marketed by Johnson & Johnson in China since 2006 and NINLARO ® (ixazomib) has been marketed by Takeda in China since 2018.

1 unchanged sentence

We commercialize the following cancer medicines in China under an exclusive license from BMS:

ABRAXANE ® (paclitaxel albumin-bound particles for injectable suspension) is a solvent-free chemotherapy product which was developed using a proprietary nanoparticle albumin-bound (nab ® ) technology platform.

This protein-bound chemotherapy agent combines paclitaxel with albumin.

Globally, ABRAXANE ® is approved for uses in breast cancer, NSCLC, pancreatic cancer, and GC, with geographic differences in labeling.

In China, ABRAXANE ® is approved for use in metastatic breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy.

Prior therapy should have included an anthracycline unless clinically contraindicated.

It is also approved for use in metastatic adenocarcinoma of the pancreas in combination with gemcitabine.

There were approximately 326,000 new cases of breast cancer and 108,000 new cases of pancreatic cancer in China in 2019, according to the China NCCR, IARC, and F&S research.

Targeted therapy, hormone therapy and chemotherapy are three main strategies to treat different types of breast cancer.

The taxanes marketed in China include two branded solvent-based formulations of paclitaxel (TAXOL ® and ANZATAX ® ), one branded formulation of docetaxel (TAXOTERE ® ), one paclitaxel liposome (LIPUSU ® ), one albumin-bound paclitaxel (ABRAXANE ® ), and a number of generic forms of solvent-based taxanes and ABRAXANE ® , including albumin-bound paclitaxel products from CSPC Pharmaceutical Group Limited, Jiangsu Hengrui Medicine Co., Ltd., Qilu Pharmaceutical Co., Ltd., and Sichuan Kelun Pharmaceutical Co., Ltd.

On March 25, 2020, the NMPA suspended the importation, sales and use of ABRAXANE ® in China supplied to us by BMS.

This suspension is based on inspection findings at BMS’s contract manufacturing facility in the United States.

We did not have any sales of ABRAXANE ® in 2020 following the suspension and do not expect revenue from ABRAXANE ® until the NMPA lifts its suspension on the importation, sale and use of ABRAXANE ® and qualified medicine is manufactured and available for sale in China.

We are working with BMS to restore supply as soon as possible, including through BMS’s remediation efforts at the current manufacturing site and application to qualify an alternative manufacturing site for China supply.

We do not know when the NMPA suspension of ABRAXANE ® will be lifted and when we will be able to re-commence sales of ABRAXANE ® in China.

REVLIMID ® (lenalidomide) is an oral immunomodulatory medicine that was approved in China in 2013 for the treatment of multiple myeloma (MM) in combination with dexamethasone in adult patients who have received at least one prior therapy.

In February 2018, REVLIMID ® received NMPA approval of a new indication for the treatment of MM in combination with dexamethasone in adult patients with previously untreated MM who are not eligible for transplant.

In 2019, there were approximately 20,700 new cases of MM in China in 2019, according to the China NCCR, IARC, and F&S research.

In 2019, there were approximately 20,700 new cases of MM in China in 2019, according to the China NCCR, IARC, and Frost & Sullivan research.

With a growing aging population and improving diagnosis, China has seen a steady increase in MM incidence.

The main treatments for MM in China include VELCADE ® , which is a proteasome inhibitor marketed by Johnson & Johnson in China since 2006, REVLIMID ® , NINLARO ® (ixazomib), an oral proteasome inhibitor developed by Takeda, DARZALEX ® (daratumumab), an infusion CD38 monoclonal antibody marketed by Johnson & Johnson since 2019, and a number of generic forms of VELCADE ® and REVLIMID ® , including generic lenalidomide from Shuanglu Pharmaceutical Co., Ltd., Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Qilu Pharmaceutical Co., Ltd., and Yangtze River Pharmaceutical Group Co., Ltd.

Chinese guidelines recommend lenalidomide as a standard of care for the treatment of R/R and newly diagnosed MM as well as in the maintenance setting.

Chinese Society of Clinical Oncology (CSCO) guidelines recommend lenalidomide as a standard of care for the treatment of R/R and newly diagnosed MM as well as in the maintenance setting.

REVLIMID ® was listed on the NRDL in June 2017.

5 unchanged sentences

MDSs are among the most common hematological malignant diseases.

In 2019, there were approximately 22,100 new cases of MDS in China in 2019, according to the China NCCR, IARC, and F&S research.

In 2019, there were approximately 22,100 new cases of MDS in China in 2019, according to the China NCCR, IARC, and Frost & Sullivan research.

The typical age of onset is 70 years.

The higher-risk MDS (intermediate-2 and high-risk MDS) is considered fatal because the median overall survival is only

0.4-1.1 years, and nearly 30% of these patients progress to AML.

The higher-risk MDS (intermediate-2 and high-risk MDS) is considered fatal because the median overall survival is only 0.4-1.1 years, and nearly 30% of these patients progress to AML.

In China, the main treatments for intermediate-2 and high-risk MDS are conventional care regimen (CCR) (best supportive care, low-dose cytarabine and intensive chemotherapy), and hypomethylating agents (HMAs).

1 unchanged sentence

In the past several years, at least nine decitabine generics have become available.

In 2017, decitabine was listed in the NRDL.

There are also two approved generic forms of azacitidine from manufacturers Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

3 unchanged sentences

VIDAZA ® was listed in the NRDL in October 2018.

We are planning to commercialize the following cancer medicines in China under an exclusive license from EUSA Pharma:

SYLVANT ® (siltuximab), an interleukin-6 ("IL-6") antagonist, was approved as a treatment for patients with idiopathic multicentric Castleman disease ("iMCD") who are human immunodeficiency virus ("HIV") negative and human herpesvirus-8 (HHV-8) negative.

We announced on January 25, 2021 that the biologics license application ("BLA") for siltuximab was accepted by the China NMPA and granted priority review.

In addition to REVLIMID ® and VIDAZA ® , we previously commercialized ABRAXANE ® (paclitaxel albumin-bound particles for injectable suspension), a solvent-free chemotherapy approved for use in certain patients with metastatic breast cancer, in China until March 2020.

On March 25, 2020, the NMPA suspended the importation, sales and use of ABRAXANE ® in China supplied to us by BMS, and the drug was subsequently recalled by BMS and is not currently available for sale in China.

This suspension was based on inspection findings at BMS’s contract manufacturing facility in the United States.

Additionally, in October 2021, BMS provided 180-days' notice to us, which we dispute, purporting to terminate our license to market ABRAXANE ® in China.

We have not had any sales of ABRAXANE ® since the suspension and do not expect future revenue from ABRAXANE ® .

We have initiated an arbitration proceeding against BMS asserting that it has breached and continues to breach the terms and conditions of the license and supply agreement.

For additional information, please see the section of this report titled “Legal Proceedings”.

We are commercializing or planning to commercialize the following medicines in China under an exclusive license from EUSA Pharma:

SYLVANT ® (siltuximab), an interleukin-6 (IL-6) antagonist, was approved as a treatment for patients with idiopathic multicentric Castleman disease (iMCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8

(HHV-8) negative.

SYLVANT ® was approved in China in December 2021 for the treatment of adult patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpes virus-8 (HHV-8) negative, also known as idiopathic MCD (iMCD).

It is estimated that approximately 6,500 to 7,700 new cases of Castleman disease (CD) are diagnosed each year in the United States, of which approximately 75% are estimated to be unicentric and the remaining 25% are estimated to be HHV-8-associated multicentric Castleman disease (MCD) or HHV-8-negative/idiopathic MCD.

2 unchanged sentences

There are few published data regarding the epidemiology in China, but there are no clear associations between epidemiology and particular ethnicities.

SYLVANT ® is the preferred treatment for patients with iMCD according to the NCCN guidelines, and when SYLVANT ® is not available, tocilizumab, a monoclonal antibody targeted against the IL6 receptor, could be used to treat iMCD.

QARZIBA ® ▼ (dinutuximab beta), a mouse-human chimeric monoclonal GD2 antibody, was approved as a treatment of high-risk neuroblastoma in patients aged 12 months and above who have previously received induction chemotherapy and achieved at least a partial response (PR).

We announced on November 9, 2020 that the BLA for dinutuximab was accepted by the China NMPA and granted priority review.

QARZIBA ® ▼ (dinutuximab beta), a mouse-human chimeric monoclonal GD2 antibody, was granted conditional approval by the NMPA for the treatment of high-risk neuroblastoma in patients aged 12 months and above who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with a history of relapsed or refractory (R/R) neuroblastoma with or without residual disease.

Neuroblastoma is almost exclusively a disease of children.

1 unchanged sentence

There are limited publications on the epidemiology of the disease, and it is estimated there are 5-9 cases of neuroblastoma in one million children under the age of 19.

High-risk neuroblastoma patients are managed with induction chemotherapy, surgical resection, tandem autologous hematopoietic stem cell transplantation, radiotherapy, and maintenance with biologic/immunologic therapy, e.g., dinutuximab.

We are planning to commercialize the following product in China under an exclusive license from Bio-Thera:

BAT1706 is an investigational biosimilar to Avastin ® (bevacizumab) that is in development by Bio-Thera Solutions, Ltd., a commercial-stage biopharmaceutical company located in Guangzhou, China.

We began commercializing QARZIBA ® ▼ in December 2021.

We commercialize the following product in China under an exclusive license from Bio-Thera:

POBEVCY (BAT1706)

POBEVCY ® is a biosimilar to Avastin ® (bevacizumab) developed by Bio-Thera Solutions, Ltd., a commercial-stage biopharmaceutical company located in Guangzhou, China.

In China, Avastin ® is approved for the treatment of patients with metastatic colorectal cancer, liver cancer and NSCLC.

We have acquired the right to develop, manufacture and commercialize BAT1706 in China, including Hong Kong, Macau, and Taiwan.

BAT1706 is an investigational compound and has not received regulatory approval in any country.

The China NMPA accepted the BLA for BAT1706 in June 2020.

Bio-Thera has submitted a marketing authorization application ("MAA") to the EMA and submitted a BLA to the FDA in November 2020.

In China, two bevacizumab biosimilars have been approved, marked by Qilu Pharmaceutical Co., Ltd.

and Innovent Biologics, Inc., and there are also a number of bevacizumab biosimilars in development, including by Sunshine Guojian Pharmaceutical Co., Ltd.

and Shanghai Henlius Biotech Inc.

POBEVCY ® was approved by the NMPA in China in November 2021 and launched in late 2021 for the treatment of patients with advanced, metastatic or recurrent NSCLC and metastatic colorectal cancer.

We have acquired the right to develop, manufacture and commercialize POBEVCY ® in China, including Hong Kong, Macau, and Taiwan.

Bio-Thera submitted a marketing application to the EMA and a BLA to the FDA in November 2020.

In China, three bevacizumab biosimilars have been approved, marked by Qilu Pharmaceutical Co., Ltd.

and Innovent Biologics, Inc., and Shanghai Henlius Biotech Inc., and there are also a number of bevacizumab biosimilars in development, including by Sunshine Guojian Pharmaceutical Co., Ltd.

Reimbursement and Market Access

1 unchanged sentence

In many markets these third parties are government health systems and in some markets such as the United States there are also private payors such as private health insurers and health systems.

During 2020 we commercialized our products in two markets, China and the United States.

In China there is one main payor, the government’s national health care coverage system, which provides Basic Medical Insurance ("BMI") to the majority (greater than 95%) of China’s approximate 1.4 billion people.

There are three types of

coverage plans in China at the national level that depend on if a resident lives in an urban versus rural setting and if they are employed.

In 2021 we commercialized our products in 43 markets.

In China there is one main payor, the government’s national health care coverage system, which provides Basic Medical Insurance (BMI) to the majority (greater than 95%) of China’s approximately 1.4 billion people.

There are three types of coverage plans in China at the national level that depend on if a resident lives in an urban or rural setting and if they are employed.

The different plans have different characteristics in terms of how the plan is paid for and what it covers.

6 unchanged sentences

Typically, inclusion on the C list is accompanied by a discount to the prevailing list price in China for the medicine at the time of inclusion.

The NRDL price for a medicine is its prevailing price in China, but the actual price that is used can be modified at the provincial level.

The NRDL price for a medicine is its prevailing price in China, but the actual reimbursement rate that is used can be modified at the provincial level.

In addition to the NRDL, there are provincial reimbursement drug lists, or PRDLs.

Provinces have been allowed to omit reimbursement for 10-15% of the products on the NRDL in order to direct resources to other products to better serve their specific populations.

This ability is being phased out by 2022 according to a July 2019 NHSA policy memo.

Provinces have been allowed to omit reimbursement for 10-15% of the products and indications on the NRDL in order to direct resources to other products to better serve their specific populations.

This ability is being phased out by 2022 in principle

according to a July 2019 NHSA policy memo.

The PRDLs are thus, at this time, the official list of what is available to China’s citizens.

In addition to insurance reimbursement, patients can elect to self-pay for needed medicines.

Several of BeiGene’s medicines are listed on the NRDL.

In the most recent NRDL list announced in December 2020, the following medicines were included in the NRDL, effective March 1, 2021:

• Tislelizumab for the treatment of patients with CHL who received at least two prior therapies (approved in December 2019);

• Tislelizumab for the treatment of patients with locally advanced or metastatic 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 (approved in April 2020);

• BRUKINSA ® for the treatment of adult patients with MCL who have received at least one prior therapy (approved in June 2020);

• BRUKINSA ® for the treatment of adult patients with CLL/SLL who have received at least one prior therapy (approved in June 2020);

• XGEVA ® for the treatment of adults and skeletally mature adolescents with GCTB that is unresectable or where surgical resection is likely to result in severe morbidity (Amgen obtained approval of XGEVA in China in May 2019).

Several of our medicines are listed on the NRDL.

In the most recent NRDL list announced in December 2021, the following medicines were included in the NRDL, effective January 1, 2022:

• Tislelizumab in all five of its eligible approved indications – three new indications in 2021 and two indications included last year:

– For use in combination with pemetrexed and platinum chemotherapy as a first-line treatment in patients with unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC), with EGFR genomic tumor aberrations negative and ALK genomic tumor negative (approved in June 2021 and included in the NRDL in 2021);

– For the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with at least one systemic therapy (conditionally approved in June 2021 and included in the NRDL in 2021);

– For use in combination with paclitaxel and carboplatin as a first-line treatment in patients with unresectable, locally advanced or metastatic squamous NSCLC (approved in January 2021 and included in the NRDL in 2021);

– 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 (conditionally approved in April 2020 and included in NRDL in 2020);

– For the treatment of patients with classical Hodgkin’s lymphoma (cHL) who have received at least two prior therapies (conditionally approved in December 2019 and included in the NRDL in 2020).

• BRUKINSA in all three of its approved indications – one new indication in November 2021 and two indications included last year:

– For the treatment of adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy (conditionally approved in June 2021 and included in the NRDL in 2021);

– For the treatment of adult patients with MCL who have received at least one prior therapy (conditionally approved in June 2020 and included in the NRDL in 2020);

– For the treatment of adult patients with chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) who have received at least one prior therapy (conditionally approved in June 2020 and included in the NRDL in 2020).

• Pamiparib was initially included in the NRDL in its approved indication:

– For the treatment of patients with germline BRCA (gBRCA) mutation-associated recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy (conditionally approved in May and included in the NRDL in 2021).

Additionally, two of our medicines were listed in past NRDLs:

REVLIMID ® was included in the 2017 NRDL negotiation list and later received formal inclusion in the 2019 B list, while VIDAZA ® was listed in the 2018 NRDL negotiation list and later received formal inclusion to the 2020 B list.

In 2018, China started a new program to centrally purchase generic medicines for the nation’s health care system called "volume-based procurement", or GPO (group purchasing organization) or "4+7" (4 municipalities and 7 provincial cities) when the program was first piloted in 11 major cities.

In 2018, China started a new program to centrally purchase generic medicines for the nation’s health care system called "volume-based procurement" (VBP), or GPO (group purchasing organization) or "4+7" (4 municipalities and 7 provincial cities) when the program was first piloted in 11 major cities.

After the 2018 pilot program, it was implemented nationally in 2019.

6 unchanged sentences

Usually these programs have been offered to patients who are self-paying.

A typical program provides a certain number of free doses to patients after a certain number of doses have been paid for.

A typical program provides a

certain number of free doses to patients after a certain number of doses have been paid for.

Usually these programs end when a medicine is included in the NRDL.

15 unchanged sentences

zanubrutinib (BTK)

monotherapy R/R MCL (Accelerated Approval in the U.S.

WM (filings accepted in multiple geographies)

R/R MCL, R/R CLL/SLL (approved by NMPA in China June 3, 2020)

1L CLL/SLL, R/R CLL/SLL

monotherapy R/R MCL (approved in multiple geographies)

WM (approved by FDA in the U.S.

R/R MZL (accelerated approval by FDA in the U.S.

9/15/2021, approved by Health Canada 2/18/2022)

R/R MCL, R/R CLL/SLL (conditionally approved by NMPA in China 6/3/2020)

R/R WM (conditionally approved by NMPA in China 6/18/2021)

CLL/SLL (filing accepted by the FDA in the U.S., PDUFA date 10/22/2022)

CLL, MZL (filing accepted by the EMA in the EU)

Lupus nephritis

Previously treated CLL/SLL (ibrutinib acalabrutinib intolerant)

combination +rituximab 1LMCL

combination +rituximab 1L MCL

+obinutuzumab R/R FL

1 unchanged sentence

tislelizumab (PD-1)

monotherapy R/R cHL (approved December 26, 2019), 2L + UC (approved April 10, 2020)

2L NSCLC, 1L HCC, 2L ESCC

monotherapy R/R cHL (conditionally approved 12/26/2019), 2L + UC (conditionally approved 4/10/2020), 2L/3L HCC (conditionally approved 6/23/2021), 2L/3L NSCLC (approved 1/6/2022)

2L/3L MSI-H or dMMR solid tumors, 2L ESCC

2L ESCC (filing accepted by the FDA in the U.S.;

PDUFA date 7/12/2022)

R/R NK/T-cell lymphoma

+ chemo 1L Sq.

NSCLC (approved January 13, 2021)

NSCLC (sNDA accepted June 19, 2020)

1L NPC, 1L SCLC, Stage II/IIIA NSCLC, Localized ESCC

NSCLC (approved 1/13/2021), 1L non-Sq.

NSCLC (approved 6/23/2021)

1L SCLC, Stage II/IIIA NSCLC, Localized ESCC, 1L UC

1L GC, 1L ESCC

1 unchanged sentence

+ zanubrutinib (BTK) B-cell malignancies

pamiparib (PARP) monotherapy 3L gBRCA+ OC

pamiparib ( PARP )

monotherapy 3L gBRCA+ OC (approved 5/7/2021)

2L platinum-sensitive OC maintenance

3 unchanged sentences

(RT/chemo) Glioblastoma

ociperlimab (BGB-A1217, TIGIT + tislelizumab Solid tumors

(RAF Dimer) + mirdametinib B-Raf- or K-RAS/N-RAS-mutated solid tumors

(PD-L1) monotherapy + tislelizumab Solid tumors

DRUG CANDIDATES PROGRAMS DOSE ESC.

DOSE EXPANSION PIVOTAL FILED MARKETED

Phase 1a Phase 1b Phase 2* Phase 2** Phase 3

ociperlimab (TIGIT)

+ tislelizumab 1L NSCLC

R/M Cervical Cancer, R/M ESCC ∧

+ tislelizumab + cCRT 1L SCLC

Stage III unresectable NSCLC

+ tislelizumab + chemo 1L NSCLC

+ tislelizumab + BAT1706 1L HCC

(BRAF Dimer) + mirdametinib B-Raf- or K-RAS/N-RAS-mutated solid tumors

BGB-A425 (TIM-3) monotherapy & + tislelizumab Solid tumors

(PD-L1) monotherapy & + tislelizumab Solid tumors

BGB-A445 (OX40) + tislelizumab Solid tumors

BGB-11417 (Bcl-2) monotherapy & + zanubrutinib B-cell malignancies

BGB-10188 (PI3-ko) mono;

+ dexamethasone & + carfilzomib R/R Multiple Myeloma

+ azacytidine AML, MDS

BGB-10188 (PI3K Delta) mono;

+ tislelizumab;

+ zanubrutinib B-cell malignancies;

BGB-15025 (HPK1) monotherapy & + tislelizumab IND accepted

BGB-15025 (HPK1) monotherapy & + tislelizumab Advanced solid tumors

BGB-23339 (TYK2) monotherapy Inflammation and Immunity

*Some indications will not require a non-pivotal Phase 2 clinical trial prior to beginning pivotal Phase 2 or Phase 3 clinical trials.

**Confirmatory clinical trials post approval are required for accelerated or conditional approvals.

Abbreviations:

1L = first line;

2L = second line;

3L = third line;

AML = acute myeloid leukemia;

Bcl-2 = B-cell lymphoma 2;

BTK = Bruton's tyrosine kinase;

cHL = classical Hodgkin’s lymphoma;

CLL = chronic lymphocytic leukemia;

Dose Esc = dose escalation;

ESCC = esophageal squamous cell carcinoma;

FL = follicular lymphoma;

gBRCA = germline BRCA (Breast Cancer);

GC = gastric cancer;

HCC = hepatocellular carcinoma;

MCL = mantle cell lymphoma;

MZL = marginal zone lymphoma;

NSCLC = non-small cell lung cancer;

NDA = new drug application;

NK = natural killer;

NMPA = National Medical Products Administration;

NPC = nasopharyngeal carcinoma;

OC = ovarian cancer;

PARP = poly ADP-ribose polymerase;

PD-1 = programmed cell death protein 1;

R/R = relapsed / refractory;

RT = radiotherapy;

SLL = small lymphocytic lymphoma;

SCLC = small cell lung cancer;

Sq = squamous;

TIGIT = T-cell immunoreceptor with Ig and ITIM domains;

TMZ = temozolomide;

UC = urothelial carcinoma;

WM = Waldenström’s macroglobulinemia.

†R/R or not suitable for chemo-immunotherapy.

recurrent/metastatic

1 Approved in Canada (3/1/2021);

Australia (10/7/2021);

EU (27 member states) plus Iceland, Lichtenstein, and Norway (11/23/2021);

UK (12/14/2021);

Switzerland (2/17/2022);

South Korea (2/24/2022)

The following table summarizes the status of our in-licensed drug candidates as of February 28, 2022:

DRUG CANDIDATES DESCRIPTION DOSE ESCALATION / EXPANSION PIVOTAL COMMERCIAL RIGHTS

Phase 1 Phase 2* Phase 2^ Phase 3

(KRAS G12C, SM) Solid tumors, NSCLC, CRC China 1

(BCMA, HLE BiTE) MM

(Mcl-1, SM (i.v.)) Hematologic

(Mcl-1, SM (oral)) Hematologic

(CD33, BiTE) AML

(CD33, HLE BiTE) AML

(FLT3, HLE BiTE) AML

(DLL3, HLE BiTE) SCLC

(PSMA, HLE BiTE) Prostate

(STEAP1 XmAb, BiTE) Prostate

COMPOUND (TARGET) / PROGRAM DOSE ESC.

DOSE EXPANSION PIVOTAL COMM.

RIGHTS PARTNER

Phase 1a Phase 1b Phase 2* Phase 2** Phase 3

sotorasib (KRAS G12C) Solid tumors, NSCLC, CRC China

tarlatamab ∧ ∧

pavurutamab ∧ ∧

AMG 176 (Mcl-1, SM) Hematologic malignancies

(CD33) Myeloid malignancies

acapatamab ∧ ∧

(PSMA) Prostate cancer

(STEAPI XmAb) Prostate cancer

(MUC17) GC/GEJC

(Anti-CLDN18.2, BiTE) GC/GEJC

(oral small molecule) Solid tumors

(FAP x 4-1BB, DARPin ® )

(Anti-PD-1 x IL21 mutein) Solid tumors

AMG 650 (oral small molecule) Solid tumors

AMG 506 (FAP x 4-1BB, DARPin ® )

AMG 994 Bispecific antibody Solid tumors

AMG 256 (Anti-PD-1 x IL21 mutein) Solid tumors

Sitravatinib †

(multi-kinase inhibitor) + tislelizumab

NSCLC, RCC, OC, MEL Asia ex-Japan, NZ, AU

NSCLC, RCC, OC, MEL Asia ex-Japan, AU, NZ

Mono + tislelizumab HCC, GC/GEJC

zanidatamab ††

(bispecific HER2 antibody) Breast cancer, GEA Asia ex-Japan, NZ, AU

Biliary tract cancers

(bispecific anti-HER2 ADC) HER2-expressing cancers Asia ex-Japan, NZ, AU

(HER2, bispecific antibody) + chemo + tislelizumab GEA Asia ex-Japan, AU, NZ

Monotherapy Bilary tract cancers

+ chemo, +/- tislelizumab Breast cancer, GC, GEA

ZW49 (HER2, bispecific ADC) HER2-expressing cancers Asia ex-Japan, AU, NZ

(B-RAF) Solid tumors Asia ex-Japan

(CTLA4) Mono, + tislelizumab Tech transfer in progress Global

(anti-CD70) MDS, AML Asia ex-Japan, AU, NZ

(DKK1) + tislelizumab +/- chemo GC/GEJC Asia ex-Japan, AU, NZ

SEA-CD70 (anti-CD70) MDS, AML Asia ex-Japan, AU, NZ

DKN-01 (DKK1) + tislelizumab +/- chemo GC/GEJC Asia ex-Japan, AU, NZ

LBL-007 (LAG-3) + tislelizumab Advanced solid tumors ex-China

vebicorvir ††† (ABI-H0731) ®

(HBV core inhibitor) Chronic Hepatitis B Virus China

Chronic Hepatitis B virus

ABI-H3733 (HBV core inhibitor) Chronic Hepatitis B virus

*Some indications will not require a non-pivotal Phase 2 clinical trial prior to beginning pivotal Phase 2 or Phase 3 clinical trials.

**Confirmatory clinical trials post approval are required for accelerated or conditional approvals.

Collaboration with Amgen.

BeiGene also receives royalties on sales outside China except for sotorasib.

Collaboration with Mirati Therapeutics, Inc.

Collaboration with Zymeworks.

ZW49 study conducted by Zymeworks.

Study conducted by MapKure, a JV with SpringWorks.

Licensed from BioAtla.

Collaboration with SeaGen.

Collaboration with Leap Therapeutics (option to license).

Collaboration with Assembly Biosciences.

∧ BiTE, ∧ ∧ HLE BiTE (Global trials are being conducted outside of China.), † Mirati is also conducting its own clinical studies with sitravatinib, including the Phase 3 SAPPHIRE trial in non-sq NSCLC.

†† ZW25, ††† Assembly is conducting Phase 2 triple combination studies with VBR and a Ph1 study of ABI-H3733.

Abbreviations:

ADC = antibody drug conjugate;

AML = acute myeloid leukemia;

AU = Australia;

BCMA = B-cell maturation antigen;

BiTE = Bi-specific T-cell engager;

B-RAF = B-version Rapidly Accelerated Fibrosarcoma;

BTK = Bruton's tyrosine kinase;

CD## = cluster of differentiation;

CTLA4 = cytotoxic T-lymphocyte-associated protein 4;

DKK1 = Dickkopf protein 1;

DLL3 = delta-like ligand 3;

FAP = familial adenomatous polyposis;

FLT3 = fms-like tyrosine

GEJC = gastro-esophageal junction cancer;

HER2 = human epidermal growth factor receptor 2;

HBV = hepatitis B virus;

HCC = hepatocellular carcinoma;

HLE = half-life extended;

= intravenous;

IL21 = interleukin 21;

KRAS = gene for K version of Ras (rat sarcoma) protein;

Mcl-1 = Myeloid cell leukemia-1;

MEL = melanoma;

MM = multiple myeloma;

NSCLC = non-small cell lung cancer;

NZ = New Zealand;

OC = ovarian cancer;

PD-1 = Programmed cell death protein 1;

PSMA = prostate-specific membrane antigen;

RCC = renal cell carcinoma;

SCLC = small cell lung cancer;

SM = small molecule.

acute myeloid leukemia, HLE BiTE:

Half-life extended Bi-specific T-cell engagers, GC/GEJ:

gastric cancer/gastroesophageal junction, HCC:

hepatocellular carcinoma, IND:

Investigational New Drug, MEL:

melanoma, MM:

multiple myeloma, NHL:

non-Hodgkin's lymphoma, N/SCLC:

non-small cell lung cancer, OC:

ovarian cancer, RCC:

renal cell carcinoma, SM:

small molecule;

(1) By MapKure, a joint venture with SpringWorks Therapeutics

Our Commercial- and Clinical-Stage Drug Candidates

1 unchanged sentence

Historically, we have made available, and we intend to continue to make available, clinical data and/or topline results from clinical trials of our drug candidates in our press releases and/or filings with the U.S.

Securities and Exchange Commission ("SEC") and the Stock Exchange of Hong Kong Limited ("HKEx"), copies of which are available on the Investors section of our website.

Securities and Exchange Commission (SEC), the Stock Exchange of Hong Kong Limited (HKEx), and the Shanghai Stock Exchange (SSE), copies of which are available on the Investors section of our website.

BRUKINSA (zanubrutinib), a BTK Inhibitor

3 unchanged sentences

and sustained 24-hour BTK occupancy in both the peripheral blood and lymph node compartments in patients.

We reported data from our Phase 3 ASPEN study, which compared zanubrutinib with ibrutinib in WM.

While the trial did not achieve statistical significance on its primary endpoint of superiority in complete response and very good partial response (“VGPR”) rates for zanubrutinib compared to ibrutinib, zanubrutinib demonstrated a numerically higher VGPR rate as well as improvements in safety and tolerability.

Mechanism of Action

BTK is a key component of the B-cell receptor ("BCR") signaling pathway and is an important regulator of cell proliferation and cell survival in various lymphomas.

BTK inhibitors block BCR-induced BTK activation and its downstream signaling, leading to growth inhibition and cell death in certain malignant white blood cells called B-cells.

Zanubrutinib is an orally active inhibitor that covalently binds to BTK, resulting in irreversible inactivation of the enzyme.

Overview of Clinical Development Program and Regulatory Status

We received accelerated approval from the FDA in November 2019 for zanubrutinib for the treatment of adult MCL patients who have received at least one prior therapy.

We announced approval from China’s NMPA in June 2020 for use in two indications - the treatment of adult patients with CLL/SLL who have received at least one prior therapy, and the treatment of adult patients with MCL who have received at least one prior therapy.

We have announced filings of BRUKINSA ® with regulatory authorities globally, including in the United States, China, the EU, Canada, and Australia for WM, and in Canada, Australia and Israel for MCL.

As of February 2021, more than 20 marketing authorization applications for BRUKINSA ® have been submitted outside of the United States and China, covering 45 countries and regions, including by BeiGene in the EU and Canada and with support from our five distribution partners:

Adium Pharma S.A.

in Latin America and the Caribbean, NewBridge Pharmaceuticals in the Middle East and North Africa, Erkim in Turkey, Nanolek in Russia, and Medison in Israel.

We have announced BRUKINSA ® approvals around the world, including in the United States, China, the EU, the U.K., Canada, and Australia.

As of February 2022, 43 additional marketing authorization applications for BRUKINSA ® have been submitted, including by BeiGene and with support from our five distribution partners:

Adium Pharma in Latin America and the Caribbean, NewBridge Pharmaceuticals in the Middle East and North Africa, Erkim in Turkey, Nanolek in Russia, and Medison in Israel.

Based on the clinical data to date, we believe that BRUKINSA ® has a potentially best-in-class profile, and we are running a broad global pivotal program in multiple indications, including nine registration or registration-enabling clinical trials.

3 unchanged sentences

We have completed patient enrollment in SEQUOIA and ALPINE.

Our fourth Phase 3 trial is an ongoing Phase 3 confirmatory trial in patients with TN MCL (NCT04002297).

Additionally, we have five filed or ongoing Phase 2 trials that are designed to be registration-enabling, including four monotherapy studies in R/R MCL, R/R WM, R/R CLL/SLL (NCT03206970, NCT03332173, NCT03206918), and R/R MZL (MAGNOLIA, NCT03846427) and an ongoing pivotal Phase 2 trial in combination with GAZYVA ® (obinutuzumab) in patients with R/R FL (ROSEWOOD, NCT03332017), which is designed as a pivotal trial for accelerated or conditional approval and will require a confirmatory study if approved.

Our fourth Phase 3 trial is an ongoing Phase 3 confirmatory trial in patients with treatment-naive (TN) MCL (NCT04002297).

Finally, we are also investigating zanubrutinib in several combination studies in DLBCL and CLL/SLL, including two studies in CLL/SLL investigating venetoclax combinations.

We continue to pursue regulatory approvals for BRUKINSA ® globally.

We expect regulatory decisions for some of the filings this year, including those for certain patients with MCL in the EU, Middle East, South America, Canada, Australia, and Russia, and for patients with WM in the United States, EU, Canada and Australia.

We expect topline results to be available from two of our Phase 3 studies in CLL/SLL, SEQUOIA (as early as 2021) and ALPINE (first half 2022).

The former is examining BRUKINSA ® in 1L CLL/SLL against bendamustine plus rituximab, and the latter is a head-to-head study comparing BRUKINSA ® versus ibrutinib in second line CLL/SLL.

Finally, we expect to complete enrollment in the pivotal Phase 2 ROSEWOOD trial comparing BRUKINSA ® plus obinutuzumab to obinutuzumab alone in R/R follicular lymphoma patients in 2021.

Summary of Clinical Results

As of January 2021, we had enrolled more than 3,100 patients in clinical trials of zanubrutinib, including trials of zanubrutinib in combination with other therapies.

Our first-in-human study is a multi-center, open-label Phase 1 trial being conducted in Australia, New Zealand, the United States, South Korea and Europe to assess the safety, tolerability, pharmacokinetic properties and preliminary activity of zanubrutinib as a monotherapy in patients with different subtypes of B-cell malignancies, such as WM, CLL/SLL, follicular lymphoma ("FL"), and MCL.

The initial results of the dose-escalation phase and dose-expansion phase of this trial demonstrated that, consistent with zanubrutinib’s pharmacokinetic profile, complete and sustained 24-hour BTK occupancy in the blood was observed in all tested patients, starting at the lowest dose of 40 mg once daily ("QD").

In addition, sustained full BTK occupancy was observed in the lymph nodes with the 160 mg twice-daily ("BID") dosing regimen.

We substantially expanded the clinical development program for zanubrutinib based on these early results to include late stage clinical studies in WM, CLL/SLL, MCL, FL and MZL.

In addition, we have several studies ongoing in DLBCL, both monotherapy and combinations, and we have several combination studies in CLL, including combinations with the Bcl-2 inhibitor venetoclax and a planned study with our internally-discovered BCL-2 inhibitor, BGB-14417.

All of the studies discussed below were presented at major medical conferences and were included in press releases issued at the time of the medical conferences and included in our current reports or announcements filed with the SEC and HKEx, respectively.

Those sources have further details on each study.

Waldenström’s Macroglobulinemia - ASPEN Study

In December 2019, we announced topline results from our Phase 3 ASPEN trial of zanubrutinib compared to ibrutinib for the treatment of patients with WM.

We presented the results of the trial at the 2020 Annual Meeting of the American Society of Clinical Oncology ("ASCO").

The ASPEN trial is a randomized Phase 3 trial in 229 patients with WM conducted in 61 centers in Europe, Australia, and the United States.

ASPEN was the largest Phase 3 trial yet conducted in WM and the first comparative trial readout for two BTK inhibitors.

Cohort 1 enrolled 201 patients and randomized 102 to receive zanubrutinib and 99 to receive ibrutinib.

The trial did not achieve statistical significance on its primary endpoint of superiority in CR and VGPR rates for zanubrutinib compared to ibrutinib, but zanubrutinib demonstrated numerically more frequent VGPRs, higher PFS and OS at 12 months, and advantages in safety and tolerability.

Efficacy Zanubrutinib

(N = 83) Ibrutinib

(N = 81) Zanubrutinib

(N = 102) Ibrutinib

VGPR + CR Rate 28.9% 1

PFS (12 month) 92.4% 85.9% 89.7% 87.2%

OS (12 month) 98.8% 92.5% 97.0% 93.9%

Data cutoff of August 31, 2019, with a median follow-up of 19.4 months.

2-sided p=0.1160, no patients achieved a CR in either arm.

2-sided descriptive p=0.0921, no patients achieved a CR in either arm.

Zanubrutinib showed a more favorable safety profile overall compared to ibrutinib, as shown in the table below, including overall fewer grade >3 events and less incidence of AEs known to be of interest in BTK inhibitor usage such as atrial fibrillation or flutter.

Zanubrutinib Ibrutinib

Safety Overall

(n = 101) Overall

Grade >3 AEs 58.4% 63.3%

Treatment discontinuation due to AEs 4 (4.0%) 9 (9.2%)

Fatal AEs 1 (1.0%) 4 (4.1%)

Atrial fibrillation / flutter of any grade 2.0% 15.3%

Minor bleeding 48.5% 59.2%

Major hemorrhage 5.9% 9.2%

Diarrhea 20.8% 31.6%

Neutropenia 29.7% 13.3%

Waldenström’s Macroglobulinemia - ASPEN Study – MYD88 WT Cohort

ASPEN enrolled patients with the wild type MYD88 gene, which is believed to result in lower response rates and shorter progression-free survival rates when treated with BTK inhibitors.

This cohort of 26 MYD88 WT patients were all treated with zanubrutinib (160mg bid).

The overall response rate was 80.8%, with a major response rate of 50.0%, including a VGPR rate of 26.9%.

The progression-free survival event-free rate at 12 months was 72.4%.

The most frequently reported AEs were diarrhea, anemia, contusion, pyrexia, and upper respiratory tract infection.

Major hemorrhage was reported in 2 patients, and atrial fibrillation was reported in 1 patient.

There were no fatal AEs.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma – SEQUOIA 17p Deletion Arm C

We presented updated results from Arm C of the SEQUOIA trial (NCT03336333).

Patients who have the 17p13.1 deletion [del(17p)] have a poor prognosis and respond poorly to standard chemo-immunotherapy.

A total of 109 of these patients were enrolled into Arm C of the SEQUOIA trial, a non-randomized arm due to the unfavorable response of these patients to bendamustine plus rituximab.

With median follow-up of 21.9 months, the overall response rate was 94.5%, including a CR/CRi rate of 6.4% and a PR/nPR rate of 87.1%.

The 18-month PFS rate was 90.6%.

Adverse events of interest that were the most common included infections, minor bleeding, bruising and neutropenia (65%, 28%, 25% and 19%).

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma - BOVen

Zanubrutinib has been tested in investigator-sponsored studies.

One study, called the BOVen study (NCT03824483), investigated the use of zanubrutinib in combination with obinutuzumab and venetoclax in 39 previously untreated CLL/SLL patients.

The study investigated if the combination would be able to produce frequent uMRD (undetectable minimal residual disease), thus allowing for an MRD-driven treatment discontinuation approach.

At a median follow up time of 11 months, the rate of uMRD in peripheral blood and bone marrow was 84% and 73%, respectively, and 62% of patients were able to stop therapy.

The most common TEAEs were neutropenia, thrombocytopenia, infusion reactions, bruising, and diarrhea (51%, 46%, 41%, 41%, 41%).

There was one death of a patient experiencing an intracerebral hemorrhage on cycle 1 after receiving intravenous heparin for pulmonary emboli.

Marginal Zone Lymphoma - MAGNOLIA

Zanubrutinib is also being investigated for use in marginal zone lymphoma, a rare and heterogeneous disease in which it has been difficult to define optimal therapeutic strategies.

This Phase 2 single arm study (NCT03846427) enrolled 68 patients who received zanubrutinib monotherapy (160mg BID) after having received at least one prior line of anti-CD20-directed therapy.

The overall response rate seen with a median follow up of 11 months was 74%, including 24% complete response based on investigator assessment.

The nine-month PFS rate was 67%.

In the study 96% of patients had at least one treatment-emergent adverse event ("TEAE") and 38% experienced a TEAE of grade 3 or higher.

TEAEs of interest in at least 10% of patients included:

infection, hemorrhage, diarrhea, neutropenia and thrombocytopenia (40%, 32%, 21%, 13%, 10%).

Other Lymphomas

We are also investigating zanubrutinib for the treatment of patients with other lymphomas.

We have studies ongoing in MCL, FL, and DLBCL.

Analysis of Safety Data from Monotherapy Trials

Pooled safety data from 682 patients enrolled in six Phase 1 and Phase 2 clinical trials of zanubrutinib as a monotherapy for WM, MCL, CLL/SLL, DLBCL and other B-cell malignancies were presented at the 2019 European Hematology Association ("EHA").

The majority of patients had R/R disease;

almost all patients received zanubrutinib at a dose of 320mg QD or 160mg

The median duration of zanubrutinib exposure was 13.4 months (0.1-49.7).

This analysis included an evaluation of the frequency and severity of AEs, AEs of special interest ("AESIs"), and AEs leading to death, dose reduction, or treatment discontinuation.

Ninety-seven percent of patients reported at least one AE, which were primarily grade 1 or 2.

The most common AEs of all grades included upper respiratory tract infection (32.4%), neutrophil count decreased (25.2%), diarrhea (19.4%), cough (19.1%), contusion (18.6%), and rash (18%).

The most common grade ≥3 AEs included neutrophil count decreased (14.4%), anemia (7.6%), neutropenia (6.6%), pneumonia (4.5%), platelet count decreased (4.3%), and lung infection (4.1%).

Serious AEs ("SAEs"), consisting primarily of infectious complications such as pneumonia/lung infection, were reported in 36% of patients.

AESIs such as atrial fibrillation/flutter (1.9%), major hemorrhage (2.5%), and grade ≥3 hypertension (3.4%) were infrequent, and treatment discontinuation due to AEs was uncommon (9.1% overall, including 3.5% for whom the event(s) were treatment-related).

In February 2022, we announced that the FDA accepted for review a sNDA for CLL/SLL, with a Prescription Drug User Fee Act (PDUFA) target action date of October 22, 2022, and that the EMA accepted for review two marketing authorization applications for MZL and CLL.

We expect continued regulatory decisions for some of our global filings this year, including potential additional approvals in more than 10 markets We expect topline results to be available from the ALPINE trial comparing BRUKINSA ® versus ibrutinib in second line CLL/SLL in the first half 2022.

Finally, we expect to announce clinical data on the fully enrolled pivotal Phase 2 ROSEWOOD trial comparing BRUKINSA ® plus obinutuzumab to obinutuzumab alone in R/R follicular lymphoma patients in 2022.

Tislelizumab, an anti-PD-1 Antibody

Tislelizumab is a humanized monoclonal antibody against the immune checkpoint receptor PD-1 that is currently being evaluated in pivotal clinical trials globally and in China and for which we plan to commence additional pivotal trials as a monotherapy and in combination with standard of care to treat various solid and hematological cancers.

Mechanism of Action

Cells called cytotoxic T-lymphocytes ("CTLs") provide an important self-defense mechanism against cancer, patrolling the body, recognizing cancer cells due to immunogenic features that differ from normal cells, and killing cancer cells by injecting deleterious proteins into them.

T-lymphocytes have various mechanisms that prevent them from damaging normal cells, among which is a protein called PD-1 receptor, that is expressed on the surface of T-lymphocytes.

PD-L1 is an important signaling protein that can engage PD-1.

PD-L1 binding to PD-1 sends an inhibitory signal inside the T-lymphocyte and suppresses its cytotoxic effects.

Many types of cancer cells have hijacked the PD-L1 expression system that normally exists in healthy cells.

By expressing PD-L1, cancer cells protect themselves from being killed by CTLs.

Anti-PD-1 therapies are designed to bind to and block downstream activity of PD-1, allowing the immune system to combat cancer cells.

Tislelizumab is a monoclonal antibody designed to specifically bind to PD-1, thereby blocking engagement of PD-1 by its ligands PD-L1 and PD-L2.

Tislelizumab has demonstrated high affinity and specificity for PD-1 in preclinical studies.

It is differentiated mechanistically from the currently approved PD-1 antibodies by an engineered Fc region designed to minimize binding to FcγR on macrophages, thereby abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance, which we believe may minimize potentially negative interactions with other immune cells based on preclinical data.

Clinical Development Program, Regulatory Status and Collaboration

Tislelizumab has received conditional approval in China for the treatment of:

(i) cHL patients who have received at least two prior therapies (December 2019);

and (ii) 2L+ UC PD-L1 positive patients (April 2020).

Tislelizumab has also received full approval in China for the treatment of 1L squamous NSCLC patients in combination with chemotherapy (January 2021).

It is currently under review by the NMPA for use in front line non-squamous NSCLC and second or third line HCC.

In January 2021, we announced a collaboration with Novartis Pharma AG (“Novartis”) to develop and commercialize tislelizumab in North America, Japan, the EU, and six other European countries.

We and Novartis have agreed to jointly develop tislelizumab in these licensed countries, with Novartis responsible for regulatory submissions after a transition period and for commercialization upon regulatory approvals.

In addition, both companies may conduct clinical trials globally to explore combinations of tislelizumab with other cancer treatments, and we have an option to co-detail the product in North America, funded in part by Novartis.

The transaction is expected to close in the first quarter of 2021, subject to expiration or early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

We have a broad development program for tislelizumab, including 16 filed, approved or registration-enabling clinical trials.

These include global pivotal trials in Asia-prevalent cancers, NSCLC, HCC, GC, and ESCC, which are intended to support regulatory submissions globally and in China.

Overview of Clinical Development Program and Regulatory Status

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 intended to support regulatory submissions globally and in China.

Our trials in lung cancer include:

2 unchanged sentences

• A Phase 3 trial in China in 1L SCLC evaluating tislelizumab plus chemotherapy versus chemotherapy (NCT04005716);

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

Our trials in liver cancer include:

• A global Phase 3 trial comparing tislelizumab with sorafenib as first-line treatment for patients with HCC (NCT03412773);

• A global single-arm pivotal Phase 2 trial evaluating tislelizumab in second or third line unresectable HCC (NCT03419897).

• A global single-arm pivotal Phase 2 trial in second or third line unresectable HCC (NCT03419897).

Our trials in gastric cancer include:

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

Finally, our trials in ESCC include:

Our trials in lymphoma include:

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

NCT04486391);

• A Phase 2 trial in China in patients with relapsed or refractory cHL (NCT03209973).

Our trials in urothelial carcinoma include:

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

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

Our trials in ESCC include:

• A global Phase 3 trial comparing tislelizumab with chemotherapy as second-line treatment for patients with advanced ESCC (NCT03430843);

1 unchanged sentence

• A Phase 3 trial in China of tislelizumab versus placebo in combination with chemoradiotherapy in patients with localized ESCC (NCT03957590).

We are also evaluating tislelizumab in registration-enabling trials in UC, MSI-high or dMMR solid tumors, and NPC.

We have two China studies in UC, including a pivotal Phase 2 (NCT04004221) in second-line UC evaluating tislelizumab as monotherapy that was the basis for our UC approval in China in May 2020, and a Phase 3 trial (NCT03967977) in first line UC comparing tislelizumab plus chemotherapy versus chemotherapy alone.

In MSI-high or dMMR solid tumors we have an ongoing pivotal Phase 2 trial (NCT03736889) in China examining tislelizumab as monotherapy, and in NPC we have a Phase 3 trial (NCT03924986) in China in first line evaluating tislelizumab plus chemotherapy versus chemotherapy alone.

We have announced that four of Phase 3 trials for tislelizumab have met their respective primary endpoints, in 1L squamous NSCLC, 1L non-squamous NSCLC, 2L NSCLC, and 2L ESCC.

In 1L NSCLC, tislezumab in combination with chemotherapy has shown improved PFS when compared to PFS in both squamous and non-squamous patients.

In 2L NSCLC and 2L ESCC, tislelizumab has shown improved overall survival compared to chemotherapy.

We expect several milestones from the tislelizumab program in 2021.

Finalizing the transaction with Novartis is expected in the first quarter of 2021.

Submission of the first BLA outside of China is expected during the year.

Submission of sBLAs in China for 2L/3L NSCLC and MSI-H/dMMR solid tumors is expected in the first half of 2021, and for 2L ESCC in mid-2021.

Regulatory decision on sBLAs in 1L non-squamous NSCLC and 2L/3L HCC are expected in China in 2021.

We expect to announce topline results of the Phase 3 trial of 1L treatment combined with chemotherapy in patients with NPC in 2021.

Completion of enrollment of the Phase 3 trial in 1L SCLC is expected in the first half of 2021.

Completion of enrollment in the Phase 3 trial versus placebo in combination with chemoradiotherapy in patients with localized ESCC is expected in 2021.

Summary of Clinical Results

As of Janua ry 2021, we had enrolled over 7,700 patients in clinical trials of tislelizumab, including combination trials.

Finally, our trials in solid tumors and nasopharyngeal cancer include:

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

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

As of Janua ry 2022, we had enrolled over 9,000 subjects in clinical trials of tislelizumab in 35 countries, including close to 3,000 subjects outside of China.

These studies include 11 multi-regional registrational trials that are designed for global regulatory approvals.

Data from our trials thus far suggested that tislelizumab was generally well-tolerated and exhibited anti-tumor activity in a variety of tumor types.

Those sources have further details on each study.

Non-Small Cell Lung Cancer

In January 2020, we announced that our Phase 3 clinical study evaluating tislelizumab plus two chemotherapy regimens versus chemotherapy alone in first-line treatment of squamous NSCLC patients (NCT03594747) met the primary endpoint of progression-free survival at the planned interim analysis, as determined by independent review committee.

In this study, patients with previously untreated advanced squamous NSCLC were randomized to receive either tislelizumab in combination with paclitaxel and carboplatin, tislelizumab in combination with nanoparticle albumin-bound (nab) paclitaxel (ABRAXANE ® )

and carboplatin, or paclitaxel and carboplatin alone.

Based on the pre-planned interim analysis, both tislelizumab treatment arms crossed the pre-specified efficacy boundary compared to chemotherapy alone.

The data from this trial were presented at the 2020 annual meeting of ASCO and are briefly summarized below.

Arm A Arm B Arm C

Tislelizumab + PC (n = 120) Tislelizumab + nab -PC (n = 119)

PFS, median in months

Stratified hazard ratio versus placebo

ORR, % 73 75 50

paclitaxel and carboplatin.

Safety data from the study are briefly summarized below.

Arm A Arm B Arm C

Tislelizumab + PC (n = 120) Tislelizumab + nab -PC (n = 119)

Patients with ≥ 1 TEAE, % 100 99 100

Serious TEAE, % 37 38 25

TEAE leading to permanent discontinuation of any study treatment component, % 13 30 15

TEAE leading to death, n 4 5 5

In April 2020, we announced that our Phase 3 clinical study evaluating tislelizumab plus platinum doublet chemotherapy versus chemotherapy alone in first-line treatment of non-squamous NSCLC patients (NCT03663205) met the primary endpoint of progression-free survival at the planned interim analysis, as determined by independent review committee.

In this study, patients with previously untreated advanced non-squamous NSCLC were randomized to receive either tislelizumab in combination with pemetrexed and investigator’s choice of platinum chemotherapy (either carboplatin or cisplatin) versus pemetrexed and platinum chemotherapy alone.

Based on the pre-planned interim analysis, the tislelizumab treatment arm crossed the pre-specified efficacy boundary compared to chemotherapy alone.

The data from this trial were presented at the 2020 virtual congress of the European Society for Medical Oncology ("ESMO") and are briefly summarized below.

Tislelizumab + PP (n = 223) PP (n = 111)

PFS, median in months

Stratified hazard ratio versus chemotherapy alone

Safety data from the study are briefly summarized below.

Tislelizumab + PP (n = 223) PP (n = 111)

Patients with ≥ 1 TEAE, % 100 99

Grade ≥ 3 TEAE, % 68 54

TEAE leading to permanent discontinuation of any study treatment component, % 26 9

TEAE leading to death, n 7 2

In Arm A, fatal TEAEs were pneumonitis (n=3), asphyxia, atrial fibrillation, cerebellar hemorrhage, and unspecified death (n=1 each);

in Arm B, fatal TEAEs were pneumonitis and embolism (n=1 each);

four patients experienced AEs leading to death that were considered by the investigator to be treatment-related.

Two reports of preliminary efficacy and safety from a clinical trial (NCT03493451) investigating use of tislelizumab in lymphoma were reported at the 2020 virtual congress of EHA.

The two reports were each from one arm of the study, one in natural killer/T-cell lymphoma and one in peripheral T-cell lymphoma.

Safety Results

The safety results of tislelizumab in clinical trials to date have been consistent with its therapeutic class, having a relatively low rate of drug-related grade 3 or above toxicity.

The safety data of tislelizumab described below was obtained from 934 patients treated with tislelizumab monotherapy from the following four clinical studies as of April 2020:

BGB-A317-001 (N=451), BGB-A317-102 (N=300), BGB-A317-203 (N=70) and BGB-A317-204 (N=113).

Types of tumors studied included:

urothelial carcinoma (N=152), non-small cell lung cancer (N=105), esophageal carcinoma (N=81), gastric cancer (N=78), classical Hodgkin lymphoma (N=70), hepatocellular carcinoma (N=69), colorectal cancer (N=54), ovarian cancer (N=51) , renal cell carcinoma (N=37), melanoma (N=36), breast cancer (N=32), head and neck squamous cell carcinoma (N=29), nasopharyngeal carcinoma (N=27), cholangiocarcinoma (N=18), pancreatic cancer (N=10), small cell neuroendocrine carcinoma (N=10), sarcoma (N=10), mesothelioma (N=9), cervical cancer (N=7), and others (N=49).

In the above studies, 496 patients received tislelizumab 200 mg once every 3 weeks, 355 patients received tislelizumab at a dose of 5 mg/kg once every 3 weeks, 26 patients received 2 mg/kg once every 2 weeks, 26 patients received 5 mg/kg once every 2 weeks, 21 patients received 2 mg/kg once every 3 weeks, 7 patients received 10 mg/kg once every 2 weeks, and 3 patients received 0.5 mg/kg once every 2 weeks.

The median duration of treatment was 16 weeks (range:

0.6 - 160.4 weeks);

36.1% patients received treatment with tislelizumab for ≥ 6 months and 20.6% for ≥ 12 months.

The incidence of adverse reactions of all grades was 70.8% in 934 patients treated with tislelizumab.

Those occurring in ≥10% of patients included rash, fatigue, and alanine aminotransferase increased.

The incidence of Grade 3 or higher AEs was 21.8%.

Those occurring in ≥1% of patients included:

gamma‑glutamyl transferase increased, anemia, aspartate aminotransferase increased, alanine aminotransferase increased, pneumonitis, severe skin reactions, and hypokalemia.

irTEAEs and Deaths

The specific irAE rates listed below are from the four studies of tislelizumab in 934 patients summarized above.

These irAEs have well-established algorithms for treatment and are considered manageable.

irAEs seen in >1.0% of patients were as follows:

All Grades, n Grade ≥ 3, n

Immune-related pneumonitis 25 14

Immune-related diarrhea and colitis 10 (3 diarrhea, 7 colitis) 6 (2 diarrhea, 4 colitis)

Immune-related hepatitis 20 13

Immune-related hypothyroidism 70 0

Immune-related hyperthyroidism 35 0

Immune-related thyroiditis 9 0

Immune-related skin adverse reactions 67 10

In total, there were four deaths in the pooled data set of 934 patients across the four studies.

The four deaths occurred in one patient experiencing immune-related pneumonitis, two patients experiencing immune-related hepatitis, and one patient experiencing immune-related nephritis (all-grade immune-related nephritis incidence was 0.6%).

Pamiparib, a PARP1 and PARP2 Inhibitor

Pamiparib is an investigational, selective small molecule inhibitor of poly ADP-ribose polymerase 1 ("PARP1") and PARP2 enzymes that is being evaluated as a potential monotherapy and in combinations for the treatment of various solid tumors.

Pamiparib is a selective small molecule inhibitor of poly ADP-ribose polymerase 1 (PARP1) and PARP2 enzymes that is being evaluated as a potential monotherapy and in combinations for the treatment of various solid tumors.

We believe that pamiparib has the potential to be differentiated from other PARP inhibitors because of its brain penetration, greater selectivity, strong DNA-trapping activity, and good oral bioavailability demonstrated in preclinical models.

Mechanism of Action

PARP family members PARP1 and PARP2 play essential roles in cell survival in response to DNA damage.

Inhibition of PARPs prevents the repair of common single-strand DNA breaks, which leads to formation of double-strand breaks during DNA replication.

Cancer cells with mutations in the breast cancer susceptibility gene, or BRCA1/2 genes, are highly sensitive to PARP inhibition.

This phenomenon is called “synthetic lethality” and is the foundation of the therapeutic utility of PARP

inhibitors as a monotherapy for BRCA mutant cancers.

In addition to hereditary BRCA1/2 mutations, the synthetic lethality concept has been broadened to include sporadic tumors that display homologous recombination deficiency ("HRD", a double stranded DNA repair mechanism), a gene expression profile that resembles that of a BRCA deficient tumor.

Another potential therapeutic utility of PARP inhibitors is in combination therapy.

PARP inhibitors are hypothesized to potentiate cytotoxicity of DNA-alkylating agents such as platinum compounds, temozolomide and ionizing radiation, and may be used in combination with these agents in treating various cancers.

Summary of Clinical Results

We presented preliminary results from a Phase 2 registration trial at ESMO 2020.

The data are from a Phase 2 dose-expansion portion of a Phase 1/2 trial of pamiparib in patients with advanced ovarian cancer, fallopian cancer, and primary peritoneal cancer or advanced triple negative breast cancer (NCT03333915).

A total of 113 patients in China with high-grade, non-mucinous, epithelial OC (including fallopian or primary peritoneal cancer), harboring germline BRCA1/2 mutation, following at least two prior lines of standard chemotherapy were enrolled in the pivotal Phase 2 portion of the trial, including 90 patients with advanced platinum-sensitive OC (PSOC) in Cohort 1, and 23 patients with advanced platinum-resistant OC (PROC) in Cohort 2.

As of the data cutoff on February 2, 2020, there was a median follow-up time of 12.2 months.

In Cohort 1, the patients with PSOC, the ORR was 65%.

In Cohort 2, the patients with PROC, the ORR was 32%.

Pamiparib was generally tolerated in patients with PSOC and PROC, which is similar to other PARP inhibitors.

Across the trial, the most common (≥20%) TEAEs of any grade included anemia (89%), nausea (68%), decreased neutrophil count (61%), decreased white blood cell count (60%), vomiting (50%), decreased platelet count (31%), decreased appetite (30%), asthenia (28%), diarrhea (22%), increased AST (21%), decreased lymphocyte count (21%), increased ALT (20%), and leukopenia (20%).

Clinical Development Program and Regulatory Status

In July 2020, we filed an NDA for pamiparib in China for use in third-line BRCA-mutated ovarian cancer based on the pivotal study results described above.

In addition to this study, our clinical development program includes a Phase 3 trial as a maintenance therapy in patients with platinum-sensitive recurrent OC (NCT03519230), a Phase 2 trial in BRCA-mutated HER2-negative breast cancer (NCT03575065), a Phase 2 trial in first-line platinum-sensitive GC maintenance (NCT03427814), and a Phase 1b/2 trial in combination with temozolomide in glioblastoma multiforme (NCT03150862).

We expect to announce top-line results from the Phase 3 maintenance study in patients with platinum-sensitive recurrent OC in 2021 or the first half of 2022.

Ociperlimab (BGB-A1217), an TIGIT Inhibitor

Overview of Clinical Development Program and Regulatory Status

In China, pamiparib received conditional approval in May 2021 for treatment of patients with germline BRCA (gBRCA) mutation-associated recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy.

Full approval for this indication is contingent upon results from ongoing corroborative trials confirming the clinical benefit of pamiparib in this population.

In addition, our clinical development program includes a Phase 3 trial as a maintenance therapy in patients with platinum-sensitive recurrent OC (NCT03519230), a Phase 2 trial in BRCA-mutated HER2-negative breast cancer (NCT03575065), a Phase 2 trial in first-line platinum-sensitive GC maintenance (NCT03427814), and a Phase 1b/2 trial in combination with temozolomide in glioblastoma multiforme (NCT03150862).

We expect to announce top-line results from the Phase 3 maintenance study in patients with platinum-sensitive recurrent OC in the first half of 2022.

Ociperlimab (BGB-A1217), a TIGIT Inhibitor

Ociperlimab (BGB-A1217) is an investigational humanized IgG1-variant monoclonal antibody directed against TIGIT.

We have an ongoing Phase 1a/1b trial (NCT04047862) in Australia investigating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BGB-A1217 in combination with tislelizumab in patients with advanced solid tumors.

The molecule has exhibited high potency in our experiments, and possesses a competent Fc moiety which our experiments suggest is required for optimal efficacy.

Further, no DLTs have been observed and full target occupancy has been seen in PBMCs at the lowest dose tested.

We have selected the randomized Phase 2 dose for ociperlimab and are studying the molecule in combination with tislelizumab.

We plan to present Phase 1a/1b data in 2021, and a registrational program is expected to begin in the first half of 2021.

An immune checkpoint molecule, ociperlimab is currently being investigated in two global Phase 3 clinical trials, the AdvanTIG-301 (NCT04866017) and AdvanTIG-302 (NCT04746924) trials, in combination with tislelizumab in NSCLC.

To date, approximately 800 subjects have been enrolled across the ociperlimab development program, which includes six global trials in patients with lung cancers, esophageal squamous cell carcinoma, and cervical cancer.

In December 2021 we announced an option, collaboration and license agreement with Novartis to develop, manufacture and commercialize ociperlimab in North America, Europe, and Japan, as discussed further below under "Novartis Collaboration — Option Collaboration and License Agreement for Ociperlimab" .

We have completed patient enrollment in the AdvanTIG-202 trial (NCT04693234) in patients with previously treated recurrent or metastatic cervical cancer.

We expect to initiate additional pivotal clinical trials and announce data from Phase 2 trial expansion cohorts in 2022.

Lifirafenib (BGB-283) and BGB-3245, Inhibitors of RAF

3 unchanged sentences

We believe that lifirafenib as monotherapy or in combination with other agents may have potential for treating various malignancies such as melanoma, NSCLC, and endometrial cancer.

Currently approved BRAF inhibitors include Roche’s ZELBORAF ® (vemurafenib), Novartis’ TAFINLAR ® (dabrafenib) and Pfizer / Array BioPharma's BRAFTOVI ® (encorafenib).

The combination of BRAF and MEK inhibitors is approved in patients with BRAF V600E/K mutation-positive metastatic melanoma, such as Novartis’ dabrafenib and MEKINIST ® (trametinib), Roche’s vemurafenib and COTELLIC ® (cobimetinib), and Pfizer / Array Biopharma’s BRAFTOVI ® (encorafenib)

and MEKTOVI ® (binimetinib).

We are aware of several other BRAF inhibitors in clinical development, such as Roche’s belvarafenib and Novartis’ LXH254.

BeiGene is working together with SpringWorks Therapeutics, Inc.

2 unchanged sentences

MapKure has an ongoing Phase 1 clinical trial of BGB-3245 (NCT04249843) in patients with advanced or refractory tumors harboring specific v-RAF murine sarcoma viral oncogene homolog B (B-RAF) genetic mutations.

Sitravatinib (MGCD-0516), a Multi-Kinase Inhibitor

Sitravatinib, a Multi-Kinase Inhibitor

In January 2018, we entered into an exclusive license agreement with Mirati Therapeutics, Inc.

("Mirati") for the development, manufacturing and commercialization of Mirati’s sitravatinib in Asia (excluding Japan and certain other countries), Australia and New Zealand.

(Mirati) for the development, manufacturing and commercialization of Mirati’s sitravatinib in Asia (excluding Japan and certain other

countries), Australia and New Zealand.

Sitravatinib is an investigational spectrum-selective kinase inhibitor, which potently inhibits receptor tyrosine kinases, including RET, TAM family receptors (TYRO3, Axl, MER), and split family receptors (VEGFR2, KIT).

Sitravatinib is being evaluated by Mirati in multiple clinical trials to treat patients who are refractory to prior immune checkpoint inhibitor therapy, including a Phase 3 trial of sitravatinib in NSCLC initiated in 2019.

Sitravatinib is also being evaluated as a single agent in patients with NSCLC, melanoma and other solid tumor types whose tumors harbor specific genetic alterations in the CBL protein.

In recent data readouts by Mirati, sitravatinib has demonstrated durable responses in lung cancer patients who progressed after treatment with checkpoint inhibitors.

We have an ongoing Phase 1 trial (NCT03666143) of sitravatinib in combination with tislelizumab in various solid tumors in Australia and China, and a Phase 1/2 trial (NCT03941873) is investigating sitravatinib monotherapy and combining sitravatinib with tislelizumab focused on HCC or gastroesophageal junction cancer.

Sitravatinib is being evaluated by Mirati in multiple clinical trials to treat patients who are refractory to prior immune checkpoint inhibitor therapy, including a Phase 3 SAPPHIRE trial of sitravatinib in NSCLC initiated in 2019.

In data readouts at the American Association for Cancer Research (AACR) Annual Meeting 2021, two cohorts from BeiGene’s Phase 1b trial (NCT03666143) of sitravatinib in combination with tislelizumab in unresectable or metastatic melanoma who were R/R to PD-1/LI inhibitors and in patients with advanced platinum-resistant ovarian cancer (PROC) were presented.

Sitravatinib is being evaluated by BeiGene in multiple clinical trials including a Phase 3 trial combining sitravatinib with tislelizumab in NSCLC.

BGB-11417, a Small Molecule Bcl-2 Inhibitor

5 unchanged sentences

We have an ongoing Phase 1 trial (NCT04277637) in Australia and the United States to investigate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BGB-11417 and its combination with zanubrutinib in patients with mature B-cell malignancies.

We expect to start pivotal trials for BGB-11417 in 2022.

BGB-A445, an OX40 Agonist Antibody

1 unchanged sentence

BGB-A445 is a non-ligand competing antibody that does not disrupt OX40 to OX40 ligand engagement.

Preclinical experiments showed that our antibody has increasing effectiveness at higher doses versus an antibody that was ligand-competing, which showed falling effectiveness at higher doses.

Preclinical experiments showed that BGB-A445 has increasing effectiveness at higher doses versus an antibody that was ligand-competing, which showed falling effectiveness at higher doses.

BGB-A445 has also showed in preclinical tests the potential to be combined with several agents, such as tislelizumab, as well as a TLR9 agonist, a PI3Kδ inhibitor, sitravatinib, and chemotherapy.

We have an ongoing Phase 1 trial (NCT04215978) of our OX40 antibody in combination with tislelizumab in patients with advanced solid tumors.

Zanidatamab (ZW25), a bispecific HER2 inhibitor

Zanidatamab (ZW25), a novel investigational Azymetric™ bispecific antibody against HER2, is currently in late-stage clinical development with Zymeworks Inc.

We have an ongoing Phase 1 trial (NCT04215978) of BGB-A445 in combination with tislelizumab in patients with advanced solid tumors and expect to initiate dose expansion for BGB-A445 (OX-40) in the first half of 2022.

ZW25 (Zanidatamab), a bispecific HER2-targeted antibody

Zanidatamab, a novel investigational Azymetric ™ bispecific antibody targeting HER2, is currently in late-stage clinical development with Zymeworks Inc.

BeiGene has development and commercial rights to zanidatamab in Asia (excluding Japan), Australia, and New Zealand.

We have two clinical studies ongoing with zanidatamab.

We are participating in three ongoing clinical studies with zanidatamab.

The first is a Phase 1/2 study (NCT04215978) in HER2-positive breast and gastric cancer.

The breast cancer arm combines zanidatmab with docetaxel, and the gastric arm combines zanidatamab with our PD-1 inhibitor tislelizumab and chemotherapy.

The breast cancer arm combines zanidatamab with docetaxel, and the gastric cancer arm combines zanidatamab with our PD-1 inhibitor tislelizumab and chemotherapy.

The second study (NCT04466891) is a Phase 2b study in patients with advanced or metastatic HER2-amplified biliary tract cancers (BTC) in which zanidatamab is being used as monotherapy.

We expect to initiate a Phase 3 study examining zanidatamab in combination with chemotherapy with and without tislelizumab in HER2 positive gastroesophageal cancer in 2021.

BGB-A333, a PD-L1 Inhibitor

BGB-A333 is an investigational humanized IgG1-variant monoclonal antibody against PD-L1, the ligand of PD-1.

We have investigated BGB-A333 as a monotherapy and in combination with other cancer therapies, such as tislelizumab, to treat

various cancers.

We recently completed a Phase 1 clinical trial (NCT03379259) in Australia to assess the safety and antitumor effect of BGB-A333 alone and in combination with tislelizumab in patients with advanced solid tumors.

We initiated a global Phase 3 clinical trial (NCT05152147) examining zanidatamab in combination with chemotherapy with and without tislelizumab in HER2-positive gastroesophageal cancer in late 2021.

We expect to complete enrollment in 2L biliary tract cancer in 2022.

BGB-A425, a TIM-3 Inhibitor

5 unchanged sentences

In addition, preclinical studies showed that BGB-15025 exhibits combination activity with tislelizumab and has a wide therapeutic window.

We plan to initiate clinical studies in the first quarter of 2021.

We initiated a Phase 1 trial (NCT04649385) of BGB-15025 alone and in combination with tislelizumab in patients with advanced solid tumors in 2021.

This trial is being conducted in multiple countries globally.

We expect to initiate dose-expansion for BGB-15025 in the second half of 2022.

Our Preclinical Programs

We have a proprietary biology research platform that has allowed us to research and develop both small molecules and biologic molecules.

In the last decade, this platform has generated more than 10 clinical stage assets, including two internally-developed molecules that have been approved by regulatory bodies in the United States and China and in China, respectively, with other filings pending globally and planned to be submitted.

In the last decade, this platform has generated more than 10 clinical stage assets, including three internally-

developed molecules that have been approved by regulatory bodies in the United States, China, EU and other markets, with other filings pending globally and planned to be submitted.

The platform is a full-process technology system spanning from early discovery to commercialization of oncology medicines based on multiple drug technology platforms that can be applied to oncology and other fields.

We have core technology platforms for the development of small molecule and antibody medicines and the manufacturing of our own and potentially other medicines.

Currently, we have over 50 pre-clinical programs and we believe that half of them have best-in-class or first-in-class potential.

We anticipate advancing multiple our preclinical drug candidates into the clinic in the next 12 months.

2 unchanged sentences

Manufacturing and Supply

We manufacture our medicines and drug candidates internally and with the help of third-party contract manufacturing organizations ("CMOs").

We manufacture our medicines and drug candidates internally and in some cases with the help of third-party contract manufacturing organizations (CMOs).

The manufacturing of our medicines and drug candidates is subject to extensive regulations that impose various procedural and documentation requirements governing recordkeeping, manufacturing processes and controls, personnel, quality control, and quality assurance, among others.

2 unchanged sentences

Our Manufacturing Facilities

We have manufacturing facilities for small molecule drugs and large molecule biologics in Suzhou and Guangzhou, China, respectively, to support the commercialization and potential future demand of our internally developed products.

Our manufacturing facility in Suzhou is over 13,000 square meters and consists of a manufacturing base for small molecule drug products with an annual production capacity of about 100 million tablets and a pilot test biologics production facility with 500 liters capacity.

In addition, our Suzhou facility produces biologics candidates for clinical supply.

It is aligned with the design criteria of the United States, EU, and China regulatory requirements.

The facility has a manufacturing license, which is required for the commercial manufacture of zanubrutinib in China.

We are also building a state-of-the-art commercial-scale manufacturing facility of approximately 100,000 square meters in Guangzhou for the manufacturing of large molecule biologics.

Phase I and Phase II of the facility have been completed in September 2019 and December 2020, respectively, with biologics capacity of 24,000 liters, and Phase III is expected to be completed by the end of 2021 with capacity of 40,000 liters.

Upon completion, the total capacity will reach 64,000 liters.

In the future, we intend to expand the production capacity of the Guangzhou facility to exceed 120,000 liters and to reach up to 200,000 liters.

We have received a manufacturing license for drug substances and drug products for this facility and approval to manufacture commercial product is expected in the first half of 2021.

Following regulatory inspection and approval, the first commercial product to be manufactured at this facility is expected to be tislelizumab.

We are also looking to expand our biologics manufacturing capabilities to include a future manufacturing facility in the United States, with multiple sites currently under review.

We also have pilot scale (approximately 140 square meter) manufacturing capabilities at our research facility in Beijing, China, which produces preclinical and clinical trial materials for some of our small molecule drug candidates.

Our manufacturing facility in Suzhou is over 13,000 square meters and consists of a manufacturing base for small molecule drug products with an annual production capacity of about 100 million tablets and capsules and a biologics clinical development production facility with 2 x 500 liters capacity to produce biologics candidates for clinical supply.

The facility meets or exceeds design criteria of the United States, EU, and China regulatory requirements.

The facility has received a manufacturing license to produce commercial volumes of BRUKINSA and pamiparib for the China market.

As a result of our growing commercial and clinical demands, we have broken ground on a new small molecule manufacturing facility nearby in Suzhou that will have the capability to produce up to 600 million solid oral dosages annually.

This approximately 50,000 square meter facility is expected to replace our current Suzhou site and support our growing pipeline of small molecule medicines and drug candidates.

We continue to invest in our state-of-the-art commercial-scale manufacturing facility in Guangzhou of approximately 100,000 square meters for the manufacturing of large molecule biologics.

Phases 1 and 2 of the facility were completed in September 2019 and December 2020, respectively, with 24,000 liters of single use disposable capacity, while Phase 3 completed construction in December 2021 that will add an additional 40,000 liters of capacity.

Phase 1 is currently approved for the end to end commercial production of tislelizumab for the China market.

Upon completion, the facility will have a total capacity of 64,000 liters.

We have purchased an adjacent tract of land to the south of the current site and are currently evaluating a fourth phase of expansion to support our growing pipeline of large molecule medicines and drug candidates.

We are also planning to expand our biologics manufacturing capabilities to include a future manufacturing facility in the United States and have closed on a 42-acre site at the Princeton West Innovation Park in Hopewell, New Jersey to be developed as a new commercial-stage manufacturing and clinical R&D campus.

Construction of the initial phase is expected to commence in 2022.

The property, located strategically in the Interstate 95 corridor of New Jersey, with a deep and rich talent pool, has more than one million square feet of developable real estate for potential future expansion to cover our existing medicines and pipeline.

Contract Manufacturing Organizations

3 unchanged sentences

We have commercial supply and related agreements with most of our manufacturing service providers.

For example, we entered into a commercial supply agreement with Catalent Pharma Solutions, LLC ("Catalent") to produce BRUKINSA ® at Catalent’s Kansas City, MO site for clinical and commercial use in the United States and other countries outside of China.

We currently source the active pharmaceutical ingredient ("API") for BRUKINSA ® from a supplier in China and are in the process of bringing an additional source of supply online outside of China.

For example, we entered into a commercial supply agreement with Catalent Pharma Solutions, LLC (Catalent) to produce BRUKINSA ® at Catalent’s Kansas City, Missouri site for clinical and commercial use in the United States and other countries outside of China.

We currently source the active pharmaceutical ingredient (API) for BRUKINSA ® from a supplier in China and are in the process of bringing online an additional source of supply outside of China.

In addition, we entered into a commercial supply agreement with Boehringer Ingelheim Biopharmaceuticals (China) Ltd.

("Boehringer Ingelheim") for tislelizumab, which is being manufactured at Boehringer Ingelheim’s facility in Shanghai, China as part of a marketing authorization holder ("MAH") project pioneered by us and Boehringer Ingelheim.

Additionally, our collaboration and license agreement with Novartis includes the right for Novartis to manufacture tislelizumab for the licensed territory, to be managed by Novartis following tech transfer.

For our commercial and clinical stage products licensed from Amgen and BMS, we rely on Amgen and BMS and their manufacturing facilities or CMOs outside of China for the supply of those medicines and drug candidates.

(Boehringer Ingelheim) for tislelizumab, which is being manufactured at Boehringer Ingelheim’s facility in Shanghai, China.

Additionally, our collaboration agreements with Novartis include the right for Novartis to manufacture tislelizumab and ociperlimab for its territory, to be managed by Novartis following tech transfer, and our right to conduct a specified percentage of production at our planned U.S.

manufacturing site, subject to the terms of the agreements.

For our commercial and clinical stage products in-licensed from Amgen, BMS and others, we rely on the licensors and their manufacturing facilities or their CMOs for the supply of those medicines and drug candidates.

Our agreements with the outsourced suppliers engaged by us generally set out terms, including product quality or service details, technical standards or methods, delivery terms, agreed price and payment, and product inspection and acceptance criteria.

17 unchanged sentences

After expiration of the commercialization period for each product, the products not retained will be transitioned back to Amgen and we will be eligible to receive tiered mid-single to low-double digit royalties on net sales in China of each product for an additional five years.

Additionally, pursuant to the terms of the Amgen Collaboration Agreement, we and Amgen have agreed to collaborate on the global development and commercialization of a portfolio of Amgen clinical- and late-preclinical-stage oncology pipeline products.

Starting from the commencement of the Amgen Collaboration Agreement, we and Amgen will co-fund global

development costs, with BeiGene contributing up to $1.25 billion worth of development services and cash over the term of the collaboration.

Additionally, pursuant to the terms of the Amgen Collaboration Agreement, we and Amgen have agreed to collaborate on the global clinical development and commercialization of a portfolio of Amgen clinical- and late-preclinical-stage oncology pipeline products.

Starting from the commencement of the Amgen Collaboration Agreement, we and Amgen will co-fund global development costs, with BeiGene contributing up to $1.25 billion worth of development services and cash over the term of the collaboration.

We will be eligible to receive tiered mid-single digit royalties on net sales of each product globally outside of China, other than sotorasib (AMG 510) , on a product-by-product and country-by-country basis, until the latest of the expiration of the last valid patent claim, the expiration of regulatory exclusivity, or the earlier of eight years after the first commercial sale of such product in the country of sale and 20 years from the date of first commercial sale of such product anywhere in the world.

1 unchanged sentence

In addition, we will have the right to retain approximately one of every three approved products, up to a total of six, other than sotorasib (AMG 510), to commercialize for as long as each such product is sold in China.

After the expiration of the seven-year commercialization period, each product will be transitioned back to Amgen and we will be eligible to received tiered mid-single to low-double digit royalties on net sales in China for an additional five years.

sales in China for an additional five years.

The parties are subject to specified exclusivity requirements in China and the rest of the world.

20 unchanged sentences

The Direct Purchase Option (i) is exercisable by Amgen solely as a result of dilution arising from issuance of new shares by us under our equity incentive plans from time to time, and (ii) is subject to annual approval by our independent shareholders each year during the term of the Restated Second Amendment.

The exercise period of the Direct Purchase Option

commenced on December 1, 2020 and will terminate on the earliest of:

The exercise period of the Direct Purchase Option commenced on December 1, 2020 and will terminate on the earliest of:

(a) the date on which Amgen and its affiliates collectively own less than 20% of the outstanding share capital of the Company as a result of Amgen’s sale of shares;

3 unchanged sentences

Novartis Collaboration

On January 11, 2021, our wholly-owned subsidiary, BeiGene Switzerland GmbH, entered into a Collaboration and License Agreement (the “Novartis Collaboration and License Agreement”) with Novartis Pharma AG (“Novartis”), pursuant to which Novartis will have the right to develop, manufacture and commercialize tislelizumab in the United States, Canada, Mexico, member countries of the European Union, United Kingdom, Norway, Switzerland, Iceland, Liechtenstein, Russia, and Japan (the “Licensed Territory”).

Under the Novartis Collaboration and License Agreement, we will receive an upfront cash payment of $650 million from Novartis.

Collaboration and License Agreement for Tislelizumab

On January 11, 2021, our wholly-owned subsidiary, BeiGene Switzerland GmbH, entered into a Collaboration and License Agreement, which became effective on February 26, 2021 (the “Novartis Collaboration and License Agreement”) with Novartis, pursuant to which Novartis will have the right to develop, manufacture and commercialize tislelizumab in the United

States, Canada, Mexico, member countries of the European Union, United Kingdom, Norway, Switzerland, Iceland, Liechtenstein, Russia, and Japan (the “Licensed Territory”).

Under the Novartis Collaboration and License Agreement, we received an upfront cash payment of $650 million from Novartis.

Additionally, we are eligible to receive up to $1.3 billion upon the achievement of regulatory milestones, $250 million upon the achievement of sales milestones, and tiered royalties based on percentages of annual net sales of tislelizumab in the Licensed Territory ranging from the high-teens to high-twenties, with customary reductions in specified circumstances.

7 unchanged sentences

Each party retains the worldwide right to commercialize its propriety products in combination with tislelizumab.

We retain the rights to manufacture and supply a specified percentage of commercial supply of tislelizumab from our planned U.S.

manufacturing facility to be built in Hopewell, New Jersey, subject to the terms of the agreement.

The Novartis Collaboration and License Agreement contains customary representations, warranties and covenants by the parties.

2 unchanged sentences

The agreement may be terminated by Novartis upon 120 days’ prior written notice if delivered before first commercial sale or 180 days’ prior written notice if delivered following first commercial sale of tislelizumab in the Licensed Territory, or by either party upon the other party’s bankruptcy or uncured material breach.

The transaction contemplated under the Collaboration and License Agreement is expected to close in the first quarter of 2021, subject to expiration or early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

Option, Collaboration and License Agreement for Ociperlimab

On December 19, 2021, BeiGene Switzerland GmbH entered into an Option, Collaboration and License Agreement (the “Novartis Option, Collaboration and License Agreement”) with Novartis, pursuant to which we have granted Novartis an exclusive time-based option to receive an exclusive license to develop, manufacture and commercialize our investigational TIGIT inhibitor ociperlimab in the Licensed Territory.

Under the Novartis Option, Collaboration and License Agreement, we received an upfront cash payment of $300 million from Novartis and are eligible to receive an additional payment of $600 million or $700 million upon exercise by Novartis of an exclusive time-based option prior to mid-2023 or late-2023, respectively, subject to receipt of required antitrust approval.

Additionally, following option exercise, we are eligible to receive up to $745 million upon the achievement of regulatory approval milestones, $1.15 billion upon the achievement of sales milestones, and tiered royalties based on percentages of annual net sales of ociperlimab in the Licensed Territory ranging from the high-teens to mid-twenties, with customary reductions in specified circumstances.

Royalties are payable on a country-by-country basis from the time of the first commercial sale until the latest of the expiration of the last valid patent claim, the expiration of regulatory exclusivity, or 10 years after the first commercial sale of ociperlimab in the country of sale.

Under the Novartis Option, Collaboration and License Agreement, during the option period, Novartis has agreed to initiate, conduct and fund additional global clinical trials of ociperlimab in combination with tislelizumab in selected tumor types and we have agreed to expand enrollment in two ongoing trials.

Additionally, following the option exercise, the companies have agreed to jointly develop ociperlimab in the Licensed Territory, with Novartis sharing development costs of global trials and responsible for regulatory submissions after a transition period and for commercialization upon regulatory approvals in the Licensed Territory.

In addition, both companies may conduct clinical trials globally to explore potential combinations of

ociperlimab with other cancer treatments.

We will initially be responsible for supplying ociperlimab to Novartis, with Novartis having the right to conduct manufacturing for its use in the Licensed Territory after successful transfer of the manufacturing process.

Following approval, we have agreed to provide 50% of the co-detailing and co-field medical efforts in the United States and have an option to co-detail up to 25% in Canada and Mexico, in each case funded in part by Novartis.

Each party retains the worldwide right to commercialize its proprietary products in combination with ociperlimab, as is the case with tislelizumab under the parties' existing collaboration agreement.

We retain the rights to manufacture and supply a specified percentage of commercial supply of ociperlimab from our planned U.S.

manufacturing facility to be built in Hopewell, New Jersey, subject to the terms of the agreement.

The Novartis Option, Collaboration and License Agreement contains customary representations, warranties and covenants by BeiGene and Novartis.

Unless earlier terminated, the agreement will expire on a country-by-country basis upon the expiration of the royalty term in such country.

The Novartis Option, Collaboration and License Agreement will expire in its entirety upon the expiration of all applicable royalty terms under the agreement in all countries in the Licensed Territory.

The agreement may be terminated by Novartis upon 120 days’ prior written notice if delivered before first commercial sale or 180 days’ prior written notice if delivered following first commercial sale of ociperlimab in the Licensed Territory, or by either party upon the other party’s bankruptcy or uncured material breach.

BeiGene may terminate the agreement in its entirety upon written notice if Novartis challenges the licensed BeiGene patents.

Either party may terminate the agreement in its entirety effective immediately upon written notice to the other party (i) if the option terminates or expires, or (ii) in the event that the license effective date has not occurred within six months after the date of the Hart-Scott-Rodino Antitrust Improvements Act filing, subject to extension.

Celgene License and Supply Agreement

2 unchanged sentences

We subsequently assigned the agreement to our wholly-owned subsidiary, BeiGene Switzerland.

The term of the China License Agreement is 10 years and may be terminated by either party upon written notice in the event of uncured material breach or bankruptcy of the other party, or if the underlying regulatory approvals for the covered

products are revoked.

This suspension was based on inspection findings at BMS’s contract manufacturing facility in the United States.

Additionally, in October 2021, BMS provided 180-days' notice to us, which we dispute, purporting to terminate our license to market ABRAXANE ® in China.

We have not had any sales of ABRAXANE ® since the suspension and do not expect future revenue from ABRAXANE ® .

We have initiated an arbitration proceeding against BMS asserting that it has breached and continues to breach the terms and conditions of the license and supply agreement.

For additional information, please see the section of this report titled “Legal Proceedings”.

BMS also has the right to terminate the agreement with respect to REVLIMID ® at any time upon written notice to us under certain circumstances.

9 unchanged sentences

In addition, we owned pending international patent applications under the Patent Cooperation Treaty (PCT), which we plan to file nationally in the United States and other jurisdictions, as well as additional priority PCT applications.

With respect to any issued patents in the United States and Europe, we may be entitled to obtain a patent term extension to extend the patent expiration date, provided that we meet the applicable requirements for obtaining such patent term extensions.

With respect to any issued patents in the United

States and Europe, we may be entitled to obtain a patent term extension to extend the patent expiration date, provided that we meet the applicable requirements for obtaining such patent term extensions.

For example, in the United States, we can apply for a patent term extension of up to five years for one of the patents covering a drug product once the product is approved by the FDA.

The exact duration of the extension depends on the time that we spend in clinical studies as well as getting approval from the FDA.

In China, the Amended PRC Patent Law, which will become effective on June 1, 2021, provides a patent term extension of up to five years, similar to the United States.

In China, the Amended PRC Patent Law, which became effective on June 1, 2021, provides a patent term extension of up to five years, similar to the United States.

The key patents for our medicines and late-stage clinical drug candidates as of January 31, 2022, are summarized below:

4 unchanged sentences

Use for the treatment of B-cell proliferative disorder 2034

Crystalline forms 2037

China Compound and composition 2034

4 unchanged sentences

Antibodies 2033

China Antibodies 2033

11 unchanged sentences

China Use for the treatment of cancer 2031

China Crystalline forms 2036

Ociperlimab U.S.

Antibodies 2038

(1) The expected expiration does not include any additional term for patent term extensions

We have three in-licensed medicines in China from Bristol Myers Squibb company ("BMS").

The key patents for them as of January 31, 2021 are summarized below:

We currently have two in-licensed medicines in China from BMS.

The key patents for them in China as of January 31, 2022 are summarized below:

Product Territory General Subject Matter Expiration

6 unchanged sentences

China No patent N/A

ABRAXANE ® (a nanoparticle albumin-bound paclitaxel)

China Use for the treatment of cancer 2026

China Use for the treatment of cancer 2031

Under our collaboration with Amgen, we have the right to commercialize in China two medicines and, upon approval in China, one late-stage product candidate.

The key patents necessary for these products in China are summarized below:

Under our collaboration with Amgen, we have the right to commercialize three medicines in China.

The key patents for them in China as of January 31, 2022 are summarized below:

Product Territory General Subject Matter Expiration

6 unchanged sentences

Although various extensions may be available, the life of a patent and the protection it affords, is limited.

REVLIMID ® , VIDAZA ® and ABRAXANE ® face competition from generic medications, and we may face similar competition for our medicines and any approved drug candidates even if we successfully obtain patent protection.

REVLIMID ® and VIDAZA ® face competition from generic medications, and we may face similar competition for our medicines and any approved drug candidates even if we successfully obtain patent protection.

The scope, validity or enforceability of our or our collaborators' patents may be challenged in court or other authorities, and we or they may not be successful in enforcing or defending those intellectual property rights and, as a result, may not be able to develop or market the relevant product exclusively, which would have a material adverse effect on any potential sales of that product.

For example, the China patents for KYPROLIS ® (carfilzomib) are currently in an invalidation proceeding brought by another company.

Additionally, in China, the NMPA may approve a generic version of a brand-name medicine that still has patent protection, such as has occurred with REVLIMID ® .

3 unchanged sentences

In most countries in which we file, including the United States and China, the term of an issued patent is generally 20 years from the earliest claimed filing date of a non-provisional patent application in the applicable country.

In the United States, a patent’s term may be lengthened in some cases by a patent term adjustment, which extends the term of a patent to account for administrative delays by the United States Patent and Trademark Office (the "USPTO"), in excess of a patent applicant’s own delays during the prosecution process, or may be shortened if a patent is terminally disclaimed over a commonly owned patent having an earlier expiration date.

In the United States, a patent’s term may be lengthened in some cases by a patent term adjustment, which extends the term of a patent to account for administrative delays by the United States Patent and Trademark Office (USPTO), in excess of a patent applicant’s own delays during the prosecution process, or may be shortened if a patent is terminally disclaimed over a commonly owned patent having an earlier expiration date.

In addition, in certain instances, a patent term can be extended to recapture a portion of the term effectively lost in obtaining FDA regulatory approval.

However, the restoration period cannot be longer than five years and the total patent term including the restoration period must not exceed 14 years following FDA approval.

In China, the Amended PRC Patent Law, which will become effective on June 1, 2021, provides both patent term adjustment and patent term extension, similar to the United States.

In China, the Amended PRC Patent Law, which became effective on June 1, 2021, provides both patent term adjustment and patent term extension, similar to the United States.

In certain foreign jurisdictions similar extensions as compensation for regulatory delays are also available.

4 unchanged sentences

Additionally, we currently own a number of registered trademarks and pending trademark applications.

We currently have registered trademarks for BeiGene, our corporate logo and product names and logos in the United States, China, the EU and

other jurisdictions, and we are seeking further trademark protection for BeiGene, our corporate logo, product names and logos, and other marks in jurisdictions where available and appropriate.

We currently have registered trademarks for BeiGene, our corporate logo and product names and logos in the United States, China, the EU and other jurisdictions, and we are seeking further trademark protection for BeiGene, our corporate logo, product names and logos, and other marks in jurisdictions where available and appropriate.

We operate in a highly competitive environment and our marketed products face intense competition in regulated markets around the world.

Our main competitors include other global research-based biopharmaceutical companies as well as smaller regional and local companies.

These companies participate in one or more activities including the development, production, and promotion of products that are intended to treat diseases or indications that are like products we currently market or are in the process of developing to market.

BRUKINSA ® – Conventional methods of treating lymphomas vary according to the specific disease or histology, but generally include chemotherapy, antibodies directed at CD20, a molecular marker found on the surface of B-cells, and, less frequently, radiation.

Recently, significant progress has been made in the development of new therapies for lymphomas, including BTK inhibitors.

The BTK inhibitor IMBRUVICA ® (ibrutinib), marketed by AbbVie and Janssen, was first approved by the FDA in 2013 for the treatment of patients with MCL who have received at least one prior therapy.

Since that time, ibrutinib has been approved in over 90 countries and regions and has expanded its indications.

Another BTK inhibitor,

AstraZeneca's CALQUENCE ® (acalabrutinib), was approved by the FDA in 2017 under accelerated approval for the treatment of patients with MCL who have received at least one prior therapy, and in November 2019 for use in adults with CLL/SLL as a single agent or in combination with obinutuzumab.

In China, BRUKINSA ® competes with IMBRUVICA ® (ibrutinib), which received approval in 2017, and YINUOKAI ® (orelabrutinib) from Innocare, which was approved in 2020.

Tislelizumab – A number of PD-1 or PD-L1 antibody medicines have been approved by the FDA.

These include Merck’s KEYTRUDA ® (pembrolizumab), BMS’s OPDIVO ® (nivolumab), Roche’s TECENTRIQ ® (atezolizumab), AstraZeneca’s IMFINZI ® (durvalumab), Pfizer and Merck Sereno’s BAVENCIO ® (avelumab), Regeneron and Sanofi’s LIBTAYO ® (cemiplimab), and GSK's JEMPERLI ® (dostarlimab).

In the global setting, several PD-1 or PD-L1 antibody agents are in late-stage clinical development in addition to tislelizumab.

In China, as of February 1, 2022, there are seven other approved PD-1 antibodies:

OPDIVO ® (nivolumab) and KEYTRUDA ® (pembrolizumab), Junshi’s TUOYI ® (toripalimab), Innovent’s TYVYT ® (sintilimab), Hengrui’s AIRUIKA ® (camrelizumab), Akeso's ANNIKE ® (penpulimab) and Gloria's YUTUO ® (zimberelimab).

There are four approved PD-L1 antibody agents:

AstraZeneca's IMFINZI ® (durvalumab), Roche's TECENTRIQ ® (atezolizomab), CStone's ZEJIEMEI ® (sugemalimab) and Alphamab's ENWEIDA ® (envafolimab).

There are approximately 40 more PD-1 and PD-L1 agents in clinical development in China.

Pamiparib – We are competing with multiple PARP inhibitors in China.

AstraZeneca received approval for olaparib in August 2018.

Zai Labs obtained development and commercial rights for niraparib in China, and its NDA was approved by the NMPA in December 2019.

Fluzoparib from Hengrui/Hansoh was approved in December 2020.

Ociperlimab - We are aware of several pharmaceutical companies developing TIGIT antibodies, including Agenus, Arcus, BMS, Compugen, Roche/Genentech, Innovent, iTeos Therapeutics, Merck KGaA, Mereo BioPharma, Seagen, Junshi, Bio-Thera and Akeso.

To our knowledge, there are currently no approved anti-TIGIT antibodies and the most advanced agent is in Phase 3 development.

Many of the larger companies we compete with are well-capitalized and dedicate a significant number of financial resources to support their research and development, while using business development to supplement their internal pipelines.

As a result, we must continuously invest and gain experience in the development, acquisition, and marketing of innovative and branded medicines and drug candidates to compete effectively in both current and future markets.

This requires us to devote substantial funds and resources to R&D to prevent or slow the erosion of the sales of our existing products and potential sales of products in development.

The main forms of competition include efficacy, safety, and cost.

The long-term success of our products depends on our ability to effectively demonstrate the value that each one of them offers to physicians, patients, and third-party payers.

This requires a much greater use of a direct sales force to realize significant revenues.

We also have and will continue to enter into co-promotion, contract sales force or other such arrangements with third parties, for example, where our own direct sales force is not large enough or sufficiently well-aligned to achieve maximum market penetration.

Government Regulation

8 unchanged sentences

Second line therapies often consist of more chemotherapy, radiation, antibody drugs, tumor targeted small molecule drugs or a combination of these.

Third line therapies can include bone marrow transplantation, antibody and small molecule targeted therapies, more invasive forms of surgery.

Third line therapies can include bone marrow transplantation, antibody and small molecule targeted therapies, more invasive forms of

In some cases, new technologies and investigational medicines, as part of a clinical trial, may be used as any line of therapy.

7 unchanged sentences

• satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product, or components thereof, are produced to assess compliance with cGMP;

• review of the product candidate by an FDA advisory committee, where appropriate and if applicable;

• payment of user fees for FDA review of the NDA or BLA (unless a fee waiver applies);

• FDA audits of some clinical trial sites to ensure compliance with GCPs;

3 unchanged sentences

Preclinical tests include laboratory evaluations of product chemistry, toxicity, formulation and stability, as well as in vitro and animal studies.

The conduct of the preclinical tests must comply with federal regulations and requirements, including GLP.

An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data and any available clinical data or literature, to the FDA as part of the IND.

The sponsor must also include a protocol detailing, among other things, the objectives of the initial clinical trial, dosing procedures, subject selection and exclusion criteria, the parameters

to be used in monitoring safety and the effectiveness criteria to be evaluated if the initial clinical trial lends itself to an efficacy evaluation.

The sponsor must also include a protocol detailing, among other things, the objectives of the initial clinical trial, dosing procedures, subject selection and exclusion criteria, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated if the initial clinical trial lends itself to an efficacy evaluation.

Some preclinical testing may continue even after the IND is submitted.

8 unchanged sentences

The IRB also approves the information regarding the clinical trial and the consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the clinical trial until completed.

Some trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board or committee.

This group provides authorization as to whether or not a trial may move forward at designated check points based on access that only the group maintains to available data from the trial and may recommend

halting the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

Each new clinical protocol and any amendments to the protocol must be filed with the FDA as an IND amendment and submitted to the IRBs for approval.

A sponsor who wishes to conduct a clinical trial outside of the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND.

If a foreign clinical trial is not conducted under an IND, the sponsor may submit data from the clinical trial to the FDA in support of a BLA or NDA.

If a foreign clinical trial is not conducted under an IND, the sponsor may submit data from the clinical trial to the FDA in support of an NDA or BLA.

The FDA will accept a well-designed and well-conducted foreign clinical study not conducted under an IND if the study was conducted in accordance with GCP requirements, and the FDA is able to validate the data through an onsite inspection if deemed necessary.

10 unchanged sentences

We refer to our Phase 1 programs as dose-escalation and dose-expansion trials.

In addition, we refer to some of our Phase 2 programs as pivotal or registrational programs, where the results can be used to support regulatory approval in specific jurisdictions without the need to conduct a Phase 3 trial.

Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and safety reports must be submitted to the FDA and the investigators for serious and unexpected suspected AEs, any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator’s brochure, or any findings from other studies or animal or in vitro testing that suggest a significant risk in humans exposed to the product drug.

In addition, we refer to some of our Phase 2 programs as pivotal or registrational programs, where the results may be used to support regulatory approval in specific jurisdictions without the need to conduct a Phase 3 trial.

The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting.

1 unchanged sentence

Phase 1, Phase 2, and Phase 3 studies may not be completed successfully within any specified period, or at all.

The FDA or the sponsor may suspend or terminate a clinical

trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.

The FDA or the sponsor may suspend or terminate, or a data safety monitoring board may recommend the suspension or termination of, a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the product has been associated with unexpected serious harm to subjects.

6 unchanged sentences

However, if a company decides to make one of its investigational products available for expanded access, the FDA reviews each request for expanded access and determines if treatment may proceed.

A manufacturer of an investigational drug for a serious disease or condition is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for individual patient access to such investigational drug.

A sponsor of an investigational drug for a serious disease or condition is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for individual patient access to such investigational drug.

This requirement applies on the earlier of the first initiation of a Phase 2 or Phase 3 trial of the investigational drug or, as applicable, 15 days after the drug receives a designation as a breakthrough therapy, fast track product, or regenerative advanced therapy.

23 unchanged sentences

Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling.

In addition, the FDA may

require post-approval studies, including Phase 4 clinical trials, to further assess a product’s safety and effectiveness after NDA or BLA approval and may require testing and surveillance programs to monitor the safety of approved products that have been commercialized.

In addition, the FDA may require post-approval studies, including Phase 4 clinical trials, to further assess a product’s safety and effectiveness after NDA or BLA approval and may require testing and surveillance programs to monitor the safety of approved products that have been commercialized.

The FDA may also approve an NDA or BLA with a Risk Evaluation and Mitigation Strategy (REMS) program to mitigate risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.

9 unchanged sentences

According to the guidance, for novel drugs, a companion diagnostic device and its corresponding therapeutic should be approved or cleared contemporaneously by the FDA for the use indicated in the therapeutic product’s labeling.

Once cleared or approved, the companion diagnostic must adhere to post-marketing requirements including the requirements of FDA’s quality system regulation, medical device reporting, recalls and corrections along with product marketing requirements and limitations.

Companion diagnostic manufacturers are subject to unannounced FDA inspections at any time during which the FDA will conduct an audit of the product(s) and the company’s facilities for compliance with its authorities.

Expedited Programs

16 unchanged sentences

Failure to conduct required post-approval studies, or to confirm a clinical benefit during post-marketing studies, will allow the FDA to withdraw the drug from the market.

All promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA.

Zanubrutinib was granted accelerated approval by FDA for the treatment of adult patients with MCL who have received at least one prior therapy.

All promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA unless otherwise informed by the agency.

Zanubrutinib was granted accelerated approval by FDA for the treatment of adult patients with MCL who have received at least one prior therapy and for the treatment of adult patients with relapsed or refractory MZL who have received at least one anti-CD20-based regimen.

Breakthrough Designation

Breakthrough therapy designation is intended to expedite the development and review of a breakthrough therapy.

A drug or biologic product candidate can be designated as a breakthrough therapy if it is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug or biologic, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

A sponsor may request that a product candidate be designated as a breakthrough therapy concurrently with, or at any time after, the submission of an IND, and the FDA must determine if the candidate qualifies for breakthrough therapy designation within 60 days of receipt of the sponsor’s request.

3 unchanged sentences

Priority Review

The FDA may grant an NDA for a new molecular entity or BLA a priority review designation, which sets the target date for FDA action on the application at six months after the FDA accepts the application for filing.

The FDA may grant an NDA or BLA a priority review designation, which sets the target date for FDA action on the application at six months after the FDA accepts the application for filing.

Priority review is granted where there is evidence that the proposed product would be a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition.

12 unchanged sentences

Any products for which we receive FDA approval are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, complying with certain electronic records and signature requirements and complying with FDA promotion and advertising requirements.

The FDA strictly regulates labeling,

advertising, promotion and other types of information on products that are placed on the market.

The FDA strictly regulates labeling, advertising, promotion and other types of information on products that are placed on the market.

Products may be promoted only for the approved indications and in accordance with the provisions of the approved label.

4 unchanged sentences

The law’s requirements include the quarantine and prompt investigation of a suspect product to determine if it is illegitimate, and notifying trading partners and FDA of any illegitimate product.

Drug manufacturers and their collaborators are also required to place a unique product identifier on prescription drug packages.

Drug manufacturers and other parties involved in the supply chain must also meet chain of distribution requirements for product tracking and tracing, including a requirement to place a unique product identifier on prescription drug packages.

This identifier consists of the National Drug Code, serial number, lot number and expiration date, in the form of a 2 dimensional data matrix barcode that can be read by humans and machines.

22 unchanged sentences

The FDCA also provides three years of data exclusivity for an NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, for new indications, dosages or strengths of an existing drug.

This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the original

active agent.

This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the original active agent.

Five-year and three-year exclusivity will not delay the submission or approval of a full NDA.

1 unchanged sentence

Regulatory exclusivity in the United States can also include pediatric exclusivity and orphan drug exclusivity.

Pediatric exclusivity, if granted, provides an additional six months of exclusivity, which runs from the end of other regulatory exclusivity or patent periods.

Pediatric exclusivity, if granted, provides an additional six months of exclusivity, which runs from the end of other regulatory exclusivity

or patent periods.

This six-month exclusivity may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued ‘‘Written Request’’ for such a trial.

21 unchanged sentences

Sponsors are also obligated to disclose the results of their clinical trials after completion.

of the results of these trials can be delayed until the new product or new indication being studied has been approved.

Disclosure of the results of these trials can be delayed until the new product or new indication being studied has been approved.

Competitors may use this publicly available information to gain knowledge regarding the progress of development programs.

Pharmaceutical Coverage, Pricing, and Reimbursement

In the United States and in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part on the availability of coverage and reimbursement from third-party payors, including government authorities, managed care providers, private health insurers and other organizations.

authorities, managed care providers, private health insurers and other organizations.

Patients generally rely on third-party payors to reimburse all or part of the associated healthcare costs and no uniform policy of coverage and reimbursement for drug products exists among third-party payors.

12 unchanged sentences

Since its enactment, some of the provisions of the ACA have yet to be fully implemented, while certain provisions have been subject to judicial, Congressional, and Executive challenges.

For example, various portions of the ACA are currently undergoing legal and constitutional challenges in the United States Supreme Court.

Additionally, the former Trump Administration issued various Executive Orders which eliminated cost sharing subsidies and various provisions that would impose a fiscal burden on states or a cost, fee, tax, penalty or regulatory burden on individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical devices;

and Congress has introduced several pieces of legislation aimed at significantly revising or repealing the ACA.

It is unclear whether the ACA will be overturned, repealed, replaced, or further amended.

We cannot predict what affect further changes to the ACA would have on our business, especially given the new administration.

On June 17, 2021, the U.S.

Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.

Prior to the Supreme Court's decision, President Biden issued an Executive Order to initiate a special enrollment period from February 15, 2021 through August 15, 2021 for purposes of obtaining health insurance coverage through the ACA marketplace.

The Executive Order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

It is unclear how other healthcare reform measures of the Biden administrations or other efforts, if any, to challenge repeal or replace the ACA, will impact our business.

Other legislative changes have been proposed and adopted in the United States since the ACA was enacted.

1 unchanged sentence

In addition, the Budget Control Act of 2011 and the Bipartisan Budget Act of 2015 led to aggregate reductions of Medicare payments to providers of up to 2% per fiscal year that will remain in effect through 2030 unless additional Congressional action is taken.

Pursuant to the Coronavirus Aid, Relief, and Economic Security Act, also known as the CARES Act, and subsequent legislation, these reductions have been suspended from May 1, 2020 through March 31, 2021 due to the COVID-19 pandemic.

Proposed legislation, if passed, would extend this suspension until the end of the pandemic.

Further, on January 2, 2013, the American Taxpayer Relief Act was signed into law, which, among other things, reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

More recently, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several recent Congressional inquiries and proposed bills designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for pharmaceutical products.

On April 13, 2017, CMS published a final rule that gives states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces.

On May 23, 2019, CMS published a final rule to allow Medicare Advantage Plans the option of using step therapy for Part B drugs beginning January 1, 2020.

On December 20, 2019, former President Trump signed into law the Further Consolidated Appropriations Act (H.R.

1865), which repealed the Cadillac tax, the health

insurance provider tax, and the medical device excise tax.

It is impossible to determine whether similar taxes could be instated in the future.

There has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed bills designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for pharmaceutical products.

It is unclear whether the Biden administration will challenge, reverse, revoke or otherwise modify the former Trump Administration’s executive and administrative actions after January 20, 2021.

14 unchanged sentences

The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers.

Implementation of the amendments to the discount safe harbor have been delayed until at least January 1, 2023.

Pursuant to an order entered by the U.S.

District Court for the District of Columbia, the portion of the rule eliminating safe harbor protection for certain rebates related to the sale or purchase of a pharmaceutical product from a manufacturer to a plan sponsor under Medicare Part D has been delayed to January 1, 2023.

Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation of the rule until January 1, 2026.

Further, implementation of this change and new safe harbors for point-of-sale reductions in price for prescription pharmaceutical products and pharmacy benefit manager service fees are currently under review by the Biden administration and may be amended or repealed.

11 unchanged sentences

These laws may impact, among other things, our sales, marketing and education programs.

In addition, we may be subject to patient privacy

regulation by both the federal government and the states in which we conduct our business prior to and after receiving regulatory approval of our product candidates.

In addition, we may be subject to patient privacy regulation by both the federal government and the states in which we conduct our business prior to and after receiving regulatory approval of our product candidates.

The laws that may affect our ability to operate include:

• the federal Anti-Kickback Statute ("AKS"), which prohibits, among other things, knowingly and willfully soliciting, receiving, providing, offering or paying any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual, or the purchase, lease, order or recommendation or arrangement of any good, facility, item or service for which payment may be made, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs.

• the federal healthcare Anti-Kickback Statute (AKS), which prohibits, among other things, knowingly and willfully soliciting, receiving, providing, offering or paying any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual, or the purchase, lease, order or recommendation or arrangement of any good, facility, item or service for which payment may be made, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs.

This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other.

2 unchanged sentences

In addition, the government may assert that a claim including items or services resulting from a violation of the AKS constitutes a false or fraudulent claim for purposes of the federal False Claims Act (FCA) or federal civil money penalties statute.

Violations of the AKS carry potentially significant civil and criminal penalties, including imprisonment, fines, administrative civil monetary penalties, and exclusion from participation in federal healthcare programs.

Violations of the AKS carry potentially significant civil fines and criminal penalties, including imprisonment, fines, administrative federal civil monetary penalties, and exclusion from participation in federal healthcare programs.

This law applies to our marketing practices, educational programs, pricing policies and relationships with healthcare providers, by prohibiting, among other things, soliciting, receiving, offering or providing remuneration intended to induce the purchase or recommendation of an item or service reimbursable under a federal healthcare program, such as the Medicare or Medicaid programs.

3 unchanged sentences

We continue to evaluate what effect, if any, these rules will have on our business;

• federal civil and criminal false claims and civil monetary penalty laws, such as the federal FCA, which impose criminal and civil penalties and authorize civil whistleblower or qui tam actions, against individuals or entities for, among other things:

• the federal civil and criminal false claims and civil monetary penalty laws, such as the federal FCA, which impose criminal and civil penalties and authorize civil whistleblower or qui tam actions, against individuals or entities for, among other things:

knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false, fictitious or fraudulent;

7 unchanged sentences

Our marketing and activities relating to the reporting of wholesaler or estimated retail prices for our products, the reporting of prices used to calculate Medicaid rebate information and other information affecting federal, state and third-party reimbursement for our products, and the sale and marketing of our products and any future product candidates are subject to scrutiny under this law;

• the Health Insurance Portability and Accountability Act of 1996 ("HIPAA"), which prohibits knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters;

• HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 ("HITECH"), and their respective implementing regulations, which impose requirements on certain covered healthcare providers, health plans and healthcare clearinghouses as well as their respective business associates who perform services for them that involve the use, or disclosure of, individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information.

HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business

associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs;

• the federal transparency requirements under the ACA, including the provision commonly referred to as the Physician Payments Sunshine Act, which require manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to the HHS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.

Effective January 1, 2022, these reporting obligations will extend to include transfers of value made to certain non-physician providers such as physician assistants and nurse practitioners;

• federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers;

• the Health Insurance Portability and Accountability Act of 1996 (HIPAA), which prohibits, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters.

Similar to the federal Anti-Kickback Statute, a person or entity can be found guilty of violating HIPAA without actual knowledge of the statute or specific intent to violate it;

• HIPAA, as further amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (HITECH), and their respective implementing regulations, including the Final Omnibus Rule published in January 2013, which impose certain requirements on certain covered healthcare providers, health plans and healthcare clearinghouses as well as their respective business associates who perform services for them that involve the creation, maintenance, receipt, use, or disclosure of, individually identifiable health information, relating to the privacy, security and transmission of individually identifiable health information.

HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs.

In addition, there may be additional federal, state and non-U.S.

laws which govern the privacy and security of health and other personal information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts;

• the federal transparency requirements under the ACA, including the provision commonly referred to as the Physician Payments Sunshine Act, which require manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to Centers for Medicare & Medicaid Services information related to payments or other transfers of value made to physicians, nurse practitioners, certified nurse anesthetists, physician assistants, clinical nurse specialists, and certified nurse midwives as well as teaching hospitals.

Manufacturers are also required to disclose ownership and investment interest held by physicians and their immediate family members;

• federal price reporting laws, which require manufacturers to calculate and report complex pricing metrics in an accurate and timely manner to government programs;

2 unchanged sentences

officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment.

The ACA broadened the reach of the fraud and abuse laws by, among other things, amending the intent requirement of the federal AKS and the applicable criminal healthcare fraud statutes contained within 42 U.S.C.

Pursuant to the statutory amendment, a person or entity no longer needs to have actual knowledge of this statute or specific intent to violate it in order to have committed a violation.

In addition, the ACA provides that a claim including items or services resulting from a violation of the federal AKS constitutes a false or fraudulent claim for purposes of the civil FCA or the civil monetary penalties statute.

Many states have adopted laws similar to the federal AKS and FCA, some of which apply to claims for, and referral of patients for, healthcare items or services reimbursed by any source, not only the Medicare and Medicaid programs.

Similarly, state privacy laws may be broader and require greater protections than HIPAA.

12 unchanged sentences

Several states and local laws also impose other marketing restrictions or require pharmaceutical companies to make marketing or price disclosures to the state, require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers, and require the registration of pharmaceutical sales representatives.

Violations of fraud and abuse laws may be punishable by administrative, criminal and/or civil sanctions, including penalties, damages, disgorgement, fines, individual imprisonment, reputational harm, the curtailment or restructuring of our operations, and/or exclusion or suspension from federal and state healthcare programs such as Medicare and Medicaid and debarment from contracting with the U.S.

In addition, private individuals have the ability to bring actions on behalf of the U.S.

government under the federal FCA as well as under the false claims laws of several states.

European Data Collection and Privacy Laws

The collection, use, storage, disclosure, transfer, or other processing of personal data, including personal health data, regarding individuals in the EU are governed by, as of May 2018, the General Data Protection Regulation (“GDPR”).

The GDPR is wide-ranging in scope and imposes several requirements relating to the legal bases for processing personal information, the information provided to the individuals regarding data processing activities, the notification of data breaches, certain measures to take when engaging third-party processors, and the implementation of safeguards to protect the security and confidentiality of personal data.

GDPR also impose strict rules on the transfer of personal data out of the European Economic Area.

GDPR includes substantial fines for breaches of the data protection rules, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater.

GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of GDPR.

In addition, GDPR includes restrictions on cross-border data transfers.

GDPR regulations may impose additional responsibility and liability in relation to personal data that we process where such processing is subject to GDPR, and we may be required to put in place additional mechanisms ensuring compliance with GDPR, including as implemented by individual countries.

This may be onerous and adversely affect our business, financial condition, results of operations, and prospects.

Further, the United Kingdom’s decision to leave the EU, often referred to as Brexit, has created uncertainty with regard to data protection regulation in the United Kingdom.

In particular, it is unclear how data transfers to and from the United Kingdom will be regulated now that the United Kingdom has left the EU.

State and foreign laws, including for example the European Union General Data Protection Regulation, which became effective May 2018 also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

There are ambiguities as to what is required to comply with these state requirements and if we fail to comply with an applicable state law requirement we could be subject to penalties.

there are state and foreign laws governing the privacy and security of health information, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

The scope and enforcement of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations.

Federal and state enforcement has led to a number of investigations, prosecutions, convictions and settlements in the healthcare industry.

Ensuring that our internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs.

It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations.

EU and UK Data Protection Laws

In the European Union (EU), the General Data Protection Regulation (GDPR) governs the processing of personal data.

The GDPR imposes a broad range of strict requirements on companies subject to the GDPR, such as including requirements relating to having legal bases for processing personal data relating to identifiable individuals and transferring such information outside the European Economic Area, or EEA, including to the U.S.

(see below), providing details to those individuals regarding the processing of their personal data, implementing safeguards to keep personal data secure, having data processing agreements with third parties who process personal data, providing information to individuals regarding data processing activities, responding to individuals’ requests to exercise their rights in respect of their personal data, obtaining consent of the individuals to whom the personal data relates, reporting security and privacy breaches involving personal data to the competent national data protection authority and affected individuals, appointing data protection officers, conducting data protection impact assessments, and record-keeping.

The GDPR substantially increases the penalties to which we could be subject in the event of any non-compliance, including fines of up to €20,000,000 or 4% of total annual global revenue, whichever is greater.

The GDPR increases the responsibility and liability of pharmaceutical companies in relation to processing personal data, and companies may be required to put in place additional mechanisms to ensure compliance with the new EU data protection rules.

In addition, further to the UK’s exit from the EU on January 31, 2020, the GDPR ceased to apply in the UK at the end of the transition period on December 31, 2020.

However, as of January 1, 2021, the UK’s European Union (Withdrawal) Act 2018 incorporated the GDPR (as it existed on December 31, 2020 but subject to certain UK specific amendments) into UK law, referred to as the UK GDPR.

The UK GDPR and the UK Data Protection Act 2018 set out the UK’s data protection regime, which is independent from but aligned to the EU’s data protection regime.

Non-compliance with the UK GDPR may result in monetary penalties of up to £17.5 million or 4% of worldwide revenue, whichever is higher.

Although the UK is regarded as a third country under the EU’s GDPR, the European Commission (EC) has now issued a decision recognizing the UK as providing adequate protection under the EU GDPR and, therefore, transfers of personal data originating in the EU to the UK remain unrestricted.

Like the EU GDPR, the UK GDPR restricts personal data transfers outside the UK to countries not regarded by the UK as providing adequate protection.

The UK government has confirmed that personal data transfers from the UK to the EEA remain free flowing.

To enable the transfer of personal data outside of the EEA or the UK, adequate safeguards must be implemented in compliance with European and UK data protection laws.

On June 4, 2021, the EC issued new forms of standard contractual clauses for data transfers from controllers or processors in the EU/EEA (or otherwise subject to the GDPR) to controllers or processors established outside the EU/EEA (and not subject to the GDPR).

The new standard contractual clauses replace the standard contractual clauses that were adopted previously under the EU Data Protection Directive.

The UK is not subject to the EC’s new standard contractual clauses but has published a draft version of a UK-specific transfer mechanism, which, once finalized, will enable transfers from the UK.

We will be required to implement these new safeguards when conducting restricted data transfers under the EU and UK GDPR and doing so will require significant effort and cost.

PRC Regulation

6 unchanged sentences

The DAL applies to entities and individuals engaged in the development, production, trade, clinical use, as well as supervision and administration of pharmaceutical products by regulatory agencies.

It provides for a framework for regulating pharmaceutical manufacturers, pharmaceutical trading companies, medical institutions, and the research, development, manufacturing, distribution, packaging, pricing, and advertisement activities related to pharmaceutical products.

It provides for a framework for

regulating pharmaceutical manufacturers, pharmaceutical trading companies, medical institutions, and the research, development, manufacturing, distribution, packaging, pricing, and advertisement activities related to pharmaceutical products.

The Implementing Measures of the Drug Administration Law as amended in 2019 provides detailed implementation regulations for the DAL.

24 unchanged sentences

The rDAL also significantly increases and expands penalties for violations.

Depending on various types of violations, the DAL imposes different penalties, including warnings, confiscation of illegal gains, fines of up to RMB5 million (about $725,000) or up to 30 times of illegal gains, revocation of required business and operating licenses, certificates or approval documents for drugs, suspension of business, temporary (10 years) or permanent debarment of companies, institutions and responsible persons, and criminal liabilities in the case of serious violations.

Depending on various types of violations, the rDAL imposes different penalties, including warnings, confiscation of illegal gains, fines of up to RMB5 million (about $725,000) or up to 30 times of illegal gains, revocation of required business and operating licenses, certificates or approval documents for drugs, suspension of business, temporary (10 years) or permanent debarment of companies, institutions and responsible persons, and criminal liabilities in the case of serious violations.

There are still uncertainties with respect to the interpretation and implementation of the rDAL.

We plan to closely monitor the implementation of the rDAL and its impact on our operations in China.

Regulatory Authorities and Recent Government Reorganization

Regulatory Authorities and Government Reorganization

In China, the NMPA is the primary regulator for pharmaceutical products and businesses.

The agency was newly formed from the prior China Food and Drug Administration ("CFDA") in 2018 as part of a complete government reorganization.

The agency was formed from the prior China Food and Drug Administration (CFDA) in 2018 as part of a complete government reorganization.

The NMPA is no longer an independent agency.

Its parent agency is now the newly organized the State Administration of Market Regulation (the “SAMR”), into which agencies responsible for, among other areas, consumer protection, advertising, anticorruption, antitrust, fair competition and intellectual property have been merged.

Like the CFDA, the NMPA is still the chief drug regulatory agency and implements the same laws, regulations, rules, and guidelines as the CFDA, and it regulates almost all of the key stages of the life-cycle of pharmaceutical products, including nonclinical studies, clinical trials, marketing approvals, manufacturing, advertising and promotion, distribution, and pharmacovigilance (i.e., post-marketing safety reporting obligations).

Its parent agency is the State Administration of Market Regulation (the SAMR), into which agencies responsible for, among other areas, consumer protection, advertising, anticorruption, antitrust, fair competition and intellectual property have been merged.

pharmacovigilance (i.e., post-marketing safety reporting obligations).

The Center for Drug Evaluation (CDE), which remains under the NMPA, conducts the technical evaluation of each drug and biologic application for safety and efficacy.

4 unchanged sentences

This is the primary way that public hospitals and their internal pharmacies procure drugs.

Also, as part of the 2018 reorganization, the PRC government formed a new State Medical Insurance Bureau which focuses on regulating reimbursement under state-sponsored insurance plans.

Also, as part of the 2018 reorganization, the PRC government formed the State Medical Insurance Bureau which focuses on regulating reimbursement under state-sponsored insurance plans.

Preclinical and Clinical Development

15 unchanged sentences

Each of zanubrutinib, tislelizumab, pamiparib and lifirafenib is classified as Category 1 based on the defined registration category by the NMPA.

Zanubrutinib and tislelizumab have been approved by the NMPA as Category 1 drugs.

Zanubrutinib, pamiparib and tislelizumab have been approved by the NMPA as Category 1 drugs.

Expedited Programs

7 unchanged sentences

If admitted to one of these expedited programs, an applicant will be entitled to more frequent and timely communication with reviewers at the CDE, expedited review and approval, and more agency resources throughout the approval process.

Our NDA for pamiparib and our BLAs for QARZIBA ® and SYLVANT ® have been accepted by CDE and granted priority status .

Amgen's sBLA for BLINCYTO ® has been accepted by the CDE and granted priority status.

Our sNDA for tislelizumab for MSI-H/dMMR solid tumor has been accepted by the CDE and granted priority status.

Conditional Approval

5 unchanged sentences

Following approval, the MAH is required to take risk mitigation measures and complete a post-market study as required by the NMPA within a prescribed timeline.

BRUKINSA ® received conditional approval for the treatment of MCL in adult patients who have received at least one prior therapy and CLL or SLL in adult patients who have received at least one prior therapy.

Tislelizumab received conditional approval as a treatment for patients with cHL who have received at least two prior therapies and as a treatment for patients with locally advanced or metastatic UC, a form of bladder cancer, 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.

and for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors and in patients with multiple myeloma.

BRUKINSA ® received conditional approval for the treatment of MCL in adult patients who have received at least one prior therapy, CLL or SLL in adult patients who have received at least one prior therapy, and for adult patients with WM who have received at least one prior therapy.

Pamiparib received conditional approval for the treatment of patients with germline BRCA (gBRCA) mutation-associated recurrent advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more lines of chemotherapy.

XGEVA ® received conditional approval for the treatment of adults and skeletally mature adolescents with giant cell tumor of the bone (GCTB) that is unresectable or where surgical resection is likely to result in severe morbidity and for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors and in patients with multiple myeloma.

BLINCYTO ® received conditional approval for the treatment of adult patients with R/R B-cell precursor acute lymphoblastic leukemia.

KYPROLIS ® received conditional approval for the treatment of adult patients with R/R multiple myeloma.

QARZIBA ® received conditional approval for high-risk neuroblastoma.

Breakthrough Therapy Designation

2 unchanged sentences

Applicants of drugs designated as breakthrough therapies will be entitled to direct communications with CDE at key states during the clinical trials, and may seek CDE’s opinion on study progress.

Amgen's investigational KRAS G12C inhibitor sotorasib was granted BTD in China for patients with KRAS G12C -mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy.

Amgen's KRAS G12C inhibitor sotorasib was granted BTD in China for patients with KRAS p.G12C -mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy.

BRUKINSA ® as a treatment for adult patients with CLL/SLL was granted BTD in China.

ZW25 (zanidatamab) as a treatment for R/R HER2-expressing biliary tract cancer was granted BTD.

New Policies on Expediting Approval of Imported Oncology Drugs

13 unchanged sentences

The rDAL also expands the number of trial sites by abolishing the GCP accreditation system and requiring trial sites to follow a more simplified notification procedure.

New Policies on Clinical Value-Oriented R&D for Oncology Drugs

The NMPA finalized in November 2011 the Guideline on Clinical Value-Oriented Research and Development for Oncology Drugs, as part of its policies intended to encourage the research and development of innovative oncology drugs with significant clinical value, and discourage repeated research and development of “me-too” drugs with minimal or no clinical value to patients.

Clinical Trial Register

7 unchanged sentences

As BeiGene, Ltd.

is a Cayman Islands company, we and our activities in China are subject to

the HGR Regulation.

is a Cayman Islands company, we and our activities in China are subject to the HGR Regulation.

Such foreign parties seeking access to China’s HGRs for scientific research, including clinical trials intended to support marketing approval of drugs and medical devices in China, must do so only through collaborations with Chinese parties, such as Chinese hospitals.

7 unchanged sentences

As the joint ownership requirement is rather broad, it is unclear how this requirement will be implemented in practice.

The HGR Regulation also significantly increases and expands penalties for various violations, including warnings, disgorgement of illegal gains, confiscation of illegal HGR, fines up to RMB10 million ($1,450,000) or 5-10 times of illegal gains in the event such illegal gains exceed RMB1 million ($145,000), and temporary (1-5 years) or permanent debarment of companies, institutions and responsible persons from future HGR projects regulated by the HGR Regulation.

gains in the event such illegal gains exceed RMB1 million ($145,000), and temporary (1-5 years) or permanent debarment of companies, institutions and responsible persons from future HGR projects regulated by the HGR Regulation.

We expect that HGR-related activities will receive greater attention and focus from regulators going forward.

Trial Exemptions and Acceptance of Foreign Data

The NMPA may be flexible on the requirements of trials and data generated in China, depending on the drug and the existing data.The NMPA has granted waivers for all or part of trials, and has stated that it will accept data generated abroad (even if not part of a global study), including early phase data, that meets its requirements.

The NMPA may be flexible on the requirements of trials and data generated in China, depending on the drug and the existing data.

The NMPA has granted waivers for all or part of trials, and has stated that it will accept data generated abroad (even if not part of a global study), including early phase data, that meets its requirements.

In 2018, the NMPA issued the Technical Guidance Principles on Accepting Foreign Drug Clinical Trial Data (the “Guidance Principles”), as one of the implementing rules for the Opinions on Deepening the Reform of the Evaluation and Approval Systems and Encouraging Innovation on Drugs and Medical Devices (the “Innovation Opinion”).

27 unchanged sentences

This license must be renewed every five years, and the manufacturing facility is also required to be in compliance with GMP.

Similarly, to conduct sales, importation, shipping and storage, a company must obtain a Drug Distribution License from the local drug regulatory authority, subject to renewal every five years.

Similarly, to conduct sales, importation, shipping and storage, a company must obtain a Drug Distribution License (DDL) from the local drug regulatory authority, subject to renewal every five years.

As with GMPs, companies are required to be in compliance with GSP.

One exception is that the rDAL and relevant implementation rules allow the MAH to conduct wholesales of its drugs directly without holding a separate DDL for wholesale, however, a retail DDL would still be required if the MHA intends to conduct direct retail to patients.

China has developed a “Two-Invoice System” to control distribution of prescription drugs.

22 unchanged sentences

Regulatory Intellectual Property Protections

In January 2020, the United States and China signed the Economic and Trade Agreement Between the United States of America and the PRC (the “Trade Agreement”).

Among other things, China agreed to provide for effective protection and enforcement of pharmaceutical-related intellectual property rights, including patents and undisclosed test or other data submitted as a condition of marketing approval, as further described below.

These provisions of the Trade Agreement will need to be implemented in China.

In October 2020, amendments to the PRC Patent Law (the “Amended PRC Patent Law”) were adopted that will become effective on June 1, 2021.

The amendments to the PRC Patent Law (the “Amended PRC Patent Law”) became effective on June 1, 2021.

The Amended PRC Patent Law contains both patent term extension and a mechanism for early resolution of patent disputes, which may be comparable to patent linkage in the United States.

However, the provisions for patent term extension and an early resolution mechanism are unclear and/or remain subject to the approval of implementing regulations that are still in draft form or have not yet been proposed, leading to uncertainty about their scope and implementation.

However, the provisions for patent term extension are unclear and/or remain subject to the approval of implementing regulations that are still in draft form or have not yet been proposed, leading to uncertainty about its scope and implementation.

Non-Patent Exclusivities

New Drug Monitoring Period

Previously, new varieties of domestically produced drugs approved under Categories 1 or 2 in China could be placed under a monitoring period for three to five years.

Category 1 innovative drugs were monitored for five years.

During the monitoring period, the NMPA would not approve another CTA from another applicant for the same type of drug, except if another sponsor had an approved CTA at the time that the monitoring period was initiated, it could proceed with its trial and once approved become another drug that was part of the monitoring period.

The DRR has abolished these new drug monitoring period programs;

however, drugs that had been placed under a monitoring period before the DRR took effect are still entitled to exclusivity before the monitoring periods end.

Regulatory Data Protection

The Innovation Opinion provided a foundation to improve and implement a system for regulatory data protection to protect innovative drugs.

This protection will be available for undisclosed clinical trial data of drugs falling into the following categories:

This protection will be available for undisclosed clinical trial data of drugs falling into the following

innovative drugs, innovative therapeutic biologics, drugs that treat orphan diseases, pediatric drugs, and drugs for which there has been a successful patent challenge.

10 unchanged sentences

Patent Linkage

The Innovation Opinion also sets forth the basic elements of a patent linkage system to protect innovators, in which a follow-on applicant will be required to specify patents that are relevant to its application and notify relevant patent right holders (including, innovators) within a specified period after filing its application, permitting them to sue to protect their rights.

The system will require that the NMPA continue to review the potentially infringing follow-on application during any lawsuit by the innovator.

However, the NMPA may not approve the follow-on application pending resolution of the patent litigation in favor of the follow-on application or for a specified period of time, whichever is shorter.

Similarly, the Trade Agreement also adopted

certain elements of a patent linkage system:

notice to the patent right holder of the follow-on application;

and time and opportunity for that right holder to sue and seek expeditious remedies to obtain a timely resolution of the patent dispute.

However, the Trade Agreement did not explicitly mention a stay of marketing approval of the follow-on application.

The Amended PRC Patent Law provides a cause of action to allow a patent holder to initiate a declarative action during the regulatory review process of a drug to determine whether the drug falls within the patent scope, which may be comparable to the patent linkage system in the United States.

However, the provisions for the early resolution mechanism are unclear and/or remain subject to the approval of implementing regulations that are still in draft form, leading to uncertainty about the scope of implementation.

The system requires that the NMPA continue to review the potentially infringing follow-on application during any lawsuit by the innovator.

However, the NMPA may not approve the follow-on application pending resolution of the patent litigation in favor of the follow-on application or for a specified period of time, whichever is shorter.

Patent Term Extension

In early 2019, pursuant to the Innovation Opinion, the National People’s Congress issued a proposal for patent term extension as part of a proposed amendment to the Patent Law.

Under this proposal, the State Council may grant a patent term extension of up to five years to compensate for delays in the review process for innovative drugs that are applying simultaneously for marketing approval in both China and abroad.

The patent term may not be extended to more than 14 years post-marketing.

The Trade Agreement also provides for patent term extension to compensate for unreasonable delay that occurs during pharmaceutical product marketing approvals.

The Amended PRC Patent Law provides that the China National Intellectual Property Administration shall provide patent term extension, similar to the United States, for the patent term lost during the regulatory review process of a new drug upon the patent holder’s request.

The Amended PRC Patent Law provides patent term extension, similar to the United States, for the patent term lost during the regulatory review process of a new drug upon the patent holder’s request.

The extended term shall not exceed five years, and the total patent term after market entry of the new drug shall not exceed 14 years.

10 unchanged sentences

In addition, the government has also been negotiating with manufacturers of expensive drugs with high clinical demands and proven effectiveness for price cuts in exchange for inclusion into the NRDL.

The version of the NRDL released in 2021 covers 2,800 drugs in total, including 221 drugs for which the prices were determined through negotiations between the drug companies and government.

The version of the NRDL released in 2021 covers approximately 2,800 drugs in total, including 221 drugs for which the prices were determined through negotiations between the drug companies and government.

China has been pursuing a policy of expediting the addition of innovative oncology drugs to this list.

1 unchanged sentence

VIDAZA ® has been included in the NRDL since 2018.

BRUKINSA ® (zanubrutinib), tislelizumab, and XGEVA ® (120-mg denosumab) will be included in the NRDL in March 2021.

BRUKINSA ® (zanubrutinib), tislelizumab, and XGEVA ® (120-mg denosumab) have been included in the NRDL in March 2021.

PARP inhibitor pamiparib has been included in the NRDL in 2021, which became effective as of January 1, 2022.

Government Price Controls

3 unchanged sentences

Under current regulations, public medical institutions owned by the government or owned by state-owned or controlled enterprises are required to purchase pharmaceutical products through centralized online procurement processes.

There are exceptions for drugs on the National List of Essential Drugs, which must comply with their own procurement rules, and for

certain drugs subject to the central government’s special control, such as toxic, radioactive and narcotic drugs, and traditional Chinese medicines.

There are exceptions for drugs on the National List of Essential Drugs, which must comply with their own procurement rules, and for certain drugs subject to the central government’s special control, such as toxic, radioactive and narcotic drugs, and traditional Chinese medicines.

The centralized procurement process takes the form of public tenders that are typically conducted once every year by provincial or municipal-level government agencies.

20 unchanged sentences

The Foreign Investment Law of the PRC (the “Foreign Investment Law”) and its implementing rules (the “Implementing Rules”) took effect in 2020 and replaced previous laws and regulations governing foreign investment in China.

The Foreign Investment Law and Implementating Rules establish a basic framework for access to, and the promotion and administration of foreign investments in China.

The Foreign Investment Law and Implementing Rules establish a basic framework for access to, and the promotion and administration of foreign investments in China.

They reflected China’s legislative efforts to rationalize China’s foreign investment regulatory regime in line with prevailing international practice and to unify legal requirements for both foreign and domestic investments.

5 unchanged sentences

Foreign investors shall not invest in the prohibited fields as specified in the negative list, and foreign investors who invest in the restricted fields shall comply with certain special requirements including the shareholding percentage and citizenship of senior executives.

The current industry entry clearance requirements governing foreign investment activities in the PRC are set out in two categories, namely the Special Entry Management Measures for the Access of Foreign Investment (2019 version) (the “Negative List”), and the Encouraged Industry Catalogue for Foreign Investment (2019 version) (the “2019 Encouraged Industry Catalogue”).

The current industry entry clearance requirements governing foreign investment activities in the PRC are set out in two categories, namely the Special Entry Management Measures for the Access of Foreign Investment (Negative List) (2021 version), and the Encouraged Industry Catalogue for Foreign Investment (2020 version) (the “2020 Encouraged Industry Catalogue”).

Industries not listed in these two categories are generally deemed “permitted” for foreign investments unless specifically restricted by other applicable PRC laws or regulations.

Pursuant to the

2019 Encouraged Industry Catalogue, the research, development and manufacture of innovative oncology drugs and certain other types of pharmaceutical products belongs to the encouraged industries for foreign investment.

Pursuant to the 2020 Encouraged Industry Catalogue, the research, development and manufacture of innovative oncology drugs and certain other types of pharmaceutical products belongs to the encouraged industries for foreign investment.

Regulations Relating to Product Liability

Under a new law which took effect in 2021, a defective product which causes property damage or physical injury to any person may subject the manufacturer or vendor of such product to civil liability for such damage or injury.

Additionally, China's Product Quality Law, first adopted in 1993 and most recently amended in 2018, governs the supervision and administration of product quality, aiming to protect the rights end-users and consumers.

Under a law which took effect in 2021, a defective product which causes property damage or physical injury to any person may subject the manufacturer or vendor of such product to civil liability for such damage or injury.

Additionally, China's Product Quality Law, first adopted in 1993 and amended in 2018, governs the supervision and administration of product quality, aiming to protect the rights end-users and consumers.

According to the Product Quality Law, manufacturers is liable for the quality of products produced by them, and sellers are required take measures to ensure the quality of the products sold by them.

4 unchanged sentences

A seller is liable for compensating for any bodily injury or property damage of others caused by the defects in the product if such defects are attributable to the seller.

A seller is required t pay compensation if it fails to indicate either the manufacturer or the supplier of the defective product.

A seller is required to pay compensation if it fails to indicate either the manufacturer or the supplier of the defective product.

A person who is injured or whose property is damaged by the defects in the product may claim compensation from the manufacturer or the seller.

14 unchanged sentences

In 2019, SAFE issued the Circular of the State Administration of Foreign Exchange on Further Promoting the Facilitation of Cross-border Trade and Investment (Circular 28).

Circular 28 allows non-investment foreign-invested enterprises to use their capital funds to make equity investments in China, provided that such investments do not violate the effective special entry management measures for foreign investment (negative list) and the target investment projects are genuine and in compliance with laws.

Circular 28 allows non-investment foreign-invested enterprises to use their

capital funds to make equity investments in China, provided that such investments do not violate the effective Special Entry Management Measures for Foreign Investment (Negative List) and the target investment projects are genuine and in compliance with laws.

The interpretation and implementation of Circular 28 in practice are subject to substantial uncertainty.

23 unchanged sentences

and that offer choice where possible so they can customize benefits to meet their needs and the needs of their families.

In response to the COVID-19 pandemic, we implemented significant changes that we determined were in the best interest of our employees, as well as the communities in which we operate, and which comply with government regulations.

This included having our employees work from home and implementing additional safety measures for employees continuing critical work at our offices or in the field.

In order to support our employees during the COVID-19 pandemic, we implemented significant changes that we determined were in the best interest of our employees, as well as the communities in which we operate, and which comply with government regulations.

This included initiating a number of mental-health programs and offering supplemental resources that are available to all of our employees, having our employees work from home and implementing additional safety measures for employees continuing critical work at our offices or in the field, as well as encouraging employees to adhere to preventative measures recommended by the World Health Organization, U.S.

Centers for Disease Control and Prevention, and similar public health authorities.

Our worldwide teams are united by a common mission.

1 unchanged sentence

Our management team routinely makes themselves available to all employees, including in regular town hall events that encourage open dialogue.

Fostering a culture of accountability and compliance is also central to our human resource management.

All of our employees complete trainings

on applicable corporate policies including our global Code of Conduct;

Harassment, Discrimination, and Retaliation Policy;

Conflicts of Interest Policy;

Insider Trading Policy;

and Anti-Corruption Policy.

We strive to provide competitive compensation and benefits programs to help meet the needs of our employees.

In addition to base salaries, these programs include potential annual discretionary bonuses, stock awards, a 401(k) plan in the United States and pension plans in other jurisdictions, healthcare and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, and flexible work schedules, among others.

In addition to base salaries, these programs include potential annual discretionary bonuses, equity awards, a 401(k) plan in the United States and pension plans in other jurisdictions, healthcare and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, and flexible work schedules, among others.

In addition to our broad-based equity award programs, we have used targeted equity-based grants with vesting conditions to facilitate retention of personnel.

1 unchanged sentence

We seek to remain competitive in our compensation and benefits by routinely benchmarking against industry peers.

As part of our mission to create the innovative medicines to serve the patients, we continue to advance our environmental, social and governance efforts, including enhancing the diversity and inclusiveness of our workplace.

As part of our mission to create the innovative medicines to serve the patients, we continue to advance our environmental, social and governance (ESG) efforts, including enhancing the diversity and inclusiveness of our workplace.

We believe that diversity of backgrounds and ideas inspires creativity and helps us create the innovative medicines patients need.

We appreciate one another’s differences and strengths, and are proud to be an equal opportunity employer.

BeiGene does not discriminate on the basis of race, religion, color, sex, gender identity, sexual orientation, age, non-disqualifying physical or mental disability, national origin, veteran status or any other basis covered by appropriate law.

All employment is decided on the basis of qualifications, merit, and business need.

1 unchanged sentence

We maintain an inclusive culture where all voices are welcomed, heard, and respected.

As of January 31, 2021, we had approximately 5,300 full-time employees.

As of January 31, 2022, we had approximately 8,200 full-time employees worldwide, with approximately 1,200 employees in the United States and approximately 7,000 employees outside of the United States.

We have also engaged and may continue to engage independent contractors to assist us with our operations.

1 unchanged sentence

We have never experienced any employment-related work stoppages, we also track voluntary and involuntary turnover rates and we consider our relations with our employees to be good.

Environmental, Social and Governance (ESG) Strategy

BeiGene’s mission is to expand access to high-quality, affordable medicines to billions more people globally.

We are driven to deliver affordable medicines to all and create a more equitable and sustainable world for our patients, employees, and our communities.

In 2021, we formalized our ESG function, led by a new Senior Director, Global Reputation and ESG Lead who has led the development of a new global ESG strategy and framework which will be announced in our 2021 ESG Report, published in late April 2022.

We expect to use this new framework to guide the development of goals and targets for our most material issues, and it will center around five key focus areas that are designed to speak to the needs of our diverse stakeholders.

Within each focus area, we have identified two strategic priorities against which we will set concrete targets and report our progress.

While we are at the start of our ESG journey, we are proud of the progress we have made to date.

We have conducted our first global greenhouse gas inventory for scopes 1 and 2 emissions and plan to announce new measures to understand and further mitigate our climate impacts in 2022.

We have implemented a new Supplier Code of Conduct which outlines our expectations related to good governance, labor practices, environment, health and safety (EHS), and transparency.

In 2021, we refined our company values to four that encapsulate what it means to be a part of BeiGene.

These values are:

Patients First;

Collaborative Spirit;

Bold Ingenuity;

and Driving Excellence.

We believe that our people are critical to our success and, as a global company, we know that sharing diverse ideas and perspectives spurs greater innovation and enhances our ability to deliver results.

Our culture celebrates and encourages the voices of all our employees and promotes a respectful, collaborative environment.

In 2020, we formed the Inclusion, Diversity, Equity, and Awareness (IDEA) Council to provide a forum for U.S.

employees to explore issues of diversity, equity, inclusion, and belonging.

In 2021, we hired a Vice President to lead diversity, equity, and inclusion (DEI) and will expand the IDEA Council to have representation beyond the U.S.

In addition to directly supporting patients through the delivery of cutting-edge therapies, we strive to support our communities through research, education, and sponsorships.

We support patient advocacy organizations, charitable foundations, and hospitals through cash and in-kind donations.

More details about our ESG strategy, goals and progress to date will be available in our 2021 ESG Report, which will be developed with reference to the Global Reporting Initiative Standards and published in late April 2022.

Our previous ESG Reports can be found online at:

https://hkexir.beigene.com/governance/esg-report/ .

Financial Information

14 unchanged sentences

We also make available, free of charge on our website, the reports filed with the SEC by our executive officers, directors and 10% shareholders pursuant to Section 16 under the Exchange Act.

Additionally, we make available on our website our securities filings with the HKEx.

We make this information available on or through our website free of charge as soon as reasonably practicable after we electronically file the information with, or furnish it to, the SEC and the HKEx.

Additionally, we make available on our website our securities filings with the HKEx and the Shanghai Stock Exchange (SSE).

We use our website as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business