What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2023-02-27 compared with 2022-02-28 · 552 added, 458 removed, 1132 unchanged (47% of the section changed)

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

We are a global biotechnology company that is developing and commercializing innovative and affordable oncology medicines to improve treatment outcomes and access for patients worldwide.

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

1 unchanged sentence

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

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

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

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

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

Supported by our global clinical development and commercial capabilities, we have entered into collaborations with world-leading biopharmaceutical companies such as Amgen Inc.

("Amgen") and Novartis Pharma AG ("Novartis") to develop and commercialize innovative medicines.

We are committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe.

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

Our internal clinical development capabilities are deep, including a more than 2,700-person global clinical development and medical affairs team that is running more than 80 ongoing or planned clinical trials in over 50 medicines and drug candidates.

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

We have enrolled in our clinical trials more than 18,000 subjects, of which approximately one-half have been outside of China.

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

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

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

Since our inception in 2010, we have become a fully integrated global organization of over 9,000 employees in 29 countries and regions, including the United States, China, Europe, and Australia.

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

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

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

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

Research and innovation focus .

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

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

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

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

BRUKINSA ® , tislelizumab, and pamiparib.

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

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

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

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

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

World-class clinical development .

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

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

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

We believe this approach has several benefits:

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

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

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

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

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

China commercial leadership .

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

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

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

Global leadership, access, and reputation .

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

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

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

as we expand our label in multiple new indications.

Our Holding Company Structure

We are a holding company incorporated in the Cayman Islands with operations primarily conducted through our subsidiaries in the United States, China, United Kingdom, Switzerland and Australia.

The following diagram depicts a summary of our corporate structure.

Currently, our corporate structure contains no variable interest entities.

We were founded with the vision to create an integrated biopharmaceutical company to transform the biotech industry, creating impactful medicines that will be affordable and accessible to far more patients around the world.

We have made significant progress towards accomplishing this vision over our first 12 years and have five strategic competitive advantages positioning us for success both near- and long-term:

We have built one of the world's largest, most productive and cost-effective oncology research teams with more than 950 scientists.

Their efforts have been validated by commercial approvals, clinical data, and collaborations that have secured $1.4 billion in collaboration payments to the company.

We have successfully developed three commercially approved medicines from our internal discovery engine, including BRUKINSA and tislelizumab.

We design each research program with a differentiated biological hypothesis or a first-in-class mechanism of action.

Our lead medicine, BRUKINSA, has demonstrated superiority for both progression-free survival and overall response rate versus ibrutinib in relapsed or refractory CLL.

Our broad pipeline also includes internally developed products with the potential to be best-in-class or first-in-class, including our BCL-2 inhibitor, BGB-11417, our HPK1 inhibitor, BGB-15025, and BGB-16673, a BTK-targeted CDAC program that has demonstrated its potential with early data.

Our pipeline also includes many early-stage assets for targets like OX40, LAG-3, and TIM-3.

We have invested in technology platforms, including CDAC protein degraders, bispecific antibodies, tri-specific antibodies, ADC, CAR-NK, and mRNA.

Our research and innovation capabilities will ensure we discover high-quality and impactful medicines for patients.

We have built a substantial global clinical development team of 2,300 people on five continents, allowing us to run clinical trials predominantly without reliance on third party contract research organizations ("CROs").

Clinical development accounts for over 75% of the cost and most of the time to develop a medicine.

We believe that by fully integrating these capabilities, we can create a strategic competitive advantage.

By retaining clinical development activities internally, we can decrease the costs of our trials, increase enrollment speed, and leverage technology to ensure quality and consistency across trials and clinical sites.

It also allows us to become more inclusive in the location and number of clinical sites to help improve the diversity of patients in our trials.

Our demonstrated ability to complete large-scale, multi-regional clinical trials is one of our most important strategic competitive advantages and addresses an immense challenge in the pharmaceutical industry.

We have built a strong commercial portfolio, centered around two cornerstone medicines, BRUKINSA and tislelizumab, that are becoming primary revenue sources and will support the development of our future pipeline and

additional combination therapies.

Our hematological franchise is led by BRUKINSA, which is supported by a broad clinical program with over 4,800 patients in 35 trials in 29 markets.

We ran two extensive head-to-head studies versus ibrutinib with over 800 patients enrolled.

We are the first and only BTK inhibitor to demonstrate superior efficacy versus ibrutinib, and the data from the head-to-head ALPINE trial were selected for the prestigious late-breaker session at the American Society of Hematology ("ASH") meeting in late 2022, with simultaneous publication in The New England Journal of Medicine .

Based on the pooled safety data generated from our trials, we have shown a very favorable safety profile, especially when compared to ibrutinib in cardiovascular safety, including atrial fibrillation, ventricle arrhythmia, and hypertension.

We believe BRUKINSA allows us to build a strong position in heme-oncology with our pipeline medicines, including our BCL-2 inhibitor, in both monotherapy and combination settings.

Our solid tumor franchise is led by our anti-PD-1 monoclonal antibody, tislelizumab, which is currently approved in China in ten indications.

Tislelizumab has achieved the commercial market leader position in China in the PD-1/PDL-1 class.

Outside of China, in conjunction with our partner Novartis, we have filed applications for approval in the U.S.

With tislelizumab and the potentially best-in-class or first-in-class pipeline assets targeting OX40, TIGIT, LAG-3, and TIM-3, we are well-positioned to build our immuno-oncology business and deliver innovative therapies and combinations to patients.

We have a differentiated international commercial organization of over 3,500 people to deliver medicines to patients around the globe.

In China, the commercial team is actively driving the uptake of our internally developed and partnered medicines across solid tumors and hematology.

BRUKINSA and tislelizumab have achieved market leadership positions in China in the BTKi and PD-1/PDL-1 classes, respectively, and we have launched and sell more than 13 products from our business partners around the globe.

In North America, our U.S.

team has continued to grow BRUKINSA sales as we launch new indications and expand to Canada.

In Europe, we have built a targeted commercial team focused on medical thought leaders in blood cancer treatments.

Altogether, BRUKINSA has been approved in over 65 markets, with additional filings pending or planned.

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

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

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

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

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

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

Broad accessibility.

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

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

Our commercial capabilities have expanded into the Asia Pacific region through our affiliates, the Latin America region, and other emerging markets through distribution partners.

We have built a global commercial organization that will drive the delivery of highly effective and differentiated medicines to patients around the globe, and will collaborate with business partners to bridge health inequities.

We have financial strength .

In a time when the cost of capital has risen, we are well positioned financially.

We already have substantial revenue from our cornerstone assets, which we expect to continue to grow significantly in 2023 and beyond.

We expect product revenue growth to outpace our operating expense growth in the near-term, which will allow us to continue to improve our operating leverage.

We will continue to be thoughtful and strategic in how we deploy our capital, and we are committed to generating long-term value.

Our Commercial and Registration Stage Products

1 unchanged sentence

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

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

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

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

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

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

WM, R/R MZL, R/R CLL/SLL

BTK inhibitor Approved in more than 65 markets, incl.

U.S., China, EU and other markets Global N/A

1L Squamous and Non-Squamous NSCLC/ 2/3 L NSCLC/ R/R classical Hodgkin’s lymphoma 2 / 2/3 L HCC 2 / R/R PD-L1+ UC 2 , MSI-H or dMMR solid tumors, 2L ESCC, 1L NPC, 1L GC/GEJC

Anti-PD-1 antibody Approved in China;

BLA accepted in U.S.

MAA accepted in EU 4

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

pamiparib 3L BRCA-mutated ovarian cancer 2

3L BRCA-mutated ovarian cancer 2

PARP inhibitor Approved in China Global N/A

28 unchanged sentences

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

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

For patients with unresectable recurrent locally advanced or metastatic ESCC after prior systemic therapy.

For patients with advanced or metastatic ESCC after prior systemic chemotherapy and for patients with NSCLC including:

locally advanced or metastatic NSCLC after prior chemo, in combination with chemotherapy for 1L advanced or metastatic squamous NSCLC, and in combination with chemotherapy for 1L locally advanced or metastatic non-squamous NSCLC with no EGFR or ALK positive mutations.

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

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

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

Rights to promote and market in China's broad markets pursuant to a Market Development Agreement with an affiliate of Novartis Pharma AG.

Conditionally approved.

Full approval of any particular indication will depend on the results of required post-marketing study(ies) in China.

Abbreviations:

3 unchanged sentences

CLL = chronic lymphocytic leukemia;

EGFR = epidermal growth factor receptor;

ESCC = esophageal squamous cell carcinoma;

GC = gastric cancer;

GEJC = gastroesophageal junction cancer;

HCC = hepatocellular carcinoma;

MAA = marketing aothorization application;

MCL = mantle cell lymphoma;

2 unchanged sentences

MZL = marginal zone lymphoma;

NPC = nasopharyngeal cancer;

NSCLC = non-small cell lung cancer;

5 unchanged sentences

We commercialize the following internally developed cancer medicines:

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

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

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

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

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

3 unchanged sentences

Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

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

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

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

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

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

and Switzerland.

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

In January 2023, BRUKINSA was approved by the U.S.

Food and Drug Administration (FDA) for the treatment of adult patients with CLL or small lymphocytic lymphoma (SLL).

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

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

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

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

In addition, a supplemental new drug application ("sNDA") has been accepted for review by the China National Medical Products Administration ("NMPA") for the treatment of adult patients with treatment-naïve CLL or SLL and WM.

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

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

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

BRUKINSA is approved across several indications in more than 65 markets as of February 2023.

Market Opportunity

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

They can be broadly categorized into non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL).

Depending on the origin of the cancer cells, lymphomas can also be characterized as B-cell or T-cell lymphomas.

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

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

They can be broadly categorized into non-Hodgkin’s lymphoma and Hodgkin’s lymphoma.

In 2022, estimated global revenues for BTK inhibitors were approximately $8.5 billion according to published reports.

Global revenues are projected to be more than $20 billion in 2026, according to published reports.

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

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

The China National Medical Products Administration (NMPA) also granted conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies, for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, and for the treatment of patients with hepatocellular carcinoma (HCC) who have received at least one systemic therapy.

Tislelizumab is approved in China in ten indications, including full approval for the first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma with high PD-L1 expression in combination with fluoropyrimidine and platinum chemotherapy, first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy, for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy, for the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have disease progression following or are intolerant to first-line standard chemotherapy, and for first-line treatment of patients with recurrent or metastatic nasopharyngeal cancer (NPC).

The NMPA also granted conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies, for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, for the treatment of patients with hepatocellular carcinoma (HCC) who have received at least one systemic therapy, for patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors.

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

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

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

Tislelizumab was included in the NRDL in 2020 for cHL and UC, in 2021 for non-squamous NSCLC, squamous NSCLC and HCC, and in 2022 for locally advanced or metastatic NSCLC, for MSI-H solid tumors, for locally advanced or metastatic ESCC following progression or intolerance to prior first-line chemotherapy, and for first-line recurrent or metastatic NPC.

In addition, we have submitted two supplemental Biologics License Applications ("sBLAs") for tislelizumab that are under review by the Center for Drug Evaluation ("CDE") of the NMPA, including for patients with first-line unresectable or metastatic hepatocellular carcinoma (HCC), and in combination with chemotherapy as first-line treatment in patients with unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

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

3 unchanged sentences

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

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

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

1 unchanged sentence

Globally, the top four PD-1/PD-L1 antibody medicines had revenues of approximately $36 billion in 2022 based on public reports.

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

The 2022 China PD-1/L1 market (net revenue) was approximately $2.2 billion.

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

6 unchanged sentences

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

Market Opportunity

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

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

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

3 unchanged sentences

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 Frost & Sullivan 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.

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

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

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

In December 2020, we announced the inclusion of XGEVA in the NRDL for the treatment of GCTB, which was successfully renewed for inclusion in 2023.

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 began commercializing BLINCYTO ® in the August 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.

In China, BLINCYTO received conditional approval as a treatment for adult patients with R/R ALL in December 2020 and was conditionally approved in April 2022 for pediatric patients with R/R B-cell precursor ALL.

We began commercializing BLINCYTO in August 2021.

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

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

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

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.

KYPROLIS was included on the NRDL beginning in March 2023 for its approved indication in China.

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

1 unchanged sentence

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

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

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

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

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

REVLIMID was listed on the NRDL in June 2017.

4 unchanged sentences

In January 2018, VIDAZA became commercially available in China.

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 Frost & Sullivan research.

The typical age of onset is 70 years.

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

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 nine decitabine generics have become available.

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

VIDAZA ® was listed in the NRDL in October 2018.

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

4 unchanged sentences

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

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

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

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

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

(HHV-8) negative.

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

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

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

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.

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

Neuroblastoma is almost exclusively a disease of children.

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 beta.

We began commercializing QARZIBA in December 2021.

6 unchanged sentences

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

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

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

Reimbursement and Market Access

2 unchanged sentences

In 2022, we commercialized our products in 60 markets.

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

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

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

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

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

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

The NRDL is composed of three lists.

5 unchanged sentences

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

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

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

This ability is being phased out by 2022 in principle

according to a July 2019 NHSA policy memo.

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

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

Innovatively, in the 2022 NRDL, a price bidding process for non-exclusive drugs was undertaken on the C list to set the national reimbursement price benchmark.

Several of our medicines are listed on the NRDL.

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

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

In the most recent NRDL list announced in January 2023, the following medicines were included in the NRDL, effective March 1, 2023:

• Tislelizumab in nine of its eligible approved indications:

– For the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who are negative for epidermal growth factor receptor (EGFR) and anaplastic mesenchymal lymphoma kinase (ALK) mutations and have progressed after or are intolerant of prior chemotherapy with platinum-containing regimens;

and adult patients with locally advanced or metastatic squamous NSCLC who are negative

or unknown for EGFR and ALK mutations and have progressed after or are intolerant of prior chemotherapy with platinum-containing regimens (approved in January 2022 and included in the NRDL in 2023);

– For the treatment of adult patients with advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors:

patients with advanced colorectal cancer with disease progression after prior treatment with fluoropyrimidines, oxaliplatin and irinotecan;

patients with other advanced solid tumors with disease progression after prior treatment and no satisfactory alternative treatment options (approved in March 2022 and included in the NRDL in 2023);

– For the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma who have progressed after or are intolerant of prior first-line standard chemotherapy (approved in April 2022 and included in the NRDL in 2023);

– As a first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer (approved in June 2022 and included in the NRDL in 2023);

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

3 unchanged sentences

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

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

• BRUKINSA in all three of its approved indications:

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

1 unchanged sentence

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

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

• Pamiparib in its approved indication:

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

• KYPROLIS in its approved indication as of March 1, 2023:

– For the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least two prior therapies, including a proteasome inhibitor and an immunomodulatory agent.

• XGEVA was successfully renewed in NRDL as of March 2023 in its approved indication:

– For the treatment of patients with giant cell tumor of the bone (GCTB) that is unresectable or where surgical resection is likely to result in severe morbidity (first included in NRDL in 2020).

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" (VBP), or GPO (group purchasing organization) or "4+7" (4 municipalities and 7 provincial cities) when the program was first piloted in 11 major cities.

In 2018, China started a new program to centrally purchase non-exclusive medicines for the nation’s health care system called "volume-based procurement", or "group purchasing organization" or "4+7" 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.

Participation in the program requires a product to have passed a generic quality consistency evaluation, which in turn requires passing a bioequivalence comparison to the reference listed drug (RLD).

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

3 unchanged sentences

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

A typical program provides a

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

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

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

2 unchanged sentences

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

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

Often this is through a pharmacy benefit manager ("PBM").

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

6 unchanged sentences

The following table summarizes the status of our internally-discovered drug candidates as of February 27, 2023:

DRUG CANDIDATES PROGRAMS DOSE ESC.

DOSE EXPANSION PIVOTAL FILED MARKETED

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

zanubrutinib (BTK)

monotherapy R/R MCL (approved in multiple geographies)

WM (approved by FDA in the U.S.

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

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

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

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

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

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

Lupus nephritis

Previously treated CLL/SLL (ibrutinib acalabrutinib intolerant)

combination +rituximab 1L MCL

ASSET PROGRAM PHASE 1 PHASE 2 PHASE 3

Zanubrutinib monotherapy R/R CLL/SLL

+ rituximab TN MCL and R/R MZL

+/- venetoclax TN CLL/SLL

+ obinutuzumab R/R FL

+ lenalidomide +/- rituximab R/R DLBCL

tislelizumab (PD-1)

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

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

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

PDUFA date 7/12/2022)

R/R NK/T-cell lymphoma

+ chemo 1L Sq.

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

NSCLC (approved 6/23/2021)

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

1L GC, 1L ESCC

+ pamiparib (PARP) Solid tumors

+ zanubrutinib (BTK) B-cell malignancies

pamiparib ( PARP )

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

2L platinum-sensitive OC maintenance

1L platinum-sensitive GC maintenance

HER2-BRCA mutated breast cancer

+ TMZ (chemo) Solid tumors

(RT/chemo) Glioblastoma

DRUG CANDIDATES PROGRAMS DOSE ESC.

DOSE EXPANSION PIVOTAL FILED MARKETED

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

ociperlimab (TIGIT)

+ tislelizumab 1L NSCLC

R/M Cervical Cancer, R/M ESCC ∧

+ tislelizumab + cCRT 1L SCLC

Stage III unresectable NSCLC

+ tislelizumab + chemo 1L NSCLC

+ tislelizumab + BAT1706 1L HCC

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

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

(PD-L1) monotherapy & + tislelizumab Solid tumors

BGB-A445 (OX40) + tislelizumab Solid tumors

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

+ dexamethasone & + carfilzomib R/R Multiple Myeloma

+ azacytidine AML, MDS

BGB-10188 (PI3K Delta) mono;

+ tislelizumab;

+ zanubrutinib B-cell malignancies;

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

BGB-23339 (TYK2) monotherapy Inflammation and Immunity

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

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

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

recurrent/metastatic

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

Australia (10/7/2021);

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

UK (12/14/2021);

Switzerland (2/17/2022);

South Korea (2/24/2022)

Tislelizumab monotherapy 2L advanced ESCC, 1L HCC, 2L/3L NSCLC

Previously treated HCC, R/R cHL

+ chemotherapy 1L advanced ESCC, 1L GC/GEJC, 1L NPC

+ zanidatamab + chemotherapy 1L GEA

+ sitravatinib 2L NSCLC

+ fruquintinib Solid tumors

Ociperlimab + tislelizumab 1L PD-L1 high NSCLC

2L PD-L1+ESCC, 2/3 L cervical cancer

+ tislelizumab + chemotherapy 1L NSCLC

+ tislelzumab + concurrent chemoradiotherapy LA NSCLC (PD-L!+)

Surzebiclimab + tislelizumab +/- LBL-007 Solid tumors

BGB-A445 + tislelizumab Solid tumors

BGB-10188 + tislelizumab Solid tumors

+/- zanubrutinib B-cell lymphoid malignancies

+/- tislelizumab B-cell malignancies

BGB-15025 + tislelizumab Solid tumors

Pamiparib monotherapy 1L maintenance platinum-sensitive GC

+ temozolomide Solid tumors

BGB-3245 monotherapy Solid tumors with BRAF mutations

Lifirafenib + mirdametinib Solid tumors

BGB-11417 monotherapy R/R MCL, R/R CLL/SLL

+/- zanubrutinib Mature B-cell malignancies

+ azacitidine +/- posaconazole Myeloid malignancies

+ dexamethasone +/- carfilzomib R/R multiple myelome with t (11;14)

BGB-16673 monotherapy B-cell malignancies

BGB-23339 monotherapy Inflammation and immunology

BGB-24714 +/- chemotherapy Solid tumors

BGB-B167 +/- tislelizumab Solid tumors

Abbreviations:

cHL = classical Hodgkin lymphoma;

CLL = chronic lymphocytic leukemia;

ESCC = esophageal squamous-cell carcinoma;

FL = follicular lymphoma;

GC = gastric cancer;

GEA = gastroesophageal adenocarcinoma;

GEJC = gastroesophaegeal junction cancer;

HCC = hepatocellular carcinoma;

MCL = mantle cell lymphoma;

MZL = marginal zone lymphoma;

NPC = nasopharyngeal carcinoma;

NSCLC = non-small cell lung cancer;

R/R = relapsed/refractory;

SCLC = small cell lung cancer;

SLL = small lymphocytic lymphoma;

TN = treatment treatment-naïve

The following table summarizes the status of our in-licensed drug candidates as of February 27, 2023:

COMPOUND (TARGET) / PROGRAM DOSE ESC.

DOSE EXPANSION PIVOTAL COMM.

RIGHTS PARTNER

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

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

Partner Molecule / Asset Indications Phase Commercial Rights

Sotorasib Solid tumors, CRC, NSCLC Phase 3 China

tarlatamab ^^

pavurutamab ∧ ∧

AMG 176 (Mcl-1, SM) Hematologic malignancies

(CD33) Myeloid malignancies

acapatamab ∧ ∧

(PSMA) Prostate cancer

(STEAPI XmAb) Prostate cancer

(MUC17) GC/GEJC

AMG 650 (oral small molecule) Solid tumors

AMG 506 (FAP x 4-1BB, DARPin ® )

AMG 994 Bispecific antibody Solid tumors

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

Sitravatinib †

(multi-kinase inhibitor) + tislelizumab

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

Mono + tislelizumab HCC, GC/GEJC

zanidatamab ††

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

Monotherapy Bilary tract cancers

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

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

(B-RAF) Solid tumors Asia ex-Japan

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

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

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

vebicorvir ††† (ABI-H0731) ®

(HBV core inhibitor) Chronic Hepatitis B Virus China

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

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

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

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

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

SCLC Phase 2 China

acapatamab ^^ Prostate cancer, NSCLC Phase 1 China

AMG 176 Hematologic malignancies Phase 1 China

AMG 427 ^^ AML Phase 1 China

AMG 509 Prostate cancer Phase 1 China

AMG 199 ^^ GC/GEJC Phase 1 China

AMG 650 Solid tumors Phase 1 China

AMG 256 Solid tumors Phase 1 China

Sitravatinib † + Tislelizumab

NSCLC Phase 3 Asia, Australia, New Zealand

Sitravatinib † + Tislelizumab

HCC, GC/GEJC Phase 2 Asia, Australia, New Zealand

Sitravatinib † + Tislelizumab

Solid tumors Phase 1 Asia, Australia, New Zealand

Zanidatamab + chemo + Tislelizumab GEA Phase 3 Asia, Australia, New Zealand

Zanidatamab (monotherapy) BTC Phase 2 Asia, Australia, New Zealand

Zanidatamab BC, GC, GEA Phase 2 Asia, Australia, New Zealand

ZW49 HER2 expressing cancers Phase 1 Asia, Australia, New Zealand

Solid tumors Phase 1 Asia

SEA-CD70 MDS, AML Phase 1 Asia, Australia, New Zealand

DKN-01 + Tislelizumab + Chemo GC/GEJC Phase 2 Asia, Australia, New Zealand

LBL-007 + Tislelizumab Advanced solid tumors Phase 2 Ex-China

ABI-H3733 Chronic hepatitis B virus Phase 1 China

^ BiTE ® molecule;

^^ Half-life extended BiTE ® ;

† XmAb ® is a registered trademark of Xencor, Inc.

Mirati is also conducting its own clinical studies with sitravatinib, including the Phas3 SAPPHIRE trial in non Sq NSCLC;

1 By MapKure, a JV with SpringWorks

Abbreviations:

acute myeloid leukemia, HLE BiTE:

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

gastric cancer/gastroesophageal junction, HCC:

hepatocellular carcinoma, IND:

Investigational New Drug, MEL:

melanoma, MM:

multiple myeloma, NHL:

non-Hodgkin's lymphoma, N/SCLC:

non-small cell lung cancer, OC:

ovarian cancer, RCC:

renal cell carcinoma, SM:

small molecule;

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

AML = acute myelogenous leukemia;

BC = breast cancer;

BTC = biliary tract cancers;

CRC = colorectal cancer;

GC = gastric cancer;

GEA = gastroesophageal adenocarcinoma;

GEJC = gastroesophaegeal junction cancer;

HCC = hepatocellular carcinoma;

MDS = myelodysplastic syndromes;

NSCLC = non-small cell lung cancer;

SCLC = small cell lung cancer

Our Commercial- and Clinical-Stage Drug Candidates

2 unchanged sentences

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

Commercial-Stage

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 in patients.

We are currently evaluating zanubrutinib in a broad pivotal clinical program globally to treat a number of B-cell malignancies.

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

Zanubrutinib is the only BTK inhibitor to demonstrate superior progression-free survival versus IMBRUVICA ® (ibrutinib), an approved BTK inhibitor.

Overview of Clinical Development Program and Regulatory Status

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

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

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

As of December 2022, 26 additional marketing authorization applications for BRUKINSA have been submitted and are under review, including by BeiGene and with support from our five distribution partners:

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

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

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 treatment-naive (TN) MCL (NCT04002297).

Based on the clinical data to date, we believe that BRUKINSA has a best-in-class profile, and we are running a broad global pivotal program in multiple indications, including 10 registration or registration-enabling clinical trials.

Five of the 10 trials 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 has been included in several filings globally.

We have also reported results from the Phase 3 trial comparing BRUKINSA to bendamustine and rituximab in patients with treatment-naïve (TN) CLL/SLL (SEQUOIA, NCT03336333) and the head-to-head Phase 3 trial in R/R CLL/SLL versus ibrutinib (ALPINE, NCT03734016).

Both trials are the basis for our approvals in CLL in the U.S.

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

Our fifth Phase 3 trial is an ongoing Phase 3 confirmatory trial in patients with R/R follicular lymphoma (FL) or R/R MZL (NCT05100862).

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).

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

Data from the ROSEWOOD trial were presented at the European Hematology Association (EHA) 2022, meeting its primary endpoint.

Finally, we are also investigating zanubrutinib in several combination studies in MCL, MZL and CLL/SLL, including a Phase 3 trial in combination with venetoclax in front-line CLL/SLL.

We continue to pursue regulatory approvals for BRUKINSA globally.

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

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

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

Besides our recent approvals in CLL/SLL in the United States (January 2023) and EU (November 2022) we expect continued regulatory decisions for some of our global filings this year, including potential additional approvals in more than 10 markets.

Tislelizumab, an anti-PD-1 Antibody

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

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

Overview of Clinical Development Program and Regulatory Status

24 unchanged sentences

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

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

As of December 2022, we had enrolled over 11,000 subjects in clinical trials of tislelizumab in 31 geographies, including more than 4,000 subjects outside of China.

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

6 unchanged sentences

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

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

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

In addition, our clinical development program includes a Phase 3 trial as a maintenance therapy in patients with platinum-sensitive recurrent OC (NCT03519230), a Phase 2 trial in first-line platinum-sensitive GC maintenance (NCT03427814), and a Phase 1b trial in combination with temozolomide in solid tumors (NCT03150810).

Clinical-Stage

Ociperlimab (BGB-A1217), a TIGIT Inhibitor

1 unchanged sentence

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

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

As of December 2022, more than 1,600 subjects have been enrolled across the ociperlimab development program, which includes eight global trials in patients with lung cancers, esophageal squamous cell carcinoma, and cervical cancer.

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

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

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

We expect to initiate additional pivotal clinical trials and announce data from Phase 2 trial expansion cohorts in 2023 to inform our subsequent development for ociperlimab.

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

9 unchanged sentences

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

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

countries), Australia and New Zealand.

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

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

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

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

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

In 2022, as part of our collaboration with Mirati, we initiated patient enrollment for a Phase 2 clinical trial of sitravatinib in combination with tislelizumab in locally advanced unresectable or metastatic ESCC that progressed on or after anti-PD-L1 antibody therapy (NCT05461794).

We are evaluating sitravatinib in multiple clinical trials including a Phase 3 trial combined with tislelizumab in NSCLC (NCT04921358).

BGB-11417, a Small Molecule Bcl-2 Inhibitor

4 unchanged sentences

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.

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

Phase 1 clinical data for non-Hodgkin's lymphoma, CLL, acute myeloid leukemia (AML) and multiple myeloma (MM) (NCT04883957, NCT04277637, NCT04771130, and NCT04973605) were presented at ASH 2022.

We initiated patient dosing in a Phase 2 study to evaluate BCL-2 inhibitor BGB-11417 in patients with relapsed or

refractory mantle cell lymphoma (NCT05471843) and relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (NCT05479994) in 2022 and expect data readouts from ongoing studies in 2023.

BGB-A445, an OX40 Agonist Antibody

3 unchanged sentences

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 BGB-A445 in combination with tislelizumab in patients with advanced solid tumors and expect to initiate dose expansion for BGB-A445 (OX-40) in the first half of 2022.

We have an ongoing Phase 1 trial (NCT04215978) of BGB-A445 in combination with tislelizumab in patients with advanced solid tumors and initiated tumor-specific dose expansion cohorts in a Phase 1 monotherapy trial (NCT04215978) in patients with solid tumors in 2022.

We initiated patient dosing in a Phase 2 basket trial in melanoma, renal cell cancer and bladder cancer (NCT05661955).

ZW25 (Zanidatamab), a bispecific HER2-targeted antibody

4 unchanged sentences

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

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

The second study HERIZON-BTC-01 (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.

Positive topline results from this trial were announced in 2022.

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

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

BGB-A425, a TIM-3 Inhibitor

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

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

We completed enrollment in 2L biliary tract cancer in 2022.

Surzebiclimab (BGB-A425), a TIM-3 Inhibitor

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

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

BGB-15025, a Small Molecule HPK1 Inhibitor

4 unchanged sentences

This trial is being conducted in multiple countries globally.

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

We expect to initiate dose-expansion for BGB-15025 in 2023.

BGB-16673, a BTK-targeted CDAC

BGB-16733 is an investigational BTK‑targeting chimeric degradation activation compound (CDAC) active against both wild‑type and mutant BTK.

BGB‑16673 has demonstrated preclinical antitumor activity in models with wild‑type BTK and models with BTK inhibitor–resistant mutations commonly observed in patients who have progressed on prior BTK inhibitor treatment.

A Phase 1 open‑label, dose‑escalation, and dose‑expansion trial (NCT05006716) in adult patients with relapsed/refractory (R/R) B‑cell malignancies is currently enrolling.

BGB-23339, a TYK2 inhibitor

BGB-23339 is a potent, highly selective, allosteric, investigational tyrosine kinase 2 (TYK2) inhibitor discovered and being developed by BeiGene.

TYK2 is a member of the JAK family and functions as a critical mediator in cytokine signaling pathways implicated in multiple immune-mediated disorders.

Designed to target the regulatory pseudokinase (JH2) domain on TYK2, BGB-23339 has demonstrated strong selectivity in preclinical studies with potent inhibition of interleukin (IL)-12, IL-23, and Type 1 interferons (IFNs)—pro-inflammatory cytokines that play a determinant role in the induction of inflammation.

BGB-23339 is currently being evaluated in a Phase 1 clinical study (NCT05093270).

BGB-24714, a SMAC mimetic

BGB-24714 is an investigational Second Mitochondrial-derived Activator of Caspase (SMAC) mimetic currently enrolling in a Phase 1 clinical trial (NCT05381909) as monotherapy or in combination with paclitaxel in advanced solid tumors.

BGB-B167, a CEA x 4-1BB bispecific

BGB-B167 is an investigational first-in-class CEA x 4-1BB bispecific antibody.

It is currently enrolling in a Phase 1 clinical trial (NCT05494762) as a monotherapy and in combination with tislelizumab in patients with selected CEA-expressing advanced or metastatic solid tumors, including colorectal cancer (CRC).

BGB-10188 (PI3K inhibitor)

BGB-10188 is an investigational PI3Kδ inhibitor being evaluated in a Phase 1 clinical trial ( NCT04282018 ) as monotherapy or in combination with BRUKINSA in hematology malignancies, or in combination with tislelizumab in solid tumors.

Our Preclinical Programs

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

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

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

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

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

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

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

Currently, we have over 60 pre-clinical programs and we believe the majority have best-in-class or first-in-class potential.

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

2 unchanged sentences

Manufacturing and Supply

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

We manufacture our medicines and drug candidates internally and in some cases with the help of third-party 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 and the facilities of the CMOs we use to manufacture our medicines and drug candidates operate under current good manufacturing practice regulations ("cGMP") conditions.

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

Our Manufacturing Facilities

6 unchanged sentences

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

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

Phases 1 and 2 of the facility were completed in September 2019 and December 2020, respectively, with 24,000 liters of single use disposable capacity.

Additionally, total capacity has been increased to 54,000 liters, with an additional expansion of 10,000 liters expected in the second quarter of 2023, which will bring the final capacity to 64,000.

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

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

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

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

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

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

We have purchased an adjacent tract of land to the south of the current site and initiated the next phase of expansion to support our growing pipeline of large molecule medicines and drug candidates.

We have also commenced construction on our commercial-stage manufacturing and clinical R&D campus at the 42-acre site at the Princeton West Innovation Park in Hopewell, New Jersey.

The property, located strategically in the Interstate 95

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

Contract Manufacturing Organizations

4 unchanged sentences

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

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

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

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

17 unchanged sentences

Collaboration Agreement

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").

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 (as amended, the "Amgen Collaboration Agreement").

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.

2 unchanged sentences

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

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

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.

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

In addition, we 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.

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

Recently, in connection with our ongoing assessment of the Collaboration Agreement cost-share contributions, we determined that our further investment in the development of AMG 510 was no longer commercially viable for BeiGene.

As a result, in February 2023, we entered into an amendment to the Collaboration Agreement to (i) stop sharing costs with Amgen for the further development of AMG 510 during the period starting January 1, 2023 and ending August 31, 2023;

and (ii) cooperate in good faith to prepare a transition plan with the anticipated termination of AMG 510 from the Collaboration Agreement.

BeiGene, Ltd.

6 unchanged sentences

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 to Amgen 206,635,013 ordinary shares in the form of 15,895,001 American Depositary Shares (ADSs) of BeiGene, Ltd.

and Amgen (as amended, 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.

Following the later of (i) the expiration of the lock-up period and (ii) the expiration of the standstill period, Amgen has agreed not to sell shares representing more than 5% of our then outstanding shares in any rolling 12-month period, subject to specified exceptions.

In addition, Amgen will have the right to designate an independent director to serve on our board of directors until the earlier of (a) the date on which Amgen holds less than 10% of our then outstanding shares as a result of Amgen’s sale of ordinary shares or Amgen’s failure to participate in future offerings and (b) the third anniversary of the date of the expiration or termination of the Amgen Collaboration Agreement.

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 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.

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

5 unchanged sentences

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 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:

5 unchanged sentences

Collaboration and License Agreement for Tislelizumab

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

On January 11, 2021, our wholly-owned subsidiary, BeiGene Switzerland GmbH, entered into a Collaboration and License Agreement, which became effective on February 26, 2021 (the “Novartis Collaboration and License Agreement”) with Novartis, pursuant to which Novartis will have the right to develop, manufacture and commercialize tislelizumab in the United States, Canada, Mexico, member countries of the European Union, United Kingdom, Norway, Switzerland, Iceland, Liechtenstein, Russia, and Japan (the “Licensed Territory”).

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

21 unchanged sentences

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

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

ociperlimab with other cancer treatments.

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

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

18 unchanged sentences

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

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

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

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.

10 unchanged sentences

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

With respect to any issued patents in the United

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

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

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

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

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

In China, the Amended PRC Patent Law 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 30, 2023, are summarized below:

16 unchanged sentences

China Antibodies 2033

Pamiparib U.S.

27 unchanged sentences

BLINCYTO ® (blinatumomab)

China No patent N/A

China Use for the treatment of pediatric acute lymphoblastic leukemia 2029

KYPROLIS ® (carfilzomib)

11 unchanged sentences

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 became effective on June 1, 2021, provides both patent term adjustment and patent term extension, similar to the United States.

In China, the Amended PRC Patent Law 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.

12 unchanged sentences

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

Another BTK inhibitor,

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

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

On January 27, 2023, the FDA approved Lilly's JAYPIRCA ™ (pirtobrutinib, a reversible BTK inhibitor) for the treatment of adult patients with R/R MCL after at least two lines of systemic therapy, including a BTK inhibitor.

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

2 unchanged sentences

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

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

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

In China, as of February 1, 2023, there are nine other approved PD-1 antibodies:

There are four approved PD-L1 antibody agents:

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

Akeso's PD-1xCTLA-4 bispecific antibody, KAITANNI ® (cadonilimab) was approved in China.

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

13 unchanged sentences

Government Regulation

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.

Government authorities in the United States, China, Europe and other jurisdictions extensively regulate 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.

6 unchanged sentences

Second line therapies often consist of more chemotherapy, radiation, antibody drugs, tumor targeted small molecule drugs or a combination of these.

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

Third line therapies can include bone marrow transplantation, antibody and small molecule targeted therapies, and 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.

1 unchanged sentence

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 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;

• completion of preclinical laboratory tests and animal studies according to Good Laboratory Practices ("GLP") guidance;

• completion of extensive chemistry, manufacturing, and control ("CMC") studies;

• submission to the FDA of an IND application, which must become effective before human clinical trials may begin;

• 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;

• preparation and submission to the FDA of an NDA for a small molecule drug or a 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;

11 unchanged sentences

Some preclinical testing may continue even after the IND is submitted.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions related to the proposed clinical trial and places the trial on a clinical hold within that 30-day time period.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions related to the proposed clinical trial and places the trial on a

clinical hold within that 30-day time period.

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

7 unchanged sentences

Some trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board or committee.

halting the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

This group provides authorization as to whether or not a trial may move forward at designated check points based on access that only the group maintains to available data from the trial and may recommend halting the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

Each new clinical protocol and any amendments to the protocol must be filed with the FDA as an IND amendment and submitted to the IRBs for approval.

8 unchanged sentences

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

In March 2022, the FDA released a final guidance entitled "Expansion Cohorts:

Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics," which outlines how drug developers can utilize an adaptive trial design commonly referred to as a seamless trial design in early stages of oncology drug development (i.e., the first-in-human clinical trial) to compress the traditional three phases of trials into one continuous trial called an expansion cohort trial.

Information to support the design of individual expansion cohorts are included in IND applications and assessed by the FDA.

Expansion cohort trials can potentially bring efficiency to drug development and reduce developmental costs and time.

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

19 unchanged sentences

This requirement applies on the earlier of the first initiation of a Phase 2 or Phase 3 trial of the investigational drug or, as applicable, 15 days after the drug receives a designation as a breakthrough therapy, fast track product, or regenerative advanced therapy.

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.

Review and Approval Processes

14 unchanged sentences

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.

Data obtained from clinical trials are not always conclusive, and the FDA may interpret data differently than we interpret the same data.

Data obtained from clinical trials are not always conclusive, and the FDA may interpret data differently than we interpret the same

The FDA will issue a complete response letter if the agency decides not to approve the NDA or BLA in its present form.

6 unchanged sentences

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.

The FDA may also approve an NDA or BLA with a Risk Evaluation and Mitigation Strategy 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.

Regulation of Combination Products in the United States

27 unchanged sentences

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 unless otherwise informed by the agency.

Under the Food and Drug Omnibus Reform Act of 2022 ("FDORA"), the FDA is now permitted to require, as appropriate, that post-approval confirmatory trials be underway prior to approval or within a specific time period after accelerated approval is granted.

Failure to conduct required post-approval studies with due diligence, or to confirm a clinical benefit during post-marketing studies, will allow the FDA to withdraw the drug from the market and, under FDORA, the FDA has increased authority for expedited procedures to withdraw approval of a product granted accelerated approval.

In general, all promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA unless otherwise informed by the agency.

Zanubrutinib was granted accelerated approval by FDA for the treatment of adult patients with MCL who have received at least one prior therapy and for the treatment of adult patients with relapsed or refractory MZL who have received at least one anti-CD20-based regimen.

1 unchanged sentence

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

more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

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.

8 unchanged sentences

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.

Designated Platform Technology

Under FDORA, a platform technology incorporated within or utilized by a drug or biologic is eligible for designation as a designated platform technology if (1) the platform technology is incorporated in, or utilized by, a product approved under an NDA or BLA;

(2) preliminary evidence submitted by the sponsor of the approved or licensed product, or a sponsor that has been granted a right of reference to data submitted in the application for such product, demonstrates that the platform

technology has the potential to be incorporated in, or utilized by, more than one product without an adverse effect on quality, manufacturing, or safety;

and (3) data or information submitted by the applicable person indicates that incorporation or utilization of the platform technology has a reasonable likelihood to bring significant efficiencies to the drug development or manufacturing process and to the review process.

A sponsor may request the FDA to designate a platform technology as a designated platform technology concurrently with, or at any time after, submission of an IND application for a product that incorporates or utilizes the platform technology that is the subject of the request.

If so designated, the FDA may expedite the development and review of any subsequent original NDA or BLA for a product that uses or incorporates the platform technology.

Designated platform technology status does not ensure that a product will be developed more quickly or receive FDA approval.

In addition, the FDA may revoke a designation if the FDA determines that a designated platform technology no longer meets the criteria for such designation.

Pediatric Information

18 unchanged sentences

Manufacturers and other entities involved in the manufacturing and distribution of approved products are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws.

The cGMP requirements apply to all stages of the manufacturing process, including the production, processing, sterilization, packaging, labeling, storage and shipment of the product.

The cGMP requirements apply to all stages of the manufacturing process, including the production, processing, sterilization, packaging, labeling, storage and shipment of the

Manufacturers must establish validated systems to ensure that products meet specifications and regulatory requirements and test each product batch or lot prior to its release.

5 unchanged sentences

Depending upon the timing, duration and specifics of FDA approval of the use of our drug candidates, some of our U.S.

patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Amendments.

The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process.

patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Act.

The Hatch-Waxman Act permits a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process.

However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.

14 unchanged sentences

Regulatory exclusivity in the United States can also include pediatric exclusivity and orphan drug exclusivity.

Pediatric exclusivity, if granted, provides an additional six months of exclusivity, which runs from the end of other regulatory exclusivity

or patent periods.

Pediatric exclusivity, if granted, provides an additional six months of exclusivity, which runs from the end of other regulatory exclusivity or patent periods.

This six-month exclusivity may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued ‘‘Written Request’’ for such a trial.

5 unchanged sentences

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

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.

The first biologic product submitted under the abbreviated approval pathway that is determined to be interchangeable with the reference product is eligible for a period of exclusivity against other biologics submitted under the abbreviated approval pathway during which time the FDA may not determine that another product is interchangeable with the same reference product for any condition of use.

The FDA may approve multiple "first" interchangeable products so long as they are all approved on the same first day of marketing.

This exclusivity period, which may be shared amongst multiple first interchangeable products, lasts 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.

16 unchanged sentences

Pharmaceutical Coverage, Pricing, and Reimbursement

In the United States and in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part on the availability of coverage and reimbursement from third-party payors, including government

authorities, managed care providers, private health insurers and other organizations.

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.

7 unchanged sentences

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.

In some foreign countries, the proposed pricing for a drug must be approved before it may be lawfully marketed.

The requirements governing drug pricing vary widely from country to country.

For example, the European Union provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.

To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials that compare the cost effectiveness of a particular product candidate to currently available therapies.

A member state may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our product candidates.

Historically, products launched in the European Union do not follow price structures of the United States and generally prices tend to be significantly lower.

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.

For example, the Affordable Care Act (the ACA) contains provisions that may reduce the profitability of drug products, including, for example, increased rebates for drugs reimbursed by Medicaid programs, extension of Medicaid rebates to Medicaid managed care plans, mandatory discounts for certain Medicare Part D beneficiaries and annual fees based on pharmaceutical companies’ share of sales to federal health care programs.

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

Such adoption of government controls and tightening of restrictive policies could limit payments for pharmaceuticals.

For example, the Affordable Care Act (the "ACA") contains provisions that may reduce the profitability of drug products, including increased rebates for drugs reimbursed by Medicaid programs, extension of Medicaid rebates to Medicaid managed care plans, mandatory discounts for certain Medicare Part D beneficiaries and annual fees based on pharmaceutical companies’ share of sales to federal health care programs.

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.

On June 17, 2021, the U.S.

Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.

Prior to the Supreme Court's decision, President Biden issued an Executive Order to initiate a special enrollment period from February 15, 2021 through August 15, 2021 for purposes of obtaining health insurance coverage through the ACA marketplace.

The Executive Order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

It is unclear how other healthcare reform measures of the Biden administrations or other efforts, if any, to challenge repeal or replace the ACA, will impact our business.

As a result, it is unclear how such efforts to challenge, repeal or replace the ACA, will impact our business.

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

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.”

For example, the Bipartisan Budget Act of 2018 amended the ACA by increasing the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D from 50% to 70% and closing the coverage gap in most Medicare drug plans.

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 December 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.

On April 13, 2017, CMS published a final rule that gives states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces.

On May 23, 2019, CMS published a final rule to allow Medicare Advantage Plans the option of using step therapy for Part B drugs beginning January 1, 2020.

On December 20, 2019, former President Trump signed into law the Further Consolidated Appropriations Act (H.R.

1865), which repealed the Cadillac tax, the health

insurance provider tax, and the medical device excise tax.

It is impossible to determine whether similar taxes could be instated in the future.

There has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed bills designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for pharmaceutical products.

It is unclear whether the Biden administration will challenge, reverse, revoke or otherwise modify the former Trump Administration’s executive and administrative actions after January 20, 2021.

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.

In relation to the COVID-19 pandemic and pursuant to subsequent legislation, this 2% reduction was periodically suspended, but resumed on July 1, 2022.

Further, the American Taxpayer Relief Act 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.

The Centers for Medicare and Medicaid Services ("CMS") published a final rule that gives states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces.

CMS also published a final rule to allow Medicare Advantage Plans the option of using step therapy for Part B drugs.

There has also been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed bills designed to bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for pharmaceutical products.

At the federal level, President Biden directed the FDA to work with states and Indian Tribes that propose to develop section 804 Importation Programs in accordance with the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, and the FDA’s implementing regulations.

The FDA released a final rule, which went into effect in November 2020, providing guidance for states to build and submit importation plans for drugs from Canada.

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 30, 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.

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

In November 2020, the U.S.

Department of Health and Human Services ("HHS") finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through PBMs, 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 PBMs and manufacturers.

Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation of the rule until January 1, 2032.

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.

Further, implementation of this change and new safe harbors for point-of-sale reductions in price for prescription pharmaceutical products and PBM service fees are currently under review by the Biden administration and may be amended or repealed.

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

10 unchanged sentences

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.

There are safe harbor protections under the AKS for certain coordinated care and value-based arrangements among clinicians, providers, and others.

We continue to evaluate what effect, if any, these rules will have on our business;

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

• the federal civil and criminal false claims and civil monetary penalty laws, such as the 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;

6 unchanged sentences

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;

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, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters.

4 unchanged sentences

laws which govern the privacy and security of health and other personal information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts;

• the federal transparency requirements under the ACA, including the provision commonly referred to as the Physician Payments Sunshine Act, which require manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to Centers for Medicare & Medicaid Services information related to payments or other transfers of value made to physicians, nurse practitioners, certified nurse anesthetists, physician assistants, clinical nurse specialists, and certified nurse midwives as well as teaching hospitals.

• the federal transparency requirements under the ACA, including the provision commonly referred to as the Physician Payments Sunshine Act, which require manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to Centers for Medicare & Medicaid Services information related to payments or other transfers of value made to physicians, nurse practitioners, certified nurse anesthetists, anesthesiologist assistants, physician assistants, clinical nurse specialists, and certified nurse midwives as well as teaching hospitals.

Manufacturers are also required to disclose ownership and investment interest held by physicians and their immediate family members;

5 unchanged sentences

These data privacy and security laws may differ from each other in significant ways and often are not pre-empted by HIPAA, which may complicate compliance efforts.

For example, in June 2018, the State of California enacted the California Consumer Privacy Act of 2018 (CCPA), which came into effect on January 1, 2020 and provides new data privacy rights for consumers and new operational requirements for companies.

The CCPA gives California residents expanded rights to access and delete their personal information, opt out of certain personal information sharing, and receive detailed information about how their personal information is used.

For example, in June 2018, the State of California enacted the California Consumer Privacy Act of 2018 ("CCPA"), which gives California residents expanded rights to access and delete their personal information, opt out of certain personal information sharing, and receive detailed information about how their personal information is used.

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.

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).

Further, the California Privacy Rights Act ("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.

3 unchanged sentences

These laws are enforced by various state agencies and through private actions.

Some states have passed laws that require pharmaceutical companies to comply with the April 2003 Office of Inspector General Compliance Program Guidance for Pharmaceutical Manufacturers and/or other voluntary industry codes of conduct that restrict the payments made to healthcare providers and other potential referral sources.

Some states have passed laws that require pharmaceutical companies to comply with the April 2003 Office of Inspector General

Compliance Program Guidance for Pharmaceutical Manufacturers and/or other voluntary industry codes of conduct that restrict the payments made to healthcare providers and other potential referral sources.

Several states and local laws also impose other marketing restrictions or require pharmaceutical companies to make marketing or price disclosures to the state, require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers, and require the registration of pharmaceutical sales representatives.

1 unchanged sentence

There are ambiguities as to what is required to comply with these state requirements and if we fail to comply with an applicable state law requirement we could be subject to penalties.

there are state and foreign laws governing the privacy and security of health information, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

Finally, there are state and foreign laws governing the privacy and security of health information, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

In the United States, to help patients afford our approved product, we may utilize programs to assist them, including patient assistance programs and co-pay coupon programs for eligible patients.

Government enforcement agencies have shown increased interest in pharmaceutical companies' product and patient assistance programs, including reimbursement support services, and investigations into these programs have resulted in significant civil and criminal settlements.

In addition, at least one insurer has directed its network pharmacies to no longer accept co-pay coupons for certain specialty drugs the insurer identified.

Our co-pay coupon programs could become the target of similar insurer actions.

In addition, the CMS issued guidance to the issuers of qualified health plans sold through the ACA's marketplaces encouraging such plans to reject patient cost-sharing support from third parties and indicating that the CMS intends to monitor the provision of such support and may take regulatory action to limit it in the future.

The CMS subsequently issued a rule requiring individual market qualified health plans to accept third-party premium and cost-sharing payments from certain government-related entities.

Furthermore, the Office of Inspector General (“OIG”) of the HHS issued a Special Advisory Bulletin warning manufacturers that they may be subject to sanctions under the federal anti-kickback statute and/or civil monetary penalty laws if they do not take appropriate steps to exclude Part D beneficiaries from using co-pay coupons.

Accordingly, companies exclude these Part D beneficiaries from using co-pay coupons.

It is possible that changes in insurer policies regarding co-pay coupons and/or the introduction and enactment of new legislation or regulatory action could restrict or otherwise negatively affect these patient support programs, which could result in fewer patients using affected products, and therefore could have a material adverse effect on our sales, business, and financial condition.

Third party patient assistance programs that receive financial support from companies have become the subject of enhanced government and regulatory scrutiny.

The OIG has established guidelines that suggest that it is lawful for pharmaceutical manufacturers to make donations to charitable organizations who provide co-pay assistance to Medicare patients, provided that such organizations, among other things, are bona fide charities, are entirely independent of and not controlled by the manufacturer, provide aid to applicants on a first-come basis according to consistent financial criteria and do not link aid to use of a donor's product.

However, donations to patient assistance programs have received some negative publicity and been the subject of multiple government enforcement actions, related to allegations regarding their use to promote branded pharmaceutical products over other less costly alternatives.

Specifically, in recent years, there have been multiple settlements resulting out of government claims challenging the legality of their patient assistance programs under a variety of federal and state laws.

The scope and enforcement of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of applicable precedent and regulations.

3 unchanged sentences

EU and UK Data Protection Laws

In the European Union (EU), the General Data Protection Regulation (GDPR) governs the processing of personal data.

(see below), providing details to those individuals regarding the processing of their personal data, implementing safeguards to keep personal data secure, having data processing agreements with third parties who process personal data, providing information to individuals regarding data processing activities, responding to individuals’ requests to exercise their rights in respect of their personal data, obtaining consent of the individuals to whom the personal data relates, reporting security and privacy breaches involving personal data to the competent national data protection authority and affected individuals, appointing data protection officers, conducting data protection impact assessments, and record-keeping.

The GDPR substantially increases the penalties to which we could be subject in the event of any non-compliance, including fines of up to €20,000,000 or 4% of total annual global revenue, whichever is greater.

In the EU, the General Data Protection Regulation ("GDPR") governs the processing of personal data.

The GDPR imposes a broad range of strict requirements on companies subject to the GDPR, such as including requirements relating to having legal bases for processing personal data relating to identifiable individuals and transferring such information outside the European Economic Area ("EEA"), including to the U.S., providing details to those individuals regarding the processing of their personal data, implementing safeguards to keep personal data secure, having data processing agreements with third parties who process personal data, providing information to individuals regarding data processing activities, responding to individuals’ requests to exercise their rights in respect of their personal data, obtaining consent of the individuals to whom the personal data relates, reporting security and privacy breaches involving personal data to the competent national data protection authority and affected individuals, appointing data protection officers, conducting data protection impact assessments, and record-keeping.

substantially increases the penalties to which we could be subject in the event of any non-compliance, including fines of up to €20,000,000 or 4% of total annual global revenue, whichever is greater.

The GDPR increases the responsibility and liability of pharmaceutical companies in relation to processing personal data, and companies may be required to put in place additional mechanisms to ensure compliance with the new EU data protection rules.

3 unchanged sentences

Non-compliance with the UK GDPR may result in monetary penalties of up to £17.5 million or 4% of worldwide revenue, whichever is higher.

Although the UK is regarded as a third country under the EU’s GDPR, the European Commission (EC) has now issued a decision recognizing the UK as providing adequate protection under the EU GDPR and, therefore, transfers of personal data originating in the EU to the UK remain unrestricted.

Although the UK is regarded as a third country under the EU’s GDPR, the EC has now issued a decision recognizing the UK as providing adequate protection under the EU GDPR and, therefore, transfers of personal data originating in the EU to the UK remain unrestricted.

Like the EU GDPR, the UK GDPR restricts personal data transfers outside the UK to countries not regarded by the UK as providing adequate protection.

13 unchanged sentences

The DAL applies to entities and individuals engaged in the development, production, trade, clinical use, as well as supervision and administration of pharmaceutical products by regulatory agencies.

It provides for a framework for

regulating pharmaceutical manufacturers, pharmaceutical trading companies, medical institutions, and the research, development, manufacturing, distribution, packaging, pricing, and advertisement activities related to pharmaceutical products.

It provides for a framework for regulating pharmaceutical manufacturers, pharmaceutical trading companies, medical institutions, and the research, development, manufacturing, distribution, packaging, pricing, and advertisement activities related to pharmaceutical products.

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

9 unchanged sentences

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

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

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

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

Pursuant to the rDAL, NMPA and its local counterparts are directed to strengthen their surveillance of drug manufacturers and distributors, including through regular and continuous site inspections, to ensure their compliance.

Pursuant to the rDAL, NMPA

and its local counterparts are directed to strengthen their surveillance of drug manufacturers and distributors, including through regular and continuous site inspections, to ensure their compliance.

It remains to be seen how clinical trial institutions will ensure self-compliance with GCP requirements and whether there will be more inspections of clinical trial institutions.

17 unchanged sentences

The NMPA is no longer an independent agency.

Its parent agency is the State Administration of Market Regulation (the SAMR), into which agencies responsible for, among other areas, consumer protection, advertising, anticorruption, antitrust, fair competition and intellectual property have been merged.

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).

The Center for Drug Evaluation (CDE), which remains under the NMPA, conducts the technical evaluation of each drug and biologic application for safety and efficacy.

The National Health Commission (NHC) (formerly known by the names Ministry of Health (MOH) and National Health and Family Planning Commission (NHFPC)), is China’s chief healthcare regulator.

Its parent agency is the State Administration for 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.

The CDE, which remains under the NMPA, conducts the technical evaluation of each drug and biologic application for safety and efficacy.

The National Health Commission ("NHC") is China’s chief healthcare regulator.

It is primarily responsible for overseeing the operation of medical institutions, which also serve as clinical trial sites, and regulating the licensure of hospitals and other medical personnel.

9 unchanged sentences

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;

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;

(2) lab animals must be qualified and sourced from institutions with Certificates for Production of Lab Animals;

30 unchanged sentences

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

XGEVA ® received conditional approval for the treatment of adults and skeletally mature adolescents with giant cell tumor of the bone (GCTB) that is unresectable or where surgical resection is likely to result in severe morbidity and for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors and in patients with multiple myeloma.

BLINCYTO ® received conditional approval for the treatment of adult patients with R/R B-cell precursor acute lymphoblastic leukemia.

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 SREs in patients with bone metastases from solid tumors and in patients with multiple myeloma.

BLINCYTO received conditional approvals for the treatment of both adult and pediatric patients with R/R B-cell precursor acute lymphoblastic leukemia.

KYPROLIS received conditional approval for the treatment of adult patients with R/R multiple myeloma.

27 unchanged sentences

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.

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

10 unchanged sentences

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.

The HGR Regulation retains the provision in the Interim Measures for the Administration of Human Genetic Resources issued in 1998 that parties should jointly apply for and own the patent rights arising from the results generated from international collaborations that utilize China HGR.

Subject to approval, the parties may contractually agree on how to dispose of their patent rights and non-patent proprietary rights arising from the collaboration.

As the joint ownership requirement is rather broad, it is unclear how this requirement will be implemented in practice.

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.

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.

We expect that HGR-related activities will receive greater attention and focus from regulators going forward.

3 unchanged sentences

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.

38 unchanged sentences

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.

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

17 unchanged sentences

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

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.

22 unchanged sentences

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.

Program participants are eligible for full or partial reimbursement of the cost of medicines included in the National Reimbursement Drug List (the NRDL).

Program participants are eligible for full or partial reimbursement of the cost of medicines included in the NRDL.

A pharmaceutical product listed in the NRDL must be clinically needed, safe, effective, reasonably priced, easy to use, and available in sufficient quantity.

1 unchanged sentence

Since 2016, special consideration has been given to, among others, innovative drugs with high clinical value and drugs for 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.

In addition, the government has also been negotiating with manufacturers of exclusive 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 2023 covers approximately 3,000 drugs in total, including 147 drugs for which the prices were determined through negotiations between the drug companies and government.

2 unchanged sentences

VIDAZA has been included in the NRDL since 2018.

BRUKINSA ® (zanubrutinib), tislelizumab, and XGEVA ® (120-mg denosumab) have been included in the NRDL in March 2021.

PARP inhibitor pamiparib has been included in the NRDL in 2021, which became effective as of January 1, 2022.

BRUKINSA (zanubrutinib), tislelizumab, and XGEVA (120-mg denosumab) have been included in the NRDL since 2021.

PARP inhibitor pamiparib has been included in the NRDL since 2022.

KYPROLIS was included for the first time in the NRDL in January 2023, which will take effect on March 1, 2023.

Government Price Controls

63 unchanged sentences

In 2019, SAFE issued the Circular of the State Administration of Foreign Exchange on Further Promoting the Facilitation of Cross-border Trade and Investment ("Circular 28").

Circular 28 allows non-investment foreign-invested enterprises to use their

capital funds to make equity investments in China, provided that such investments do not violate the effective Special Entry Management Measures for Foreign Investment (Negative List) and the target investment projects are genuine and in compliance with laws.

Circular 28 allows non-investment foreign-invested enterprises to use their capital funds to make equity investments in China, provided that such investments do not violate the effective Special Entry Management Measures for the Access of Foreign Investment (Negative List) and the target investment projects are genuine and in compliance with laws.

The interpretation and implementation of Circular 28 in practice are subject to substantial uncertainty.

10 unchanged sentences

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.

Regulations Relating to Overseas Listing

On February 17, 2023, the CSRC released the Trial Administrative Measures of Overseas Securities Offering and Listing by Domestic Companies, or the Overseas Listing Trial Measures, and five relevant guidelines, which will take effect from March 31, 2023, requiring Chinese domestic companies’ overseas offerings and listings of equity securities be filed with the CSRC.

The Overseas Listing Trial Measures clarify the scope of overseas offerings and listings by Chinese domestic companies which are subject to the filing and reporting requirements thereunder, and provide, among others, that Chinese domestic companies that have already directly or indirectly offered and listed securities in overseas markets prior to the effectiveness of the Overseas Listing Trial Measures shall fulfil their filing obligations and report relevant information to the CSRC within three working days after conducting a follow-on offering of equity securities on the same overseas market, and follow the relevant reporting requirements within three working days upon the occurrence of any specified circumstances provided thereunder.

According to the Overseas Listing Trial Measures, if we were deemed as an indirect overseas listed Chinese domestic company but fail to complete the filing procedures with the CSRC for any of our follow-on offerings or follow any other reporting requirements required thereunder, we may be subject to penalties, sanctions and fines imposed by the CSRC and relevant departments of the State Council.

Rest of World Regulation

1 unchanged sentence

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.

Status under Holding Foreign Companies Accountable Act

In December 2021, the SEC adopted rules (the “Final Rules”) to implement the Holding Foreign Companies Accountable Act (the “HFCAA”).

The HFCAA includes requirements for the SEC to identify issuers who file annual reports with audit reports issued by independent registered public accounting firms located in foreign jurisdictions that the Public Company Accounting Oversight Board (“PCAOB”) is unable to inspect or investigate completely because of a position taken by a non-U.S.

authority in the accounting firm’s jurisdiction (“Commission-Identified Issuers”).

The HFCAA also requires that, to the extent that the PCAOB has been unable to inspect an issuer’s independent registered public accounting firm for three consecutive years since 2021, the SEC shall prohibit the issuer’s securities registered in the United States from being traded on any national securities exchange or over-the-counter markets in the United States.

In December 2022, the Accelerating Holding Foreign Companies Accountable Act amended the HFCAA to shorten the three-year period to two years.

Under the Final Rules, the SEC adopted submission and disclosure requirements by amending Form 10-K and other annual reporting forms and established procedures to identify issuers and prohibit the trading of the securities of certain registrants as required by the HFCAA.

Specifically, the Final Rules require each Commission-Identified Issuer to submit documentation to the SEC annually on or before its annual report due date that establishes that it is not owned or controlled by a government entity in its public accounting firm’s foreign jurisdiction and require additional specified disclosures by “foreign issuers” as defined in Rule 3b-4 promulgated under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

The SEC identifies an issuer as a Commission-Identified Issuer after the issuer files its annual report and on a rolling basis, and will impose an initial trading prohibition on an issuer as soon as practicable after it has been conclusively identified as a Commission-Identified Issuer for two consecutive years.

To end an initial or subsequent trading prohibition, a Commission-Identified Issuer must certify that it has retained a registered public accounting firm that the PCAOB has determined it is able to inspect or investigate.

To make that certification, the Commission-Identified Issuer must file financial statements that include an audit report signed by such a registered public accounting firm.

On March 30, 2022, as expected following its adoption of the Final Rules, the SEC added BeiGene, Ltd.

to its conclusive list of issuers identified under the HFCAA, after being provisionally named as a Commission-Identified Issuer on March 8, 2022, following the filing of its annual report on Form 10-K with the SEC on February 28, 2022.

Ernst & Young Hua Ming LLP, located in the PRC, served as our independent registered public accounting firm from 2014 to 2021, including for our annual report on Form 10-K for the year ended December 31, 2021.

However, as our global business has expanded, we have built substantial organizational capabilities outside of the PRC and have evaluated, designed and implemented business processes and control changes.

Therefore, on March 23, 2022, following a review process carried out by our audit committee, Ernst & Young Hua Ming LLP resigned as our independent registered public accounting firm for the audits of our financial statements and internal control over financial reporting to be filed with the SEC.

On the same day, our audit committee approved the engagement of Ernst & Young LLP, located in Boston, Massachusetts, United States, as the Company’s

independent registered public accounting firm for the audits of our financial statements and internal control over financial reporting for the fiscal year ending December 31, 2022.

No changes were made to the accounting firms who audit our financial statements filed with the Shanghai Stock Exchange and the Hong Kong Stock Exchange, which will remain Ernst & Young Hua Ming LLP, located in Beijing, PRC, and Ernst & Young, located in Hong Kong, PRC, respectively.

In August 2022, the PCAOB signed a Statement of Protocol with the CSRC and the Ministry of Finance of the People's Republic of China, taking the first step toward opening access for the PCAOB to inspect and investigate registered public accounting firms headquartered in mainland China and Hong Kong.

PCAOB staff members conducted on-site inspections and investigations from September to November 2022, and in December 2022, the PCAOB announced that it has secured complete access to inspect and investigate registered public accounting firms headquartered in mainland China and Hong Kong and confirmed that until such time as the PCAOB issues any new determination, there are no Commission-Identified Issuers at risk of having their securities subject to a trading prohibition under the HFCAA.

Given that Ernst and Young LLP (United States) now serves as the principal accountant to audit our consolidated financial statements to be filed with the SEC, we believe we are compliant with the HFCAA, which should preclude a further finding by the SEC that we are a Commission-Identified Issuer and therefore the delisting of our American Depositary Shares from the NASDAQ Global Select Market.

For a detailed description of risks related to our doing business in China and status under the HFCAA, see "Item 1A.

Risk Factors - Risks Related to Our Doing Business in the PRC.".

Doing Business in the PRC

As a result of our operations in the PRC, the PRC government may exert influence over our operations at any time, which could result in a material change in our operations and/or the value of our ADSs, ordinary shares, or RMB Shares.

For example, the PRC government has recently published new policies that significantly affected certain industries such as the education and internet industries, and we cannot rule out the possibility that it will in the future release regulations or policies regarding any industry that could adversely affect the business, financial condition and results of operations of our company.

Furthermore, the PRC government has also recently indicated an intent to exert more oversight and control over securities offerings and other capital markets activities that are conducted outside of China and over foreign investment in China-based companies.

Any such action, once taken by the PRC government, could significantly limit or completely hinder our ability to offer or continue to offer securities to investors and cause the value of such securities to significantly decline or in extreme cases, become worthless.

Recently, the PRC government initiated a series of regulatory actions and statements to regulate business operations in China, including enforcement actions against illegal activities in the securities market, enhancing supervision over China-based companies listed outside of China using the variable interest entity structure, adopting new measures to extend the scope of cybersecurity reviews, and expanding the efforts in anti-monopoly enforcement.

For example, in July 2021, the relevant PRC government authorities made public the Opinions on Intensifying Crack-Down on Illegal Securities Activities (the "Securities Opinions") which emphasized the need to strengthen the administration over illegal securities activities and the supervision on overseas listings by China-based companies and proposed to take measures, such as promoting the construction of relevant regulatory systems to deal with the risks and incidents faced by China-based overseas-listed companies.

In November 2021, the Cyberspace Administration of China (the “CAC”) released the draft Administrative Regulations on Cyber Data Security for public comments, which requires, among others, that a prior cybersecurity review should be required for listing abroad of data processors which process over one million users’ personal information, and the listing of data processors in Hong Kong which affects or may affect national security.

On February 17, 2023, the CSRC released the Overseas Listing Trial Measures, and five relevant guidelines, which will take effect from March 31, 2023, requiring the Chinese domestic companies’ overseas offerings and listings of equity securities be filed with the CSRC.

The Chinese government may further promulgate relevant laws, rules and regulations that may impose additional and significant obligations and liabilities on overseas listed PRC companies regarding data security, cross-border data flow, anti-monopoly and unfair competition, and compliance with China’s securities laws.

It is uncertain whether or how these new laws, rules and regulations and the interpretation and implementation thereof may affect us, but among other things, our ability to obtain external financing through the issuance of equity securities in the United States, Hong Kong or other markets could be negatively affected, and as a result, the trading prices of our ADSs, ordinary shares and RMB Shares could significantly decline or become worthless.

For a detailed description of risks related to our doing business in China, please see the section of this Annual Report titled “Item 1A.

Risk Factors—Risks Related to Our Doing Business in the PRC.”

Flow of Funds with our PRC Operations

We are a holding company incorporated in the Cayman Islands with operations primarily conducted through subsidiaries in the United States, China, United Kingdom, Switzerland and Australia.

The intercompany flow of funds within the organization is effected through capital contributions and intercompany loans.

Since our formation in 2010, BeiGene, Ltd.

has raised over $10.0 billion in various public and private stock offerings as of December 31, 2022.

Of this amount, $1.9 billion and RMB 18.6

billion have been transferred as capital contributions to its operating subsidiaries;

and $79 million and RMB 4.4 billion have been transferred as intercompany loans to its operating subsidiaries.

BeiGene, Ltd., by itself or through its affiliates, is also the holder or licensee and developer of biopharmaceutical patents.

Certain of these patents have been transferred to operating subsidiaries for further development and commercialization.

BeiGene’s wholly owned subsidiaries compensate each other for the intercompany provision of goods and services on an arm’s length basis.

As of December 31, 2022, BeiGene, Ltd.

held $4.5 billion in cash, cash equivalents and short-term investments which are available for future investment in its programs and in our operating subsidiaries.

To date, BeiGene, Ltd.

has not received any dividends or distributions from its operating subsidiaries.

Further, our board of directors has adopted a dividend policy which provides that we currently intend to retain all available funds and earnings, if any, to fund the development and expansion of our business, and we do not anticipate paying any cash dividends in the foreseeable future.

Subject to applicable law and our amended and restated articles of association, any future determination to pay dividends will be made at the discretion of our board of directors and may be based on a number of factors, including our future operations and earnings, capital requirements and surplus, general financial condition, contractual restrictions and other factors that our board of directors may deem relevant.

This dividend policy reflects our board of directors’ current views on our financial and cash flow position.

We intend to continue to review our dividend policy from time to time, and there can be no assurance that dividends will be paid in any particular amount, if at all, for any given period.

We have never declared or paid any dividends on our ordinary shares or any other securities.

If we pay dividends in the future, in order for us to distribute dividends to our shareholders and holders of ADSs, we may rely to some extent on dividends distributed by our PRC subsidiaries.

PRC regulations may restrict the ability of our PRC subsidiaries to pay dividends to us, and such distributions will be subject to PRC withholding tax.

In addition, PRC regulations currently permit payment of dividends of a PRC company only out of accumulated distributable after-tax profits, as determined in accordance with our articles of association and the accounting standards and regulations in the PRC.

We may rely on dividends and other distributions on equity paid by our PRC subsidiaries for our cash and financing requirements, including the funds necessary to pay dividends and other cash distributions to our shareholders or to service any debt we may incur.

If any of our PRC subsidiaries incur debt on their own behalf in the future, the instruments governing the debt may restrict their ability to pay dividends or make other distributions to us.

Under PRC laws and regulations, our PRC subsidiaries may pay dividends only out of their respective accumulated profits as determined in accordance with PRC accounting standards and regulations.

In addition, a wholly foreign-owned enterprise is required to set aside at least 10% of its accumulated after-tax profits each year, if any, to fund a certain statutory reserve fund, until the aggregate amount of such fund reaches 50% of its registered capital.

Such reserve funds cannot be distributed to us as dividends.

At its discretion, a wholly foreign-owned enterprise may allocate a portion of its after-tax profits based on PRC accounting standards to an enterprise expansion fund, or a staff welfare and bonus fund.

In addition, registered share capital and capital reserve accounts are also restricted from withdrawal in the PRC, up to the amount of net assets held in each operating subsidiary.

As of December 31, 2022, these restricted assets totaled $3.5 billion.

Our PRC subsidiaries generate primarily all of their revenue in RMB, which is not freely convertible into other currencies.

As a result, any restriction on currency exchange may limit the ability of our PRC subsidiaries to use their RMB revenues to pay dividends to us.

However, conversion of RMB to other currencies are permitted for the purpose of dividends according to the PRC’s regulations on Foreign Exchange Control.

Further, in response to the persistent capital outflow in the PRC and RMB’s depreciation against the U.S.

dollar in the fourth quarter of 2016, the People’s Bank of China and the SAFE promulgated a series of capital control measures, including stricter vetting procedures for domestic companies to remit foreign currency for overseas investments, dividends payments and shareholder loan repayments.

Such measures were relaxed in mid-2017 with the slowdown of the capital outflow and stabilizing of the RMB.

However, the PRC government may revert to strengthen its capital controls, and more restrictions and substantial vetting process may be put forward by the SAFE for cross-border transactions falling under both the current account and the capital account.

Any limitation on the ability of our PRC subsidiaries to pay dividends or make other kinds of payments to us could materially and adversely limit our ability to grow, make investments or acquisitions that could be beneficial to our business, pay dividends, or otherwise fund and conduct our business.

The PRC Enterprise Income Tax Law and its implementation rules provide that China-sourced income of foreign enterprises, such as dividends paid by a PRC subsidiary to its equity holders that are non-PRC resident enterprises, will normally be subject to PRC withholding tax at a rate of 10%, unless any such foreign investor’s jurisdiction of incorporation has a tax treaty with China that provides for a reduced withholding rate arrangement and such non-PRC resident enterprises constitute the beneficiary of such income.

Pursuant to an arrangement between Mainland China and the Hong Kong Special Administrative Region and relevant tax regulations of the PRC, subject to certain conditions, a reduced withholding tax rate of 5% will be available for dividends from

PRC entities provided that the recipient can demonstrate it is a Hong Kong tax resident and it is the beneficial owner of the dividends.

The government adopted regulations in 2018 which stipulate that in determining whether a non-resident enterprise has the status as a beneficial owner, comprehensive analysis shall be conducted based on the factors listed therein and the actual circumstances of the specific case shall be taken into consideration.

Specifically, it expressly excludes an agent or a designated payee from being considered as a “beneficial owner.” We own the PRC subsidiaries through BeiGene HK.

BeiGene HK currently does not hold a Hong Kong tax resident certificate from the Inland Revenue Department of Hong Kong, and there is no assurance that the reduced withholding tax rate will be available.

Permissions Required from the PRC Authorities for Our Operations

We conduct our business in the PRC through our PRC subsidiaries.

Our operations in the PRC are governed by PRC laws and regulations.

As of the date of this annual report, our PRC subsidiaries have obtained all requisite licenses and permits from the PRC government authorities that are material for their business operations in the PRC, including, among others, business licenses issued by local counterparts of the SAMR, drug manufacturing licenses, drug trade license, CTAs, drug registration certificates, licenses for use of experimental animals, pollutant discharge licenses and permits for urban sewage discharge into drainage pipe network.

No material permissions have been denied to us by relevant government authorities in China.

As of the date of this annual report, we do not operate our businesses in China or elsewhere through variable interest entities, or VIEs, and therefore are not subject to risks associated with contractual arrangements with VIEs.

As of the date of this annual report, we have not received any inquiry, notice, warning, or sanctions regarding our business operations and corporate structure from the CSRC, CAC or any other PRC governmental agency that would have a material impact on our business, results of operations or financial condition.

However, given the uncertainties of interpretation and implementation of relevant laws and regulations and the enforcement practice by government authorities, we cannot assure you that we have obtained all the permits or licenses required for conducting our business in the PRC.

If (i) we have inadvertently concluded that such permissions, approvals, licenses or permits have been acquired or are not required, or (ii) applicable laws, regulations, or interpretations change and we are required to obtain such permissions, approvals, licenses or permits in the future, then we may have to expend time and costs to procure them.

If we are unable to do so on commercially reasonable terms or in a timely manner, it could cause significant disruption to our business operations and damage our reputation, which would in turn have a material adverse effect on our business, results of operations and financial condition.

In connection with our previous issuance of securities to foreign investors in stock markets outside the PRC, under current PRC laws, regulations and regulatory rules, as of the date of this annual report, we and our PRC subsidiaries, (i) are not required to obtain permissions from the CSRC, (ii) are not required to go through cybersecurity review by the Cyberspace Administration of China, or the CAC, and (iii) have not received or were denied such requisite permissions by any PRC authority.

On February 17, 2023, the CSRC released the Overseas Listing Trial Measures and five relevant guidelines, which will take effect from March 31, 2023.

The Overseas Listing Trial Measures require the Chinese domestic companies’ overseas offerings and listings of equity shares, depositary receipts, convertible bonds, preferred shares or other equity securities be filed with the CSRC.

Business – Government Regulation – PRC Regulation – Regulations Relating to Overseas Listing”.

If we were deemed as an indirect overseas listed Chinese domestic company subject to the filing requirements under the Overseas Listing Trial Measures, our offering of equity securities on the NASDAQ Global Select Market or Hong Kong Stock Exchange in the future would be required to be filed with the CSRC within three working days after the offering is completed.

As of the date of this annual report, we have not received any inquiry, notice, warning or sanction regarding obtaining approval, completing filing or other procedures in connection with offering our equity securities in overseas stock markets from the CSRC or any other PRC governmental or regulatory authorities that have jurisdiction over our operations.

However, there remains significant uncertainty as to the interpretation and implementation of regulatory requirements related to overseas securities offerings and other capital markets activities, including the Overseas Listing Trial Measures.

If it is determined that filing or other procedure with the CSRC or any other regulatory authority is required for issuing our equity securities in overseas stock markets, it is uncertain whether we will be able to and how long it would take for us to complete the filing despite our efforts.

If we, for any reason, are unable to complete, or experience significant delays in completing the requisite filing or other procedure(s), we may face sanctions by the CSRC or other Chinese regulatory authorities as applicable.

These regulatory authorities may impose fines and penalties on our operations in the PRC, limit our ability to pay dividends outside of China, limit our operations in the PRC, delay or restrict the repatriation of funds into the PRC or take other actions that could have a material adverse effect on our business, financial condition, results of operations and prospects, as well as the trading price of our ADSs, ordinary shares and RMB Shares.

Cash Management Policies and Procedures

Under our Capitalization and Financing Policy, the frequency and amount of intercompany transfers of funds is determined based on the working capital needs of our subsidiaries and intercompany transactions, and is subject to internal approval

processes and funding arrangements.

Our management reviews and monitors our cash flow forecast and working capital needs of our subsidiaries on a regular basis.

In addition, capital contributions and intercompany loan arrangements are subject to local jurisdiction and banking regulations.

In this regard, we have not faced difficulties or limitations in our ability to transfer cash between subsidiaries in any of our operating jurisdictions.

During the normal course of our business, cash is transferred between our subsidiaries via wire transfer to and from bank accounts to pay certain business expenses.

Cash is maintained by BeiGene, Ltd.

in its bank account and transferred to its subsidiaries when necessary to strengthen our business capabilities, such as paying for new office development, or marketing expenses.

In addition, cash may be used by BeiGene, Ltd.

to meet corporate expenses such as audit fees, attorneys’ fees, stock exchange listing fees, IR/PR expenses, research and development costs and corporate administrative support expenses.

Cash is transferred between subsidiaries in the form of capital contributions or through intercompany advances or loans, as follows:

• Cash may be transferred between BeiGene HK and its operating subsidiaries in mainland China through intercompany loans and capital contributions, and there are currently no restrictions on transferring funds between BeiGene HK and its subsidiaries in mainland China.

Cash generated from BeiGene HK is used to fund operations of its subsidiaries, and no funds were transferred from BeiGene HK’s subsidiaries in mainland China to fund operations of other BeiGene subsidiaries outside of mainland China for the year ended on December 31, 2021 and December 31, 2022.

For the year ended December 31, 2021 and December 31, 2022, the amount of cash transferred between BeiGene HK and its subsidiaries in mainland China was $44 million and $351 million, respectively.

• Cash may be transferred between BeiGene UK and/or BeiGene Switzerland and their respective operating subsidiaries through intercompany fund advances and capital contributions.

There are currently no restrictions on transferring funds between BeiGene UK or BeiGene Switzerland and their respective operating subsidiaries.

Cash generated from BeiGene UK and BeiGene Switzerland are used to fund operations of their respective subsidiaries, and no funds were transferred from BeiGene UK’s subsidiaries or from BeiGene Switzerland’s subsidiaries to fund operations of other BeiGene subsidiaries (such as BeiGene HK and its subsidiaries in mainland China) for the year ended on December 31, 2021 and December 31, 2022.

For the year ended December 31, 2021 and December 31, 2022, the amount of cash transferred between BeiGene UK to its respective subsidiaries was $2 million and $4 million, respectively.

For the years ended December 31, 2021 and December 31, 2022, the amount of cash transferred between BeiGene Switzerland to its respective subsidiaries was $25 million and $65 million, respectively.

Human Capital Resources

37 unchanged sentences

We have never experienced any employment-related work stoppages, we also track voluntary and involuntary turnover rates and we consider our relations with our employees to be good.

Environmental, Social and Governance (ESG) Strategy

Environmental, Social and Governance Strategy

BeiGene’s mission is to expand access to high-quality, affordable medicines to billions more people globally.

We are driven to deliver affordable medicines to all and create a more equitable and sustainable world for our patients, employees, and our communities.

In 2021, we formalized our ESG function, led by a new Senior Director, Global Reputation and ESG Lead who has led the development of a new global ESG strategy and framework which will be announced in our 2021 ESG Report, published in late April 2022.

We expect to use this new framework to guide the development of goals and targets for our most material issues, and it will center around five key focus areas that are designed to speak to the needs of our diverse stakeholders.

Within each focus area, we have identified two strategic priorities against which we will set concrete targets and report our progress.

In 2022, we announced our global ESG strategy, Change Is the Cure , which guides our efforts across five focus areas:

advancing global health, empowering people, innovating sustainably, supporting communities, and operating responsibly.

Within each focus area, we have identified two strategic priorities against which we have set concrete targets.

We will report our progress against these targets and announce new goals in our 2022 ESG Report which will be published in late April 2023.

While we are at the start of our ESG journey, we are proud of the progress we have made to date.

We have conducted our first global greenhouse gas inventory for scopes 1 and 2 emissions and plan to announce new measures to understand and further mitigate our climate impacts in 2022.

We have implemented a new Supplier Code of Conduct which outlines our expectations related to good governance, labor practices, environment, health and safety (EHS), and transparency.

In 2021, we refined our company values to four that encapsulate what it means to be a part of BeiGene.

These values are:

Patients First;

Collaborative Spirit;

Bold Ingenuity;

and Driving Excellence.

We joined the United Nations Global Compact in 2022 and have aligned our efforts with UN Sustainable Development Goals.

In 2022, we announced new measures to understand and further mitigate our climate impacts.

We will share progress on those measures and announce new targets in our 2022 ESG Report.

We know that access to oncology treatments lags in many parts of the world, particularly in low-income countries.

To help close this health equity gap, BeiGene became a founding member of the Union for International Cancer Control’s Access to Oncology Medicines Coalition which focuses on improving access to innovative medicines in lower-income countries and supporting them in developing the capacity to provide proper treatment for patients.

We believe that our people are critical to our success and, as a global company, we know that sharing diverse ideas and perspectives spurs greater innovation and enhances our ability to deliver results.

2 unchanged sentences

employees to explore issues of diversity, equity, inclusion, and belonging.

In 2021, we hired a Vice President to lead diversity, equity, and inclusion (DEI) and will expand the IDEA Council to have representation beyond the U.S.

Introduced first in the U.S., the IDEA Council is now global, with members in geographies including Canada, Europe, China, and Australia.

In 2022, we completed a three-year diversity, equity, inclusion and belonging strategy.

Details will be shared in our 2022 ESG Report.

In addition to directly supporting patients through the delivery of cutting-edge therapies, we strive to support our communities through research, education, and sponsorships.

4 unchanged sentences

Financial Information

The financial information required under this Item 1 is incorporated herein by reference to the section of this Annual Report titled “Part II-Item 8-Financial Statements and Supplementary Data.” For financial information regarding our business, see “Part II-Item 7-Management’s Discussion and Analysis of Financial Condition and Results of Operations” of this Annual Report and our consolidated audited financial statements and related notes included elsewhere in this Annual Report.

The financial information required under this Item 1 is incorporated herein by reference to the section of this Annual Report titled “Part II-Item 8-Financial Statements and Supplementary Data.” For financial information regarding our business, please see the section of this Annual Report titled “Part II-Item 7-Management’s Discussion and Analysis of Financial Condition and Results of Operations” of this Annual Report and our consolidated audited financial statements and related notes included elsewhere in this Annual Report.

Corporate Information

9 unchanged sentences

Available Information

We make available on or through our website certain reports and amendments to those reports that we file with or furnish to the SEC, in accordance with the Securities Exchange Act of 1934, as amended (the "Exchange Act").

We make available on or through our website certain reports and amendments to those reports that we file with or furnish to the SEC, in accordance with the Exchange Act.

These include our annual reports on Form 10-K, our quarterly reports on Form 10-Q, and our current reports on Form 8-K, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act.

We also make available, free of charge on our website, the reports filed with the SEC by our executive officers, directors and 10% shareholders pursuant to Section 16 under the Exchange Act.

Additionally, we make available on our website our securities filings with the HKEx and the Shanghai Stock Exchange (SSE).

Additionally, we make available on our website our securities filings with the HKEx and the Shanghai Stock Exchange.

We make this information available on or through our website free of charge as soon as reasonably practicable after we electronically file the information with, or furnish it to, the SEC, the HKEx, and the SSE.

1 unchanged sentence

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