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Item 1. Business

2021-02-25 compared with 2020-03-02 · 1063 added, 953 removed, 635 unchanged (76% of the section changed)

We are a global commercial-stage biotechnology company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology cancer therapeutics.

We started as a research and development company in Beijing in 2010.

Over the last ten years, we have developed into a fully-integrated global biotechnology company, with significant commercial, manufacturing, and research and development capabilities.

We have built substantial commercial capabilities in the People's Republic of China ("PRC" or "China") and the United States, and are currently marketing two internally-developed drugs and three in-licensed drugs.

We also anticipate introducing five more in-licensed drugs into the China market in the next one to two years.

In the United States, we market BRUKINSA ™ (zanubrutinib) for adult patients with mantle cell lymphoma ("MCL") who have received at least one prior therapy and in China, we have received marketing approval and are in the process of launching tislelizumab for patients with classical Hodgkin’s Lymphoma ("cHL") who have received at least two prior therapies.

We have filed four additional supplementary new drug applications ("sNDA") for regulatory approvals in China and are planning for launches in these additional indications in 2020.

Our in-licensed portfolio includes ABRAXANE ® , REVLIMID ® and VIDAZA ® , which we have been marketing in China since 2017 under a license from Celgene Logistics Sàrl, a Bristol-Myers Squibb company ("BMS").

We plan on launching additional in-licensed products in China from our collaborations, including XGEVA ® (denosumab), KYPROLIS ® (carfilzomib) and BLINCYTO ® (blinatumomab) from Amgen Inc.

("Amgen"), and SYLVANT ® (siltuximab) and QARZIBA ® ▼ (dinutuximab beta), from EUSA Pharma ("EUSA").

We have built deep clinical development capabilities, including a more than 1,100-person global clinical development team that is running over 60 ongoing or planned clinical trials that have enrolled over 7,500 patients and healthy subjects.

We are conducting late-stage clinical trials of BRUKINSA and tislelizumab, including 26 registration or registration-enabling trials in 15 discrete cancer indications.

Our internal research capabilities have yielded another late-stage asset, pamiparib, and five other internally-developed drug candidates are currently in early-stage clinical development.

In addition, we have been able to leverage our capabilities and China’s rising importance as a clinical science center to expand our clinical and pre-clinical portfolio with in-licensed drug candidates.

We are also working with high-quality contract manufacturing organizations ("CMOs") to manufacture our internally-developed commercial and clinical products in China and globally and have built state-of-the-art small molecule and biologic manufacturing facilities in China to support the launches and potential future demand of our internally-developed products.

Based on the strength of our China-inclusive global development and commercial capabilities, we have entered into collaborations with leading pharmaceutical and biotechnology companies to develop and commercialize innovative medicines in China and the Asia-Pacific region.

In October 2019, we entered into a strategic collaboration with Amgen pursuant to which we have agreed to collaborate on the commercialization of Amgen’s oncology products XGEVA, KYPROLIS, and BLINCYTO in China, and the global development and future commercialization in China of up to 20 of Amgen's clinical- and late pre-clinical-stage pipeline products, including AMG 510, Amgen’s first-in-class investigational KRAS G12C inhibitor.

Our mission is to become a global leader in the discovery, development, and commercialization of innovative medicines for the treatment of cancer.

Key elements of our strategy are as follows:

Realize Two Large Commercial Opportunities with BRUKINSA (zanubrutinib) and tislelizumab.

Zanubrutinib is a wholly-owned, potentially best-in-class small molecule inhibitor of Bruton’s tyrosine kinase ("BTK") for B-cell malignancies.

We believe zanubrutinib may have efficacy and safety advantages compared to the other approved BTK therapies based on its ability to achieve full BTK occupancy and minimize off-target binding.

There is a large global commercial opportunity for BTK inhibitors, with global revenues totaling approximately $5.8 billion in 2019 according to published reports.

We believe that our clinical experience to date in over 2,500 patients, along with our broad clinical development plan, position us to capitalize on this commercial opportunity.

In November 2019, we received accelerated approval for BRUKINSA from the U.S.

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

We have built a commercial team in the United States and launched BRUKINSA in late 2019.

In addition, we have submitted two new drug applications ("NDAs") in China for zanubrutinib for the treatment of patients with relapsed or refractory ("R/R") MCL and patients

with R/R chronic lymphocytic leukemia ("CLL") or small lymphocytic lymphoma ("SLL").

Both applications are being reviewed under priority review status.

We are conducting a broad clinical program for zanubrutinib, with near-term data readouts expected, both as a monotherapy and in combination with other therapies.

Our most recently approved drug is tislelizumab, a wholly-owned antibody against the immune checkpoint receptor programmed cell death protein 1 ("PD-1") that was designed to minimize Fc-gamma receptor binding, which is believed to play an essential role in activating phagocytosis in macrophages, to minimize its negative impact on T effector cells.

We received approval from China’s National Medical Products Administration ("NMPA") in December 2019 to market tislelizumab for the treatment of patients with cHL who have received at least two prior therapies.

In addition, we have filed an sNDA in China for tislelizumab in patients with previously treated locally advanced or metastatic urothelial carcinoma ("UC") which has been granted priority review by the Center for Drug Evaluation ("CDE") at the NMPA and is currently under review.

We believe that there is a large and growing opportunity for novel cancer therapeutics in China and the market opportunity for PD-1/PD-L1 antibody therapies may be especially attractive, as this class of agents has demonstrated anti-tumor activity in all four of the most common tumors in China:

lung cancer, gastric cancer ("GC"), liver cancer and esophageal cancer ("EC").

According to published reports, China has a higher proportion of PD-1 responsive tumors in its total annual cancer incidence in comparison to other geographies like the U.S.

According to a published study (Chen et al., Cancer Statistics in China, 2015, CA:

66(2):115-32), which we refer to as 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.

We believe that we are uniquely positioned to capture this opportunity with our strong presence and experience in China, our global clinical development capabilities, the breadth of our development plan, which has enrolled more than 5,000 patients to date, including 15 registration or potentially registration-enabling trials, and high-quality manufacturing.

Utilize Our Key Strategic Clinical and Commercial Capabilities.

We believe that recent changes in the regulatory environment in China have led to an unprecedented opportunity in our industry.

Historically, the regulatory environment in China was considered highly challenging, with clinical development delays and regulatory approvals taking much longer than in the United States and the EU.

To address these challenges, the NMPA issued a series of reform policies and opinions, which, among other things, has expanded access to clinical patients and created an opportunity to expedite drug development and approval by removing delays and creating an environment with international quality standards for drug development, manufacturing and commercialization in China.

These regulatory reforms allow clinical trials in China to play a major role in global drug development programs, with the data generated in China used to support approvals outside of China.

However, challenges to benefit from these reforms remain, including limited contract research organization ("CRO") capability, a limited talent pool and clinical data and trial management challenges.

Our strategy has been to aggressively build our clinical development and commercial capabilities in China to take advantage of these changes and mitigate the challenges with accessing China as a clinical science center.

Our global oncology development team is made up of more than 1,100 employees, approximately 60% of whom are in China.

We are dedicated to performing studies that conform to the highest global International Council for Harmonisation ("ICH") standards.

We have initiated 12 global, China-inclusive pivotal studies and 26 pivotal or potentially registration-enabling studies.

We have over 60 ongoing or planned trials and have enrolled over 7,500 patients and healthy subjects in our clinical trials.

From a commercial perspective, our strategy in China is to seek broader access to patients in need of innovative medicines through national reimbursement.

This strategy requires a large commercial organization.

We have increased our commercial capability from just over 150 people when we acquired the commercial operations of Celgene (now part of BMS) in China in 2017 to over 900 people as of the end of 2019.

We believe that we are well-positioned to launch our current and future pipeline of internally-developed and in-licensed drugs in China and take advantage of the opportunity of improved national reimbursement.

Expand Our Portfolio by Leveraging Our Clinical and Commercial Capabilities.

As many leading pharmaceutical and biotechnology companies evaluate opportunities in China, we believe that collaborating with us could allow these companies to efficiently and effectively access deep local clinical development, commercial and manufacturing capabilities at global quality standards.

For example, we have leveraged our unique China-inclusive development and commercial capabilities to expand our portfolio through our collaboration with Amgen.

In addition, we have entered into over 10 transactions since 2017 in which we have added innovative pre-clinical, clinical and/or commercial-stage drugs and drug candidates to our portfolio.

Our strategy is to continue to aggressively evaluate licensing opportunities to add to our pipeline of drugs and drug candidates.

Pursue a New Model for Global Growth.

We believe that the large addressable patient population and the expansion of reimbursement of innovative medicines in China can support a new business model for growth in our industry by allowing R&D investment for these drugs to be leveraged over a significantly larger patient pool, which can enable broader access worldwide with more affordable pricing as compared to the traditional priority market model.

global access and pricing model will allow us to leverage our strong clinical and commercial capabilities in China and globally.

It also provides an opportunity to obtain return on the investments made to develop our portfolio of drug candidates.

We evaluate worldwide markets by researching the opportunities, start-up risks and costs, and our capabilities.

Subsequently, we design targeted market entrance strategies and plan to pursue these global markets in a staged manner based on investment and return analyses.

We plan to seek approvals of our portfolio compounds globally in order for us to capitalize on these opportunities.

Our Commercial Products

The following table summarizes the status of our commercial products as of February 29, 2020:

LEAD INDICATIONS

MECHANISM OF ACTION

REGULATORY STATUS

BEIGENE COMMERCIAL RIGHTS

R/R mantle cell lymphoma

BTK inhibitor

Approved in the United States

R/R classical Hodgkin’s lymphoma

Anti-PD-1 antibody

Approved in China

Breast cancer

Microtubule inhibitor

Approved in China

Mainland China

R/R adult multiple myeloma, newly diagnosed multiple myeloma

Anti-angiogenesis, immuno-modulation

Approved in China

Mainland China

Myelodysplastic syndromes, acute myeloid leukemia, chronic myelomonocytic leukemia

DNA hypomethylation

Approved in China

Mainland China

Giant cell tumor of bone

Anti-RANK ligand antibody

Approved in China

Mainland China

Multiple myeloma

Proteasome inhibitor

NDA filed in China

Mainland China

Acute lymphocytic leukemia

Anti-CD19 x anti-CD3 bispecific (BiTE) antibody

NDA filed in China

Mainland China

Idiopathic multicentric Castleman disease

IL-6 antagonist

Fast track listed in China

Greater China

QARZIBA (dinutuximab beta)

High-risk neuroblastoma

Anti-GD2 antibody

Fast track listed in China

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:

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.

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.

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.

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.

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 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.

Our Commercial and Registration Stage Products

The following table summarizes the status of our commercial products and new products that are pending approval as of February 25, 2021:

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

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

We commercialize the following wholly-owned cancer medicines, for which we have worldwide commercial rights:

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

Approved under accelerated approval.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial 2.

Conditionally approved.

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.

Abbreviations:

CLL = chronic lymphocytic leukemia;

MCL = mantle cell lymphoma;

NSCLC = non-small cell lung cancer;

R/R = relapsed / refractory;

RT = radiotherapy;

SLL = small lymphocytic lymphoma.

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.

On November 14, 2019, BRUKINSA received accelerated approval from the FDA as a treatment for MCL in adult patients who have received at least one prior therapy.

BRUKINSA is the first BeiGene-discovered product to be approved.

Currently, we have a 100-plus person commercial team marketing BRUKINSA in the United States.

In China, we have filed NDAs for the treatment of patients with R/R MCL and patients with R/R CLL/SLL, and those applications are pending under priority review.

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

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

National Cancer Institute, there were 74,200 new NHL cases and 19,970 deaths, and of these NHL cases the incidence of CLL was 20,720 and there were 3,930 deaths from CLL in 2019 in the United States.

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 Waldenström’s macroglobulinemia ("WM").

According to Chen et al.

2016, and GLOBOCAN’s online Global Cancer Observatory analyses on cancer statistics in China, there are an estimated 88,200 to 93,097 new lymphoma cases and 52,100 to 50,865 deaths in China each year, and of the lymphoma cases, approximately 90% are NHL and approximately 4.5% of the NHL cases are CLL/SLL.

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.

Recently, cell-based therapies have been receiving approvals.

These include YESCARTA ® (axicabtagene ciloleucel) and KYMRIAH™ (tisagenlecleucel), both anti-CD19 therapies.

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

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.

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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.

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.

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 currently being evaluated in a broad pivotal clinical program for both solid tumor and hematological indications, both globally and in China.

We submitted an NDA for approval in China in 2018 for the treatment of R/R cHL, which received priority review and was approved on December 26, 2019.

We are planning to launch tislelizumab in China in the first quarter of 2020.

We have also filed a sNDA in China for the treatment of urothelial bladder cancer ("UBC") in May 2019 and expect NMPA approval in 2020, and we expect to submit a sNDA in first line squamous non-small cell lung cancer ("NSCLC") in 2020 based on the positive interim analysis of our Phase 3 study announced in January 2020.

Additionally, we plan to discuss with regulators our Phase 2 study in second- or third-line hepatocellular carcinoma ("HCC") in 2020, and we expect readouts from several studies of tislelizumab in 2020.

We have full commercial rights to tislelizumab, following the termination of our collaboration agreement with Celgene prior to its acquisition by BMS.

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 drugs have been approved by the FDA.

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 clinical development in addition to tislelizumab, such as Novartis’ PDR-001, GlaxoSmithKline/Tesaro’s TSR042, Pfizer’s PF-06801591, and AstraZeneca’s MEDI0680.

In China, as of February 14, 2020, 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 late-stage development in China, of which one has filed for approval as of the end of January 2020.

Globally, the top four PD-1/PD-L1 antibody drugs had sales of approximately $21 billion in 2019 based on public reports.

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

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.

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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 U.S.

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 10 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 10 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.

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.

We commercialize the following cancer drugs 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 BMS’s proprietary nanoparticle albumin-bound (nab ® ) technology platform.

Pamiparib is an investigational, 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").

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:

XGEVA ® (denosumab) is an antibody-based RANK ligand ("RANKL") inhibitor that was approved globally for the prevention of skeletal-related events ("SREs") in patients with bone metastases from solid tumors and in patients with multiple myeloma, and for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone ("GCTB").

XGEVA ® is approved in over 70 countries worldwide.

In China, XGEVA ® received conditional approval in the GCTB indication in May 2019 and received conditional approval for the SRE indications in November 2020.

We began marketing XGEVA ® in China in July 2020.

In December 2020, we announced the inclusion of XGEVA ® in the NRDL for the treatment of GCTB.

GCTB is a relatively rare, benign, but locally aggressive osteolytic skeletal neoplasm of young adults.

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.

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

For patients with aggressive forms of GCTB, who are not candidates for locoregional therapy, e.g., therapy or radiotherapy, XGEVA ® is the preferred treatment option over bisphosphonate, chemotherapy, or interferon.

Metastases to bone are a common site of cancer recurrence for many solid tumors.

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.

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.

It has been approved in 60 countries for use in patients with acute lymphoblastic leukemia ("ALL").

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.

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

It is estimated that there are 0.69 cases of ALL in 100,000 people in China, according to the China NCCR, IARC, and F&S research.

Approximately 15 percent of children fail initial treatment and advance to R/R stage, and BLINCYTO is indicated for the treatment of patients with R/R B-cell precursor ALL.

There are CAR-T therapies being developed for this indication, and tisagenlecleucel from Novartis has been approved by the FDA for treatment of patients including and under 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse.

Clofarabine from Sanofi is also approved in this indication by the FDA.

Neither of these two agents have been approved in China.

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.

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.

There are a number of generic forms of carfilzomib being developed in China by local manufacturers, including Jiangsu Hansoh Pharmaceutical Group Co., Ltd., Chia Tai Tianqing Pharmaceutical Group Co., Ltd., and Yangtze River Pharmaceutical Group Co., Ltd.

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 metastatic breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy.

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.

According to Chen et al.

2016, there were approximately 4.3 million new cancer cases and 2.8 million cancer deaths in China in 2015, with breast cancer as the most common tumor type in Chinese women.

It is estimated that in 2015 breast cancer affected 268,600 women and resulted in 69,500 deaths.

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.

Taxanes are the backbone chemotherapy to treat triple negative breast cancer, Her2+ or aggressive estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer patients.

ABRAXANE is the only currently approved taxane that does not need pre-medication with dexamethasone to prevent hypersensitivity reactions, and several Phase 3 trials have demonstrated its efficacy and safety based on comparison to solvent-based taxanes in both metastatic and neo-adjuvant breast cancer settings.

Unlike other taxanes, ABRAXANE has demonstrated unique and strong efficacy in pancreatic cancer and has become the backbone of first line standard of care for metastatic pancreatic cancer globally.

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

LIPUSU is currently the market leader with approximately one-third of the market share.

ABRAXANE is listed on provincial reimbursement drug lists of Hubei, Ningxia, Jiangsu, and Hunan, as well as in critical illness insurance program in Zhejiang and Shandong.

In January 2020, we were notified by the National Healthcare Security Administration of China that our tender offer for ABRAXANE was one of the winning tenders in China’s centralized procurement process, with a reduction from the current pricing, which is expected to take effect in the second quarter of 2020.

On May 30, 2019 we announced that the NMPA accepted the supplemental import drug application for ABRAXANE in combination with gemcitabine, as a first-line treatment of patients with metastatic adenocarcinoma of the pancreas ("mPC").

REVLIMID (lenalidomide) is an oral immunomodulatory drug 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.

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.

Globally, the incidence of MM is estimated at two to three per 100,000, with a male-to-female ratio of 1.6:1, and most patients are over 40 years old, according to Siegel et al., 2011 and IMS analysis.

It is estimated that the incidence rate of MM is

approximately one to two per 100,000 people in China, or approximately 21,000 new patients in 2019, out of which 10,000 are in urban populations, according to Lu et al., 2014, IMS analysis, and local market research.

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.

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

Although MM cannot be cured, the progression of the disease can be controlled.

The purpose of treatment is to extend patients’ survival and improve quality of life.

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, and generic forms of VELCADE and REVLIMID.

VELCADE currently dominates the market in first-line MM treatment in China, while VELCADE and REVLIMID share the market in the second line.

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.

REVLIMID was listed on the National Reimbursement Drug List ("NRDL") in June 2017.

On November 12, 2019, we announced that REVLIMID received formal inclusion on the NRDL in China for R/R multiple myeloma.

On December 22, 2019 we announced that our sNDA for the use of REVLIMID in R/R indolent lymphoma was accepted by the NMPA.

REVLIMID ® was listed on the NRDL in June 2017.

In November 2019, we announced that REVLIMID ® received formal inclusion on the NRDL in China for R/R multiple myeloma.

In November 2020 our sNDA for the use of REVLIMID ® in combination with rituximab in adult patients with previously treated follicular lymphoma was approved by the NMPA.

VIDAZA ® (azacitidine for injection) is a pyrimidine nucleoside analog that has been shown to reverse the effects of DNA hypermethylation and promote subsequent gene re-expression.

1 unchanged sentence

In January 2018, VIDAZA became commercially available in China.

MDS are a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells.

Approximately seven per 100,000 people are affected with approximately four per 100,000 people newly acquiring the condition each year globally according to Germing et al., 2013.

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.

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 rate is only 0.4-1.1 years and nearly 30% of these patients progress to AML, according to the U.S.

National Comprehensive Cancer Network ("NCCN"), MDS guideline 2013 and MDS Foundation.

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").

DACOGEN ® (decitabine), marketed by Johnson & Johnson, was the first HMA agent approved in China in 2009.

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

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.

and Sichuan Huiyu Pharmaceutical Co., Ltd.

Nevertheless, there are still over 50% of higher-risk MDS patients treated with CCR, and the unmet need remains large.

VIDAZA is the only approved HMA shown to prolong survival for patients with MDS.

Besides reversing the effects of DNA hypermethylation, VIDAZA inhibits protein synthesis via RNA incorporation.

VIDAZA is a Category 1 recommended treatment for patients with intermediate-2 and high-risk MDS, according to the U.S.

NCCN guideline.

It is also a first-line recommended treatment for patients with intermediate-2 and high-risk MDS, according to the Chinese MDS treatment guidelines, and was listed on the NRDL in October 2018.

We are planning to commercialize the following cancer drugs in China under an exclusive license from Amgen:

XGEVA (denosumab) is an antibody-based RANK ligand ("RANKL") inhibitor that was approved globally for the prevention of skeletal-related events ("SREs") in patients with multiple myeloma, for the prevention of SREs in patients with bone metastases from solid tumors and for treatment of adults and skeletally mature adolescents with giant cell tumor of bone ("GCTB").

XGEVA is approved in over 70 countries worldwide.

In China, it was approved in 2019 for patients with GCTB and is in development in China for prevention of skeletal-related events in cancer patients with bone metastases.

KYPROLIS (carfilzomib), a proteasome inhibitor, has been approved in over 60 countries for use in patients with relapsed and/or refractory multiple myeloma ("RRMM").

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

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

It has been approved in 60 countries for use in patients with acute lymphoblastic leukemia ("ALL").

It has been filed in China as a treatment for adult patients with R/R ALL, and the NDA has been accepted and granted priority review by the NMPA.

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

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

It has been been listed for fast-track approval in China by the NMPA under its Review and Approval Procedures for Urgently-Needed Pharmaceutical Drugs Developed Overseas.

QARZIBA (dinutuximab beta), a mouse-human chimeric monoclonal lgG1 antibody, that 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").

It has been been listed for fast-track approval in China by the NMPA under its Review and Approval Procedures for Urgently-Needed Pharmaceutical Drugs Developed Overseas.

VIDAZA ® is a first-line recommended treatment in the Chinese MDS treatment guidelines.

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.

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.

In Japan, the incidence appears to be similar to that seen in the United States;

however, in contrast, MCD appears to be more common than unicentric CD, and HHV-8-associated MCD is rare.

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.

Neuroblastoma is almost exclusively a disease of children.

It is the third most common childhood cancer, after leukemia and brain tumors, and is the most common solid extracranial tumor in children.

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.

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.

Reimbursement and Market Access

Our sales are largely dependent on the availability and extent of coverage and reimbursement by third party payors.

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.

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

Coverage and reimbursement of pharmaceuticals in China comes under the purview of the NHSA, the National Healthcare Security Administration, which oversees the NRDL.

The NRDL is composed of three lists.

The ‘A’ and ‘B’ list are commonly referred to as the ‘regular’ lists.

The A list generally includes older, off-patent medicines, while the B list generally includes newer medicines, some with remaining patent protection, which are reimbursed at a lower rate compared to the A list.

In 2017 a third list was added to the system, often referred to as the ‘C’ list or the ‘negotiation’ list.

This list generally includes newer innovative medicines which are accepted on the list after successful negotiation between the NHSA and the company.

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.

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.

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).

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.

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

It is a tender-based system that provides guaranteed volume for lowered pricing.

Participation in the program requires a product to have passed a quality consistency evaluation ("QCE"), which in turn requires passing a bioequivalence ("BE") comparison often to the originator product.

The system offers a major portion of a market’s volume to winning bidders.

More than one company can win a given tender, and more guaranteed volume is awarded as more bidders win.

The system is still evolving and, as such, the exact terms of how many bidders win and what amount of volume are won and at what price is also evolving.

It is common in China for pharmaceutical companies to employ patient assistance programs to help patients afford their innovative medicines.

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.

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

We offer these types of patient assistance programs to our patients.

In the United States most health insurance coverage is provided by private insurers, often accessed via employer-sponsored plans, and the two main public insurance programs, Medicare and Medicaid.

All three types of programs usually have some type of coverage for pharmaceutical products.

Often this is through a PBM, or pharmacy benefit manager.

The structure of the pharmacy benefit can be quite different for different beneficiaries depending on the negotiations between plan sponsors and plan purchasers.

There is no central list of covered pharmaceuticals in the United States, as there is no single payer system.

As such, the prices paid for pharmaceuticals in the United States can vary.

We offer patient assistance programs in the United States under our myBeiGene program.

This program seeks to enhance access to BRUKINSA ® by assisting with obtaining reimbursement, co-pay assistance when allowed, temporary supply of free product for insurance delays, and free product assistance for some uninsured and underinsured patients.

The programs also seek to support patients and caregivers by providing education and information about BRUKINSA ® and its approved indications, nurse advocates, and connecting patients to sources of support such as support groups and transportation/lodging assistance.

Our Pipeline Products

The following table summarizes the status of our internally-discovered drug candidates as of February 25, 2021:

DRUG CANDIDATES

DOSE EXPANSION

DRUG CANDIDATES PROGRAMS DOSE ESC.

DOSE EXPANSION PIVOTAL FILED MARKETED

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

zanubrutinib (BTK)

R/R MCL (Accelerated approval in the U.S.

R/R MCL, R/R CLL/SLL (NDAs accepted by NMPA)

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

Previously treated CLL/SLL (ibrutinib intolerant)

+ obinutuzumab

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

Previously treated CLL/SLL (ibrutinib, acalabrutinib intolerant)

combination +rituximab 1LMCL

+obinutuzumab R/R FL

+ lenalidomide +/- rituximab R/R DLBCL

tislelizumab (PD-1)

R/R cHL (approved December 26, 2019)

2L+ UC (NDA accepted by NMPA)

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

2L NSCLC, 1L HCC, 2L ESCC

R/R NK/T-cell lymphoma

NSCLC, 1L Non-Sq.

NSCLC, 1L NPC, 1L SCLC

+ chemo 1L Sq.

NSCLC (approved January 13, 2021)

NSCLC (sNDA accepted June 19, 2020)

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

1L GC, 1L ESCC

+ pamiparib (PARP)

+ zanubrutinib (BTK)

B-cell malignancies

pamiparib (PARP)

1L platinum-sensitive GC maintenance

+ pamiparib (PARP) Solid tumors

+ zanubrutinib (BTK) B-cell malignancies

pamiparib (PARP) monotherapy 3L gBRCA+ OC

2L platinum-sensitive OC maintenance

+ TMZ (chemo)

+ RT/TMZ (RT/chemo)

lifirafenib (RAF Dimer)

B-Raf- or K-RAS/N-RAS-mutated solid tumors

BGB-A333 (PD-L1)

monotherapy + tislelizumab

BGB-A425 (TIM-3)

monotherapy + tislelizumab

BGB-A1217 (TIGIT)

1L platinum-sensitive GC maintenance

HER2-BRCA mutated breast cancer

+ TMZ (chemo) Solid tumors

(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

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

BGB-A445 (OX40) + tislelizumab Solid tumors

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

BGB-10188 (PI3-ko) mono;

+ tislelizumab;

BGB-11417 (Bcl-2)

monotherapy + zanubrutinib

Phase 1 in hematologic malignancies planned in 1H 2020

+ zanubrutinib B-cell malignancies;

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

*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 approvals.

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

Abbreviations:

23 unchanged sentences

PD-1 = programmed cell death protein 1;

PD-L1 = programmed death-ligand 1;

R/R = relapsed / refractory;

4 unchanged sentences

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

TIM-3 = T-cell immunoglobulin and mucin-domain containing-3;

TMZ = temozolomide;

2 unchanged sentences

The following table summarizes the status of our in-licensed drug candidates as of February 25, 2021:

DRUG CANDIDATES

DOSE ESCALATION / EXPANSION

COMMERCIAL RIGHTS

(multi-kinase inhibitor) 1

NSCLC, RCC, OC, MEL, HCC/GEJ

Asia ex-Japan, NZ, AU

+ lifirafenib (Raf dimer)

+ zanubrutinib (BTK)

B-cell malignancies

(bispecific HER2 antibody) 2

Planned (in Ph2 ex-China by Zymeworks)

Asia ex-Japan, NZ, AU

(bispecific anti-HER2 ADC) 2

Planned (in Ph1 ex-China by Zymeworks)

Asia ex-Japan, NZ, AU

(KRAS G12C, SM) 3

(EGFRvIII, BiTE) 3

(DLL3, HLE BiTE) 3

(PSMA, HLE BiTE) 3

(PSMA, BiTE) 3

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

(MUC17) GC/GEJC

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

(oral small molecule) Solid tumors

(FAP x 4-1BB, DARPin ® )

(BCMA, HLE BiTE) 3

(BCMA, BiTE) 3

(Mcl-1, SM (i.v.)) 3

(Mcl-1, SM (oral)) 3

(CD33, BiTE) 3

(CD33, HLE BiTE) 3

(FLT3, HLE BiTE) 3

(CD19, HLE BiTE) 3

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

Sitravatinib 2

(multi-kinase inhibitor) + tislelizumab

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

Mono + tislelizumab HCC, GC/GEJC

zanidatamab 3

(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

(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

(HBV core inhibitor) Chronic Hepatitis B virus China

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 approvals.

^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.

Collaboration with Amgen.

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.

Abbreviations:

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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;

EGFRvIII = epidermal growth factor receptor variant III;

FAP = familial adenomatous polyposis;

FLT3 = fms-like tyrosine kinase 3;

GEJ = gastro-esophageal junction;

FLT3 = fms-like tyrosine

GEJC = gastro-esophageal junction cancer;

HER2 = human epidermal growth factor receptor 2;

HBV = hepatitis B virus;

HCC = hepatocellular carcinoma;

1 unchanged sentence

= intravenous;

IL21 = interleukin 21;

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

5 unchanged sentences

OC = ovarian cancer;

PD-1 = Programmed cell death protein 1;

PSMA = prostate-specific membrane antigen;

2 unchanged sentences

SM = small molecule.

Our Clinical-Stage Drug Candidates

A description of our clinical-stage drug candidates and clinical data from selected clinical trials is set forth below.

Our Commercial- and Clinical-Stage Drug Candidates

A description of our commercial- and clinical-stage drug candidates and clinical data from selected clinical trials is set forth below.

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.

Zanubrutinib, a BTK Inhibitor

Zanubrutinib, is a small molecule inhibitor of BTK that is approved in the United States for the treatment of MCL in adult patients who have received at least one prior therapy.

It is currently being evaluated in a broad pivotal clinical program globally and in China as a monotherapy and in combination with other therapies to treat various lymphomas.

Brukinsa (zanubrutinib), a BTK Inhibitor

We are currently evaluating zanubrutinib in a broad pivotal clinical program globally and in China as a monotherapy and in combination with other therapies to treat various lymphomas.

Zanubrutinib has demonstrated higher selectivity against BTK than IMBRUVICA (ibrutinib), an approved BTK inhibitor, based on our biochemical assays;

higher exposure than ibrutinib based on their respective Phase 1 experience in separate studies;

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

We recently 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 higher VGPR rate as well as improvements in safety and tolerability.

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

2 unchanged sentences

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.

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.

Four of the nine studies are Phase 3 and five are designed to be registration-enabling Phase 2 trials.

We have reported results from the monotherapy head-to-head Phase 3 trial versus ibrutinib in WM (ASPEN, NCT03053440), which are being included in several filings globally.

We are also conducting an ongoing Phase 3 trial comparing BRUKINSA ® to bendamustine and rituximab in patients with treatment-naïve ("TN") CLL/SLL (SEQUOIA, NCT03336333) and a head-to-head Phase 3 trial in R/R CLL/SLL versus ibrutinib (ALPINE, NCT03734016).

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.

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 15, 2020, we had enrolled more than 2,500 patients in clinical trials of zanubrutinib, including trials of zanubrutinib in combination with other therapies, which we refer to as combination trials.

A multi-center, open-label Phase 1 trial is 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.

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").

2 unchanged sentences

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 the subject of a press release and a filing with the SEC.

These sources have further details on each study.

The first readout of our late-stage program was recently reported, the ASPEN study in WM (NCT03053440), discussed below.

Mantle Cell Lymphoma

We presented two data sets in MCL at the 15th International Conference on Malignant Lymphoma that took place on June 18-22, 2019 in Lugano, Switzerland (the "2019 ICML"), and it was these two data sets that formed the basis for our accelerated approval in MCL in adult patients who have received at least one prior therapy that we received from the U.S.

FDA in November 2019.

The first trial (NCT03206970, also known as BGB-3111-206) is a single-arm, open-label, multi-center, pivotal Phase 2 trial of zanubrutinib as a monotherapy in patients with R/R MCL.

The trial is being conducted in China and enrolled 86 patients who had received a median of two (1-4) prior lines of therapy.

Patients were treated with zanubrutinib, dosed at 160 mg orally BID.

The primary endpoint of the trial is overall response rate ("ORR") assessed by an independent review committee ("IRC") using PET-based imaging according to the Lugano Classification 2014.

As of the February 15, 2019 data cutoff, 52 patients (60.5%) remained on study treatment.

The median follow-up time for patients enrolled in the trial was 18.4 months (0.3-23.5).

The investigator-assessed ORR was 83.7% (72/86).

The complete response ("CR") rate was 77.9% (67/86) and the PR rate was 5.8% (5/86).

At an earlier data cutoff in March 2018 (8.2 months median follow-up), the ORR, CR and PR were 84.7%, 72.9%, and 11.8% per investigator assessment, and 83.5%, 58.8%, and 24.7% per IRC assessment, respectively.

The 15-month PFS by investigator was estimated at 72.1%, and median PFS follow-up was 19.1 months (0.0-22.3).

With 16.4 months median follow-up (2.3-19.5), the duration of response (DOR) by investigator at 15 months was 67.4%.

The second set of data was the MCL cohort of our BGB-3111-AU-003 study (NCT02343120).

This open-label, multi-center Phase 1/2 trial of zanubrutinib as a monotherapy in patients with different subtypes of B-cell malignancies, including MCL, is being conducted in the United States, Australia, Italy, South Korea, New Zealand, and the United Kingdom.

As of the December 13, 2018 data cut-off, 53 patients with treatment naïve (TN, n=16) or R/R (n=37) MCL had been enrolled in the trial and the median follow-up time was 15.4 months (0.1-38.2).

Forty-eight patients (all 37 R/R and 11 TN) were evaluable for efficacy with median follow-up time of 16.7 months (1.6-38.2) in this analysis, per the Lugano 2014 Classification.

At the time of the data cutoff, 27 patients (13 TN and 14 R/R) remained on study treatment.

The investigator-assessed ORR was 85.4% (41/48);

the CR rate was 29.2% (14/48) and the PR rate was 56.3% (27/48).

The majority of patients were assessed via CT-scan;

PET scan was optional per trial protocol.

The median DOR was 16.2 months (0.03-28.2) for all patients.

The median PFS for patients with R/R MCL was 17.3 months.

Response rates shown in the table below from this study are for the 32 patients who had R/R disease and received the full 160mg BID dose of zanubrutinib.

The following table shows the efficacy data included in our label in the United States for BRUKINSA (zanubrutinib) for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy:

Study BGB-3111-206 (N=86)

Study BGB-3111-AU-003 (N=32)

Median DoR in months (95% CI)

19.5 (16.6, NE)

18.5 (12.6, NE)

overall response rate, CR:

complete response, PR:

partial response, DoR:

duration of response, CI:

confidence interval, NE:

not estimable

* FDG-PET scans were not required for response assessment

In the BGB-3111-206 study, the tolerability of zanubrutinib was generally consistent with previous reports of zanubrutinib treatment in patients with various B-cell malignancies.

The majority of treatment-emergent adverse events ("TEAEs") were grade 1 or 2 in severity, with the most frequently reported being neutrophil count decreased (44.2%), upper respiratory tract infection (34.9%), rash (33.7%), white blood cell count decrease (31.4%), and platelet count decrease (25.6%).

Grade ≥ 3 TEAEs were reported in 36 patients (41.9%), with the most frequently reported being neutrophil count decrease (18.6%), lung infection (7.0%), white blood cell count decrease (5.8%), and anemia (5.8%).

Five patients (5.8%) had TEAEs leading to death (one case each of pneumonia, cerebral hemorrhage, traffic accident, and two cases of death with unknown cause).

Among TEAEs of special interest for BTK inhibitors, hypertension was reported in 13 patients (15.1%), petechiae/purpura/contusion in four patients (4.7%), and major hemorrhage in three patients (3.5%);

no cases of atrial fibrillation/flutter, secondary primary malignancy, or tumor lysis syndrome were reported in this trial.

In the BGB-3111-AU-003 study, the majority of adverse events ("AEs") were grade 1 or 2 in severity.

The most frequently reported AEs included contusion (39.6%), diarrhea (34.0%), upper respiratory tract infection (26.4%), constipation (22.6%), fatigue (22.6%), and rash (18.9%).

Grade ≥ 3 AEs were reported in 54.7% patients, with the most frequent being anemia (9.4%), myalgia (5.7%), cellulitis (5.7%), pleural effusion (5.7%), and pneumonia (5.7%).

Discontinuation due to AEs occurred in 18.9% patients with two determined to be related to study drug (one case each of peripheral edema and subdural hematoma).

There were five deaths due to AEs, which were all determined by the investigators to be unrelated to zanubrutinib treatment.

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

On December 16, 2019, we announced topline results from our Phase 3 ASPEN trial (NCT03053440) of zanubrutinib compared to ibrutinib for the treatment of patients with WM.

The trial did not achieve statistical significance on its primary endpoint of superiority in CR and very good partial response ("VGPR") rates for zanubrutinib compared to ibrutinib, but zanubrutinib demonstrated more frequent VGPRs (28.4% versus 19.2% in overall population) and advantages in safety and tolerability.

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 is the largest Phase 3 trial yet conducted in Waldenström's Macroglobulinemia and the first comparative trial readout for two BTK inhibitors.

The study included two cohorts, a randomized cohort (cohort 1) consisting of 201 patients with a MYD88 mutation and a non-randomized cohort (cohort 2) in which 28 patients with MYD88 wild-type ("MYD88WT") received zanubrutinib because MYD88WT patients have historically responded poorly to ibrutinib therapy.

The randomized cohort 1 enrolled 102 patients (including 83 R/R patients and 19 treatment-naïve ("TN") patients) in the zanubrutinib arm and 99 patients (including 81 R/R patients and 18 TN patients) in the ibrutinib arm.

Patients in the zanubrutinib arm were assigned to receive zanubrutinib 160 mg BID and patients in the ibrutinib arm received 420 mg of ibrutinib QD.

Responses were determined according to the modified Sixth International Workshop on WM Criteria.

Results included:

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%

(88.9 - 98.8)

(75.9 - 91.9)

(81.7 - 94.3)

(78.6 - 92.5)

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

(91.6 - 99.8)

(84.1 - 96.6)

(90.9 - 99.0)

(86.8 - 97.2)

As of data cutoff of August 31, 2019, with a median follow-up of 19.4 months, results from cohort 1 are shown above.

In R/R patients, the VGPR rate as assessed by IRC was 28.9% in the zanubrutinib arm and 19.8% in the ibrutinib arm (2-sided p=0.1160, no patients achieved a CR in either arm).

In the overall patient population, the VGPR rate as assessed by IRC was 28.4% in the zanubrutinib arm and 19.2% in the ibrutinib arm (2-sided descriptive p=0.0921, no patients achieved a CR in either arm).

In the R/R patient population, the major response rate ("MRR"), which is the rate of PR or better, as assessed by IRC was 78.3% in the zanubrutinib arm and 80.2% in the ibrutinib arm;

in the overall patient population, the MRR was 77.5% in the zanubrutinib arm and 77.8% in the ibrutinib arm.

The 12-month progression-free survival (PFS) rate was 92.4% (83.8-96.5) in R/R patients and 89.7% (81.7-94.3) in all patients in the zanubrutinib arm, compared to 85.9% (75.9-91.9) in R/R patients and 87.2% (78.6-92.5) in all patients in the ibrutinib arm;

and the 12-month overall survival (OS) rate was 98.8% (91.6-99.8) for R/R patients and 97.0% (90.9-99.0) for all patients in the zanubrutinib arm, compared to 92.5% (84.1-96.6) in R/R patients and 93.9% (86.8-97.2) in all patients in the ibrutinib arm.

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%

1 unchanged sentence

Major hemorrhage 5.9% 9.2%

Zanubrutinib showed a favorable safety profile compared to ibrutinib, with grade >3 AEs of 58.4% in the zanubrutinib arm and 63.3% in the ibrutinib arm.

In the zanubrutinib arm, four (4.0%) patients discontinued treatment due to AEs and there was one (1.0%) fatal AE;

in the ibrutinib arm, nine patients (9.2%) discontinued due to AEs and there were four (4.1%) fatal AEs.

For AEs of special interest for BTK inhibitors, atrial fibrillation/flutter of any grade was 2.0% in the zanubrutinib arm and 15.3% in the ibrutinib arm;

minor bleeding was 48.5% for zanubrutinib and 59.2% for ibrutinib;

major hemorrhage was 5.9% for zanubrutinib and 9.2% for ibrutinib;

and diarrhea was 20.8% for zanubrutinib and 31.6% for ibrutinib;

and the rate of neutropenia was higher in the zanubrutinib arm (29.7%) as compared to the ibrutinib arm (13.3%).

Waldenström’s Macroglobulinemia and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

In general, the most recent data that we have presented on the use of zanubrutinib in patients with WM and CLL/SLL are consistent with our earlier data, which we believe supports our pursuit of a broad development program including these two indications.

Data from several trials investigating the use of zanubrutinib in WM and CLL/SLL were presented during 2019.

At the 24 th Congress of the European Hematology Association that took place on June 13-16 in Amsterdam (the "2019 EHA"), we presented data from the MYD88 WT cohort of the ASPEN study (NCT03053440) as well as the WM cohort of our first-in-human global Phase 1/2 study (NCT02343120).

At the 2019 ICML, we reported on two data sets, our pivotal Phase 2 results (NCT03206918) and a combination study with obinutuzumab (NCT02569476).

We also reported data in CLL/SLL from two studies at the 61st American Society of Hematology ("ASH") Annual Meeting in Orlando, FL from Arm C of the SEQUOIA trial (NCT03336333) in patients with the deletion of chromosome 17p13.1 (del17p) and from the CLL/SLL cohort of our first in man global Phase 1/2 study (NCT02343120).

Data from these studies and the other studies summarized in this Annual Report 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.

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 several other lymphomas.

We have studies ongoing in FL, MZL, and DLBCL, and we reported data from two FL studies in 2019, one monotherapy study and one in combination with obinutuzumab.

Results from the combination study with obinutuzumab (NCT02569476) in FL were presented at the 2019 ICML, while data in FL from our Phase 1 study (NCT03189524) in Chinese patients were reported at the 22 nd Annual Meeting of the Chinese Society of Clinical Oncology that took place September 18-22, 2019 in Xiamen, China (the "2019 CSCO").

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 ongoing, Phase 1 and Phase 2 clinical trials of zanubrutinib monotherapy, for WM, MCL, CLL/SLL, DLBCL and other B-cell malignancies were presented at the 2019 EHA.

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 BID.

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).

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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).

Clinical Development Plan

We received accelerated approval from the U.S.

FDA in November 2019 for zanubrutinib for use in adult MCL patients who have received at least one prior therapy.

In addition, zanubrutinib was granted Fast Track designation by the U.S.

FDA for the treatment of patients with WM in July 2018 and Breakthrough Therapy designation in January 2019 for the treatment of adult patients with MCL who have received at least one prior therapy.

We plan to discuss our ASPEN study results in WM with the FDA and EMA in 2020.

In China, we have announced the acceptance of our filings for approval in R/R MCL and R/R CLL/SLL in August 2018 and October 2018, respectively, and we expect approval for both indications in the first half of 2020.

We also expect to submit a sNDA in China for zanubrutinib for the treatment of R/R WM in 2020.

Based on the clinical data to date, we believe that zanubrutinib 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.

Four of the nine studies are Phase 3 and five are designed to be registration-enabling Phase 2.

We have an ongoing monotherapy head-to-head Phase 3 trial versus ibrutinib in WM (ASPEN), which has reported topline results and study follow-up is underway.

We plan to report full ASPEN study details at a medical conference in 2020.

We are also conducting an ongoing Phase 3 trial compared to bendamustine and rituximab in patients with treatment-naive ("TN") CLL/SLL (SEQUOIA) and a head-to-head Phase 3 trial in R/R CLL/SLL versus ibrutinib (ALPINE).

We have completed patient enrollment in SEQUOIA and expect interim results as early as 2020.

We also expect to finish expanded patient enrollment in ALPINE in 2020.

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

Additionally, we have five 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, and R/R MZL (MAGNOLIA) and an ongoing pivotal Phase 2 trial in combination with GAZYVA ® (obinutuzumab) in patients with R/R FL (ROSEWOOD), which is designed as a pivotal trial for accelerated or conditional approval and will require a confirmatory study.

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

If we receive conditional approval instead of full approval, we will be required to conduct one or more confirmatory studies after such conditional approvals.

Tislelizumab, an anti-PD-1 Antibody

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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, without activating the receptor, thereby blocking engagement of PD-1 by its ligands PD-L1 and PD-L2.

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.

Our trials in lung cancer include:

• A global Phase 3 trial evaluating tislelizumab as a second- or third-line treatment compared to docetaxel in patients with locally advanced or metastatic NSCLC (NCT03358875);

• Two Phase 3 trials in China evaluating tislelizumab plus chemotherapy versus chemotherapy in squamous and non-squamous NSCLC (NCT03594747 and NCT03663205, respectively);

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

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).

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:

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

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

• 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 January 15, 2020, we had enrolled over 5,100 patients in clinical trials of tislelizumab, including combination trials.

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

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

Hodgkin’s Lymphoma

On December 26, 2019 tislelizumab received approval from the NMPA for the treatment of patients with cHL, who have received at least two prior therapies based on the results of a pivotal Phase 2 study (NCT03209973).

Data from that study were presented on June 14, 2019 at the 2019 EHA meeting.

The single-arm, multi-center, pivotal Phase 2 study of tislelizumab as a monotherapy in patients with R/R cHL enrolled 70 patients in China who were either R/R to autologous stem cell transplantation ("ASCT"), or received at least two prior lines of systemic therapy for cHL and were not candidates for ASCT.

Patients were treated with tislelizumab, dosed at 200 mg intravenously every three weeks.

The primary endpoint of the trial was ORR assessed by IRC according to the Lugano Classification 2014.

As of November 26, 2018, 70 patients with R/R cHL were evaluable for efficacy.

Thirteen patients received prior ASCT, and the remaining 57 patients were ineligible for ASCT.

Patients had a median of three prior lines of systemic therapy (2-11).

With a minimum of 23.8 weeks of follow-up and a median follow-up time of 13.9 months at the data cutoff, the IRC assessed efficacy data included:

Efficacy data

Full Analysis Set (n=65)

Median DOR (month)

6-month event-free rate %

12-month event-free rate %*

Median PFS, month

6-month event-free rate, %

12-month event-free rate, %*

(Based on IRC assessment, Lugano 2014)

Abbreviations:

CI=confidence interval;

NE = Not Estimable.

1 Two-side Clopper-Pearson 95%CI

† Based on Kaplan-Meier estimation

* The estimation for 12m DoR rate and 12m PFS rate is not mature.

The majority AEs were grade 1 or 2 in severity.

The summary of AEs occurring in ≥ 5% of patients is shown below:

Tislelizumab 200 mg every 3 weeks n=70^

Preferred term^^

All grades* %

≥ Grade 3** %

General disorders and administration site conditions

Endocrine disorders

Hypothyroidism

Investigations

Weight increased

Weight decreased

Skin and subcutaneous tissue disorders

Infections and infestations

Upper respiratory tract infection

Respiratory, thoracic and mediastinal disorders

Pneumonitis d

Metabolism and nutrition disorders

Hyperlipidaemia

Hyperuricaemia

Musculoskeletal and connective tissue disorders

Musculoskeletal pain e

Pain in extremity

Gastrointestinal disorders

Blood and lymphatic system disorders

Nervous system disorders

^Adverse reactions in this package insert are defined as:

adverse events that assessed by investigator as related, definitely related, probably related, possibly related, unlikely related or missing causal relationship.

Only adverse events that are assessed by investigator as definitely unrelated are excluded.

The cutoff date of the data is 26 November 2018.

^^ Preferred term is based on ICH MedDRA Chinese version 20.0.

* Severity of adverse reactions per NCI CTCAE v4.03.

** No Grade 5 adverse event was reported in this study.

Fatigue is a composite term which includes fatigue, asthenia, and malaise.

Pruritus is a composite term which includes pruritus and urticaria.

Rash is a composite term which includes G1-2 rash, dermatitis and eczema.

Pneumonitis is a composite term which includes pneumonitis, interstitial lung disease and organising pneumonia.

Musculoskeletal pain is a composite term which includes back pain, neck pain and musculoskeletal chest pain and spinal pain.

Metastatic Urothelial Carcinoma

Data in metastatic UC were presented at the European Society for Medical Oncology Congress 2019 in Barcelona, Spain on September 30, 2019 (the "2019 ESMO").

The study is a multi-center, open-label Phase 2 trial (NCT04004221) of tislelizumab being conducted in China and South Korea with PD-L1+ locally advanced or metastatic UC previously treated with > 1 platinum-containing therapy.

The trial was designed to assess safety, tolerability and efficacy of tislelizumab at the recommended Phase 2 dose (200 mg IV every three weeks), with a primary endpoint of ORR as assessed by IRC per RECIST criteria v1.1.

As of February 28, 2019, 113 patients were enrolled in the trial, including 38.9% of patients who had received two (32.7%) or at least three (6.2%) prior therapies, and 23.9% of patients with liver metastasis.

The median duration of treatment for all patients was 15.3 weeks (2-72).

At the time of the data cutoff, 30 patients (26.5%) remained on treatment.

There were 104 patients evaluable for efficacy, with results shown in the table below.

Best Overall Response

al., 2019 ESMO

Median Follow-up Time

Median Duration of Response

ORR % (confirmed)

CR % (confirmed)

Median Progression-Free Survival, months

Overall Survival, months

Clinical Trial #

Tislelizumab was generally well-tolerated.

There were 105 patients with >1 treatment-related adverse event ("TRAE");

the most common TRAEs of any grade were anemia (26.5%), decreased appetite (18.6%), pyrexia (16.8%), aspartate aminotransferase increased (15%), and pruritus (15%).

Thirty-nine patients experienced grade >3 TRAEs related to the study drug.

The most common grade >3 TRAEs were anemia (7.1%), urinary tract infection (4.4%), decreased appetite (3.5%), and hyponatremia (3.5%).

Twelve (11%) patients experienced AEs related to the study drug that resulted in treatment discontinuation.

SAEs related to study treatment were reported in 11 (9.7%) patients.

Immune-related TEAEs ("irTEAEs") occurred in 64% of patients.

Common irTEAEs included immune-mediated skin adverse reaction (34%), immune-mediated hepatitis (24%), thyroid disorders (13%), and immune-mediated nephritis and renal dysfunction (12%).

Four (3.5%) patients experienced AEs with fatal outcome, including hepatic failure (n=2), respiratory arrest (n=1), and renal impairment (n=1).

The events of hepatic failure and respiratory arrest were reported as possibly related to the study drug by the investigator.

The event of renal impairment was reported as possibly unrelated to the study drug.

Those sources have further details on each study.

Non-Small Cell Lung Cancer

On January 21, 2020 we announced that the pivotal Phase 3 trial (NCT03594747) evaluating our anti-PD-1 antibody tislelizumab in combination with two chemotherapy regimens for the first-line treatment of patients with squamous NSCLC met the primary endpoint of improved PFS at the planned interim analysis, as assessed by IRC.

In this Phase 3, randomized, open-label, multi-center trial, patients with previously untreated advanced squamous NSCLC were randomized to receive either tislelizumab in combination with paclitaxel and carboplatin, tislelizumab in combination with ABRAXANE (nanoparticle albumin-bound (nab) paclitaxel) and carboplatin, or paclitaxel and carboplatin alone.

Patients enrolled into the study were from China and had untreated stage IIIB or IV squamous NSCLC, regardless of PD-L1 expression.

The primary endpoint is PFS per IRC.

360 patients were randomized 1:1:1 to receive tislelizumab (200mg every three weeks) in combination with each of the chemotherapy regimens or chemotherapy only, until disease progression, unacceptable toxicity, physician decision or consent withdrawal.

Patients on the chemotherapy-only control arm who experienced disease progression, verified by central independent review, were eligible to cross over to receive tislelizumab monotherapy.

The safety profile of tislelizumab in both combinations in this trial was consistent with the known risks of each study treatment, and no new safety signals were identified.

Squamous NSCLC remains a significant unmet need, representing approximately 30 percent of patients with NSCLC in China.

Chinese NSCLC patients have a low rate of driver mutations, and as such are not candidates for therapeutic approaches that target such driver mutations.

In addition to the above study result, data from a Phase 2 trial in advanced lung cancer were presented at the 2019 CSCO.

This lung cancer study is an open-label, multi-cohort pivotal Phase 2 clinical trial (NCT03432598) of tislelizumab in combination with chemotherapy as first-line treatment for patients with advanced lung cancer, being conducted in China.

Patients with non-squamous NSCLC were treated with tislelizumab at a dose of 200mg and doublet chemotherapy on day one of each three-week cycle;

chemotherapy was given for up to four cycles, with pemetrexed and tislelizumab continued as scheduled if clinically appropriate.

Patients with squamous NSCLC (two cohorts) and small cell lung cancer ("SCLC"), were treated with tislelizumab at a dose of 200mg and doublet chemotherapy every three weeks, for four to six cycles, with tislelizumab continued as scheduled if clinically appropriate.

Efficacy data presented included a confirmed ORR of 67%, with

no patients having a CR.

More specifically, the confirmed ORR was 43.8% (7/16) in patients with non-squamous NSCLC;

80.0% (12/15) in patients with squamous NSCLC (cohort A);

66.7% (4/6) in patients with squamous NSCLC (cohort B);

and 76.5% (13/17) in patients with SCLC.

Esophageal Squamous Cell Carcinoma ("ESCC") and Nasopharyngeal Cancer

During 2019 data from several other studies evaluating tislelizumab in patients with esophageal and nasopharyngeal cancers were presented.

The data from esophageal cancer patients was from a Phase 2 trial in esophageal and gastric or gastroesophageal junction carcinoma being conducted in China.

Patients were treated with tislelizumab at a dose of 200mg and cisplatin on day one, and fluorouracil (5-FU) on days one through five during each 21-day cycle.

Data presented at a median follow-up time of 13 months showed an ORR of 47%, with no patients having a CR.

The nasopharyngeal cancer ("NPC") data was from a cohort of our Phase 1/2 study of tislelizumab in China.

The multi-center, open-label trial of tislelizumab in China as monotherapy in advanced solid tumors consists of a Phase 1 dose verification and pharmacokinetics component and a Phase 2 component of indication expansion in disease-specific cohorts, including patients with NPC solid tumors.

Data presented at the American Society of Clinical Oncology ("ASCO") were from 21 patients with NPC, of whom 20 were enrolled in the Phase 2 indication-expansion portion of the trial.

Patients were treated with tislelizumab at a dose of 200 mg every three weeks.

Data presented at a median follow-up time of 7.6 months showed an ORR of 23% and a CR rate of 8%.

Other Tumor Types

In addition to the studies discussed above, we are evaluating tislelizumab for the treatment of patients with a broad array of tumor types including gastric, head and neck, ovarian, natural killer/T-cell and liver cancers as well as cancers that are microsatellite instability-high ("MSI-high") or deficient mismatch repair ("dMMR").

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 are consistent with its therapeutic class, having a relatively low rate of drug-related grade 3 or above toxicity.

Across the monotherapy studies, the safety results were consistent with our two Phase 1 studies, and our first-in-human Phase 1 study.

TEAEs are indicated in the table immediately below.

Over half of the patients in our two Phase 1 studies experienced a tislelizumab-related TEAE, though ≥ grade 3 events were less frequent (8% to 10%).

System Organ Class

Preferred Term

Patients with at least one TEAE

Decreased appetite

Abdominal pain

All grades, regardless of causality;

Data cut-off April 27, 2018;

6 months after Last Patient Enrolled;

BGB-A317 IB v6.0.

Of the 451 total patients in the Safety Population for Study BGB A317_001, 203 (45.0%) experienced at least 1 grade 3 or higher TEAE.

The most commonly occurring grade 3 or higher TEAEs (≥ 2%;

9 or more patients overall incidence) were pneumonia (22 patients, 4.9%), anemia (18 patients, 3.2%), and hypokalemia (9 patients, 2.0%).

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

Immune-related TEAEs ("irTEAEs") of any grade were reported in approximately 47% of patients across the monotherapy studies but were primarily low grade (9.5% ≥ grade 3).

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

Across the monotherapy studies, the rate of treatment emergent serious AEs, or TESAEs, was 33% in patients with a variety of different disease characteristics.

TESAEs considered to be related to treatment with tislelizumab were notably lower, at 9.6%.

There have been some deaths reported across the monotherapy studies with clinical data available, of which <1% of the total patient population were considered related to study drug.

No new safety signals were observed since the last report as of February 29, 2020.

In our clinical studies to date, the safety profile of tislelizumab has been consistent with that of molecules in the same class.

Clinical Development Plan

Tislelizumab was approved on December 26, 2019 by the NMPA for use in cHL patients who have received at least two prior therapies.

We plan to launch the product in China in the first quarter of 2020.

We expect to receive approval for a second indication in R/R UBC in 2020.

If we receive conditional approval instead of full approval, we will be required to conduct one or more confirmatory studies after such conditional approvals.

We also expect to submit for approval in China for tislelizumab for the treatment of patients with NSCLC, HCC, GC, and ESCC based on our China trials and, where appropriate, our global studies.

We are running a broad development program for tislelizumab, including 15 registration 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.

We have initiated pivotal or Phase 3 trials to evaluate tislelizumab as a potential second- or third-line treatment compared to docetaxel in patients with NSCLC;

two Phase 3 trials evaluating tislelizumab plus chemotherapy versus chemotherapy in squamous and non-squamous histology NSCLC;

and a Phase 3 trial in 1L SCLC evaluating tislelizumab plus chemotherapy versus chemotherapy.

In 2020, we expect to complete enrollment in the third line versus docetaxel study, and we expect to report top-line data from the squamous and non-squamous histology Phase 3 trials.

In liver cancer we have ongoing studies investigating use of tislelizumab as a potential first-line treatment compared to sorafenib in patients with HCC and in second- or third-line HCC used as a monotherapy in a single arm pivotal Phase 2 study.

We expect to have regulatory discussions with the relevant authorities regarding the second -or third-line monotherapy HCC study in 2020.

In GC we have a study ongoing that is investigating the use of tislelizumab as a potential first-line treatment in combination with platinum and fluoropyrimidine-based chemotherapy.

Finally, in ESCC we have several studies ongoing, including as a potential second-line treatment compared to investigator-chosen chemotherapy in patients with ESCC, as a potential first-line treatment in advanced ESCC patients in combination with platinum and fluoropyrimidine-based chemotherapy, and most recently as a potential treatment in localized ESCC evaluating tislelizumab plus chemoradiotherapy versus chemoradiotherapy alone.

We expect to complete enrollment in the second-line study comparing tislelizumab to investigator-chosen chemotherapy in the first half of 2020.

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

We have initiated two studies in UC, including a pivotal Phase 2 in second-line UC using tislelizumab as monotherapy, and a Phase 3 in first line UC comparing tislelizumab plus chemotherapy versus chemotherapy alone;

a pivotal Phase 2 study in MSI-high or dMMR solid tumors using tislelizumab as monotherapy;

and a Phase 3 in first line NPC evaluating tislelizumab plus chemotherapy versus chemotherapy alone.

We have also recently initiated a global Phase 2 trial in patients with R/R mature T- and NK-cell lymphomas.

Pamiparib (BGB-290), an inhibitor of PARP1 and PARP2

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.

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

PARP1 and PARP2 are key base-excision-repair proteins that function as DNA damage sensors by binding rapidly to the site of damaged DNA and modulating a variety of proteins in DNA repair processes.

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

Double-strand DNA breaks in normal cells are repaired by homologous recombination, and normal cells are relatively tolerant of PARP inhibition.

On the other hand, cancer cells with mutations in breast cancer susceptibility gene, or BRCA1/2 genes, which are key players in homologous recombination, 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 gene expression profile that resembles that of a BRCA deficient tumor.

HRD can stem from somatic mutation of BRCA1/2, epigenetic silencing of BRCA genes or genetic or epigenetic loss of function of other genes in homologous recombination DNA damage repair pathways.

Third-party clinical studies have published results demonstrating that sensitivity to platinum-based chemotherapies confers sensitivity to PARP inhibitors in OC as well.

Thus, the application of PARP inhibitors is likely broader than BRCA or HRD mutations, and there is additional possibility to identify and enrich patient populations for PARP inhibition.

Another potential therapeutic utility of PARP inhibitors is in combination therapy, which has strong scientific rational.

PARP proteins are key factors in base-excision-repair, which is critical for the repair of DNA lesions caused by some chemotherapeutic agents and by radiation.

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.

PARP inhibitors are also considered good potential combination partners with checkpoint inhibitors in part due to increased mutations in tumor cells as a result of the blockade of DNA repair by PARP inhibitors as a higher mutational load in cancers has been shown in clinical studies to correlate with improved response to checkpoint inhibitors.

In addition, preclinical data suggest that BRCA mutant tumors which are sensitive to PARP inhibition are likely to be immunogenic and responsive to PD-1 or PD-L1 antibodies.

Market Opportunity and Competition

We believe that the market opportunity for PARP inhibitors is large and expanding in various patient segments.

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

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

In the United States, in 2019 there were approximately 22,530 new cases of OC, 271,270 new cases of breast cancer, 174,650 new cases of prostate cancer, and 27,510 new cases of GC, according to the U.S.

National Cancer Institute's SEER online database.

In China, each year there are approximately 52,000 new cases of OC, 272,000 new cases of breast cancer, 60,000 new cases of prostate cancer, and 680,000 new cases of GC according to Chen et al.

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

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

AbbVie’s veliparib is in late-stage development.

In 2019, global sales of the PARP class exceeded $1.5 billion according to company reports.

In China, AstraZeneca received approval for olaparib in August 2018 under priority review that utilized international multi-center data.

Zai Labs obtained the development and commercial rights for niraparib in China, and its NDA to the NMPA was approved on December 30, 2019.

There are other PARP inhibitors being developed by domestic Chinese companies, including fluzoparib from Hengrui and Hansoh.

Fluzoparib was submitted to the NMPA in October 2019.

Summary of Clinical Results

We have multiple ongoing studies in indications known to be responsive to PARP inhibition, including two registration studies in ovarian cancer ("OC") in China.

Advanced Solid Tumors

Data from our open-label, multi-center Phase 1b dose-escalation/expansion trial (NCT03150810) of pamiparib plus low-dose temozolomide (TMZ) were presented at the 2019 ESMO.

The trial was designed to evaluate the safety, tolerability, maximum tolerated dose (MTD), and preliminary anti-tumor activity of the combination in patients with locally advanced and metastatic tumors.

Patients received full dose pamiparib in combination with escalating doses of TMZ, administered in both pulse and continuous dosing schedules.

The recommended Phase 2 dose and schedule of the combination was determined to be 60 mg of pamiparib taken orally BID for 28 days, with TMZ at 60 mg orally QD during days one through seven.

Data were presented from three disease cohorts:

prostate, extensive-stage SCLC, and GC.

The ORR and CR rates from these cohorts were 19% and 0%, 32% and 5%, and 0% and 0%, respectively.

Median follow-up time in the SCLC and gastric cohorts was four months in each cohort.

Ovarian Cancer

At the 2019 ESMO, we reported results from a multi-center, open-label Phase 1a/1b trial (NCT02361723) of pamiparib being conducted in Australia in patients with advanced solid tumors.

The Phase 1a dose-escalation and dose-finding component identified the recommended Phase 2 dose to be 60 mg orally BID.

The ongoing Phase 1b trial consists of a component to

investigate the safety, tolerability, and antitumor activity of pamiparib in disease-specific dose-expansion cohorts, and a component investigating the effects of food on the pharmacokinetic profile of a single dose.

Data from 58 patients in the OC cohort showed an ORR of 40% and a CR rate of 7%.

Clinical Development Plan

Gastric Cancer

We are in the process of converting from Phase 3 to Phase 2 the clinical trial of our PARP inhibitor pamiparib versus placebo as maintenance therapy in patients with inoperable locally advanced or metastatic GC who have responded to platinum-based first line chemotherapy (NCT03427814, also known as the BGB-290-303 trial).

The trial has enrolled approximately 120 patients globally since it commenced in July 2018, and the enrollment has been slower than expected.

The reason for this change was not due to safety or efficacy issues.

We plan to evaluate data from the Phase 2 trial to assess the potential of pamiparib in this indication and the potential next steps of development as a monotherapy or in combination with other therapies.

Our clinical development program includes a Phase 3 trial as a maintenance therapy in patients with platinum-sensitive recurrent OC (NCT03519230), a pivotal Phase 2 study in third line BRCA mutated OC (NCT03333915), a Phase 2 trial in BRCA mutated HER2-negative breast cancer (NCT03575065), and a Phase 2 trial in HRD- metastatic prostate cancer (NCT03712930).

We plan to discuss our data in OC with regulatory authorities and potentially submit an NDA in China for use of pamiparib in OC in 2020.

We expect to announce top-line results from our pivotal Phase 2 germline BRCA ("gBRCA")-mutated OC as well as data from our Phase 3 maintenance study in patients with platinum-sensitive recurrent OC.

In addition, we expect to present data from the OC cohort of the global Phase 1 study and data from the Phase 1 study investigating pamiparib in combination with tislelizumab in 2020.

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

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.

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

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We have been developing lifirafenib for the treatment of cancers with aberrations in the mitogen-activated protein kinase ("MAPK"), pathway, including BRAF gene mutations and KRAS/NRAS gene mutations where first generation BRAF inhibitors are not effective.

The MAPK pathway consists of proteins in the cell that transmit a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.

This pathway plays an essential role in regulating cell proliferation and survival.

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 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), Genentech’s vemurafenib and COTELLIC ® (cobimetinib), and Array Biopharma’s encorafenib and MEKTOVI ® (binimetinib).

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.

In September 2018, BeiGene and SpringWorks Therapeutics, Inc.

("SpringWorks") announced a global clinical collaboration agreement to evaluate the safety, tolerability, and preliminary efficacy of combining lifirafenib and SpringWorks' investigational MEK inhibitor, PD-0325901, in patients with advanced solid tumors.

Under the collaboration, the parties began a Phase 1b clinical trial in the third quarter of 2019 to evaluate this combination in patients with advanced or refractory solid tumors that harbor RAS mutations, RAF mutations, and other MAPK pathway aberrations.

In June 2019, we and SpringWorks announced the formation of MapKure, LLC to develop BGB-3245, an investigational, selective next-generation RAF kinase inhibitor discovered by BeiGene scientists.

MapKure recently initiated a Phase 1 clinical trial (NCT04249843) in patients with advanced or refractory tumors harboring specific v-RAF murine sarcoma viral oncogene homolog B (B-RAF) genetic mutations.

BeiGene is working together with SpringWorks Therapeutics, Inc.

("SpringWorks") in a global clinical collaboration and has initiated a Phase 1b clinical trial (NCT03905148) to evaluate the safety, tolerability, and preliminary efficacy of lifirafenib in combination with SpringWorks' investigational MEK inhibitor, mirdametinib (PD-0325901), in patients with advanced solid tumors.

In addition to the collaboration, BeiGene and SpringWorks formed a separate company, MapKure, LLC, to develop BGB-3245, an investigational, selective next-generation RAF kinase inhibitor discovered by BeiGene scientists.

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

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("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 potentially registration-enabling Phase 3 trial of sitravatinib in NSCLC initiated in the second quarter of 2019.

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 began a Phase 1 study (NCT03666143) of sitravatinib in combination with tislelizumab in various solid tumors in Australia and China in the third quarter of 2018, and in the second quarter of 2019 we initiated a second study, a Phase 1/2 (NCT03941873) trial, combining sitravatinib with tislelizumab, this one focused on HCC or gastroesophageal junction cancer.

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.

BGB-11417, a Small Molecule Bcl-2 Inhibitor

BGB-11417 is an investigational small molecule Bcl-2 inhibitor.

We have completed preclinical and investigational new drug ("IND") -enabling studies of BGB-11417, which demonstrated potent activity and high selectivity against the pro-apoptotic protein Bcl-2.

The molecule appears to be more potent than venetoclax and shows the potential to overcome resistance to venetoclax.

Further, it is more selective than venetoclax for Bcl-2 relative to Bcl-xL.

Finally, we believe that it is well-positioned to be combined with BRUKINSA ® .

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.

BGB-A445, an OX40 Agonist Antibody

BGB-A445 is an investigational agonistic antibody directed to the OX40 antigen.

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.

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.

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

We have two clinical studies ongoing 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 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 intend to develop BGB-A333 either as a monotherapy or in combination with other cancer therapies, such as tislelizumab, to treat various cancers and potentially other areas of unmet need.

BGB-A333 is currently being evaluated in 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 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.

BGB-A425, a TIM-3 Inhibitor

BGB-A425 is an investigational humanized IgG1-variant monoclonal antibody against T-cell immunoglobulin and mucin-domain containing-3 ("TIM-3").

We began a Phase 1/2 trial (NCT03744468) of BGB-A433 in combination with tislelizumab in various solid tumors in the fourth quarter of 2018.

BGB-A1217, a TIGIT Inhibitor

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

We have initiated patient enrollment in a 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.

BGB-11417, a Small Molecule Bcl-2 Inhibitor

BGB-11417 is a small molecule Bcl-2 inhibitor.

We have completed preclinical and investigational new drug (IND) -enabling studies of BGB-11417, which demonstrated potent activity and high selectivity against the pro-apoptotic protein Bcl-2.

We have initiated study start-up for a Phase 1 trial (NCT04277637) in Australia and the United States to investigate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BGB-11417 in patients with mature B-cell malignancies.

BGB-A445, an OX40 Agonist Antibody

BGB-A445 is an agonistic antibody directed to the OX40 antigen.

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

We have an ongoing Phase 1/2 trial (NCT03744468) of BGB-A425 in combination with tislelizumab in various solid tumors.

BGB-15025, a Small Molecule HPK1 Inhibitor

BGB-15025 is an investigational small molecule inhibitor of HPK1, which is a key negative feedback regulator of TCR signaling.

Inhibition of HPK1 leads to enhanced T-cell activation pre-clinically.

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.

Our Preclinical Programs

We have a proprietary cancer biology platform that has also allowed us to develop our clinical-stage drug candidates and several additional preclinical-stage drug candidates in potentially important areas.

These currently consist of targeted therapies and immuno-oncology agents.

We have initiated first-in-human studies for two drug candidates and have initiated study start-up activities for a third, BGB-11417, a small molecule Bcl-2 inhibitor.

We anticipate advancing one or more of our preclinical drug candidates into the clinic in the next 12 months.

We believe we have the opportunity to combine tislelizumab with our preclinical candidates to target multiple points in the cancer immunity cycle.

We also may seek to develop companion diagnostics that will help identify patients who are most likely to benefit from the use of our drug candidates.

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.

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.

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

We believe that we have the opportunity to combine tislelizumab with our preclinical candidates to target multiple points in the cancer immunity cycle.

We also may seek to develop companion diagnostics that will help identify patients who are most likely to benefit from the use of our medicines and drug candidates.

Manufacturing and Supply

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

The manufacturing of our drugs 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.

Our manufacturing facilities and the facilities of the CMOs we use to manufacture our drugs and drug candidates operate under current good manufacturing practice regulations ("GMP") conditions.

GMP are regulatory requirements for the production of pharmaceuticals that will be used in humans.

We manufacture our medicines and drug candidates internally and 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.

Our manufacturing facilities and the facilities of the CMOs we use to manufacture our medicines and drug candidates operate under current good manufacturing practice regulations ("GMP") conditions.

GMP regulations are requirements for the production of pharmaceuticals that will be used in humans.

Our Manufacturing Facilities

We have an approximately 11,000 square meter multi-functional manufacturing facility in Suzhou, China, where we produce small molecule and biologics drug candidates for clinical supply and which we plan to use for commercial supply of our small molecule drug candidates in China and potentially outside of China, if approved.

This facility consists of one oral-solid-dosage production line for small molecule drug products and one pilot plant for monoclonal antibody drug substances and 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 following NDA approval.

In addition, we formed a joint venture with Guangzhou High-Tech Zone Technology Holding Group Co., Ltd.

(formerly GET), an affiliate of Guangzhou Development District, to build a commercial-scale biologics manufacturing facility in Guangzhou, China.

We completed the initial phase of construction in September 2019.

This facility is designed to be 100,000 square meters and have a 50,000-liter commercial scale capacity.

The initial phase of the facility utilizes General Electric’s state-of-the-art KUBio™ prefabricated bio-manufacturing equipment.

We have received the drug manufacturing license for drug substances and drug products for this facility and are now in the process of validating this facility for global commercial supplies.

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 also have an approximately 140 square meter manufacturing facility at our research and development location in Beijing, China, which produces preclinical and clinical trial materials for some of our small molecule drug candidates.

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.

Contract Manufacturing Organizations

We currently rely on, and expect to continue to rely on, a limited number of third-party CMOs and CROs for the production of some drug products and drug substances and the supply of raw materials to meet the commercial, clinical, and preclinical needs of our drugs and drug candidates.

We have adopted procedures to ensure that the production qualifications, facilities and processes of our third-party outsourced suppliers comply with the relevant regulatory requirements and our internal quality and operation guidelines.

We select our third-party suppliers carefully by considering a number of factors, including their qualifications, relevant expertise, production capacity, geographic proximity, reputation, track record, product quality, reliability in meeting delivery schedules, and terms offered by such third-party outsourced suppliers.

We have framework 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 commercial and clinical supply outside of China.

We have adopted procedures to ensure that the production qualifications, facilities, and processes of the third-party suppliers engaged by us comply with relevant regulatory requirements and our internal quality and operational guidelines.

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.

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

("Boehringer Ingelheim") for our anti-PD-1 antibody 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.

For our commercial products licensed from BMS, we rely on BMS and its contract manufacturers outside of China for the supply of those drugs.

For our clinical and commercial products that are being commercialized in collaboration with Amgen, we expect to rely on Amgen and its contract manufacturers outside of China for the supply of those drugs and drug candidates.

Our agreements with our outsourced suppliers 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.

We are generally allowed to return any products that fail to meet our quality standards.

("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.

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.

We are generally allowed to return any products that fail to meet specified quality standards.

Our outsourced suppliers procure raw materials themselves.

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Either party may terminate the agreements by serving notice to the other party under certain circumstances.

We generally obtain raw materials for our manufacturing activities from multiple suppliers who we believe have sufficient capacity to meet our demands.

We generally obtain raw materials for our manufacturing activities from various suppliers who we believe have sufficient capacity to meet our demands.

Raw materials and starting materials used at our facilities in Beijing and Suzhou include active pharmaceutical ingredients custom-made by our third-party CROs and excipients, which are commercially available from well-known vendors that meet the requirements of the relevant regulatory agencies.

The core raw materials to be used in manufacturing at our Guangzhou facility are expected to be genetically modified cell lines that we co-developed and licensed from Boehringer Ingelheim and other third parties.

The core raw materials used in manufacturing at our Guangzhou facility are genetically modified cell lines that we have co-developed and licensed from Boehringer Ingelheim and other third parties.

We typically order raw materials on a purchase order basis and do not enter into long-term, dedicated capacity or minimum supply arrangements.

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Credit periods granted to us by our suppliers generally range from 30 to 60 days.

Our suppliers are generally not responsible for the defects of our finished products.

Our suppliers are generally not responsible for any defects in our finished products.

Amgen Collaboration

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On October 31, 2019, our wholly-owned subsidiary, BeiGene Switzerland GmbH (“BeiGene Switzerland”), entered into a Collaboration Agreement with Amgen, which became effective on January 2, 2020 (the "Amgen Collaboration Agreement").

Pursuant to the terms of the Amgen Collaboration Agreement, BeiGene Switzerland will be responsible for commercializing Amgen’s oncology products XGEVA, KYPROLIS and BLINCYTO in China (excluding Hong Kong, Macao and Taiwan) for a period of five or seven years following each product’s regulatory approval in China, as specified in the Amgen Collaboration Agreement, with the commercialization period for XGEVA commencing following the transition of operational responsibilities for the product.

In addition, as specified in the agreement, BeiGene Switzerland will have the option to retain one of the three products to commercialize for as long as the product is sold in China.

The parties have agreed to equally share profits and losses for the products in China during each product’s commercialization period through BeiGene Switzerland.

After expiration of the commercialization period for each product, the products not retained will be transitioned back to Amgen and BeiGene Switzerland 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, BeiGene Switzerland and Amgen have agreed to collaborate on the global development and commercialization in China of 20 Amgen clinical- and late-preclinical-stage oncology pipeline products.

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

BeiGene Switzerland will be eligible to receive tiered mid-single digit royalties on net sales of each product globally outside of China, other than 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.

For each pipeline product that is approved in China, BeiGene Switzerland will have the right to commercialize the product for seven years, with the parties sharing profits and losses for the product in China equally.

In addition, depending on how many of the 20 pipeline products receive approval in China, BeiGene Switzerland will have the right to retain approximately one of every three approved products, up to a total of six, other than 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 BeiGene Switzerland will be eligible to received tiered mid-single to low-double digit royalties on net sales in China for an additional five years.

Pursuant to the terms of the Amgen Collaboration Agreement, we are responsible for commercializing Amgen’s oncology products XGEVA ® , BLINCYTO ® and KYPROLIS ® in China (excluding Hong Kong, Macao and Taiwan) for a period of five or seven years following each product’s regulatory approval in China, as specified in the Amgen Collaboration Agreement, with the commercialization period for XGEVA ® commencing following the transition of operational responsibilities for the product.

In addition, as specified in the agreement, we have the option to retain one of the three products to commercialize for as long as the product is sold in China.

The parties have agreed to equally share profits and losses for the products in China during each product’s commercialization period.

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.

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.

For each pipeline product that is approved in China, we will have the right to commercialize the product for seven years, with the parties sharing profits and losses for the product in China equally.

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.

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

We have guaranteed certain obligations of BeiGene Switzerland under the Amgen Collaboration Agreement pursuant to the terms of a separate Guarantee Agreement.

BeiGene, Ltd.

has guaranteed certain obligations of BeiGene Switzerland under the Amgen Collaboration Agreement pursuant to the terms of a separate Guarantee Agreement.

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

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In connection with the Amgen Collaboration Agreement, pursuant to a share purchase agreement dated October 31, 2019, as amended, by and between BeiGene, Ltd.

and Amgen (the “Share Purchase Agreement”), we issued 206,635,013 ordinary shares in the form of 15,895,001 American Depositary Shares (“ADSs”) of BeiGene, Ltd.

on January 2, 2020, representing approximately 20.5% of our outstanding shares to Amgen, for an aggregate cash price of $2.78 billion, or $13.45 per ordinary share, or $174.85 per ADS.

and Amgen (the “Share Purchase Agreement”), we issued to Amgen 206,635,013 ordinary shares in the form of 15,895,001 American Depositary Shares (“ADSs”) of BeiGene, Ltd.

on January 2, 2020, representing approximately 20.5% of our then outstanding shares, for an aggregate purchase price of $2.78 billion, or $13.45 per ordinary share, or $174.85 per ADS.

Pursuant to the Share Purchase Agreement, Amgen has agreed to (i) a lock-up on sales of its shares until the earliest of (a) the fourth anniversary of the closing, (b) the expiration or termination of the Collaboration Agreement and (c) a change of control of BeiGene, Ltd., (ii) a standstill until the later of (a) the first anniversary of the date as of which it ceases to have the right to appoint a director and (b) the date on which it holds less than 5% of our then outstanding shares, and (iii) a voting agreement to vote its shares on certain matters presented for shareholder approval until the later of (a) the fifth anniversary of the closing and (b) the expiration of the standstill period, all under specified circumstances and as set forth in the agreement.

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Under the terms of the Share Purchase Agreement, Amgen will also have specified registration rights upon expiration of the lock-up.

Additionally, we have agreed to use reasonable best efforts to provide Amgen with an opportunity to participate in subsequent new securities offerings upon the same terms and conditions as other purchasers in the offering in an amount needed to allow Amgen to hold 20.5% of our shares, subject to applicable law and HKEx rules and other specified conditions.

Additionally, we have agreed to use reasonable best efforts to provide Amgen with an opportunity to participate in subsequent new securities offerings upon the same terms and conditions as other purchasers in the offering in an amount needed to allow Amgen to hold up to 20.6% of our shares, subject to applicable law and HKEx rules and other specified conditions.

On March 17, 2020, BeiGene, Ltd.

and Amgen entered into an Amendment No.

2 (the “Second Amendment”) to the Share Purchase Agreement in order to account for periodic dilution from the issuance of shares by us, which agreement was restated in its entirety on September 24, 2020 (the “Restated Second Amendment”).

Pursuant to the Restated Second Amendment, Amgen has an option (the “Direct Purchase Option”) to subscribe for additional ADSs in an amount necessary to enable it to increase (and subsequently maintain) its ownership at approximately 20.6% of our outstanding shares.

The Direct Purchase Option is exercisable on a monthly basis, but only if Amgen’s interest in our outstanding shares at the monthly reference date is less than 20.4%.

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:

(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;

(b) at least 60-day advance written notice from either Amgen or the Company that such party wishes to terminate the Direct Purchase Option;

or (c) December 1, 2023.

The Direct Purchase Option has no vesting period.

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.

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.

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 tislelizumab in the country of sale.

Under the Novartis Collaboration and License Agreement, we and Novartis have agreed to jointly develop tislelizumab in the Licensed Territory, with Novartis responsible for regulatory submissions after a transition period and for commercialization upon regulatory approvals.

In addition, both companies may conduct clinical trials to explore potential combinations of tislelizumab with other cancer treatments.

We will be responsible for funding the ongoing clinical trials of tislelizumab, and Novartis has agreed to fund any new registrational, bridging, or post-marketing studies in the Licensed Territory.

Subject to specified conditions, both parties have agreed to jointly fund other new clinical trials in the Licensed Territory agreed by the parties, provided that each party will be responsible for funding clinical trials evaluating tislelizumab in combination with its own- or third-party cancer treatments.

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

In addition, we have an option to co-detail the product in the United States, Canada and Mexico, on an indication-by-indication basis, funded in part by Novartis.

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

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

Unless earlier terminated, the agreement will expire on a country-by-country basis upon expiration of the royalty term in such country and in its entirety upon the expiration of all applicable royalty terms in all countries in the Licensed Territory.

We may terminate the agreement in its entirety upon written notice (i) if Novartis challenges the licensed BeiGene patents, or (ii) if Novartis files a biologics license application for its anti-PD-1 antibody, spartalizumab, in the Licensed Territory, and we do not elect to include spartalizumab as a licensed product under the agreement or Novartis does not divest the product candidate, in which case Novartis would pay us a specified termination fee.

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.

Celgene License and Supply Agreement

On July 5, 2017, we and Celgene Logistics Sàrl, a wholly-owned subsidiary of BMS, entered into a License and Supply Agreement, which we refer to as the China License Agreement and which became effective on August 31, 2017, pursuant to which we were granted the right to exclusively distribute and promote BMS’s approved cancer therapies, ABRAXANE, REVLIMID and VIDAZA in China, excluding Hong Kong, Macau and Taiwan.

In addition, if BMS decides to commercialize a new oncology product through a third party in the licensed territory during the first five years of the term, we have a right of first negotiation to obtain the right to commercialize the product, subject to certain conditions.

On July 5, 2017, we and Celgene Logistics Sàrl, now a wholly-owned subsidiary of BMS, entered into a License and Supply Agreement, which we refer to as the China License Agreement and which became effective on August 31, 2017, pursuant to which we were granted the right to exclusively distribute and promote BMS’s approved cancer therapies, REVLIMID ® , VIDAZA ® and ABRAXANE ® in China, excluding Hong Kong, Macau and Taiwan.

In addition, if Celgene decides to commercialize a new oncology product through a third party in the licensed territory during the first five years of the term, we have a right of first negotiation to obtain the right to commercialize the product, subject to certain conditions.

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.

products are revoked.

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

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Intellectual Property

The proprietary nature of, and protection for, our drugs, drug candidates, and their methods of use are an important part of our strategy to develop and commercialize novel medicines, as described in more detail below.

We have obtained patents and filed patent applications in the United States and other countries and regions, such as China and Europe, relating to our drugs and certain of our drugs and drug candidates, and are pursuing additional patent protection for them and for our other drug candidates and technologies.

The proprietary nature of, and protection for, our medicines, drug candidates, and their methods of use are an important part of our strategy to develop and commercialize novel medicines, as described in more detail below.

We have filed patent applications and obtained patents in the United States and other countries and regions, such as China and Europe, relating to our medicines and certain of our drug candidates, and are pursuing additional patent protection for them and for our other drug candidates and technologies.

We rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection, including our manufacturing processes.

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

The key patents for our drugs and late-stage clinical drug candidates as of January 29, 2020, are summarized below:

General Subject Matter

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.

The key patents for our medicines and late-stage clinical drug candidates as of January 31, 2021, are summarized below:

Molecule Territory General Subject Matter Expiration 1

(Zanubrutinib)

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Use for the treatment of autoimmune diseases 2034

Compound and composition

Use for the treatment of B-cell proliferative disorder 2034

China Compound and composition 2034

Tislelizumab U.S.

Antibodies 2033

Use for the treatment of cancer 2033

Antibodies and use for the treatment of cancer 2033

Antibodies 2033

China Antibodies 2033

Pamiparib U.S.

Compound and composition 2031

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Use for the treatment of cancer 2031

Compositions 2031

Crystalline forms 2036

Compound and composition

Use for the treatment of cancer

Crystalline forms 2038

China Compound and composition 2031

China Use for the treatment of cancer 2031

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

We have three in-licensed drugs in China from BMS.

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:

General Subject Matter

ABRAXANE ® (a nanoparticle albumin-bound paclitaxel)

Use for the treatment of cancer

Product Territory General Subject Matter Expiration

REVLIMID ® (lenalidomide)

Use for the treatment of multiple myeloma

China Use for the treatment of multiple myeloma 2023

VIDAZA ® (azacitidine)

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

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:

General Subject Matter

Product Territory General Subject Matter Expiration

XGEVA ® (denosumab)

KYPROLIS ® (carfilzomibe)

Compound and Composition

China Antibodies 2022

BLINCYTO ® (blinatumomab)

China No patent N/A

KYPROLIS ® (carfilzomib)

China Compound and Composition 2025

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

ABRAXANE, REVLIMID and VIDAZA face or are expected to face competition from generic medications, and we may face similar competition for our drugs and any approved drugs even if we successfully obtain patent protection.

The scope, validity or enforceability of our patents may be challenged in court, and we 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.

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

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.

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 ® .

Under our license agreements with BMS and Amgen, they retain the responsibility for, but are not obligated, to prosecute, defend and enforce the patents for these in-licensed products.

As such, any issued patents may not protect us from generic or biosimilar competition for these drugs.

As such, any issued patents may not protect us from generic or biosimilar competition for these medicines.

The term of individual patents may vary based on the countries in which they are obtained.

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

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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 China, the EU and other jurisdictions, and we are seeking trademark protection for BeiGene, our corporate logo, product names and logos, and other marks in the United States and other countries 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.

Government Regulation

Government authorities in the United States at the federal, state and local level and in other countries extensively regulate, among other things, the research and clinical development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing, pricing and export and import of drugs such as those we are developing and commercializing.

Some jurisdictions also regulate the pricing of drugs.

Generally, before a new drug can be marketed, considerable data demonstrating its quality, safety and efficacy must be obtained, organized into a format specific to each regulatory authority, submitted for review and approved by the regulatory authority.

Government authorities in the United States, China, Europe and other jurisdictions extensively regulate, among other things, the research and clinical development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing, and export and import of drugs like those we are developing and commercializing.

Some jurisdictions also regulate drug pricing.

Generally, for a new drug to be marketed, considerable data demonstrating its quality, safety and efficacy must be obtained, organized into a format specific to each regulatory authority, submitted for review and approved by the regulatory authority.

Government Regulation and Product Approval

In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act ("FDCA"), and its implementing regulations, and biologics under the FDCA, its implementing regulations, and the Public Health Service Act ("PHSA"), and its implementing regulations.

Cancer therapies are sometimes characterized as first line, second line or third line, and the FDA often approves new therapies initially only for second or third-line use.

When cancer is detected early enough, first line therapy is sometimes adequate to cure the cancer or prolong life without a cure.

Whenever first line therapy, usually chemotherapy, hormone therapy, surgery or a combination of these, proves unsuccessful, second line therapy may be administered.

Cancer therapies are sometimes characterized according to line of therapy, and the FDA often approves new therapies initially only for second or third-line use.

When cancer is detected early enough, first line therapy may be adequate to cure the cancer or prolong life without a cure.

Whenever first line therapy, usually chemotherapy, hormone therapy, radiation, surgery or a combination of these, proves unsuccessful, second line therapy may be administered.

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 and new technologies.

Third line therapies can include bone marrow transplantation, antibody and small molecule targeted therapies, more invasive forms of surgery.

In some cases, new technologies and investigational medicines, as part of a clinical trial, may be used as any line of therapy.

Drug Development Process

The process required by the FDA before a drug or biologic may be marketed in the United States generally involves the following:

completion of preclinical laboratory tests, animal studies and formulation studies according to Good Laboratory Practices ("GLP"), regulations;

• completion of preclinical laboratory tests, animal studies and chemistry, manufacture and control (“CMC”) studies according to Good Laboratory Practices ("GLP") guidance;

• submission to the FDA of an investigational new drug ("IND") application, which must become effective before human clinical trials may begin;

performance of adequate and well-controlled human clinical trials according to GCP, to establish the safety and efficacy of the proposed drug or safety, purity and potency of the proposed biologic, for the intended use;

preparation and submission to the FDA of an NDA for a drug or a Biologics License Application ("BLA") for a biologic;

• performance of adequate and well-controlled human clinical trials according to Good Clinical Practice (“GCP”), to establish the safety and efficacy of the proposed drug or safety, purity and potency of the proposed biologic, for the intended use;

• preparation and submission to the FDA of an NDA for a small molecule drug or a Biologics License Application ("BLA") for a biologic;

• a determination by the FDA within 60 days of its receipt of an NDA or BLA to file the application for review;

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• FDA review and approval of the NDA or licensing of the BLA.

Preclinical Studies and Clinical Trials

Once a product candidate is identified for development, it enters the preclinical testing stage.

Preclinical tests include laboratory evaluations of product chemistry, toxicity, formulation and stability, as well as animal studies.

Preclinical tests include laboratory evaluations of product chemistry, toxicity, formulation and stability, as well as in vitro and animal studies.

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.

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In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.

Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns or noncompliance and may be imposed on all products within a certain class of products.

The FDA may also impose clinical holds at any time before or during clinical trials due to safety concerns or noncompliance and may be imposed on all products within a certain class of products.

The FDA also can impose partial clinical holds, for example, prohibiting the initiation of clinical trials of a certain duration or for a certain dose.

All clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with GCP regulations.

These regulations include the requirement that all research subjects provide informed consent in writing before their participation in any clinical trial.

These regulations require that all research subjects provide informed consent in writing before their participation in any clinical trial.

Further, an institutional review board ("IRB") must review and approve the plan for any clinical trial before it commences at any institution, and the IRB must conduct continuing review and reapprove the study at least annually.

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The product is initially introduced into a small number of healthy human subjects or patients and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion and, if possible, to gain early evidence on effectiveness.

In the case of some products for severe or life-threatening diseases, especially when the product is suspected or known to be unavoidably toxic, the initial human testing may be conducted in patients.

Involves clinical trials in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage and schedule.

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These clinical trials are intended to evaluate the overall risk/benefit relationship of the product and provide an adequate basis for product labeling.

Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval.

These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication and are commonly intended to generate additional safety data regarding use of the product in a clinical setting.

In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA or BLA.

Failure to exhibit due diligence with regard to conducting required Phase 4 clinical trials could result in withdrawal of approval for products.

We refer to our Phase 1 programs as dose-escalation and dose-expansion trials.

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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 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.

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Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product does not undergo unacceptable deterioration over its shelf life.

Expanded Access

Expanded access, sometimes called “compassionate use,” is the use of investigational products outside of clinical trials to treat patients with serious or immediately life-threatening diseases or conditions when there are no comparable or satisfactory alternative treatment options.

There is no requirement for a company to provide expanded access to its investigational products.

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.

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Review and Approval Processes

The results of product development, preclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the product, proposed labeling and other relevant information, are submitted to the FDA as part of an NDA for a new drug or a BLA for a biologic, requesting approval to market the product.

The results of product development, preclinical studies and clinical trials, along with descriptions of the CMC, analytical tests conducted on the product, proposed labeling and other relevant information, are submitted to the FDA as part of an NDA for a new small molecule drug or a BLA for a biologic, requesting approval to market the product.

The submission of an NDA or BLA is subject to the payment of a substantial user fee, although a waiver of such fee may be obtained under certain limited circumstances.

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The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

The approval process is lengthy and difficult, and the FDA may refuse to approve an NDA or BLA if the applicable regulatory criteria are not satisfied or may require additional clinical data or other data and information.

Additionally, before approving an NDA or BLA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP and other requirements and the integrity of the clinical data submitted to the FDA.

The approval process can be lengthy and difficult, and the FDA may refuse to approve an NDA or BLA if the applicable regulatory criteria are not satisfied or may require additional clinical data or other data and information.

Even if such data and information are submitted, the FDA may ultimately decide that the NDA or BLA does not satisfy the criteria for approval.

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Additionally, the complete response letter may include recommended actions that the applicant might take to place the application in a condition for approval.

If a complete

response letter is issued, the applicant may either resubmit the NDA or BLA, addressing all of the deficiencies identified in the letter, or withdraw the application or request an opportunity for a hearing.

If a complete response letter is issued, the applicant may either resubmit the NDA or BLA, addressing all of the deficiencies identified in the letter, or withdraw the application or request an opportunity for a hearing.

If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product.

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.

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We are developing combination products using our own drug candidates and third-party drugs.

Regulation of Companion Diagnostics in the United States

If safe and effective use of a therapeutic depends on an in vitro diagnostic, then the FDA generally will require approval or clearance of that diagnostic, known as a companion diagnostic, at the same time that the FDA approves the therapeutic product.

In August 2014, the FDA issued final guidance clarifying the requirements that will apply to approval of therapeutic products and in vitro companion diagnostics.

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.

Expedited Programs

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The FDA has a fast track program that is intended to expedite or facilitate the process for reviewing new drugs, including biologics that meet certain criteria.

Specifically, new drugs are eligible for Fast Track designation if they are intended to treat a serious or life-threatening disease or condition for which there is no effective treatment and demonstrate the potential to address unmet medical needs for the condition.

Fast track designation applies to the combination of the product and the specific indication for which it is being studied.

The sponsor of a new drug may request the FDA to designate the drug as a fast track product concurrently with, or at any time after, submission of an IND, and the FDA must determine if the drug candidate qualifies for fast track designation within 60 days of receipt of the sponsor’s request.

In addition to other benefits, such as the ability to engage in more frequent interactions with the FDA, the FDA may initiate review of sections of a fast track drug’s NDA or BLA before the application is complete.

The sponsor of a new drug or biologic product candidate may request the FDA to designate the product candidate as a fast track product concurrently with, or at any time after, submission of an IND, and the FDA must determine if the product candidate qualifies for fast track designation within 60 days of receipt of the sponsor’s request.

In addition to other benefits, such as the ability to engage in more frequent interactions with the FDA, the FDA may initiate review of sections of a fast track product’s NDA or BLA before the application is complete.

This rolling review is available if the applicant provides, and the FDA approves, a schedule for the submission of each portion of the NDA or BLA and the applicant pays the applicable user fee.

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Additionally, the fast track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process.

Zanubrutinib was granted fast track designation status by the FDA for the treatment of WM.

Tislelizumab was granted fast track designation by the FDA for the treatment of HCC.

Zanubrutinib was granted fast track designation by the FDA for the treatment of WM and MZL.

Tislelizumab was granted fast track designation by the FDA for the treatment of 1L HCC.

Accelerated Approval

Under FDA’s accelerated approval regulations, the FDA may approve a drug, including a biologic, for a serious or life-threatening illness that provides meaningful therapeutic benefit to patients over existing treatments based upon a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

Under FDA’s accelerated approval regulations, the FDA may approve a drug, including a biologic, intended to treat a serious or life-threatening disease or condition that generally provides meaningful therapeutic benefit to patients over available treatments and demonstrates an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

In clinical trials, a surrogate endpoint is a marker, such as a laboratory measurement or clinical signs of a disease or condition that is thought to predict clinical benefit but is not itself a measure of clinical benefit.

Surrogate endpoints can often be measured more easily or more rapidly than clinical endpoints.

A drug candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of post-approval clinical trials sometimes referred to as Phase 4 trials to confirm the effect on the clinical endpoint.

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 on an expedited basis.

A product candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of post-approval clinical trials to confirm the effect on irreversible morbidity or mortality or other clinical benefit.

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.

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Breakthrough therapy designation is intended to expedite the development and review of a breakthrough therapy.

A drug or biologic product 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 it may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

A sponsor may request that a product 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.

If so designated, the FDA shall act to expedite the development and review of the product’s marketing application, including by meeting with the sponsor throughout the product’s development, providing timely advice to the sponsor to ensure that the development program to gather preclinical and clinical data is as efficient as practicable, involving senior managers and experienced review staff in a cross-disciplinary review, and assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor.

The designation may be rescinded if the drug candidate does not continue to meet the criteria for breakthrough therapy designation.

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.

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.

If so designated, the FDA shall act to expedite the development and review of the product candidate’s marketing application, including by meeting with the sponsor throughout the product candidate’s development, providing timely advice to the sponsor to ensure that the development program to gather preclinical and clinical data is as efficient as practicable, involving senior managers and experienced review staff in a cross-disciplinary review, and assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor.

The designation may be rescinded if the product candidate does not continue to meet the criteria for breakthrough therapy designation.

Zanubrutinib was granted breakthrough therapy designation by the FDA for the treatment of adult patients with MCL who have received at least one prior therapy.

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The NDA for zanubrutinib was granted priority review by the FDA for the treatment of adult patients with MCL who have received at least one prior therapy.

Pediatric Information

Under the Pediatric Research Equity Act, as amended (“PREA”), certain NDAs and BLAs and certain NDA and BLA supplements must contain data that can be used to assess the safety and efficacy of the product candidate for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

The FDA may grant deferrals for submission of pediatric data or full or partial waivers.

The FDCA requires that a sponsor who is planning to submit a marketing application for a product candidate that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan, or PSP, within 60 days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 study.

The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information.

The FDA and the sponsor must reach an agreement on the PSP.

A sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials and/or other clinical development programs.

Unless otherwise required by regulation, PREA does not apply to a drug or biologic for an indication for which orphan designation has been granted except that PREA will apply to an original NDA or BLA for a new active ingredient that is orphan-designated if the drug or biologic is a molecularly targeted cancer product intended for the treatment of an adult cancer and is directed at a molecular target that FDA determines to be substantially relevant to the growth or progression of a pediatric cancer

Post-Approval Requirements

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.

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The FDA may withdraw a product approval or revoke a biologics license if compliance with regulatory requirements is not maintained or if problems occur after the product reaches the market.

Later discovery of previously unknown problems with a

product may result in restrictions on the product or even complete withdrawal of the product from the market.

Later discovery of previously unknown problems with a product may result in restrictions on the product or even complete withdrawal of the product from the market.

Further, the failure to maintain compliance with regulatory requirements may result in administrative or judicial actions, such as fines, untitled or warning letters, holds on clinical trials, product seizures, product detention or refusal to permit the import or export of products, refusal to approve pending applications or supplements, restrictions on marketing or manufacturing, injunctions or civil or criminal penalties.

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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.

However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Pediatric exclusivity is another type of regulatory exclusivity in the United States.

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.

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.

Orphan drug exclusivity is described below under "Orphan Drugs."

Biosimilars and Exclusivity

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A reference biologic is granted 12 years of exclusivity from the time of first licensure of the reference product.

resolution in the applicant’s favor of a lawsuit challenging the biologic’s patents if an application has been submitted, or (iv) 42 months after the application has been approved if a lawsuit is ongoing within the 42-month period.

The first biologic product submitted under the abbreviated approval pathway that is determined to be interchangeable with the reference product has exclusivity against other biologics submitting under the abbreviated approval pathway for the lesser of (i) one year after the first commercial marketing, (ii) 18 months after approval if there is no legal challenge, (iii) 18 months after the resolution in the applicant’s favor of a lawsuit challenging the biologic’s patents if an application has been submitted, or (iv) 42 months after the application has been approved if a lawsuit is ongoing within the 42-month period.

Under the Orphan Drug Act, the FDA may grant orphan drug designation to drugs, including biologics, intended to treat a rare disease or condition-generally a disease or condition that affects fewer than 200,000 individuals in the United States or that affects more than 200,000 individuals in the United States and for which there is no reasonable expectation that costs of research and development of the product for the indication can be recovered by sales of the product in the United States.

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Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition.

Zanubrutinib was granted orphan drug designation status by the FDA for the treatment of WM, CLL, and MCL.

Tislelizumab was granted orphan drug designation status by the FDA for the treatment of ESCC and HCC.

Zanubrutinib was granted orphan drug designation status by the FDA for the treatment of WM, CLL, MCL and MZL (3 subtypes).

Tislelizumab was granted orphan drug designation status by the FDA for the treatment of ESCC, HCC and GC.

Disclosure of Clinical Trial Information

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Sponsors are also obligated to disclose the results of their clinical trials after completion.

Disclosure of the results of these trials can be delayed until the new product or new indication being studied has been approved.

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 may 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.

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.

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.

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In order to obtain coverage and reimbursement for any product that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of any products, in addition to the costs required to obtain regulatory approvals.

If third-party payors do not consider a product to be cost-effective or medically-necessary compared to other available therapies,

they may not cover the product after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow a company to sell its products at a profit.

If third-party payors do not consider a product to be cost-effective or medically-necessary compared to other available therapies, they may not cover the product after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow a company to sell its products at a profit.

Healthcare Reform

government and state legislatures have shown significant interest in implementing cost containment programs to limit the growth of government-paid health care costs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs.

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Adoption of government controls and measures and tightening of restrictive policies in jurisdictions with existing controls and measures, could limit payments for pharmaceuticals.

The current U.S.

president's administration’s budget proposals for fiscal years 2019 and 2020 contain further drug price control measures that could be enacted during the 2020 budget process or in other future legislation, including, for example, measures to permit Medicare Part D plans to negotiate the price of certain drugs under Medicare Part B, to allow some states to negotiate drug prices under Medicaid, and to eliminate cost sharing for generic drugs for low-income patients.

Additionally, the current administration released a “Blueprint” to lower drug prices and reduce out of pocket costs of drugs that contains additional proposals to increase manufacturer competition, increase the negotiating power of certain federal healthcare programs, incentivize manufacturers to lower the list price of their products and reduce the out of pocket costs of drug products paid by consumers.

Department of Health and Human Services (the "HHS") has already started the process of soliciting feedback on some of these measures and, at the same time, is immediately implementing others under its existing authority.

Although a number of these measures and other proposed measures will require authorization through additional legislation to become effective, U.S.

Congress and the current administration have each indicated that it will continue to seek new legislative and/or administrative measures to control drug costs.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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.

Other legislative changes have been proposed and adopted in the United States since the ACA was enacted.

For example, the Bipartisan Budget Act of 2018 also amended the ACA, effective January 1, 2019, by increasing the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D from 50% to 70%, effective January 1, 2019, and closing the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole.”

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.

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.

Further, on July 24, 2020 and September 13, 2020, former President Trump announced several executive orders related to prescription drug pricing that seek to implement several of the administration's proposals.

In response, the FDA released a final rule on September 24, 2020, which went into effect on November 30, 2020, providing guidance for states to build and submit importation plans for drugs from Canada.

Further, on November 20, 2020 the Centers for Medicare and Medicaid Services (the "CMS") issued an Interim Final Rule implementing the Most Favored Nation ("MFN") Model under which Medicare Part B reimbursement rates will be calculated for certain drugs and biologics based on the lowest price drug manufacturers receive in Organization for Economic Cooperation and Development countries with a similar gross domestic product per capita.

The MFN Model regulations mandate participation by identified Part B providers and would have applied in all U.S.

states and territories for a seven-year period beginning January 1, 2021, and ending December 31, 2027.

However, in response to a lawsuit filed by several industry groups, on December 28, 2020, the U.S.

District Court for the Northern District of California issued a nationwide preliminary injunction enjoining government defendants from implementing the MFN Rule pending completion of notice-and-comment procedures under the Administrative Procedure Act.

On January 13, 2021, in a separate lawsuit brought by industry groups in the U.S.

District of Maryland, the government defendants entered a joint motion to stay litigation on the condition that the government would not appeal the preliminary injunction granted in the U.S.

District Court for the Northern District of California and that performance for any final regulation stemming from the MFN Interim Final Rule shall not commence earlier than 60 days after publication of that regulation in the Federal Register.

Further, authorities in Canada have passed rules designed to safeguard the Canadian drug supply from shortages.

If implemented, importation of drugs from Canada and the MFN Model may materially and adversely affect the price we receive for our medicines.

Additionally, on November 20, 2020, the U.S.

Department of Health and Human Services (the "HHS") finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.

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.

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.

Although a number of these and other proposed measures may require authorization through additional legislation to become effective, and the Biden administration may reverse or otherwise change these measures, Congress has each indicated that it will continue to seek new legislative and/or administrative measures to control drug costs.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

Presently, the State Medicaid combined represent less than 5% of our overall business in the U.S.

While much of the focus of state pricing policies is limited to Medicaid, we cannot assess the impact that these and other measures such as state transparency policies will have on our business.

Moreover, on May 30, 2018, the Right to Try Act, was signed into law.

The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase I clinical trial and that are undergoing investigation for FDA approval.

Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program.

There is no obligation for a drug manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act or FDA’s expanded access program authorities, but the manufacturer must develop and make publicly available its policy on expanded access availability and respond to patient requests according to that policy.

We make available on our website the BeiGene contact information for requesting access to our investigational drugs and expected timeline for us to acknowledge receiving such requests.

Healthcare Laws and Compliance Requirements

If we obtain regulatory approval of our product candidates, we may be subject to various federal and state laws targeting fraud and abuse in the healthcare industry.

These laws may impact, among other things, our proposed 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.

We are subject to various federal and state laws targeting fraud and abuse in the healthcare industry.

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.

The laws that may affect our ability to operate include:

the federal Anti-Kickback Statute, 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;

federal civil and criminal false claims and civil monetary penalty laws, such as the federal False Claims Act, which impose criminal and civil penalties and authorize civil whistleblower or qui tam actions, against individuals or entities for, among other things:

• 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.

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.

Although there are several statutory exceptions and regulatory safe harbors protecting certain common activities from prosecution, they are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exception or safe harbor.

A person or entity can be found guilty of violating the AKS without actual knowledge of the statute or specific intent to violate it.

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.

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.

On November 20, 2020, the Office of Inspector General (“OIG”) finalized further modifications to the federal Anti-Kickback Statute.

Under the final rules, OIG added safe harbor protections under the Anti-Kickback Statute for certain coordinated care and value-based arrangements among clinicians, providers, and others.

These rule (with exceptions) became effective January 19, 2021.

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:

knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false, fictitious or fraudulent;

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or knowingly concealing or knowingly and improperly avoiding or decreasing an obligation to pay money to the federal government.

In addition, the government may assert that a claim including items and services resulting from a violation of the federal Anti-Kickback Statute constitutes a false of fraudulent claim for purposes of the False Claims Act;

the federal 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;

In addition, the government may assert that a claim including items and services resulting from a violation of the federal AKS constitutes a false of fraudulent claim for purposes of the FCA.

The government may deem manufacturers to have “caused” the submission of false or fraudulent claims by, for example, providing inaccurate billing or coding information to customers or promoting a product off-label.

Companies that submit claims directly to payors may also be liable under the FCA for the direct submission of such claims.

The FCA also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery.

When an entity is determined to have violated the federal civil FCA, the government may impose civil fines and penalties for each false claim, plus treble damages, and exclude the entity from participation in Medicare, Medicaid and other federal healthcare programs.

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.

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• federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers;

The ACA broadened the reach of the fraud and abuse laws by, among other things, amending the intent requirement of the federal Anti-Kickback Statute and the applicable criminal healthcare fraud statutes contained within 42 U.S.C.

• federal price reporting laws, which require manufacturers to calculate and report complex pricing metrics in an accurate and timely manner to government programs;

• federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers;

• the Foreign Corrupt Practices Act ("FCPA"), which prohibits companies and their intermediaries from making, or offering or promising to make, improper payments to non-U.S.

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 Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act or the civil monetary penalties statute.

Many states have adopted laws similar to the federal Anti-Kickback Statute and False Claims Act, 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.

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.

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CCPA provides for civil penalties for violations, as well as a private right of action for data breaches that is expected to increase data breach litigation.

While there is currently an exception for protected health information that is subject to HIPAA and clinical trial regulations, as currently written, CCPA may impact certain of our business activities.

CCPA could mark the beginning of a trend toward more stringent state privacy legislation in the United States, which could increase our potential liability and adversely affect our business.

Further, a new California privacy law, the California Privacy Rights Act, or CPRA, was passed by California voters on November 3, 2020.

The CPRA will create additional obligations with respect to processing and storing personal information that are scheduled to take effect on January 1, 2023 (with certain provisions having retroactive effect to January 1, 2022).

We will continue to monitor developments related to the CPRA and anticipate additional costs and expenses associated with CPRA compliance.

states also are considering omnibus privacy legislation and industry organizations regularly adopt and advocate for new standards in these areas.

While the legislation and proposed regulations including the CCPA and CPRA contain an exception for certain activities that involve PHI subject to HIPAA, we cannot yet determine the impact the CCPA, CPRA or other such future laws, regulations and standards may have on our business.

Additionally, we are subject to state equivalents of each of the healthcare laws described above, among others, some of which may be broader in scope and may apply to healthcare services reimbursed by any third-party payor, not just governmental payors, but also private insurers.

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In addition, private individuals have the ability to bring actions on behalf of the U.S.

government under the federal False Claims Act as well as under the false claims laws of several states.

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 consent of the individuals to whom the personal data relates, 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 to the United States.

GDPR introduces new data protection requirements in the EU and 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.

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.

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China heavily regulates the development, approval, manufacturing and distribution of drugs, including biologics.

The legal framework for the administration of pharmaceutical products in China is established by the Drug Administration Law of the PRC (DAL) enacted by the Standing Committee of the National People’s Congress on September 20, 1984 and effective from July 1, 1985 (last amended on August 26, 2019, effective from December 1, 2019).

The Drug Administration Law 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.

The legal framework for the administration of pharmaceutical products in China was established by the Drug Administration Law of the PRC (the "DAL").

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.

The Implementing Measures of the Drug Administration Law promulgated by the State Council on August 4, 2002 and effective from September 15, 2002 and amended on February 6, 2016 and March 2, 2019 provides detailed implementation regulations for the Drug Administration Law.

The Implementing Measures of the Drug Administration Law as amended in 2019 provides detailed implementation regulations for the DAL.

The Revised DAL

The DAL revised on August 26, 2019 (the "rDAL") embodies an expected regulatory trend to strengthen the life-cycle management of drugs, to balance the development of innovative drugs and generic drugs, and to enhance drug review and enforcement.

The DAL, revised in 2019 (the "rDAL"), embodies an expected regulatory trend to strengthen the life-cycle management of drugs, to balance the development of innovative drugs and generic drugs, and to enhance drug review and enforcement.

It also reflects legislative efforts to address prominent problems of the pharmaceutical industry, such as counterfeit and substandard drugs and high drug prices.

The rDAL contains a dedicated chapter on the Marketing Authorization Holder (“MAH”) system.

The MAH system has been trialed in a pilot program across 10 provinces since 2016.

Upon the enactment of the rDAL, the MAH system will no longer be a pilot program but will be implemented nationwide.

Subject to approval by the NMPA, MAHs will be allowed to transfer their marketing authorizations.

It is not sure whether the transferability of MAH will offer more flexibility in structuring cross-border transactions.

In addition, the implementation of the MAH system will be accompanied by a range of new requirements for the MAHs.

It is uncertain whether the transferability of MAH will offer more flexibility in structuring cross-border transactions.

In addition, the implementation of the MAH system was accompanied by a range of new requirements for the MAHs.

For example, a MAH must establish a quality assurance system and be responsible for the whole process and all aspects of preclinical research, clinical trials, manufacturing and distribution, post-marketing research, adverse drug reaction monitoring and reporting.

A foreign MAH will be required to engage a local agent to fulfill the MAH’s obligations and the foreign MAH shall be subject to joint and several liability in the event of any wrongdoing.

A foreign MAH is required to engage a local agent to fulfill the MAH’s obligations and the foreign MAH is subject to joint and several liability in the event of any wrongdoing.

It is unclear how the scope of such joint liability will be defined.

The rDAL no longer requires the certification for GLP, good clinical practice ("GCP"), good supply practice ("GSP"), and GMP.

The rDAL no longer requires the certification for good clinical practice ("GCP"), good supply practice ("GSP"), and GMP.

However, drug manufacturers and drug distributors must still comply with current GMP and GSP requirements.

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The NMPA will issue related standards and regulations regarding drug track and trace system.

pharmacovigilance system will also be established to monitor, identify, evaluate and control adverse drug reactions and other possible drug-related problems.

A drug pharmacovigilance system will also be established to monitor, identify, evaluate and control adverse drug reactions and other possible drug-related problems.

The rDAL creates an expanded access pathway for investigational drugs under which a company sponsor of a clinical trial in China can apply to establish an expanded access treatment program for patients with life-threatening disease who otherwise do not satisfy the inclusion criteria of a clinical trial.

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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.

On October 15, 2019, NMPA published draft measures for soliciting comments on drug registration, and on December 10, 2019, the State Administration for Market Regulation ("SAMR") published draft measures for soliciting comments on drug manufacturing and drug supply.

These draft measures reflect the changes in the rDAL, including the MAH system, the abolishment of GLP, GCP, GSP and GMP certification, and the enhancement of administrative penalties on violations.

There are still uncertainties with respect to the interpretation and implementation of the rDAL.

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The agency was newly formed from the prior China Food and Drug Administration ("CFDA") in 2018 as part of a complete government reorganization.

NMPA is no longer an independent agency.

Its parent agency is now the newly organized SAMR, into which agencies responsible for, among other areas, consumer protection, advertising, anticorruption, antitrust, fair competition and intellectual property have been merged.

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).

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The NMPA requires preclinical data to support registration applications for new drugs.

Preclinical work, including pharmacology and toxicology studies, must meet the GLP standards, issued on August 4, 2003 and amended on July 27, 2017.

Although the rDAL no longer requires the NMPA to accredit GLP labs, it still requires that nonclinical studies of chemical drug substances and preparations and biologics that are not yet marketed in China be conducted in GLP-qualified labs.

Preclinical work, including safety assessment studies, must meet the GLP standards, issued in 2003 and amended in 2017.

The rDAL requires the NMPA to accredit GLP labs, and that nonclinical studies of chemical drug substances and preparations and biologics that are not yet marketed in China be conducted in GLP-certified labs.

There are no approvals required from the NMPA to conduct preclinical studies.

Under the Regulations for the Administration of Affairs Concerning Experimental Animals issued by the State Science and Technology Commission ("SSTC") on November 14, 1988 (last amended on March 1, 2017), the Administrative Measures on Good Practice of Experimental Animals jointly issued by the SSTC and the State Bureau of Quality and Technical Supervision

on December 11, 1997, and the Administrative Measures on the Certificate for Experimental Animals (Trial) promulgated by SSTC and other regulatory authorities on December 5, 2001, a Certificate for Use of Laboratory Animals is required for performing experimentation on animals.

A Certificate for Use of Laboratory Animals is required for performing experimentation on animals under the Regulations for the Administration of Affairs Concerning Experimental Animals issued in 1988 and last amended in 2017, the Administrative Measures on Good Practice of Experimental Animals issued in 1997, and the Administrative Measures on the Certificate for Experimental Animals (Trial) issued in 2001.

Applicants for this certificate must satisfy a number of conditions, including (1) the environment and facilities for lab animals’ living and propagating must satisfy national requirements;

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Category 1 (“innovative drugs”) refers to drugs that have a new chemical entity that has not been marketed anywhere in the world, Category 2 (“improved new drugs”) refers to drugs with a new indication, dosage form, route of administration, combination, or certain formulation changes not approved in the world, Categories 3 and 4 are for generics that reference an innovator drug (or certain well-known generic drugs) marketed either abroad or in China, respectively, and Category 5 refers to innovative or generic drugs that have already been marketed abroad but are not yet approved in China (i.e., imported drugs).

Therapeutic biologics follow a similar categorization, with Category 1 being new to the world, but with fifteen product-specific categories.

Therapeutic biologics follow a similar categorization, with Category 1 being new to the world.

Like with small molecule drugs, Category 1 is for innovative biologics that have not been approved inside or outside of China.

A clear regulatory pathway for biosimilars does not yet exist, but something was proposed in a draft revision to an NMPA regulation in 2017.

Each of zanubrutinib, tislelizumab, pamiparib and lifirafenib is classified as Category 1 based on the respective clinical trial approval from the NMPA, which is a favored category for clinical trial approval, or CTA, and marketing approval.

Biosimilars are under Category 3.

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.

Expedited Programs

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Applications for these expedited programs can be submitted after the CTA is admitted for review by the CDE.

Some of the current categories of drugs eligible for priority status that may be particularly relevant for us include:

(1) Category 1 innovative drugs that have not been approved inside or outside of China;

(2) oncology drugs;

(3) drugs using advanced technology, innovative treatment methods, and having clear therapeutic benefit;

and (4) new drugs for which clinical trials are already approved in the United States or EU, or for which marketing authorization applications have been filed simultaneously in China and in the United States or EU and are manufactured in China using the same production line that passed FDA or EMA inspection.

The NMPA’s Drug Registration Rules effective from July 1, 2020 (“DRR”) provides certain categories of drugs that may be eligible for priority status, among which, the following may be particularly relevant for us:

(1) drugs that are clinically and urgently needed but insufficient in supply;

(2) innovative drugs and improved new drugs for prevention and treatment of major contagious diseases and rare diseases;

(3) new pediatric drugs, (4) drugs designated as breakthrough therapies, and (5) drugs that satisfy the conditional approval criteria.

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.

Each of our drug candidates, zanubrutinib, tislelizumab, pamiparib and lifirafenib, is classified as Category 1 based on the respective clinical trial approval from the NMPA.

Our NDA for pamiparib and our BLAs for QARZIBA ® and SYLVANT ® have been accepted by CDE and granted priority status .

Conditional Approval

NMPA also permits conditional approval of certain medicines based on early phase data.

Post-approval the applicant may need to conduct a post-market study.

The agency has done this for drugs that meet unmet clinical needs for life-threatening illnesses and also for drugs that treat orphan indications.

In 2018, NMPA established a conditional approval program for drugs designated by the CDE that have been approved in the US, EU and Japan within the last 10 years and that meet one of three criteria (1) orphan indications, (2) drugs that treat life threatening illnesses for which there are not effective treatment or preventive methods, and (3) drugs that treat life threatening illnesses and that have a clear clinical advantage over other clinical therapies.

CDE Guideline on PD-1/L1 NDA

In addition to the programs and proposals above, the CDE has recently stated that it will permit applicants for PD-1/L1 agents to submit data on a rolling basis based on the current high unmet medical need for PD-1/L1 agents.

In February 2018, the CDE released the Guideline on the Basic Requirements of Information and Data for NDA Submissions of anti-PD-1/L1 Monoclonal Antibody Products on recurrent and refractory advanced cancers without standard-of-care therapies.

Under the guideline, the sponsor must have a pre-NDA meeting with the CDE regarding the data and the NDA submission.

The CDE will permit the following submission for these applicants:

(1) an initial NDA submission with full preliminary safety data and effectiveness data, including the results of at least two independent therapeutic efficacy assessments of all patients who are currently enrolled pursuant to all of the protocol’s requirements;

(2) during the CDE’s substantive technical review of the NDA,

submission on a rolling basis of follow-up safety and effectiveness data from at least six months from the time of the last enrolled patient showing the duration of the response;

and (3) submission of all efficacy and safety data as provided for under the protocol before final approval is granted by the NMPA.

Sponsors may also apply for priority review and approval for their NDA to accelerate the progress.

If granted, priority status will be applied to various stages of the approval process, including testing, manufacturing site inspection, technical review, and clinical site inspection.

The agency has done this for medicines that meet unmet medical needs for life-threatening illnesses and also for medicines that treat orphan indications.

Under the DRR, drugs that meet one of the three criteria might be eligible for conditional approval:

(1) drugs that treat life threatening illnesses for which there are no effective treatment or preventive methods, but their clinical trials already have the data to prove efficacy and their clinical value is predictable, (2) drugs that are urgently needed for public health reasons, and their clinical trials already have the data to prove efficacy and their clinical value is predictable;

or (3) vaccines that are urgently needed for major public health emergencies or otherwise deemed by the National Health Commission to be urgently needed, and it is concluded upon evaluation that their benefits outweigh their risks.

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.

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.

Breakthrough Therapy Designation

Breakthrough therapy designation ("BTD") is a process designed to expedite the development and review of clinical stage, innovative or improved new drugs that meet the following criteria:

(1) they are intended to treat life threatening conditions or conditions that have serious negative impact on the quality of life, and (2) there are no effective treatment or preventive methods available, or there is preliminary clinical evidence indicating that they may demonstrate substantial improvement over available therapies.

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.

New Policies on Expediting Approval of Imported Oncology Drugs

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Clinical Trials and Marketing Approval

Upon completion of preclinical studies, a sponsor typically needs to conduct clinical trials in China for registering a new drug.

Upon completion of preclinical studies and preliminary CMC studies, a sponsor typically needs to conduct clinical trials in China for registering a new drug.

The materials required for this application and the data requirements are determined by the registration category.

The NMPA has taken a number of steps to increase efficiency for approving CTAs, and it has also significantly increased monitoring and enforcement of GCP to ensure data integrity.

Trial Approval

Clinical Trial Approval

All clinical trials conducted in China for the purpose of seeking marketing approvals must be approved by the NMPA and conducted at hospitals satisfying GCP requirements.

In addition to a standalone China trial to support development, imported drug applicants may establish a site in China that is part of an international multicenter trial ("IMCT") at the outset of the global trial.

In addition to a standalone China trial to support development, imported drug applicants may include Chinese clinical sites as part of an international multicenter trial (“IMCT”).

Domestically manufactured drugs are not subject to foreign approval requirements, and in contrast to prior practice, the NMPA has decided to permit those drugs to conduct development via an IMCT as well.

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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.

Trial Register

Pursuant to the Announcement on Drug Clinical Trial Information Platform issued by the NMPA on September 6, 2013, clinical trials approved by the NMPA and conducted in China must be registered and published through the Drug Clinical Trial Information Platform (http://www.chinadrugtrials.org.cn).

The applicant shall pre-register the trial information within one month after obtaining the clinical trial approval to obtain the trial’s unique registration number and shall complete registration of certain follow-up information before the first subject’s enrollment in the trial.

Clinical Trial Register

Clinical trials conducted in China must be registered and published through the Drug Clinical Trial Information Platform (http://www.chinadrugtrials.org.cn).

Applicant are required to pre-register the trial information within one month after obtaining the clinical trial approval to obtain the trial’s unique registration number and to complete registration of certain follow-up information before the first subject’s enrollment in the trial.

If the foregoing pre-registration and registration is not obtained within one year after obtaining the clinical trial approval, the applicant shall submit an explanation, and if the procedure is not completed within three years, the clinical trial approval automatically expires.

Human Genetic Resources Regulation

On June 10, 2019, China's State Council promulgated the Regulation on the Administration of Human Genetic Resources (HGR Regulation), which became effective on July 1, 2019.

The HGR Regulation applies to all human genetic resources (HGR)-related activities for R&D purposes, including sampling, biobanking, use of HGR materials and associated data in China, and provision of such to foreign parties.

According to the HGR Regulation, foreign parties (including foreign entities and entities established or actually controlled by foreign entities and individuals) 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.

The HGR Regulation now prohibits foreign parties from independently sampling or biobanking any China HGR in China and it adds an approval requirement for the sampling of certain HGR and biobanking of all HGR by Chinese parties.

The Regulation on the Administration of Human Genetic Resources ("HGR Regulation") became effective on July 1, 2019.

The HGR Regulation applies to foreign parties, including foreign entities and entities established or actually controlled by foreign entities and individuals.

As BeiGene, Ltd.

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.

The HGR Regulation prohibits foreign parties from independently sampling or biobanking any China HGR in China and requires approval for the sampling of certain HGR and biobanking of all HGR by Chinese parties.

Any cross-border transfer of the HGR materials, either under an international collaboration or as a direct export, must be on an as-needed basis and requires approval.

In addition, providing the HGR data to foreign parties requires a record filing.

Another significant change is the HGR Regulation replaced the advance approval requirement with a record-filing procedure for international collaborations on clinical trials intended to support marketing approval of drugs in China that do not transfer HGR materials abroad, while the advance approval requirement still applies if such trials involve export of HGR

materials or the collection, testing, analysis or disposals of HGR samples during the trials are not solely conducted at the clinical trial sites.

It is unclear how this record-filing procedure will be implemented in practice and to what extent companies will benefit from it.

In addition, providing HGR data to foreign parties requires a record filing.

Companies conducting global clinical trials may benefit little from this record filing procedure because those trials would often require cross-border transfer of HGR materials and the advance approval requirement would still apply.

The HGR Regulation retains the provision in the Interim Measures for the Administration of Human Genetic Resources issued in 1998 (the "Interim Measures") that parties should jointly apply for and own the patent rights arising from the results generated from international collaborations that utilize China HGR.

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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.

As uncertainties exist as to how the HGR Regulation may be interpreted and implemented, we are still evaluating its potential impact on our HGR-related activities and practices.

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 reduce requirements for trials and data, 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.

On July 6, 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”).

According to the Guidance Principles, the data of foreign clinical trials must meet the authenticity, completeness and accuracy requirements and such data must be obtained in compliance with the relevant requirements under the GCP of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use ("ICH").

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”).

According to the Guidance Principles, data from foreign clinical trials must meet authenticity, completeness and accuracy requirements and such data must be obtained in compliance with the relevant requirements under the GCP of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (the "ICH").

Sponsors must be attentive to potentially meaningful ethnic differences in the subject population.

The NMPA now officially permits, and its predecessor agencies have permitted on a case-by-case basis in the past, drugs approved outside of China to be approved in China on a conditional basis without the need for pre-approval clinical trials in China.

Specifically, in 2018, the NMPA established a program permitting drugs that have been approved within the last ten years in the United States, EU or Japan to be approved in China on a conditional basis without local clinical trials if they (1) prevent or treat orphan diseases, (2) prevent or treat serious life-threatening illnesses for which there is either no effective therapy in China, or for which the foreign-approved drug would have clear clinical advantages.

The NMPA now permits, and its predecessor agencies have permitted on a case-by-case basis in the past, drugs approved outside of China to be approved in China on a conditional basis without the need for pre-approval clinical trials in China.

Specifically, in 2018, the NMPA established a program permitting drugs that have been approved within the last ten years in the United States, EU or Japan to be approved in China without local clinical trials if they (1) prevent or treat orphan diseases, (2) prevent or treat serious life-threatening illnesses for which there is either no effective therapy in China, or for which the foreign-approved drug would have clear clinical advantages.

Applicants for such conditional approvals will be required to establish a risk mitigation plan and may be required to complete trials in China after the drug is approved.

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Clinical Trial Process and Good Clinical Practices

Typically drug clinical trials in China have three phases.

As in other parts of the world, clinical trials in China typically have three phases.

Phase 1 refers to the initial clinical pharmacology and human safety evaluation studies.

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Phase 3 (often the pivotal study) refers to clinical trials to further verify the drug candidate’s therapeutic efficacy and safety on patients with target indication(s) and ultimately provide sufficient evidence for the review of a drug registration application.

The NMPA requires that the different phases of clinical trials in China receive ethics committee approval prior to approval of the CTA and comply with GCP.

The NMPA requires that the different phases of clinical trials in China receive ethics committee approval and comply with GCP.

The NMPA conducts inspections on clinical trials conducted in China to assess GCP compliance and may refuse to approve the drug if it finds substantial issues in the trials.

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The NMPA has released catalogues of reference products, and it released first installment of a Marketed Drug List (China’s “Orange Book”) with information about drugs that may serve as reference products.

Pursuant to GCP, the sponsor of a clinical trial shall be responsible for proper packaging and labeling of drugs used for clinical trials, and in double-blinded clinical trials, the investigational drugs shall be consistent with the control drug or placebo in appearance, odor, packaging, labeling, and certain other features.

According to the Measures for the Administration of

Pharmaceutical Packaging promulgated on February 12, 1988 and effective from September 1, 1988, pharmaceutical packaging must comply with national and professional standards.

Pursuant to GCP, sponsors of clinical trials are responsible for proper packaging and labeling of drugs used for clinical trials, and in double-blinded clinical trials, the investigational drugs shall be consistent with the control drug or placebo in appearance, odor, packaging, labeling, and certain other features.

Pharmaceutical packaging must comply with national and professional standards.

If there is no national or professional standard available, companies may formulate and implement its own standards after obtaining the approval of the provincial administration for medical products or bureau of standards.

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Upon completion of clinical trials, a sponsor may submit clinical trial data to support marketing approval for the drug.

NDA sponsors must submit data derived from domestically manufactured drugs in support of a drug approval.

For domestically manufactured drugs, NDA sponsors must submit data derived from the submitted drugs in support of their approval.

Under the rDAL, upon approval of the registration application, the NMPA will issue a drug registration certificate to the applicant which is in fact the marketing approval of the drug, and the applicant is no longer required to be equipped with relevant manufacturing capability.

Manufacturing and Distribution

According to the rDAL, all facilities that make drugs in China must receive a drug manufacturing license with an appropriate “scope of manufacturing” from the local drug regulatory authority.

All facilities that manufacture drugs in China must receive a drug manufacturing license with an appropriate “scope of manufacturing” from the local drug regulatory authority.

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 (“distribution activities”), a company must obtain a Drug Distribution License from the local drug regulatory authority, subject to renewal every five years.

Like with GMPs, companies are required to be in compliance with GSP.

China has formed a “Two-Invoice System” to control distribution of prescription drugs.

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.

As with GMPs, companies are required to be in compliance with GSP.

China has developed a “Two-Invoice System” to control distribution of prescription drugs.

The “Two-Invoice System” generally requires that no more than two invoices may be issued throughout the distribution chain, with one from the manufacturer to a distributor and another from the distributor to the end-user hospital.

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However, the system still significantly limits the options for companies to use multiple distributors to reach a larger geographic area in China.

Compliance with the Two-Invoice System will become a prerequisite for pharmaceutical companies to participate in procurement processes with public hospitals, which currently provide most of China’s healthcare.

Compliance with the Two-Invoice System is a prerequisite for pharmaceutical companies to participate in procurement processes with public hospitals, which currently provide most of China’s healthcare.

Manufacturers and distributors that fail to implement the Two-Invoice System may lose their qualifications to participate in the bidding process.

Non-compliant manufacturers may also be blacklisted from engaging in drug sales to public hospitals in a locality.

The Two-Invoice System was first implemented in 11 provinces that are involved in pilot comprehensive medical reforms, but the program has expanded to nearly all provinces, which have their own individual rules for the program.

Post-Marketing Surveillance

Under the rDAL, the MAH of a drug is ultimately responsible for pharmacovigilance, including quality assurance, adverse reaction reporting and monitoring, and product recalls.

Distributors and user entities (e.g., hospitals) are also required to report, in their respective roles, adverse reactions of the products they sell or use, and assist with the manufacturer of the product recall.

A drug that is currently under the new drug monitoring period has to report all adverse drug reactions (as opposed to just serious adverse reactions) for that period.

Distributors and user entities (e.g., hospitals) are also required to report, in their respective roles, adverse reactions of the products they sell or use, and assist the MAH with any product recalls.

An MAH for a drug that is currently under the new drug monitoring period has to report all adverse drug reactions (as opposed to just serious adverse reactions) for that period.

Advertising and Promotion of Pharmaceutical Products

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Advertising that includes content that is outside of the drug’s approval documentation (“off-label content”) is prohibited.

False advertising can result in civil suits from end users and administrative liability,

including fines.

False advertising can result in civil suits from end users and administrative liability, including fines.

In addition to advertisements, non-promotional websites that convey information about a drug must go through a separate approval process by a local drug regulatory authority.

Regulatory Intellectual Property Protections

On January 15, 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 has 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.

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 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.

Non-Patent Exclusivities

New Drug Monitoring Period

Currently, new varieties of domestically produced drugs approved under Categories 1 or 2 in China may be placed under a monitoring period for three to five years.

Category 1 innovative drugs will be monitored for five years.

During the monitoring period, the NMPA will not approve another CTA from another applicant for the same type of drug, except if another sponsor has an approved CTA at the time that the monitoring period is initiated it may proceed with its trial and once approved become another drug that is part of the 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 also lays the foundation to improve and implement the system for regulatory data protection to protect innovators.

This protection will be available to the undisclosed clinical trial data of drugs falling into the following categories:

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:

innovative drugs, innovative therapeutic biologics, drugs that treat orphan diseases, pediatric drugs, and drugs for which there has been a successful patent challenge.

In the Trade Agreement, China has committed to providing for effective protection of undisclosed test or other data submitted as a condition of marketing approval.

NMPA published a draft on Implementing Regulations for Pharmaceutical Study Data Protection for public comment that would set regulatory data protection for innovative small molecule drugs at six years and for innovative therapeutic biologics at 12 years;

In the Trade Agreement, China has committed to providing for effective protection of undisclosed clinical trial or other data submitted as a condition of marketing approval.

The NMPA has published draft regulations for public comment that would set regulatory data protection for innovative small molecule drugs at six years and for innovative therapeutic biologics at 12 years;

pediatric and orphan drugs would receive six years to run concurrently from their approval dates.

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Submissions over six years later in China may not receive protection.

There is also a reduction if the marketing application is filed in China based solely on overseas clinical data with no Chinese subjects (75% reduction) or based on supplemental “China clinical trial data” (50% reduction).

The proposed regulations also call for a reduction in exclusivity if the marketing application is filed in China based solely on overseas clinical data with no Chinese subjects (75% reduction) or based on supplemental “China clinical trial data” (50% reduction).

Information about the exclusivity term will be included in a Marketed Drug List (similar to the Orange Book in the US) at the time of approval.

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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 adopts certain elements of a patent linkage system:

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 does not explicitly mention a stay of marketing approval of the follow-on application.

It will require legislation and implementing regulations to introduce a patent linkage system into China, and it is not clear when these will be adopted and implemented.

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.

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.

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.

It is not clear when this will be implemented.

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 extended term shall not exceed five years, and the total patent term after market entry of the new drug shall not exceed 14 years.

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, leading to uncertainty about the scope of implementation.

Reimbursement and Pricing

China’s national medical insurance program was adopted pursuant to the Decision of the State Council on the Establishment of the Urban Employee Basic Medical Insurance Program issued by the State Council in 1998, under which all employers in urban cities are required to enroll their employees in the basic medical insurance program.

The insurance premium is jointly contributed by the employers and employees.

In 2007, the State Council promulgated Guiding Opinions of the State Council about the Pilot Urban Resident Basic Medical Insurance, under which urban residents of the pilot district, rather than urban employees, may voluntarily join Urban Resident Basic Medical Insurance.

China’s national medical insurance program currently consists of two fundamental sub-programs:

(1) the basic medical insurance program for urban employees, under which urban employers are required to enroll their employees in the program and the insurance premium is jointly contributed by the employers and employees;

and (2) the basic medical insurance program for urban and rural residents, which allows urban and rural residents who do not have employers to voluntarily participate in the basic medical insurance program and the insurance premium is jointly contributed by the participants and the government.

Participants of the national medical insurance program and their employers, if any, are required to contribute to the payment of insurance premiums on a monthly basis.

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A pharmaceutical product listed in the NRDL must be clinically needed, safe, effective, reasonably priced, easy to use, and available in sufficient quantity.

Factors that affect the inclusion of a pharmaceutical product in the NRDL include whether the product is consumed in large volumes and commonly prescribed for clinical use in the PRC and whether it is considered to be important in meeting the basic healthcare needs of the general public.

Factors that affect the inclusion of a pharmaceutical product in the NRDL include whether the product is used in large volumes and commonly prescribed for clinical use in the PRC and whether it is considered to be important in meeting the basic healthcare needs of the general public.

Since 2016, special consideration has been given to, among others, innovative drugs with high clinical value and drugs for serious diseases.

In addition, the PRC Ministry of Human Resources and Social Security 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 2019 covers 2,643 drugs in total, including 148 new additions and 150 new deletions as compared with the previous version, with an emphasis on innovative drugs and drugs that treat cancer and other serious diseases.

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.

China has been pursuing a policy of expediting the addition of innovative oncology drugs to this list.

In 2019, 17 more oncology drugs, including VIDAZA (azacytidine), were added into the NRDL by the State Medical Insurance Bureau.

REVLIMID ® has been included in the NRDL since 2017.

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.

Government Price Controls

The Chinese government has abolished the 15-year-old government-led pricing system for drugs, and lifted the maximum retail price for most drugs, including drugs reimbursed by government medical insurance funds, patented drugs, and some other drugs.

The government regulates prices mainly by establishing a consolidated procurement mechanism, restructuring medical insurance reimbursement standards and strengthening regulation of medical and pricing practices as discussed below.

China has abolished its previous government-led pricing system for drugs, and lifted the maximum retail price for most drugs, including drugs reimbursed by government medical insurance funds, patented drugs, and some other drugs.

The government now regulates prices mainly by establishing a consolidated procurement mechanism, restructuring medical insurance reimbursement standards and strengthening regulation of medical and pricing practices, as discussed below.

Centralized Procurement and Tenders

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.

The centralized procurement process takes the form of public tenders operated by provincial or municipal-level government agencies.

The centralized tender process is typically conducted once every year.

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.

The bids are assessed by a committee randomly selected from a database of experts.

The committee members assess the bids based on a number of factors, including but not limited to bid price, product quality, clinical effectiveness, product safety, level of technology, qualifications and reputation of the manufacturer, after-sale services and innovation.

Over the last decade, the government has been using various methods to ensure that drugs are offered at affordable prices.

The committee members assess the bids based on a number of factors, including bid price, product quality, clinical effectiveness, product safety, level of technology, the manufacturer's qualifications and reputation, after-sale services and innovation.

Over the last decade, the government has employed various methods to improve the affordability of drugs.

In 2009, the central government announced a campaign to implement a “zero markup” policy on essential drugs among basic healthcare institutions, which has been fully implemented nationwide.

In addition, some local government have begun to allow medical institutions to collectively negotiate with manufacturers for a second price to further lower the already agreed bid price.

The newly adopted Two-Invoice System is also aimed to reduce price mark-ups brought about by multi-tier distribution chains.

On January 1, 2019, the State Council approved a volume-based, centralized drug procurement program as part of a trial in 11 major cities in an effort to deepen the reform of the medical and health sector and optimize the pricing of drugs.

According to the State Council, in these 11 cities, drugs will be selected from generic brands for volume-based, centralized drug procurement.

In addition, some local governments have begun to allow medical institutions to collectively negotiate with manufacturers for a second price to further lower the already agreed bid price.

The Two-Invoice System, described above, is also designed to reduce price mark-ups brought about by multi-tier distribution chains.

In 2019, the government approved a volume-based, centralized drug procurement program in an effort to deepen the reform of the medical and health sector and optimize the pricing of drugs.

Drugs are selected from generic brands for volume-based, centralized drug procurement.

The selected drugs must pass the equivalence evaluation on quality and efficacy.

The program is aimed at further lowering drug costs for patients, reducing transaction costs for enterprises, regulating drug use by institutions, and improving the centralized drug procurement and pricing system.

All approved enterprises that produce drugs on the procurement list in

China may participate.

All approved enterprises that produce drugs on the procurement list in China may participate.

Clinical effects, adverse reactions, and batch stability of the drugs will be considered, and their consistency will be the main criteria for evaluation, while production capacity and stability of the supplier will also be considered.

On September 30, 2019, nine ministry-level agencies (including the State Medical Insurance Bureau, NMPA, and NHC) jointly issued a plan intending to expand this program nationwide.

Other PRC National and Provincial Laws and Regulations

We are subject to changing regulations under many other laws and regulations administered by governmental authorities at the national, provincial and municipal levels, some of which are or may become applicable to our business.

For example, regulations control the confidentiality of patients’ medical information and the circumstances under which patient medical information may be released for inclusion in our databases or released by us to third parties.

Pharmaceutical companies operating in China are subject to changing regulations under many other laws and regulations administered by governmental authorities at the national, provincial and municipal levels, some of which are or may become applicable to our business.

For example, regulations control the confidentiality of patient medical information and the circumstances under which patient medical information may be released for inclusion in our information systems or released by us to third parties.

The privacy of human subjects in clinical trials is also protected under regulations.

For example, the case report forms must avoid disclosing names of the human subjects.

For example, clinical trial case report forms must avoid disclosing names of human subjects.

These laws and regulations governing both the disclosure and the use of confidential patient medical information may become more restrictive in the future, including restrictions on transfer of healthcare data.

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PRC Regulation of Foreign Investment

On March 15, 2019, the National People’s Congress published the Foreign Investment Law of the PRC (the “Foreign Investment Law”), and on December 26, 2019, the State Council promulgated the Implementing Rules to the Foreign Investment Law of the PRC (the “Implementing Rules”) to further clarify and elaborate the relevant provisions of the Foreign Investment Law.

The Foreign Investment Law and the Implementing Rules, both took effect on January 1, 2020.

The Foreign Investment Law and the Implementing Rules replaced major previous laws and regulations governing foreign investment in China.

They establish the basic framework for the access to, and the promotion, protection and administration of foreign investments in view of investment protection and fair competition and embody an expected regulatory trend to rationalize China’s foreign investment regulatory regime in line with prevailing international practice and the legislative efforts to unify the corporate legal requirements for both foreign and domestic investments.

The Implementing Rules further clarified that the state encourages and promotes foreign investment, protects the lawful rights and interests of foreign investors, regulates foreign investment administration, continues to optimize foreign investment environment, and advances a higher-level opening.

The Foreign Investment Law and the Implementing Rules provide that a system of pre-entry national treatment and negative list shall be applied for the administration of foreign investments, where “pre-entry national treatment” means that the treatment given to foreign investors and their investments at market access stage is no less favorable than that given to domestic investors and their investments, and “negative list” means the special administrative measures for foreign investment’s access to specific fields or industries, which will be proposed by the competent investment department of the State Council in conjunction with the competent commerce department of the State Council and other relevant departments, and be reported to the State Council for promulgation, or be promulgated by the competent investment department or competent commerce department of the State Council after being reported to the State Council for approval.

Foreign investments beyond the negative list will be granted national treatment.

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 the special requirements on the shareholding, senior management personnel, etc.

In the meantime, relevant competent government departments will formulate a catalogue of industries for which foreign investments are encouraged according to the needs for national economic and social development, to list the specific industries, fields and regions in which foreign investors are encouraged and guided to invest.

The current industry entry clearance requirements governing investment activities in the PRC by foreign investors are set out in two categories, namely the Special Entry Management Measures (Negative List) for the Access of Foreign Investment (2019 version), and the Encouraged Industry Catalogue for Foreign Investment (2019 version) (the “2019 Encouraged Industry Catalogue”), both were promulgated by the National Development and Reform Commission and the Ministry of Commerce (the “MOFCOM”) and took effect on July 30, 2019.

Industries not listed in these two categories are generally deemed “permitted” for foreign investments unless specifically restricted by other PRC laws.

Pursuant to the 2019 Encouraged Industry Catalogue, the research, development and manufacture of innovative oncology drugs and certain other kinds of pharmaceutical products falls in the encouraged industries for foreign investment.

On December 30, 2019, the MOFCOM and the SAMR jointly promulgated Measures for Information Reporting on Foreign Investment, which became effective on January 1, 2020.

Pursuant to the Measures for Information Reporting on Foreign Investment, where a foreign investor carries out investment activities in China directly or indirectly, the foreign investor or the foreign-invested enterprise shall submit the investment information to the competent commerce department.

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.

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.

The Implementing Rules further clarified that China would encourage and promote foreign investment, protect the lawful rights and interests of foreign investors, and continue to improve the foreign investment environment in China.

The Foreign Investment Law establishes a pre-entry national treatment and negative list system for the administration of foreign investments.

“Pre-entry national treatment” means that the treatment afforded to foreign investors at the market access stage shall be no less favorable than that afforded to domestic investors.

“Negative list” refers to the special administrative measures for foreign investors' access to specific fields or industries.

Foreign investments outside of the negative list will be granted national treatment.

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”).

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.

Regulations Relating to Product Liability

In addition to the strict new drug approval process, certain PRC laws have been promulgated to protect the rights of consumers and to strengthen the control of medical products in the PRC, pursuant to which manufacturers and vendors of defective products in the PRC may incur liability for loss and injury caused by such products.

Pursuant to the General Principles of the Civil Law of the PRC (the "PRC Civil Law") promulgated on April 12, 1986 and amended on August 27, 2009, 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.

The Product Quality Law of the PRC promulgated by the Standing Committee of the National People's Congress on February 22, 1993 and amended on July 8, 2000, August 27, 2009 and December 29, 2018, respectively, is the principal governing law relating to the supervision and administration of product quality, aiming to protect the legitimate rights and interests of the end-users and consumers.

According to the Product Quality Law, manufacturers shall be liable for the quality of products produced by them, and sellers shall take measures to ensure the quality of the products sold by them.

A manufacturer shall be liable for compensating for any bodily injuries or property damages resulting from the defects in the product, unless the manufacturer is able to prove that:

(1) the product has never been distributed;

(2) the defects causing injuries or damages did not exist at the time when the product was distributed;

or (3) the science and technology at the time when the product was distributed was at a level incapable of detecting the defects.

A seller shall be liable for compensating for any bodily injuries or property damages of others caused by the defects in the product if such defects are attributable to the seller.

A seller shall 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 for compensation from the manufacturer or the seller.

Pursuant to the Tort Liability Law of the PRC promulgated by the Standing Committee of the National People's Congress on December 26, 2009 and effective from July 1, 2010, manufacturers shall assume tort liabilities where the defects in products cause damages to others.

Sellers shall assume tort liabilities where the defects in products that have caused damages to others are attributable to the sellers.

The aggrieved party may claim for compensation from the manufacturer or the seller of the defected product that has caused damage.

The Law of the PRC on the Protection of the Rights and Interests of Consumers was promulgated on October 31, 1993 and was amended on August 27, 2009 and October 25, 2013 to protect consumers’ rights when they purchase or use goods and accept services.

All business operators must comply with this law when they manufacture or sell goods and/or provide services to customers.

Under the amendment on October 25, 2013, all business operators shall pay high attention to protect the customers’ privacy and strictly keep it confidential any consumer information they obtain during the business operation.

In addition, in extreme situations, pharmaceutical product manufacturers and operators may be subject to criminal liability if their goods or services lead to the death or injuries of customers or other third parties.

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.

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.

A manufacturer is liable for compensating for any bodily injury or property damage resulting from product defects unless the manufacturer is able to prove that:

(1) the product was not distributed;

(2) the defects causing injury or damage did not exist at the time that the product was distributed;

or (3) science and technology at the time that the product was distributed was at a level incapable of detecting the defects.

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 person who is injured or whose property is damaged by the defects in the product may claim compensation from the manufacturer or the seller.

Regulations Relating to Commercial Bribery

Pharmaceutical companies involved in a criminal investigation or administrative proceedings related to bribery are listed in the Adverse Records of Commercial Briberies by the provincial health and family planning administrative departments, which have been merged into the provincial health commissions.

Pursuant to the Provisions on the Establishment of Adverse Records of Commercial Briberies in the Medicine Purchase and Sales Industry which became effective on March 1, 2014, provincial health commissions formulate the implementing measures for establishment of Adverse Records of Commercial Briberies.

If a pharmaceutical company or its agent is listed in the Adverse Records of Commercial Briberies at the provincial level, public medical institutions located in the local provincial level region are prohibited from making any purchase from the company for two years.

Pharmaceutical companies involved in a criminal investigation or administrative proceeding related to bribery are listed in the Adverse Records of Commercial Briberies by the provincial health commissions.

If a pharmaceutical company or its agent is listed, public medical institutions located in the local provincial level region are prohibited from making any purchase from the company for two years.

Where a pharmaceutical company or its agent is listed in the adverse records on two or more occasions within five years, all public medical institutions in China are not permitted to purchase any products from that company for two years.

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Under current regulations, the capital of a foreign-invested enterprise and capital in RMB obtained by the foreign-invested enterprise from foreign exchange settlement must not be used for the following purposes:

directly or indirectly used for the payment beyond the business scope of the enterprises or the payment prohibited by relevant laws and regulations;

indirectly used for investment in securities, unless otherwise provided by relevant laws and regulations;

directly or indirectly for payment beyond the business scope of the enterprises or the payment prohibited by relevant laws and regulations;

directly or indirectly for investment in securities, unless otherwise provided by relevant laws and regulations;

extending loans to non-related parties, unless permitted by the scope of business;

and/or paying the expenses related to the purchase of real estate that is not for self-use, except for the real estate enterprises.

In 2017, new regulations were adopted which, among other things, relax the policy restriction on foreign exchange inflow to further enhance trade and investment facilitation and tighten genuineness and compliance verification of cross-border transactions and cross-border capital flows.

On October 23, 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”), which took effect on the same day.

or paying expenses related to the purchase of real estate that is not for self-use, except for real estate enterprises.

In 2017, new regulations were adopted which, among other things, relax the restrictions on foreign exchange inflow to further enhance trade and investment facilitation and tighten genuineness and compliance verification of cross-border transactions and cross-border capital flows.

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.

Since Circular 28 was only issued recently, its interpretation and implementation in practice are still subject to substantial uncertainty.

The interpretation and implementation of Circular 28 in practice are subject to substantial uncertainty.

Regulations Relating to Dividend Distributions

The principal laws, rules and regulations governing dividend distributions by foreign-invested companies in the PRC are the PRC Company Law, as amended, the Foreign Investment Law and its Implementing Rules.

Under these requirements, foreign-invested companies may pay dividends only out of their accumulated profit, if any, as determined in accordance with PRC accounting standards and regulations.

Foreign-invested companies may pay dividends only out of their accumulated profit, if any, as determined in accordance with PRC accounting standards and regulations.

Both PRC domestic companies and foreign invested PRC companies are required to allocate at least 10% of their respective accumulated after-tax profits each year, if any, to fund certain capital reserve funds until the aggregate amount of these reserve funds have reached 50% of the registered capital of the companies.

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Labor Laws and Social Insurance

Pursuant to the PRC Labor Law and the PRC Labor Contract Law, employers must execute written labor contracts with full-time employees.

All employers must comply with local minimum wage standards.

Employers must establish a comprehensive management system to protect the rights of their employees, including a system governing occupational health and safety to provide employees with occupational training to prevent occupational injury, and employers are required to truthfully inform prospective employees of the job description, working conditions, location, occupational hazards and status of safe production as well as remuneration and other conditions.

Violations of the PRC Labor Contract Law and the PRC Labor Law may result in the imposition of fines and other administrative and criminal liability in the case of serious violations.

In addition, according to the PRC Social Insurance Law, employers like our PRC subsidiaries in China must provide employees with welfare schemes covering pension insurance, unemployment insurance, maternity insurance, work-related injury insurance, medical insurance and housing funds.

Under Chinese law, employers must execute written labor contracts with their full-time employees and must comply with local minimum wage standards.

Employers must establish a comprehensive management system to protect the rights of their employees, including a system governing occupational health and safety, and to truthfully inform prospective employees of the job description, working conditions, location, occupational hazards and status of safe production as well as remuneration and other conditions.

Violations of these requirements may result in the imposition of fines and other administrative and criminal liability in the case of serious violations.

In addition, employers must provide employees with welfare schemes covering pension insurance, unemployment insurance, maternity insurance, work-related injury insurance, medical insurance and housing funds.

These payments are made to local administrative authorities, and any employer who fails to contribute may be fined and ordered to pay the deficit amount within a stipulated time limit.

Rest of World Regulation

For other countries outside of the United States and the PRC, the requirements governing the conduct of clinical trials, drug licensing, pricing and reimbursement vary from country to country.

In all cases the clinical trials must be conducted in accordance with GCP requirements and the applicable regulatory requirements and the ethical principles having their origin in the Declaration of Helsinki.

As of January 31, 2020, we had approximately 3,500 employees.

For other countries outside of the United States and the PRC, the requirements governing the conduct of clinical trials, drug licensing, pricing and reimbursement, and other matters impacting our business vary from country to country.

In all cases, clinical trials must be conducted in accordance with GCP requirements, applicable regulatory requirements, and the ethical principles having their origin in the Declaration of Helsinki.

Human Capital Resources

We are committed to attracting and retaining exceptional, passionate people to work with a clear purpose:

creating impactful, affordable and accessible medicines to help more patients around the world to live better.

To this end, we support a team-oriented culture based on excellence that allows all colleagues to feel valued and challenged.

We provide opportunities for employees to grow and develop in their careers, supported by competitive compensation, benefits and health and wellness programs, and by programs that build connections among our employees worldwide.

We believe that the success of our business is fundamentally connected to the well-being of our employees.

Accordingly, we are committed to their health, safety and wellness.

We offer our employees and their families innovative, flexible and convenient health and wellness programs, including benefits that confer peace of mind around events that may require time away from work or impact their financial well-being;

that support their physical and mental health with tools and resources to help them improve or maintain their health status and encourage healthy behaviors;

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.

Our worldwide teams are united by a common mission.

We are committed to encouraging a culture of open communication where employees can ask questions, raise concerns and contribute creative solutions.

Our management team routinely makes themselves available to all employees, including in regular town hall events that encourage open dialogue.

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 our broad-based equity award programs, we have used targeted equity-based grants with vesting conditions to facilitate retention of personnel.

In addition to compensation and benefits, we provide our employees opportunities for growth through challenging job assignments, performance management and training opportunities.

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.

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.

Further, we have policies in place that prohibit harassment of all kinds.

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.

We have also engaged and may continue to engage independent contractors to assist us with our operations.

None of our employees are represented by a labor union or covered by a collective bargaining agreement.

We have never experienced any employment-related work stoppages, and we consider our relations with our employees to be good.

None of our employees are represented by a labor union or covered by a collective bargaining agreement, except as required by local laws such as in some European countries.

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.

Financial Information

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Any company that is registered in the Cayman Islands but conducts business mainly outside of the Cayman Islands may apply to be registered as an exempted company.

The principal executive office of our research and development operations is located at No.

30 Science Park Road, Zhong-Guan-Cun Life Science Park, Changping District, Beijing 102206, PRC.

Our telephone number at this address is +86 10 58958000.

Our current registered office in the Cayman Islands is located at the offices of Mourant Governance Services (Cayman) Limited, 94 Solaris Avenue, Camana Bay, Grand Cayman KY1-1108, Cayman Islands.

13 unchanged sentences

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